Ομοιοπαθητική Θεσσαλονίκη | omoiotherapeia.gr
Ομοιοπαθητική Θεσσαλονίκη | omoiotherapeia.gr
Ομοιοπαθητική Θεσσαλονίκη | omoiotherapeia.gr
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Ομοιοπαθητική Θεσσαλονίκη | omoiotherapeia.gr
Ομοιοπαθητική Θεσσαλονίκη | omoiotherapeia.gr
Ομοιοπαθητική Θεσσαλονίκη | omoiotherapeia.gr

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Περιγράφονται  ΠΕΡΙΠΤΩΣΕΙΣ με σοβαρά  ή σύνθετα χρόνια προβλήματα υγείας , οι οποιες αντιμετωπίσθηκαν με επιτυχία με Ομοιοπαθητική στην "Ομοιοπαθητική Φροντίδα Υγείας" 

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Κλείνετε το ραντεβού σας τηλεφωνικά ή μεσω email  για  συγκεκριμενη μέρα και ωρα, κατά τροπο που η συνεντευξη να γίνεται με την απαραιτητη άνεση χρόνου .Μπορειτε να στειλετε με email πριν το ραντεβου μια συνοψη των προβληματων υγείας που αντιμετωπίζετε και των θεραπειων που εχετε κανει ή κανετε ήδη

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Γίνεται μια διεξοδική συζητηση και αποτυπωση των προβλημάτων και διαταραχων της Υγείας σας και των παθήσεων,ανασκοπηση προηγούμενων εργαστηριακών εξετάσεων ,θεραπειων και των πλέον σημαντικών δεδομένων απο το ατομικό  ιστορικό

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ΟΜΟΙΟΠΑΘΗΤΙΚΕΣ ΣΥΝΕΝΤΕΥΞΕΙΣ και μέσω Skype

 

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Ιπποκρατική Ιατρική, Ομοιοπαθητική, Σύγχρονη Ιατρική
ΠΑΘΗΣΕΙΣ /

ΚΑΡΚΙΝΟΣ -KAKOΗΘΕΙΣ ΟΓΚΟΙ-ΚΑΚΟΗΘΗ ΝΕΟΠΛΑΣΜΑΤΑ

 

ΤΙ ΕΠΙΔΙΩΚΕΙ ΚΑΙ ΤΙ ΜΠΟΡΕΙ ΝΑ ΠΕΤΥΧΕΙ Η ΚΛΑΣΣΙΚΗ ΚΛΙΝΙΚΗ ΟΜΟΙΟΠΑΘΗΤΙΚΗ ΣΤΟΥΣ ΠΑΣΧΟΝΤΕΣ ΑΠΟ ΚΑΡΚΙΝΟ,ΣΤΗΝ "ΟΜΟΙΟΠΑΘΗΤΙΚΗ ΦΡΟΝΤΙΔΑ ΥΓΕΙΑΣ"  :

Οι δυνατότητες  της Kλασσικής Κλινικής Ομοιοπαθητικής προσφέρονται κατεξοχήν για την υποστήριξη του οργανισμού των καρκινοπαθών και για μια  ανθρωποκεντρική προσέγγιση του ασθενή μέσα σε ένα Ιπποκρατικό πλαίσιο. Στη διαδικασία αυτή η Ομοιοπαθητική μπορεί να χρησιμοποιείται παράλληλα με τη Συμβατική Ιατρική υποβοηθώντας τις γνωστές καθιερωμένες θεραπείες (χημειοθεραπεία, ακτινοθεραπεία, χειρουργικές επεμβάσεις, κ.α).
 
 Ο ρόλος της Κλασσικής Κλινικής Ομοιοπαθητικής στις παθήσεις αυτές είναι η ψυχολογική στήριξη των ασθενών σύμφωνα με τα σύγχρονα δεδομένα της ψυχο-ογκολογίας, η ενίσχυση των μηχανισμών άμυνας του οργανισμού σύμφωνα με τα σύγχρονα δεδομένα της ανοσολογίας και η υποβοήθηση των ομοιοστατικών μηχανισμών σύμφωνα με τα σύγχρονα δεδομένα της παθολογικής φυσιολογίας. Ουσιαστικά,η Κλασσική Κλινική Ομοιοπαθητική  απευθύνεται σε εκείνους τους μηχανισμούς,που έχουν την πλέον αποφασιστική σημασία για την ανάπτυξη του Καρκίνου και την Πρόγνωση του.

 

Σε καμία περίπτωση δεν πρέπει οι ασθενείς να εγκαταλείπουν οποιαδήποτε κλασσική (συμβατική) θεραπεία, που τους έχει συστήσει ο αρμόδιος ειδικός κλινικός ιατρός, ο οποίος έχει και τον αποκλειστικό λόγο αλλά και την ευθύνη για την ιατρική θεραπεία, θα πρέπει όμως να είναι και απολύτως ενήμεροι για τις πιθανές παρενέργειες των θεραπειών αυτών. Σε κάθε περίπτωση,στην οποία θα εφαρμοσθεί Κλασσική Κλινική Ομοιοπαθητική, επιβάλλεται η εμπεριστατωμένη μελέτη τόσο του Ιστολογικού υλικού (βιοψίες, χειρουργικά παρασκευάσματα, κτλ) όσο και του πλήρους ιστορικού  για τη διερεύνηση και αποσαφήνιση των αιτίων και της παθογένειας της ανάπτυξης καρκίνου σε κάθε μια ξεχωριστή περίπτωση. Αυτή η διερεύνηση είναι καθοριστικής σημασίας για τη συνολική και ολοκληρωμένη αντιμετώπιση του κάθε περιστατικού στην "ΟΜΟΙΟΠΑΘΗΤΙΚΗ ΦΡΟΝΤΙΔΑ ΥΓΕΙΑΣ" .

O ρόλος της Κλασσικής Κλινικής Ομοιοπαθητικής στις παθήσεις αυτές,οπως αναφέρθηκε, είναι η ενίσχυση των μηχανισμών άμυνας του οργανισμού σύμφωνα με τα σύγχρονα δεδομένα της ανοσολογίας,η υποβοήθηση των ομοιοστατικών μηχανισμών σύμφωνα με τα σύγχρονα δεδομένα της παθολογικής φυσιολογίας,η ψυχοσωματική στήριξη των ασθενών σύμφωνα με τα σύγχρονα δεδομένα της ψυχο-ογκολογίας και, ΚΑΤΕΞΟΧΗΝ, η εξυγίανση του μικροπεριβάλλοντος των κυττάρων.Το μικροπεριβάλλον των  κυττάρων (Matrix)  σήμερα θεωρείται απο την Κλασσική Έρευνα του Καρκίνου  ο πλέον σημαντικός παράγων για την ανάπτυξη των καρκινικών κυττάρων  και για την επέκταση τους τοπικά ή και σε όλο τον οργανισμό .Επομένως,η Κλασσική Κλινική Ομοιοπαθητική επιδιώκει να αξιοποιήσει την πλέον σύγχρονη ιατρικη ερευνητική γνώση στο πεδίο του Καρκίνου.

Η Ομοιοπαθητική, σαν συμπληρωματική αλλά πολύ ουσιαστική αγωγή, θα πρέπει να ξεκινάει το ταχύτερο δυνατόν παράλληλα με την όποια χειρουργική - χημειοθεραπευτική- ακτινοθεραπευτική κτλ αντιμετώπιση.Σε κάθε περίπτωση επιβάλλεται η εμπεριστατωμένη μελέτη τόσο των Εργαστηριακών εξετάσεων(βιοψίες,καρκινικοι δεικτες,απεικονιστικες εξετασεις,κτλ) όσο και του πλήρους ιστορικού για τη διερεύνηση και αποσαφήνιση των αιτίων και της παθογένειας της ανάπτυξης καρκίνου σε κάθε μια ξεχωριστή περίπτωση. Αυτή η διερεύνηση είναι καθοριστικής σημασίας για τη συνολική και ολοκληρωμένη ομοιοπαθητική αντιμετώπιση του κάθε περιστατικού ,δεδομένου ότι σαν μέθοδος ανάλυσης του ιστορικού ,κτλ χρησιμοποιείται η Ομοιοπαθητική, με το πλουσιότατο αναλυτικό υλικό της.

Η παράλληλη εφαρμογή της Ομοιοπαθητικής με τις κλασσικές ογκολογικές θεραπευτικές είναι από πολλών ετών δοκιμασμένη και επιτυχημένη στα Συστήματα Υγείας στην Ευρωπαϊκή Ένωση και κυρίως στη Γερμανία, στη Μ. Βρετανία και τη Γαλλία, όπου και ενθαρρύνεται και υποστηρίζεται από τους αρμόδιους κρατικούς φορείς.

H Ομοιοπαθητική και η Συμβατική Ογκολογία  μπορούν και πρέπει να συνεργάζονται αρμονικά ,μια και η μία συμπληρώνει την άλλη και ασφαλώς ο ρόλος και των δύο είναι εξίσου πολύτιμος.Επιπλέον,η Ομοιοπαθητική,λόγω απουσίας οιασδήποτε φαρμακολογικά δραστικής χημικής ουσίας στα Ομοιοπαθητικά σκευάσματα,δεν έχει και δεν είναι δυνατόν να έχει την παραμικρή παρενέργεια στον οργανισμό και για τον ίδιο λόγο δεν έχει την παραμικρή αλληλεπίδραση με τη Συμβατική Ογκολογική θεραπεία,της οποίας απλώς μπορεί να περιορίσει τις όποιες τυχόν παρενέργειες .Η Ομοιοπαθητική αγωγή χορηγείται αποκλειστικά σαν συμπληρωματική θεραπευτική για την υποστήριξη του οργανισμού του καρκινοπαθών,χωρίς καμμία παρέμβαση στην όποια θεραπεια, συμβουλή,κτλ των αρμόδιων Ειδικών Ιατρών,εν προκειμένω των Ογκολόγων.

 

ΜΠΟΡΕΙΤΕ ΝΑ  ΔΕΙΤΕ

 ΑΡΘΡΟ του Δρ Τασου Βαρθολομαίου ΣΤΟΝ ΔΙΕΘΝΗ ΔΙΑΔΙΚΤΥΑΚΟ ΤΥΠΟ ΥΓΕΙΑΣ ΠΑΝΩ ΣΤΗΝ ΠΡΟΣΕΓΓΙΣΗ ΤΗΣ ΟΜΟΙΟΠΑΘΗΤΙΚΗΣ ΣΤΟΝ ΚΑΡΚΙΝΟ ΜΕ ΒΑΣΗ ΤΗ ΣΥΓΧΡΟΝΗ ΚΑΙ ΕΓΚΥΡΗ ΙΑΤΡΙΚΗ ΒΙΒΛΙΟΓΡΑΦΙΑ

 

 



Ομοιοπαθητική και Παρενέργειες Χημειοθεραπείας-Ακτινοθεραπείας

Οι συμβατικές θεραπείες που γίνονται σε ασθενείς με καρκίνο συχνά δημιουργούν πολλές και σημαντικές παρενέργειες. Με τις θεραπείες αυτές μπορεί να είναι στόχος τα καρκινικά κύτταρα, αλλά δυστυχώς καταστρέφονται προσωρινά κι πολλά υγιή. Έτσι εξηγούνται και οι σοβαρές ανεπιθύμητες ενέργειες των θεραπειών αυτών.Στη συμβατική θεραπεία του καρκίνου περιλαμβάνονται η εγχείρηση, η ακτινοβολία, η χημειοθεραπεία, η ανοσοθεραπεία . Ανάλογα με το είδος και τη θέση του καρκίνου, το στάδιο το οποίο βρίσκεται η νόσος, την ηλικία και τη γενική κατάσταση της υγείας του ασθενούς, επιλέγεται και η κατάλληλη θεραπεία. Συχνά γίνεται και συνδυασμός των προαναφερόμενων  ειδών θεραπείας.Αυτές οι θεραπείες στοχεύουν στην καταστροφή των γρήγορα διαιρούμενων καρκινικών κύτταρων, αλλά παράλληλα  επηρεάζουν και τα υγιή κύτταρα του οργανισμού.

 Οι παρενέργειες των θεραπειών διαφέρουν από ασθενή σε ασθενή. Αυτό έχει να κάνει με πολλούς παράγοντες όπως για παράδειγμα από την δόση της ακτινοβολίας ή από τον συνδυασμό των φαρμάκων κατά την χημειοθεραπεία.


Η Ομοιοπαθητική έχει τεκμηριωμένο στην ιατρική βιβλιογραφία και πρακτική,δοκιμασμένο κλινικά/νοσοκομειακά "οπλοστάσιο" για την αποτελεσματική αντιμετώπιση και ουσιαστικό περιορισμό των παρενεργειών της χημειοθεραπείας και της ακτινοθεραπείας.Έτσι, και ο Ογκολόγος μπορεί να κινηθεί με την μεγαλύτερη δυνατή άνεση,αλλα κυρίως προστατεύεται ο οργανισμός όχι μόνον απο οδυνηρά συμπτώματα αλλα και απο την εξασθένηση και επιβάρυνση του αμυντικού μηχανισμου,που είναι κλειδί τόσο για την ποιότητα της ζωής όσο και για την πρόγνωση και επιβίωση των καρκινοπαθών.

 

 Oμοιοπαθητική και Μεταστάσεις καρκίνου

Mετάσταση είναι  η εμφάνιση του καρκίνου σε διαφορετικές από την πρωτοπαθή εστία, θέσεις. Το γεγονός  ότι κάποια καρκινικά κύτταρα μπορεί να αποσπασθούν από τον αρχικό όγκο και να εισέλθουν στην αιματική κυκλοφορία ή το λεμφικό σύστημα  έχει συμβατικά υιοθετηθεί ότι είναι  ο αποκλειστικός τρόπος με τον οποίο ο καρκίνος διασπείρεται σε απομακρυσμένες εστίες του σώματος. Μεταστατικός όγκος καλείται ο νέος όγκος που δημιουργείται όταν καρκινικά κύτταρα  αρχίσουν να αναπτύσσονται σε μια νέα θέση. Είναι γενικά αποδεκτό και κατανοητό ότι τα κύτταρα της μετάστασης προέρχονται από τα κύτταρα της πρωτοπαθούς εστίας και  ότι αν, π.χ, κύτταρα από καρκίνου του μαστού χορηγήσουν μετάσταση στον πνεύμονα, η πνευμονική μετάσταση αποτελείται από καρκινικά κύτταρα μαστού και όχι από καρκινικά κύτταρα πνεύμονος. Σε αυτή την περίπτωση η παθολογία των πνευμόνων είναι «μεταστατικός καρκίνος από τον μαστο» και όχι «πρωτοπαθής καρκίνος του πνεύμονα».Τα καρκινικά κύτταρα μπορούν να αναπτυχθούν σε « μεταστάσεις» σχεδόν σε οποιοδήποτε σημείο του σώματος. Συχνότατα διηθούν τους τοπικούς λεμφαδένες κοντά και  γύρω από τον όγκο . Η λεμφική επινέμηση μαζί με την πρωτοπαθή εστία καλείται και τοπική νόσος, σε αντιδιαστολή με την μεταστατική νόσο, όπου ο καρκίνος προσβάλλει όργανα ή λεμφαδένες σε απομακρυσμένες θέσεις από την πρωτοπαθή εστία.  

Παρά το γεγονός ότι  κάθε  ιστολογική μορφή καρκίνου ενός συγκεκριμένου οργάνου   έχει την τάση να χορηγεί μεταστάσεις σε διαφορετικά σημεία, οι πιο συχνές μεταστατικές εστίες από κακοήθεις όγκους είναι οι πνεύμονες, τα οστά, το ήπαρ και ο εγκέφαλος.Κάποιοι τύποι καρκίνου τείνουν να χορηγούν μεταστάσεις σε ειδικές εστίες. Για παράδειγμα ο καρκίνος του πνεύμονα συχνά προσβάλλει τον εγκέφαλο και τα οστά, ενώ ο καρκίνος του παχέος εντέρου συχνά μεθίσταται στο ήπαρ. Ο καρκίνος του προστάτη συχνά προσβάλλει τα οστά. Ο καρκίνος του μαστού  μεθίσταται συχνά σε πνεύμονες, οστά, ήπαρ και εγκέφαλο, χωρίς ιδιαίτερες διακρίσεις. Η αναζήτηση της πρωτοπαθούς εστίας περιλαμβάνει συνήθως ακτινογραφίες, εργαστηριακές και άλλες εξετάσεις. Εντούτοις, σε ορισμένες περιπτώσεις παρά τις εξονυχιστικές εξετάσεις, δεν είναι δυνατόν να αποκαλυφθεί η πρωτοπαθής εστία. Ο παθολογοανατόμος γνωρίζει ότι πρόκειται για μεταστατικά κύτταρα από το γεγονός ότι δεν εμφανίζουν τα χαρακτηριστικά των κυττάρων που φυσιολογικά βρίσκονται στον ιστό, στον οποίο εντοπίστηκε η μετάσταση και από τον οποίο προέρχεται το δείγμα που εξετάζει. Οι όγκοι αυτοί συνήθως αποκαλούνται ως αγνώστου ή κρυφής πρωτοπαθούς εστίας. Εξαιτίας της διαρκούς βελτίωσης των διαγνωστικών τεχνικών η πρωτοπαθής εστία αποκαλύπτεται τελικά σε όλο και περισσότερες περιπτώσεις.

Κάποιοι ασθενείς με μεταστάσεις δεν παρουσιάζουν ειδικά συμπτώματα. Σε αυτές τις περιπτώσεις οι μεταστάσεις τους ανευρίσκονται από ακτινογραφίες ή άλλες εξετάσεις που γίνονται για διαφορετικούς σκοπούς. Όταν υπάρχουν συμπτώματα από τις μεταστάσεις, το είδος τους εξαρτάται από το μέγεθος και την εντόπιση των μεταστατικών όγκων. Για παράδειγμα, μεταστάσεις στα οστά είναι πιθανό να προκαλούν πόνο και προδιαθέτουν σε κατάγματα. Εγκεφαλικές μεταστάσεις μπορεί να προκαλέσουν μια ποικιλία συμπτωμάτων, περιλαμβανομένων κεφαλαλγίας, επιληπτικών κρίσεων και αστάθειας. Η δύσπνοια μπορεί να είναι κάποια από τα συμπτώματα πνευμονικών μεταστάσεων. Κοιλιακή διάταση ή ίκτερος μπορεί να αποτελούν ενδείξεις ηπατικών μεταστάσεων.Κάποιες φορές ο πρωτοπαθής όγκος ενός ασθενούς διαγιγνώσκεται εξαιτίας των συμπτωμάτων της μεταστατικής εστίας. Για παράδειγμα, ένας ασθενής με καρκίνο του προστάτη και μεταστάσεις στα οστά της πυελικής ζώνης μπορεί να παρουσιάσει πόνο χαμηλά στην ράχη που προκαλείται από τις οστικές μεταστάσεις, πριν ακόμα εμφανιστούν τα συμπτώματα που προκαλεί ο πρωτοπαθής όγκος στον προστάτη.

Η παρουσία μεταστάσεων ασφαλώς επιβαρύνει σημαντικά την πρόγνωση,εντούτοις  πολλές φορές μπορεί μια μεταστική νόσος να παραμείνει στατική για πολλα έτη.Αυτο θα εξαρτηθεί και από την γενικότερη οικονομία του οργανισμού και από τον τρόπο με τον οποίο θα κινηθεί ο αμυντικός μηχανισμός σε κάθε περίπτωση.Γι’αυτό το λόγο και η Ομοιοπαθητική,σαν συμπληρωματική θεραπεία στις συμβατικές ογκολογικές,μπορεί να βοηθήσει σημαντικά,μια και απευθύνεται άμεσα στον αμυντικό μηχανισμό και στην γενική οικονομία του οργανισμού.


ΙΠΠΟΚΡΑΤΙΚΗ ΙΑΤΡΙΚΗ ΚΑΙ ΚΑΡΚΙΝΟΣ

Όσον αφορά τη θεραπευτική αγωγή την οποία ακολουθούσαν οι αρχαίοι ΄Ελληνες ιατροί στον καρκίνο, παρατηρούμε ότι στα πρώτα στάδια αναπτύξεώς του εφάρμοζαν θεραπεία με διάφορα βοηθήματα και φάρμακα και σε περίπτωση αποτυχίας επακολουθούσαν τη χειρουργική θεραπεία. Τα βοηθήματα που εφάρμοζαν ήταν σύμφωνα με τις αντιλήψεις περί αιτίου του καρκίνου, τον μελαγχολικό χυμό του αίματος, που δημιουργούσε τον καρκίνο και γι' αυτό ακολουθούσαν πρακτικές ώστε να μειωθεί ο πλεονάζον αυτός αιτιοπαθολογικός χυμός με την κάθαρση, τη φλεβοτομία και τα φάρμακα. Όπως σημειώνουν οι συγγραφείς τα θεραπευτικά αυτά μέσα είχαν αποτέλεσμα ιδιαίτερα κατά τα πρώτα στάδια του καρκίνου. Χαρακτηριστικά σημειώνει ο Ορειβάσιος ότι «δυνατόν μην τους αρχομένους καρκίνους κωλύειν αύξεσθαι καθαίροντας τον μελαγχολικόν χυμόν πριν εν τω πεπονθότι μορίω στηριχθήναι».Πολλές ήταν οι φαρμακευτικές ουσίες, σκευασίες και τα θεραπευτικά σχήματα, που χρησιμοποιούνταν για τον καρκίνο. .

Στις περιπτώσεις που αποτύγχανε η θεραπεία με τις φαρμακευτικές ουσίες και τα βοηθήματα τότε οι αρχαίοι Ελληνες ιατροί κατέφευγαν στη χειρουργική θεραπεία του καρκίνου. Βέβαια για τους «κρυπτούς», δηλ. τους εν τω βάθει καρκίνους ακολουθούσαν την προτροπή του Ιπποκράτους ο οποίος στους «Αφορισμούς», Τμήμα ΄Εκτο, 38, τονίζει ότι είναι καλλίτερο να μην θεραπεύονται διότι με την αρχή της θεραπείας οι άρρωστοι πεθαίνουν γρήγορα. Ο Γαληνός συνιστούσε την χειρουργική θεραπεία μόνον για τους επιπολής καρκίνους και μάλιστα κατορθώνοντας να τους εκτέμνει με τις ρίζες τους μέχρι τους υγιείες ιστούς, «πάσης μεν χειρουργίας εκκοπτούσης όγκον παρά φύσιν ο σκοπός εστιν εν κύκλω πάντα όγκον περικόψαι, καθ ά τω κατά φύσιν έχοντι πλησιάζει»

Πριν από την χειρουργική θεραπεία χορηγούνταν τα κατάλληλα φάρμακα για την κάθαρση του μελαγχολικού χυμού και στη συνέχεια αφαιρούνταν ο όγκος «ξυραφίοις πεπυρωμένοις ομού τέμνουσι και διακαίουσιν», ένα είδος δηλ. θερμοκαυτήρος, ώστε να αποφεύγεται η αιμορραγία από τα αγγεία. Ακολουθούσε μετά μία υγιεινή τονωτική διατροφή, γυμναστική και αναληπτική αγωγή για την ευχυμία του σώματος.

Συμπερασματικά μπορούμε να ισχυρισθούμε ότι οι αρχαίοι Ελληνες Ιατροί όχι μόνο έδωσαν το όνομα «καρκίνος» στη νοσολογική αυτή οντότητα της νεοπλασματικής κακοηθείας, αλλά επί πλέον διέκριναν την αιτιολογία και καθόρισαν την συμπτωματολογία, τον εντοπισμό, τη μορφολογία, τις εκδηλώσεις, την πρόγνωση και τη θεραπευτική αγωγή, φαρμακευτική και χειρουργική.

                

 

Kαρκίνος του Μαστού

Ο καρκίνος του μαστού αποτελεί την πιο συχνή μορφή καρκίνου μεταξύ των γυναικών, με περίπου 1.000.000 νέα κρούσματα κάθε χρόνο παγκοσμίως. Ορισμένοι αριθμοί δίνουν τη κοινωνική διάσταση του καρκίνου του μαστού. Στις ΗΠΑ το 2004 οι νέες περιπτώσεις καρκίνου του μαστού στις γυναίκες ήταν 217.000 περίπου. Στην Ελλάδα αναφέρονται 4.500 περίπου νέες περιπτώσεις το χρόνο, ενώ υπολογίζεται ότι 1 στις 8 γυναίκες παγκοσμίως θα παρουσιάσει καρκίνο μαστού σε κάποια φάση της ζωής της. Στην Ευρώπη, το 60% των κρουσμάτων καρκίνου του μαστού διαγιγνώσκεται σε πρώιμο στάδιο. Το αντίστοιχο ποσοστό στην Ελλάδα είναι μόλις 5%. Τα στοιχεία αυτά καταδεικνύουν πόσο ελλιπής είναι η σχετική ενημέρωση μεταξύ των Ελληνίδων. Ο όρος «καρκίνος του μαστού»αναφέρεται στην ανάπτυξη κακοήθους όγκου στην περιοχή του μαστού. Αποτελεί μία από τις συχνότερα εμφανιζόμενες μορφές καρκίνου παγκοσμίως και είναι η πρώτη σε αριθμό κρουσμάτων στο γυναικείο πληθυσμό. Ο όγκος αναπτύσσεται μετά  από ανεξέλεγκτο πολλαπλασιασμό παθολογικών κυττάρων που ως αποτέλεσμα προκαλούν το σχηματισμό κακοήθους όγκου στην περιοχή του μαστού και ουσιαστικά αποτελεί κυτταρική νόσο. Τα παθολογικά αυτά κύτταρα έχουν τη δυνατότητα εξάπλωσης σε γειτονικούς ιστούς σε δυσάρεστες συνέπειες για ολόκληρο τον οργανισμό. Η πιθανότητα εμφάνισης της νόσου σε άρρενες είναι υπαρκτή αλλά πολύ μικρή. Όσον αφορά στις γυναίκες όλες αντιμετωπίζουν τον κίνδυνο εμφάνισης της νόσου, όχι, όμως στον ίδιο βαθμό.

Συχνα συμπτώματα που χαρακτηρίζουν τον καρκίνο του μαστού είναι τα εξής:

Εξόγκωμα ή σκλήρυνση στην περιοχή του μαστού ή και της μασχάλης,    διόγκωση λεμφαδένων της μασχάλης,   έκκριση υγρών από τη θηλή,    εισολκή δέρματος δηλαδή έλξη του δέρματος ή της θηλής προς το εσωτερικό του μαστού,    ερυθρότητα, ευαισθησία ή πόνοι στο στήθος.Σε αρχικό στάδιο ο καρκίνος του μαστού δεν παρουσιάζει συμπτώματα. Αργότερα μπορεί να εμφανιστεί ψηλαφητό μόρφωμα, αλλαγή του χρώματος του δέρματος), εισολκή ή έκκριμα. Αν η γυναίκα δεν δώσει σημασία στα προαναφερθέντα συμπτώματα τότε μπορεί να εμφανίσει σημάδια προχωρημένης νόσου, όπως θερμό και ερυθρό μαστό (φλεγμονώδης καρκίνος), πόνους στα οστά, μεγάλη διόγκωση.Υπάρχουν 4 διαγνωστικές μέθοδοι:    Κυτταρολογική βιοψία: Γίνεται με μια λεπτή βελόνα (FNA - Fine Needle Aspiration Biopsy) που προσαρμόζεται σε μια σύριγγα και επιτρέπει την αναρρόφηση κυττάρων από την ύποπτη περιοχή του μαστού.    Ιστολογική βιοψία: η βελόνα σε αυτή την περίπτωση είναι μεγαλύτερη, απαιτείται τοπική αναισθησία και τομή και το υλικό που μελετάται είναι ιστολογικό.    Στερεοτακτική βιοψία: η λήψη του ιστολογικού υλικού γίνεται με την καθοδήγηση ειδικών μηχανημάτων     Ανοιχτή χειρουργική βιοψία: η ταυτοποίηση της φύσης της ύποπτης περιοχής γίνεται με ταχεία βιοψία κατά τη διάρκεια του χειρουργείου πριν την αφαίρεση του όγκου.


Η σταδιοποίηση της νόσου είναι σημαντική τόσο για την πρόγνωση όσο και για τη θεραπεία. Η ταξινόμηση γίνεται κατά TNM (Τ= μέγεθος πρωτοπαθούς όγκου, Ν= προσβολή μασχαλιαίων λεμφαδένων, Μ= παρουσία ή όχι μεταστάσεων). Υπάρχουν 5 στάδια:
    Στάδιο 0: εντοπίζεται στο σημείο προέλευσής του και δεν έχει αρχίσει να διηθεί τους γύρω ιστούς ή να διασπείρεται
    Στάδιο Ι: ο όγκος είναι μεγέθους 2cm ή μικρότερος και δεν υπάρχει ένδειξη διασποράς
    Στάδιο ΙΙΑ: ο όγκος είναι 2-5cm χωρίς διασπορά στους λεμφαδένες, Στάδιο ΙΙΒ: όγκος 2-5cm με θετικούς λεμφαδένες ή όγκος >5cm χωρίς λεμφαδενικές μεταστάσεις
    Στάδιο ΙΙΙΑ: όγκος >5cm και διακρίνεται προσβολή των σύστοιχων μασχαλιαίων λεμφαδένων που συμφύονται μεταξύ τους ή με άλλους ιστούς, Στάδιο ΙΙΙΒ: προσβεβλημένοι θωρακικοί λεμφαδένες και όγκος που επεκτείνεται στο θωρακικό τοίχωμα ή προσβάλλει και εξελκώνει το δέρμα.
    Στάδιο ΙV: διασπορά στους λεμφαδένες, αλλά και απομακρυσμένες μεταστάσεις ή προσβολή του δέρματος και του θωρακικού τοιχώματος πέρα από την περιοχή του μαστού.

Ομάδες υψηλού κινδύνου για καρκίνο μαστού


Γυναίκες επιρρεπείς στην εμφάνιση καρκίνου του μαστού είναι αυτές που έχουν ατομικό η οικογενειακό ιστορικό καρκίνου του μαστού, καθώς και γυναίκες με πρώιμη εμμηναρχή (πριν το 12 ο έτος της ηλικίας) και όψιμη εμμηνόπαυση (μετά το 55 ο έτος της ηλικίας).Σε αυξημένο κίνδυνο βρίσκονται επίσης παχύσαρκες γυναίκες με μεγάλη κατανάλωση οινοπνεύματος και τροφών που είναι πλούσιες σε κεκορεσμένα λίπη.

Kαρκίνος του Πνεύμονα

Παράγοντες που υπεισέρχονται στην αιτιολογία και την παθογένεια του καρκίνου του πνεύμονα:


Το κάπνισμα: Είναι απολύτως τεκμηριωμένο ότι το καταχρηστικό  κάπνισμα συμβάλλει σημαντικά στην ανάπτυξη  καρκίνου του πνεύμονα. Ο καπνός του τσιγάρου περιέχει 4.000 χημικές ουσίες, 55 από τις οποίες είναι δυνητικά καρκινογόνες. Το κάπνισμα έχει μεγαλο μερίδιο ευθύνης για το 80% των χρόνιων αναπνευστικών νοσημάτων, 20% των εμφραγμάτων του μυοκαρδίου και είναι ένας από τους κύριους αιτιολογικούς παράγοντες ανάπτυξης καρκίνου του πνεύμονα. Συγκεκριμένα το 80-85% των ασθενών με καρκίνο πνεύμονα είναι καπνιστές και οι καπνιστές έχουν 10 φορές περισσότερες πιθανότητες ανάπτυξης καρκίνου πνεύμονα από ότι οι μη καπνιστές.


Ο αμίαντος: κθεση σε αμίαντο έχει παρατηρηθεί σε ναυπηγεία, μεταλλεία αμιάντου, βιομηχανίες μονωτικών υλικών, εργασιακούς χώρους επισκευής φρένων. 'Ατομα που εκτίθενται σε αμίαντο και καπνό τσιγάρου έχουν σημαντικά αυξημένο κίνδυνο για ανάπτυξη καρκίνου του πνεύμονα. Έχει βρεθεί ότι τα σωματίδια αμιάντου μπορούν να συμβάλλουν στη μεταφορά συγκεντρωμένων καρκινογόνων του καπνού στα κύτταρα που επενδύουν τους πνεύμονες.

Το ραδόνιο:. Μπορεί να προκαλέσει βλάβες στους πνεύμονες και να οδηγήσει σε καρκίνο του πνεύμονα.


Η μόλυνση του περιβάλλοντος:Έχει βρεθεί συσχέτιση μεταξύ καρκίνου του πνεύμονα και έκθεσης σε συγκεκριμένους ρύπους της ατμόσφαιρας, όπως τα παραπροϊόντα της καύσης του πετρελαίου και άλλων φυσικών καυσίμων.


Οι ασθενείς με χρόνια αποφρακτική πνευμονοπάθεια έχουν μεγαλύτερο κίνδυνο να αναπτύξουν καρκίνο πνεύμονα ανεξάρτητα από τις καπνιστικές τους συνήθειες. Χρόνιες πνευμονικές νόσοι όπως η αμιάντωση (νόσος των πνευμόνων από αμίαντο), το άσθμα, η χρόνια βρογχίτιδα, το εμφύσημα, η φυματίωση, φαίνεται να αυξάνουν τον κίνδυνο για ανάπτυξη καρκίνου πνεύμονα.'Ατομα τα οποία αντιμετωπίζουν προβλήματα με το ανοσοποιητικό τους σύστημα παρουσιάζουν αυξημένο κίνδυνο για ανάπτυξη καρκίνου. Σε αυτή την ομάδα περιλαμβάνονται άτομα που λαμβάνουν ανοσοκατασταλτικά φάρμακα, που πάσχουν από AIDS, ή ακόμη που έχουν γεννηθεί με κάποια γενετική ασθένεια που επηρεάζει το ανοσοποιητικό σύστημα.


Τα συνηθέστερα συμπτώματα με τα οποία εμφανίζονται οι ασθενείς με καρκίνο του πνεύμονα είναι:

  • Βήχας, με ή χωρίς απόχρεμψη
  • Απώλεια σωματικού βάρους
  • Δύσπνοια
  • Θωρακικός πόνος 
  • Αιμόπτυση
  • Πληκτροδακτυλία
  • Πυρετός, ή δεκατική πυρετική κίνηση
  • Αδυναμία, καταβολή, εύκολη κόπωση
  • Συριγμός της αναπνοής κατά την εισπνοή
  • Βράγχος  φωνής

Θα πρεπει να επισημανθει,παντως,ότι ορισμένες φορές η ανακάλυψη του όγκου είναι τυχαία, οπότε ο ασθενής είναι ασυμπτωματικός.Συχνά τα σημεία και τα συμπτώματα της νόσου δεν φαίνεται να σχετίζονται με τον πνεύμονα και την αναπνοή. Αυτό συμβαίνει σε περιπτώσεις που ο καρκίνος έχει κανει μεταστάσεις. Τέτοια συμπτώματα που τελικά μπορεί να οδηγήσουν στην διάγνωση καρκίνου είναι:

  • Οστικά άλγη
  • Αδυναμία και μούδιασμα στα χέρια ή στα πόδια,
  • Ζάλη
  • ίκτερος
  • Σκληρή λεμφαδενική διόγκωση στο πλάι του αυχένα
  • Βράγχος φωνής


 Τόσο τα συμπτώματα που σχετίζονται άμεσα με το αναπνευστικό (βήχας, δύσπνοια, αιμόπτυση) όσο και τα γενικά (πυρετός, ανορεξία, απώλεια βάρους, αδυναμία) εμφανίζονται και σε παθήσεις που δεν χαρακτηρίζονται ως κακοήθεις. Συμπτώματα όμως από το αναπνευστικό σε ενεργό ή πρώην καπνιστή που επιμένουν για περισσότερο από 15 ημέρες, παρά την φαρμακευτική αγωγή, πρέπει να ελέγχονται με μεγαλύτερη προσοχή με ακτινογραφία θώρακα, εξετάσεις αίματος κλπ.
Δύσπνοια παρουσιάζεται σε ασθενείς με καρκίνο του πνεύμονα αλλά και σε πολλές άλλες πνευμονικές (όπως η χρόνια αποφρακτική πνευμονοπάθεια των καπνιστών - ΧΑΠ) ή καρδιακές (όπως η καρδιακή ανεπάρκεια) παθήσεις. Αιμόπτυση μπορεί να εμφανισθεί σε  καρκίνο του πνεύμονα, αλλά και ασθενείς με άλλες πνευμονικές παθήσεις όπως οι βρογχεκτασίες και η φυματίωση των πνευμόνων.Η πληκτροδακτυλία εμφανίζεται σε καπνιστές, καθώς και σε πολλές πνευμονικές παθήσεις, όπως και στον καρκίνο του πνεύμονα.

Καρκίνος του Παχέος Εντέρου

Ο καρκίνος του παχέος εντέρου στη μεγάλη του πλειονότητα αναπτύσσεται σε έδαφος προϋπαρχόντων πολυπόδων.  Υπάρχουν καρκίνοι του παχέος εντέρου που ονομάζονται κληρονομικοί δηλαδή αναπτύσσονται σε ασθενείς με κληρονομικά σύνδρομα καρκίνου όπως ο οικογενής καρκίνος παχέος εντέρου και ο καρκίνος του παχέος εντέρου που αναπτύσσεται σε έδαφος ελκώδους κολίτιδος και νόσου του Crohn. Με τον όρο προκαρκινικές καταστάσεις εννοούμε παθήσεις του παχέος εντέρου οι οποίες προδιαθέτουν το συγκεκριμένο άτομο στο οποίο υπάρχουν να αναπτύξει στο μέλλον καρκίνο παχέος εντέρου.Τέτοιες καταστάσεις είναι οι πολύποδες του παχέος εντέρου, η ελκώδης κολίτις και η νόσος του Crohn, το σύνδρομο οικογενούς καρκίνου του παχέος εντέρου (άτομα τα οποία εμφανίζουν καρκίνο παχέος εντέρου σε διαδοχικές γενεές).


Στις ομάδες υψηλού κινδύνου για ανάπτυξη καρκίνου του παχέος εντέρου περιλαμβάνονται: Άτομα με ατομικό ή οικογενειακό ιστορικό πολυπόδων ή καρκίνου του παχέος εντέρου, Ασθενείς με μακροχρόνια εκτεταμένη ελκώδη κολίτιδα ή νόσο του Crohn, Άτομα τα οποία ανήκουν σε οικογένειες με κληρονομική προδιάθεση για καρκίνο του παχέος εντέρου (οικογενής πολυποδίαση, σύνδρομο του κληρονομικού καρκίνου του παχέος εντέρου).Άτομα που ανήκουν στις ομάδες υψηλού κινδύνου πρέπει να υποβάλλονται σε τακτικά χρονικά διαστήματα σε κολονοσκόπηση, ανεξάρτητα από την ηλικία τους.Ο καρκίνος του παχέος εντέρου στη μεγάλη πλειονότητα των περιπτώσεων αναπτύσσεται σε έδαφος προϋπαρχόντων πολυπόδων. Ο πολύποδας είναι ένας καλοήθης όγκος μεγέθους μερικών χιλιοστών ή εκατοστών που εμφανίζεται στο εσωτερικό του εντερικού σωλήνα. Οι πολύποδες συνήθως δεν προκαλούν συμπτώματα. Όμως σε μεταγενέστερο στάδιο μπορεί να εξαλλαγούν σε καρκίνο. Η αφαίρεση των πολυπόδων μέσω του ενδοσκοπίου (κολονοσκοπίου) μπορεί να προλάβει την ανάπτυξη του καρκίνου.


 
Οι διατροφικές συνήθειες αποτελούν έναν από τους σημαντικότερους περιβαλλοντικούς παράγοντες, που εμπλέκονται στην καρκινογένεση του παχέος εντέρου. Τα διαθέσιμα στοιχεία των μελετών που έχουν πραγματοποιηθεί σε πολλές χώρες του κόσμου δείχνουν ότι ο κίνδυνος είναι χαμηλότερος σε πληθυσμούς με αυξημένη πρόσληψη φρούτων και λαχανικών καθώς και ότι ο κίνδυνος αυτός μεταβάλλεται εφ όσον επέλθει αλλαγή των διατροφικών συνηθειών.Ένας από τους διαιτητικούς παράγοντες που είχε συνδεθεί με την εμφάνιση καρκίνου του παχέος εντέρου ήταν η χαμηλή πρόσληψη φυτικών ινών (φυτικού υπολείμματος).  Η υπερβολική κατανάλωση κόκκινου κρέατος και ενδεχομένως ζωικού λίπους φαίνεται επίσης ότι σχετίζονται με την εμφάνιση του καρκίνου του παχέος εντέρου. Αντίθετα, τα πλούσια σε ω-3 λιπαρά οξέα έλαια (ιχθυέλαια) καθώς και το ελαιόλαδο ασκούν προστατευτική δράση.
 
 Η αναιμία είναι βασικό σύμπτωμα του καρκίνου του παχέος εντέρου και μπορεί να είναι μοναδικό σύμπτωμα σε καρκίνους εντοπιζόμενους στο δεξιό τμήμα (ανιόν και τυφλό). Η αιμορραγία (ορατή αποβολή αίματος από το έντερο) είναι βασικό σύμπτωμα του καρκίνου του αριστερού τμήματος του παχέος εντέρου. Ασαφής, βύθιος κοιλιακός πόνος και αδυναμία αποτελούν επίσης συμπτώματα εμφανιζόμενα σε μεγάλη αναλογία των ασθενών. Τέλος οι διαταραχές των κενώσεων (διάρροια, δυσκοιλιότητα, ή εναλλαγές διάρροιας με δυσκοιλιότητα) αποτελούν βασικά συμπτώματα της νόσου που πρέπει να εμβάλλουν σε ανησυχία τον ασθενή και τον θεράποντα ιατρό. Οι μεταστάσεις σε άλλα όργανα (κυρίως ήπαρ, πνεύμονες) μπορεί επίσης να προκαλέσουν συμπτώματα σχετιζόμενα με αυτά τα όργανα.Απόφραξη του εντέρου (ειλεός) είναι βασικό σύμπτωμα σε καρκίνους του αριστερού τμήματος του παχέος εντέρου (ορθού και σιγμοειδούς). Η αναιμία (πτώση του αιματοκρίτη και της αιμοσφαιρίνης του αίματος) εμφανίζεται σε μεγάλη αναλογία των ασθενών.Η διάγνωση τίθεται με την ενδοσκόπηση του παχέος εντέρου (κολονοσκόπηση, ορθοσκόπηση), βαριούχο υποκλυσμό «διπλής αντιθέσεως», αξονική τομογραφία κοιλίας, μαγνητική τομογραφία κοιλίας, «εικονική κολονοσκόπηση» και επιβεβαιώνεται με την ιστολογική εξέταση δειγμάτων του όγκου που λαμβάνονται μέσω των ενδοσκοπίων.

 

Καρκινος της ουροδόχου κύστης

Ο καρκίνος της ουροδόχου κύστης είναι μια από τις πιο συχνές ασθένειες που αντιμετωπίζουν οι ουρολόγοι. Οι περισσότεροι καρκίνοι της ουροδόχου κύστης είναι καρκινώματα του μεταβατικού επιθηλίου και σπάνια προέρχονται από τα τοιχώματα της κύστεως όπως τα  λειομυοσαρκώματα ή το συνδετικό ιστό, όπως τα  ινομυοσαρκώματα κ.λ.π.

Εμφανίζονται υπό δύο κυρίως μορφές: χαμηλής διαφοροποίησης επιφανειακοί όγκοι και υψηλής διαφοροποίησης διηθητικός καρκίνος.

Επιδημιολογία
1)Συχνότητα εμφάνισης.
Η ουροδόχος κύστη είναι ο πιο συχνός τόπος εμφάνισης καρκίνων του ουροποιητικού συστήματος. Στους άντρες, είναι ο τέταρτος κατά σειρά συχνότερος καρκίνος μετά τον καρκίνο του προστάτη, του πνεύμονα και του παχέος εντέρου, θεωρούμενος υπαίτιος για το 10 τοις εκατό όλων των περιπτώσεων καρκίνου. Στις γυναίκες, είναι η όγδοη κατά σειρά πιο συχνή αιτία καρκίνου, και υπολογίζεται στο 4 τοις εκατό του συνόλου των καρκίνων.

2) Θνησιμότητα-Φύλο και Φυλή.
Ο καρκίνος της ουροδόχου κύστης είναι η τέταρτη συχνότερη αιτία θανάτου από καρκίνο στους άντρες, μετά τον καρκίνο του πνεύμονα, του προστάτη και του παχέος εντέρου, με ποσοστό που ανέρχεται στο 5 τοις εκατό των θανάτων από καρκίνο στους άντρες. O καρκίνος της ουροδόχου κύστης είναι υπαίτιος για το 3 τοις εκατό περίπου του συνόλου θανάτων από καρκίνο στις γυναίκες. Τα ποσοστά θνησιμότητας στους λευκούς (6 τοις εκατό για τους άντρες και 1,7 τοις εκατό για τις γυναίκες) είναι συγκρίσιμα με αυτά των μαύρων (4,2 τοις εκατό στους άνδρες και 2,4 τοις εκατό στις γυναίκες).

Σε ασθενείς με εντοπισμένους όγκους, το ποσοστό επιβίωσης 5 ετών είναι 88 τοις εκατό για τους λευκούς σε σύγκριση με 74 τοις εκατό για τους μαύρους. Σε ασθενείς με τοπικούς όγκους, το ποσοστό επιβίωσης 5 ετών είναι 44 τοις εκατό για τους λευκούς και 30 τοις εκατό για τους μαύρους. Σ' αυτούς με απομακρυσμένες μεταστάσεις, το ποσοστό επιβίωσης 5 ετών είναι 9 τοις εκατό για τους λευκούς και 8 τοις εκατό για τους μαύρους. Γενικά, τα ποσοστά θνησιμότητας από τον καρκίνο της ουροδόχου κύστης είναι γύρω στο 20 τοις εκατό ως προς την συχνότητα εμφάνισης της νόσου, το οποίο υποδεικνύει ότι οι περισσότεροι ασθενείς με καρκίνο της ουροδόχου κύστης καταλήγουν από άλλα αίτια.

Μετά την δεκαετία του 1950, ο ρυθμός εμφάνισης καρκίνου της ουροδόχου κύστης αυξάνεται σταθερά. Η βελτίωση των διαγνωστικών τεχνικών και η αυξημένη διαθεσιμότητα των τεχνικών αυτών συνέβαλαν στην έγκαιρη διάγνωση της νόσου. Παρατηρείται σταθερή μείωση των ποσοστών θνησιμότητας από καρκίνο της ουροδόχου κύστης κατά το ίδιο χρονικό διάστημα. Η μείωση των ποσοστών θνησιμότητας οφείλεται κυρίως σε αύξηση των περιπτώσεων που η διάγνωση γίνεται στα αρχικά στάδια της νόσου αλλά επίσης, ως ένα βαθμό, και πιο αποτελεσματικές θεραπείες.

3) Ηλικία.
Θεωρείται γενικά νόσος των ηλικιωμένων με μέση ηλικία διάγνωσης τα 67 με 70 έτη. Οι νεώτεροι ασθενείς φαίνεται να έχουν καλύτερη πρόγνωση γιατί παρουσιάζουν πιο συχνά επιφανειακούς, χαμηλής διαφοροποίησης, καρκίνους. Όλοι οι ασθενείς πρέπει να υποβάλλονται σε θεραπεία βάσει του σταδίου και της διαφοροποίησης της νόσου, ανεξάρτητα από την ηλικία τους.

4) Γεωγραφικές  τοπικές  διαφορές.
Η συχνότητα εμφάνισης του καρκίνου της ουροδόχου κύστης αναφέρεται ότι είναι 30 με 50 τοις εκατό υψηλότερη στις βόρειες περιοχές των Ηνωμένων πολιτειών απ' ότι στις νότιες. Είναι υψηλότερη στις Ηνωμένες Πολιτείες και στην Αγγλία απ' ότι στην Ιαπωνία και την Φιλανδία. Στην Χαβάη, η συχνότητα εμφάνισης είναι διπλάσια στον λευκό πληθυσμό απ' ότι στους Ιάπωνες.

Μετάσταση καρκίνου

Mετάσταση είναι  η εμφάνιση του καρκίνου σε διαφορετικές από την πρωτοπαθή εστία, θέσεις. Το γεγονός  ότι κάποια καρκινικά κύτταρα μπορεί να αποσπασθούν από τον αρχικό όγκο και να εισέλθουν στην αιματική κυκλοφορία ή το λεμφικό σύστημα  έχει συμβατικά υιοθετηθεί ότι είναι  ο αποκλειστικός τρόπος με τον οποίο ο καρκίνος διασπείρεται σε απομακρυσμένες εστίες του σώματος. Μεταστατικός όγκος καλείται ο νέος όγκος που δημιουργείται όταν καρκινικά κύτταρα  αρχίσουν να αναπτύσσονται σε μια νέα θέση. Είναι γενικά αποδεκτό και κατανοητό ότι τα κύτταρα της μετάστασης προέρχονται από τα κύτταρα της πρωτοπαθούς εστίας και  ότι αν, π.χ, κύτταρα από καρκίνου του μαστού χορηγήσουν μετάσταση στον πνεύμονα, η πνευμονική μετάσταση αποτελείται από καρκινικά κύτταρα μαστού και όχι από καρκινικά κύτταρα πνεύμονος. Σε αυτή την περίπτωση η παθολογία των πνευμόνων είναι «μεταστατικός καρκίνος από τον μαστο» και όχι «πρωτοπαθής καρκίνος του πνεύμονα».Τα καρκινικά κύτταρα μπορούν να αναπτυχθούν σε « μεταστάσεις» σχεδόν σε οποιοδήποτε σημείο του σώματος. Συχνότατα διηθούν τους τοπικούς λεμφαδένες κοντά και  γύρω από τον όγκο . Η λεμφική επινέμηση μαζί με την πρωτοπαθή εστία καλείται και τοπική νόσος, σε αντιδιαστολή με την μεταστατική νόσο, όπου ο καρκίνος προσβάλλει όργανα ή λεμφαδένες σε απομακρυσμένες θέσεις από την πρωτοπαθή εστία. 

 Παρά το γεγονός ότι  κάθε  ιστολογική μορφή καρκίνου ενός συγκεκριμένου οργάνου   έχει την τάση να χορηγεί μεταστάσεις σε διαφορετικά σημεία, οι πιο συχνές μεταστατικές εστίες από κακοήθεις όγκους είναι οι πνεύμονες, τα οστά, το ήπαρ και ο εγκέφαλος.Κάποιοι τύποι καρκίνου τείνουν να χορηγούν μεταστάσεις σε ειδικές εστίες. Για παράδειγμα ο καρκίνος του πνεύμονα συχνά προσβάλλει τον εγκέφαλο και τα οστά, ενώ ο καρκίνος του παχέος εντέρου συχνά μεθίσταται στο ήπαρ. Ο καρκίνος του προστάτη συχνά προσβάλλει τα οστά. Ο καρκίνος του μαστού  μεθίσταται συχνά σε πνεύμονες, οστά, ήπαρ και εγκέφαλο, χωρίς ιδιαίτερες διακρίσεις. Η αναζήτηση της πρωτοπαθούς εστίας περιλαμβάνει συνήθως ακτινογραφίες, εργαστηριακές και άλλες εξετάσεις. Εντούτοις, σε ορισμένες περιπτώσεις παρά τις εξονυχιστικές εξετάσεις, δεν είναι δυνατόν να αποκαλυφθεί η πρωτοπαθής εστία. Ο παθολογοανατόμος γνωρίζει ότι πρόκειται για μεταστατικά κύτταρα από το γεγονός ότι δεν εμφανίζουν τα χαρακτηριστικά των κυττάρων που φυσιολογικά βρίσκονται στον ιστό, στον οποίο εντοπίστηκε η μετάσταση και από τον οποίο προέρχεται το δείγμα που εξετάζει. Οι όγκοι αυτοί συνήθως αποκαλούνται ως αγνώστου ή κρυφής πρωτοπαθούς εστίας. Εξαιτίας της διαρκούς βελτίωσης των διαγνωστικών τεχνικών η πρωτοπαθής εστία αποκαλύπτεται τελικά σε όλο και περισσότερες περιπτώσεις.

Κάποιοι ασθενείς με μεταστάσεις δεν παρουσιάζουν ειδικά συμπτώματα. Σε αυτές τις περιπτώσεις οι μεταστάσεις τους ανευρίσκονται από ακτινογραφίες ή άλλες εξετάσεις που γίνονται για διαφορετικούς σκοπούς. Όταν υπάρχουν συμπτώματα από τις μεταστάσεις, το είδος τους εξαρτάται από το μέγεθος και την εντόπιση των μεταστατικών όγκων. Για παράδειγμα, μεταστάσεις στα οστά είναι πιθανό να προκαλούν πόνο και προδιαθέτουν σε κατάγματα.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Colorectal cancer
Colorectal cancer is currently one of the most common cancers diagnosed in Australia and has the second highest incidence of cancer-related deaths after lung cancer.1 Recent advances have been made in the biological understanding of this disease, which have resulted in new surgical, chemotherapeutic and radiotherapeutic strategies.
Pathological reporting
Pathological reporting of resection specimens for colorectal cancer provides important information both for the clinical management of the affected patient and for the evaluation of health care systems as a whole. For the patient, it confirms the diagnosis and describes the variables that will affect prognosis, which will inform future clinical management. For health care evaluation, pathology reports provide information for cancer registries and clinical audit, for ensuring comparability of patient groups in clinical trials, and for assessing the accuracy of new diagnostic tests and preoperative staging techniques. In order to fulfil all of these functions, the information contained within the pathology report must be accurate and complete.
Benefits of structured reporting
Structured pathology reports with standardised definitions for each component have been shown to significantly improve the completeness and quality of data provided to clinicians, and have been recommended both in North America and the United Kingdom.2-5
Several studies have highlighted deficiencies in the content of colorectal cancer resection reports, including elements that are considered crucial for patient management.6 Many studies have shown that adherence to a checklist for colorectal cancer reporting significantly improves the rate of inclusion of these crucial features.2
The College of American Pathologists and the Royal College of Pathologists (United Kingdom) have recently published useful protocols for the reporting of cancer.7 These have been widely used in recent years in Australia and New Zealand, usually in modified formats to suit local requirements and preferences. A protocol endorsed by the Royal College of Pathologists of Australasia and other local organisations involved in the management of colorectal cancer is therefore needed. The authors have not attempted to ‘re-invent the wheel’ but have borrowed freely from pre-existing publications. The intention is to provide pathologists with a minimum dataset and guidelines that are comprehensive, easy to use, and in keeping with local capacity and practice.
Design of this protocol
This protocol defines the relevant information to be assessed and recorded in a pathology report for colorectal cancer. Mandatory elements (standards) are differentiated from those that are not mandatory but are recommended (guidelines). Also, items suited to tick boxes are distinguished from more complex elements requiring free text or narrative. The structure provided by the following chapters, headings and subheadings describes the elements of information and their groupings, but does not necessarily represent the format of either a pathology report (Chapter 7) or checklist (Chapter 6). These, and the structured pathology request form (Appendix 1), are
10
templates representing information from this protocol, organised and formatted differently to suit their respectively different purposes.
It should be noted that if the resection specimen contains two or more primary carcinomas (as indicated by the term ‘synchronous carcinomas’ on the reporting checklist) then a separate reporting checklist must be completed for each primary carcinoma.
Key documentation
• Tumours of the colon and rectum. In: Pathology and Genetics of Tumours of the Digestive System. World Health Organization Classification of Tumours, 20118
• AJCC Cancer Staging Manual, 7th edition, American Joint Committee on Cancer, 20109
• Guidelines for Authors of Structured Cancer Pathology Reporting Protocols, Royal College of Pathologists of Australasia, 200910
• The Pathology Request–Test–Report Cycle — Guidelines for Requesters and Pathology Providers, Royal College of Pathologists of Australasia, 200411
• Minimum Dataset for Colorectal Cancer, Cancer Council of NSW, 200712
Changes since last edition
• Minor change re synchronous tumours in scope.
• Changes to the definitions
• Rework of chapter 1 and appendix 1 in line with new framework
• Removal of numbering for tissue banking, specimen imaging and specimen handling in Ch 2, with subsequent renumbering
• Addition of reference to apical lymph node in specimen handling Ch 2.
• Addition of 3 new guidelines in Ch 2 – G2.01- G2.03.
• Downgrade of previous S2.12 to a guideline G2.04.
• Inclusion of 4th edition of WHO classification of tumours in Appendix 4 and subsequent updates throughout the document
• Deletion of previous S3.06 “The status of the nonperitonealised circumferential margin in colon tumours must be recorded” and subsequent renumbering.
• Additional commentary in CS3.02g and CS3.07c
• Rework of commentary in Ch 4
• Addition of a new S5.02 and S5.04 and subsequent renumbering
• Edits to G6.01
• Addition of G6.03
• Rework of the checklist in Ch 6.
• Rework of the request information sheet example in Appendix 1.
• Update of example report in Appendix 3
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Authority and development
This section provides details of the committee involved in developing this protocol and the process by which it was developed.
This document is based on the Minimum Dataset for Colorectal Cancer, 1st Edition, June 200712 and was developed in collaboration with Dr Jill Farmer, the NSW Oncology Group for Colorectal Cancer and local pathologists.
Protocol developers
This protocol was developed by an expert committee, with assistance from relevant stakeholders.
Expert committee
Associate Professor Robert Eckstein (Chair and lead author 1st edition), Pathologist
Conjoint Professor Stephen Ackland, Medical Oncologist
Dr Ian Brown (Chair and lead author 2nd edition), Pathologist
Associate Professor David Ellis, Pathologist
Professor Nicholas Hawkins, Pathologist
Dr Sian Hicks, Medical Scientist
Dr Andrew Hunter, Colorectal Surgeon
Dr Andrew Kneebone, Radiation Oncologist
Dr Andrew Ruszkiewicz, Pathologist
Dr Mee Ling Yeong, Pathologist
Acknowledgements
The Colorectal expert committee wish to thank all the pathologists and clinicians who contributed to the discussion around this document.
Stakeholders
ACT Health
Anatomical Pathology Advisory Committee (APAC)
Australian Association of Pathology Practices Inc (AAPP)
Australian Cancer Network
Australian Commission on Safety and Quality in Health Care
Cancer Australia
Cancer Council ACT
Cancer Council NSW
Cancer Council Queensland
Cancer Council SA
Cancer Council Tasmania
Cancer Council Victoria
Cancer Council Western Australia
Cancer Institute NSW
Cancer Services Advisory Committee (CanSAC)
Cancer specific expert groups – engaged in the development of the protocols
12
Cancer Voices
Colorectal Cancer Research Consortium
Clinical Oncology Society of Australia (COSA)
Colorectal Surgical Society of Australia and New Zealand (CSSANZ)
Department of Health and Ageing
Grampians Integrated Cancer Services (GICS)
Health Informatics Society of Australia (HISA)
Independent Review Group of Pathologists
Medical Software Industry Association (MSIA)
National Breast and Ovarian Cancer Centre (NBOCC)
National Coalition of Public Pathology (NCOPP)
National E-Health Transition Authority (NEHTA)
National Pathology Accreditation Advisory Council (NPAAC)
National Round Table Working Party for Structured Pathology Reporting of Cancer.
New Zealand Guidelines Group (NZGG)
NSW Department of Health
NZ Ministry of Health
Peter MacCallum Cancer Institute
Queensland Cooperative Oncology Group (QCOG)
Representatives from laboratories specialising in anatomical pathology across Australia
Royal Australasian College of Physicians (RACP)
Southern Cancer Network, Christchurch, New Zealand
Southern Melbourne Integrated Cancer Service (SMICS)
Standards Australia
The Australasian Gastro-Intestinal Trials Group (AGITG)
The Medical Oncology Group of Australia
The Royal Australasian College of Surgeons (RACS)
The Royal Australian and New Zealand College of Radiologists (RANZCR)
The Royal Australian College of General Practitioners (RACGP)
The Royal College of Pathologists of Australasia (RCPA)
Victorian Cooperative Oncology Group (VCOG)
Western Australia Clinical Oncology Group (WACOG)
Secretariat
Meagan Judge, Royal College of Pathologists of Australasia
Development process
This protocol has been developed following the seven-step process set out in Guidelines for Authors of Structured Cancer Pathology Reporting Protocols.10
Where no reference is provided, the authority is the consensus of the expert group.
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1 Pre-analytical
This chapter relates to information that should be recorded on receipt of the specimen in the laboratory.
The pathologist is reliant on the quality of information received from the clinicians or requestor. Some of this information may be received in generic pathology request forms, however, the additional information required by the pathologist specifically for the reporting of colorectal cancer is outlined in Appendix 1. Appendix 1 also includes a standardised request information sheet that may be useful in obtaining all relevant information from the requestor.
Surgical handling procedures affect the quality of the specimen and recommendations for appropriate surgical handling are included in Appendix 1.
S1.01
All demographic information provided on the request form and with the specimen must be recorded.
CS1.01a
The Royal College of Pathologists of Australasia (RCPA) The Pathology Request-Test-Report Cycle — Guidelines for Requesters and Pathology Providers must be adhered to.11 This document specifies the minimum information to be provided by the requesting clinician for any pathology test.
CS1.01b
The patient’s ethnicity must be recorded, if known. In particular whether the patient is of aboriginal or Torres Strait islander origin. This is in support of a government initiative to monitor the health of indigenous Australians particularly in relation to cancer.
CS1.01c
The patient’s health identifiers may include the patient’s Medical Record Number as well as a national health number such as a patient’s Medicare number (Australia), Individual Healthcare Identifier (IHI) (Australia) or the National Healthcare Identifier (New Zealand).
S1.02
All clinical information as documented on the request form must be recorded verbatim.
CS1.02a
The request information may be recorded as a single text (narrative) field or it may be recorded atomically.
S1.03
The pathology accession number of the specimen must be recorded.
G1.01
Any clinical information received in other communications from the requestor or other clinician should be recorded together with the source of that information.
14
2 Specimen handling and macroscopic findings
This chapter relates to the procedures required after the information has been handed over from the requesting clinician and the specimen has been received in the laboratory.
Tissue banking

Pathologists may be asked to provide tissue samples from fresh specimens for tissue banking or research purposes. The decision to provide tissue should only be made if the pathologist is sure that the diagnostic process will not be compromised. As a safeguard, research use of the tissue samples may be put on hold until the diagnostic process is complete.
Specimen imaging

Images of the gross specimen showing the overall conformation of the tumour and, especially in the case of rectal resections, images showing the relation of the tumour to the resection margins, are desirable, and useful for multidisciplinary meetings.
Specimen handling

The specimen must be handled in a systematic and thorough fashion to ensure completeness and accuracy of pathological data.

Specimen reception: Specimens are best received fresh and without delay. The subsequent fixation, macroscopic assessment and sampling for histology are crucial. The aim is to make a diagnosis, assess resection status and glean all other prognostic information.
The opened, cleaned specimen should be fixed, at least overnight, in an adequate volume of formalin.
Despite the pressure by clinicians on the pathologist for rapid turnaround, adequate fixation and processing of colorectal specimens is vital for high quality pathology. Full fixation facilitates obtaining thin transverse slices through the tumour and it has also been shown to increase lymph node yield.
Slices can be made into mesocolic adipose tissue to aid fixation.

Specimen inspection: The specimen needs to be thoroughly examined before opening and areas of possible serosal involvement, possible distant tumour deposits and possible lymph nodes deposits identified. Serosal nodules away from the primary tumour are regarded as distant metastases in the TNM classification. Assessment of tumour perforation is best made in the freshly received and unopened specimen.

Tumour inspection: There are two recommended methods of opening a
15
colorectal resection specimen.
The first method involves opening the specimen with scissors anteriorly up and down to the level of the tumour, which is left unopened. A wick of formalin soaked paper or gauze is then inserted into the unopened lumen to aid exposure of the tumour to the fixative. The entire specimen is then placed in formalin for complete fixation.
The second method involves opening the specimen along its length. If the tumour is not circumferential, then the specimen should be opened through an area not involved by tumour. If the tumour is circumferential then it will have to be cut through at some point, but this should avoid areas of possible serosal or nonperitonealised resection margin involvement. Again, the entire specimen should then be placed in an adequate amount of formalin for complete fixation.
For rectal tumours, leaving the tumour intact and bread-slicing it when fixed is recommended. This method facilitates assessment of the very important nonperitonealised resection margin. The relationship of the tumour, nodes, or extramural tumour deposits to the nonperitonealised resection margin must be assessed and measured (see S2.04 below). This facilitates correlation with pre-operative imaging and subsequent microscopic examination.

Marking of resection margins: The nonperitonealised resection margin of the rectum or colon needs to be inked. Other cut surgical resection margins can be inked if the tumour is nearby.
The serosal surface is not a resection margin and is therefore not inked. Inking of the serosa may result in misinterpretation of serosal surface involvement as representing margin involvement. It can also mask the presence of tumour cells on the serosal surface.

Block selection: The tumour needs to be sliced transversely at 3–4 mm intervals and the tumour slices laid out sequentially. Block selection must target the prognostic questions that need to be answered. It is not possible to give an absolute number. Sufficient blocks (generally at least 4) should be taken to enable the pathologist to fully assess all the necessary parameters for staging and prognosis. The likelihood of identifying prognostically useful features, such as extramural venous invasion and serosal penetration, increases with the number of blocks taken.
Select blocks that show the greatest depth of tumour invasion. Select blocks that show tumour close to or at a serosal surface. Serosal involvement is especially prone to occur at or adjacent to peritoneal reflections, especially in the clefts adjacent to the bowel wall, and should be suspected in any areas of serosa that appear granular, dull or haemorrhagic.
Rectal tumours previously treated with neoadjuvant therapy show varying degrees of regression, altering their appearance, and tumour may be difficult to recognise grossly. Blocking of the whole area of abnormality may be required to confirm the presence of tumour.
Tumour at a longitudinal margin occurs only very rarely and several studies have questioned the necessity of sampling the cut end margins. If
16
the tumour is >30 mm from the cut end it is not always necessary to examine the margin microscopically (see below S2.03). However it is often useful to have normal tissue for control purposes and uninvolved margins can provide this.
The relationship of rectal tumours to the circumferential margin must be assessed with appropriate blocks (see S2.05). Most of the colon has a long mesentery, so the assessment of this resection margin is rarely an issue. However, the cut margin of the mesentery is a surgical margin and if the tumour is advanced, it may potentially be involved, either by direct spread, or by involved nodes, at its apex. The caecum and the proximal ascending colon do not have a mesentery and posteriorly have a non-peritonealised bare area of variable size which is potentially an area of surgical margin involvement, especially in tumours arising from the posterior wall or in circumferential tumours. Involvement of the non-peritonealised resection margin in tumours at these sites should be sought and recorded when present.
Lymph node sampling is described below (see below).
Sampling should be performed on any background abnormalities, and in particular polyps or inflammatory bowel disease.
If there is tumour perforation, then a block should be taken for histological record.

All regional lymph nodes must be harvested from the specimen and examined histologically.

The finding of positive lymph nodes is a major determinant of whether a patient receives adjuvant therapy. The probability of finding a positive lymph node increases with the number of nodes found, although this probability curve flattens out after finding 12–15 nodes. The number of nodes present depends on a number of factors, including the size of the specimen, the amount of mesenteric tissue present and whether the patient has received neo-adjuvant therapy. Whilst for purposes of audit an average of 12 lymph nodes should be found, lesser numbers of nodes are present in individual cases.

Lymph nodes are difficult to find in a poorly fixed specimen. The lymph node bearing tissue needs to be methodically palpated and sliced at small intervals. All macroscopically uninvolved nodes need to be embedded completely. Macroscopically involved nodes require only 1 block for confirmation. To aid in accurate microscopic examination, strip the lymph nodes of fat; nodes of dissimilar size should not be embedded in the same block.
In the case of extended or total colectomy specimens, it may not be necessary to examine all non regional lymph nodes. All lymph nodes received in the form of separately identified specimens must be examined microscopically.

Any lymph nodes lying close to the non-peritonealised resection margin need to be sampled in continuity with that margin. If there is tumour in any of the lymph nodes then it is the measurement from the involved lymph node to the nonperitonealised resection margin, if it is closer, rather than from the primary tumour, that is important. This is also true
17
for any isolated tumour deposit in the perirectal or pericolic fat.

It is good practice that the apical lymph node should be identified as it is commonly used in clinical staging.

In the case of two synchronous primary carcinomas, where appropriate, lymph nodes need to be assigned and assessed for each cancer separately.

A block containing tumour should be nominated for further ancillary studies.
Macroscopic findings
S2.01
The specimen length must be recorded.
CS2.01a
This and all other measurements in this protocol should be made in millimetres unless otherwise stated.
S2.02
The site of the tumour must be recorded.
CS2.02a
The determination of the site is based on the assessment by the pathologist and the information provided by the surgeon on the request form. The anatomical site of the tumour is relevant for the following reasons:
• It provides correlation with previous investigations.
• It indicates whether a non-peritonealised (circumferential) margin is likely to be present.
• The natural history and treatment of rectal cancer differs significantly from colonic cancer.
• It defines the presence of regional lymph nodes versus non-regional lymph nodes.
CS2.02b
Strictly the rectum is that part of the large bowel distal to the sigmoid colon and its upper limit is indicated by the end of the sigmoid mesocolon. Standard anatomical texts put this at the level of the 3rd sacral vertebra13 but it is generally agreed by surgeons that the rectum starts at the sacral promontory14. It was agreed by an international expert advisory committee10 that any tumour whose distal margin is seen at 15 cm or less from the anal verge using a rigid sigmoidoscope should be classified as rectal. The pathologist can identify the upper end of the rectum as the point where the colonic taeniae coli merge to form a single external muscle layer.
S2.03
The maximum tumour diameter must be recorded.
CS2.03a
The prognostic significance of maximum tumour size is not established.15-16
CS2.03b
Tumour size must be recorded for correlation with subsequent microscopic examination and to allow correlation with imaging
18
undertaken prior to surgery.
CS2.03c
If possible, distinguish carcinoma from inflammatory changes, as the latter may account for a considerable volume of tumour in some cases.
S2.04
The distance of the tumour to the nearer proximal or distal ‘cut end’ margin must be recorded.
CS2.04a
This is the measurement from the nearer cut end of the specimen and not the non-peritonealised (circumferential, radial) margin.
CS2.04b
Tumour at a longitudinal margin has always been considered a poor prognostic feature but it occurs very rarely.17-18 The necessity of sampling this margin has therefore been questioned.19-21 It is essential to sample this margin and examine it histologically if the tumour is close to the margin (within 30 mm), or if the tumour is found by histology to have an exceptionally infiltrative growth pattern, to show extensive blood vascular or lymphatic permeation, or to be a signet ring, small cell or undifferentiated carcinoma.21
CS2.04c
If included, doughnuts must be embedded for histological examination.
CS2.04d
The difficulty presented by staples is recognised. In this situation, it is important for blocks taken immediately adjacent to the line of staples along the plane of the staple line to be examined.
S2.05
The distance of the tumour to the circumferential margin must be recorded.
CS2.05a
This is the measurement to the nonperitonealised (ie the circumferential or radial) margin.
CS2.05b
This measurement is useful for comparison with and validation of the microscopic measurement.
CS2.05c
It is not only the continuous spread of the primary tumour that is important for this measurement, but also discontinuous spread in the form of lymph node metastases, extramural deposits, and tumour in vessels and lymphatics. Even if the main tumour appears ‘well clear’ of this margin, it is important to block the tissue between the nearest tumour edge and the nonperitonealised resection margin to ensure picking up any discontinuous areas of spread. It may be that the tissue has to be embedded in two or more sequential blocks but this margin must be well sampled.
CS2.05d
This combined with the clinical and microscopic findings is used to define the R code status (see Chapter 5).
S2.06
The presence or absence of tumour perforation must be recorded.
CS2.06a
Perforation through the tumour into the peritoneal cavity is a well established adverse prognostic factor in colonic22 and rectal cancer.23 It is suggested that a block be taken from the area of
19
perforation for histological confirmation. If perforation is present, then this is regarded as pT4 in the TNM staging system, regardless of other factors.9
CS2.06b
Perforation of the proximal bowel as a result of a distal obstructing tumour must not be recorded as tumour perforation, but should be noted (see below).
CS2.06c
It is important to distinguish, where possible, between perforation occurring at the time of surgery and perforation before surgery.
S2.07
For rectal tumours the relationship of the tumour to the anterior peritoneal reflection must be recorded (refer to Figure S2.07a).
CS2.07a
Rectal tumours are classified according to whether they are:
• entirely above the level of the peritoneal reflection anteriorly
• astride (or at) the level of the peritoneal reflection anteriorly
• entirely below the level of the peritoneal reflection anteriorly.
Figure S2.07a Site of tumour in relation to the anterior level of the peritoneal reflection
CS2.07b
The anterior aspect of the rectum is covered by peritoneum down to the peritoneal reflection. On the posterior aspect the nonperitonealised margin extends upwards as a triangular shaped bare area containing the rectal arteries, which then continues up
20
to the start of the sigmoid mesocolon (see Figure S2.07b).
CS2.07c
The nonperitonealised margin is also known as the radial or circumferential resection margin. It consists of a ‘bare’ area of connective tissue at the surgical plane of excision that is not covered by serosa (see Figure S2.07b). Low rectal tumours will be completely surrounded by a non-peritonealised margin (the circumferential margin), while upper rectal tumours have a non-peritonealised margin posterolaterally and a peritonealised (serosal) surface anteriorly. Tumours below the peritoneal reflection have the highest rates of local recurrence.23-26
Figure S2.07b Site of non-peritonealised margin (bare area of mesorectum) in relation to the peritoneal reflection
S2.08
For rectal resections the intactness of the mesorectum must be recorded.
CS2.08a
The prognosis of rectal carcinoma has significantly improved with the use of total mesorectal excision (TME). Gross pathological assessment of the intactness of the mesorectum has been shown to correlate with patient outcome.
CS2.08b
The intactness of the specimen is recorded as one of the following:27
• Incomplete: little bulk to the rectum, defects in the mesorectum down to the muscularis propria, after transverse sectioning the circumferential margin appears very irregular.
• Nearly complete: moderate bulk to the mesorectum,
21
irregularity of the mesorectal surface with defects greater than 5 mm but none extending to the muscularis propria, no areas of visibility of the muscularis propria except at the insertion site of the levator ani muscles.
• Complete: Intact bulky mesorectum with a smooth surface, only minor irregularities of the mesorectal surface, no surface defects greater than 5 mm in depth, no coning towards the distal margin of the specimen, after circumferential sectioning the circumferential margin appears smooth.
• The intactness may be graded as follows:
– Incomplete (grade 1)
– Nearly complete (grade 2)
– Complete (grade 3)
G2.01
Any involvement of the peritoneum should be recorded.
CG2.01a
This should be recorded as one of the following :
• Tumour invades to the peritoneal surface
• Tumour has formed nodule(s) discrete from the tumour mass along the serosal surface
CG2.01b
Tumour involvement of the serosa discontinuous from the site of the main tumour is to be recorded as a metastasis.
G2.02
The number of lymph nodes placed in each cassette should be recorded.
CG2.02a
The number of lymph nodes placed in each cassette should be recorded as a quality measure.
G2.03
The number, diameter and gross configuration of polyps should be summarised.
CG2.03a
The pathologist should be cognisant of the presence of polyposis syndromes. These include:
• Familial Adenomatous Polyposis (FAP)
• Serrated
• MutYH
• Juvenile
• Peutz–Jeghers
CG2.03b
At the present time the criteria for hyperplastic (serrated) polyposis syndrome:
1. At least five histologically confirmed hyperplastic (serrated) polyps proximal to the sigmoid colon, of which two are greater
22
than 1 cm in diameter
2. Any number of hyperplastic (serrated) polyps proximal to the sigmoid colon in a subject with a first-degree relative with hyperplastic polyposis
3. More than 20 hyperplastic (serrated) polyps of any size distributed evenly throughout the colon.28-29
G2.04
A descriptive or narrative field should be provided to record any macroscopic information that is not recorded in the above standards and guidelines, and that would normally form part of the macroscopic description.
CG2.04a
Examples include the presence of tissues and organs adherent to the colon, the presence of tumours other than primary adenocarcinoma, and coexistent chronic inflammatory bowel disease.
CG2.04b
Other information related to the primary tumour may also be recorded here such as gross configuration of the tumour and lymph nodes, appearance of the serosa over the tumour, etc.
CG2.04c
The traditional macroscopic narrative recorded at the time of specimen dissection is often reported separately from the cancer dataset. Although this remains an option, it is recommended that macroscopic information be recorded within the overall structure of this protocol.
CG2.04d
Some of these elements are formally recorded in the ‘Microscopic findings’ (see Chapter 3).
CG2.03e
Much of the information recorded in a traditional macroscopic narrative is covered in the standards and guidelines above and in many cases, no further description is required.
S2.09
The nature and sites of all blocks must be recorded.
23
3 Microscopic findings
Microscopic findings relate to purely histological or morphological assessment. Information derived from more than one type of investigation (eg clinical, macroscopic and microscopic findings), are described in Chapter 5.
S3.01
The tumour type must be recorded.
CS3.01a
The description must be based on the WHO Histological Classification of Tumours of the Colon and Rectum (refer to Appendix 4).8 This publication, as well as a current version of the American Joint Commission on Cancer (AJCC) Cancer Staging Manual9 should be readily accessible to the reporting pathologist.
CS3.01b
Virtually all colorectal cancers are adenocarcinomas. The term ‘Adenocarcinoma NOS’ on the reporting checklist is used to indicate conventional adenocarcinoma without any of the special features of the tumour types listed below it.
CS3.01c
For most tumours, histological type is not prognostically significant. Exceptions include tumour types that are, by definition, high grade (ie signet-ring cell carcinoma); and the medullary subtype, which is invariably associated with mismatch repair gene deficiency and has a favourable prognosis when compared to other poorly differentiated and undifferentiated colorectal carcinomas.8 Note that well differentiated neuroendocrine (carcinoid) tumours are listed separately to carcinoma in the WHO histological classification.8
S3.02
The histological grading of the tumour must be recorded.
CS3.02a
The practical difficulties of the application of grading criteria and the reproducibility of grading are widely recognised, and reflected in the commentary below.30
CS3.02b
In the WHO histological classification,8 grading is based on the percentage of tumour showing formation of gland-like structures:
• Well differentiated adenocarcinoma shows glandular structures in >95% of the tumour.
• Moderately differentiated adenocarcinoma show 50–95% glandular structures.
• Poorly differentiated adenocarcinoma show 0-49% glandular structures.
CS3.02c
Medullary carcinoma needs to be recognised separately and not graded31-32 Mucinous carcinomas are generally not graded, but there is recent evidence that grading has prognostic significance.33 The 4th edition of the WHO suggests that mucinous carcinomas that are MSI-high should be regarded as low grade.8
CS3.02d
Histological grade is a stage-independent prognostic factor.24,34 Multiple grading systems with variation in the number of strata
24
within them have been suggested over the years. The distinction between well- and moderately differentiated adenocarcinoma (low grade) versus poorly differentiated or undifferentiated carcinoma (high grade) has been shown to be prognostically useful.32 The terms well, moderately, poorly differentiated and undifferentiated are equivalent to Grades 1–4 in the TNM staging system.35
CS3.02e
For the most part a pathological distinction between low-grade and high-grade carcinomas can be made with acceptable interobserver variability. Distinction between well and moderately differentiated carcinomas is less reproducible and associated with significant interobserver variability.32 The majority of carcinomas are well or moderately differentiated, having a ‘conventional’ appearance, and should be placed in the low-grade category. Jass et al31defined ‘well differentiated’ as showing ‘simple or complex tubules, easily discerned nuclear polarity, uniformity of nuclear size, and close resemblance to benign precursor lesion’ and ‘moderately differentiated’ as showing ‘less regular glandular differentiation and nuclear polarity poorly discerned or lost’. High-grade tumours are poorly differentiated or undifferentiated; Jass et al31described ‘poorly differentiated’ as showing ‘highly irregular glands or loss of glandular differentiation and loss of nuclear polarity.’
CS3.02f
Whether grading should be based on the predominant pattern of differentiation or the area of worst differentiation is controversial.31,36 In this protocol, it is recommended that, “when a carcinoma has heterogeneity in differentiation, grading should be based on the least differentiated component, not including the leading front of invasion”, as stated in the WHO classification.37
Small foci of apparent poor differentiation may be seen at the advancing edge of tumours but these should not be used to classify the tumour as poorly differentiated (see also ‘tumour budding’ below).
CS3.02g
A two tiered grading system is recommended, based on the WHO classification:
• low grade — well differentiated and moderately differentiated
• high grade — poorly differentiated and undifferentiated
The two tiered grading system is much more reproducible and more prognostically representative.
CS3.02h
There is considerable attention being paid to the process of ‘tumour budding’ (ie dedifferentiation at the advancing margin of the carcinoma, giving rise to single tumour cells and small clusters of up to four cells). There is increasing evidence that this has adverse prognostic significance.38 However, this is not yet sufficiently established or standardised to justify its inclusion as an item for routine reporting.
S3.03
The maximum degree of local invasion into or through the bowel wall must be recorded.
25
CS3.03a
This is based on the T component of the TNM staging system, as outlined in the AJCC Cancer Staging Manual.9
Table CS3.03a
Pathological tumour (T) classification for colorectal cancer. Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer Science and Business Media LLC, www.springerlink.com.
pTX
Primary tumour cannot be assessed
pT0
No evidence of primary tumour
pTis
Carcinoma in-situ: intraepithelial or invasion of lamina propria
pT1
Tumour invades submucosa
pT2
Tumour invades muscularis propria
pT3
Tumour invades through muscularis propria into pericolorectal tissues
pT4a
Tumour penetrates to the surface of the visceral peritoneum
pT4b
Tumour directly invades or is adherent to other organs or structures
Comments on T stages:
• pTis: This category is included to help achieve a uniform staging system across all organ systems and represents either in situ carcinoma or carcinoma showing invasion of the lamina propria (intramucosal carcinoma). However, colorectal neoplasia has not been shown to have metastatic potential until it has invaded through the muscularis mucosae. Therefore, the term pTis is generally avoided in the colorectum and the term high grade dysplasia is preferred. pTis tumours should be regarded as adenomas and not as carcinomas for the purpose of diagnosis and cancer registration.
• pT3: Tumour invades through muscularis propria into pericolorectal tissues. pT3 indicates spread in continuity beyond the bowel wall. The microscopic presence of tumour cells confined within the lumen of lymph vessels or veins does not qualify as local spread in the T classification.9 Occasionally cancer has spread as far as the outer edge of the muscularis propria but not beyond. If no muscle separates the cancer from the mesenteric tissue then the muscle coat should be interpreted as breached (pT3)31 Whilst the subdivision of pT3 into T3a, b, c and d has been dispensed with in the current TNM staging, the subdivision has been shown to have prognostic significance as well as being useful in the planning of further therapy.39-40 If desired, as an alternative, the distance of tumour invasion beyond the muscularis propria may be given as a measurement in
26
millimetres.
• pT4: Note the reversal of T4a and T4b that has occurred between the 6th and 7th editions of the AJCC cancer staging manual. T4b includes cases in which tumour is adherent to other organs or structures, and tumour cells are histologically demonstrated in the adhesions. Stage pT4b also includes direct invasion of other segments of the colorectum by way of the serosa; for example, invasion of sigmoid colon by a carcinoma of the caecum.9,35,41 By contrast, intramural or longitudinal extension of tumour into an adjacent part of the bowel (eg extension of a caecal tumour into the terminal ileum) does not affect the pT stage. Stage pT4a indicates that tumour invades through serosa with tumour cells visualised on the serosal surface or free in the peritoneal cavity. The adverse prognostic significance of involvement of the serosal surface has been emphasised and this should be sought by careful microscopic examination.
Recent studies and commentaries42-43 have drawn attention to the fact that tumour near the serosa may in fact have breached the serosal elastic lamina but not appear on the surface of the colon as it elicits a fibroblastic reaction that forms a cap over the tumour. This finding appears to have adverse significance and tumours showing this feature may have the significance of a pT4a stage. An elastic tissue stain such as VVG or orcein can highlight invasion of the serosal elastic lamina and should be considered in all cases where tumour is close to the colon surface.
Serosal involvement through direct continuity with the primary tumour (pT4) is recorded differently from peritoneal tumour deposits that are separate from the primary. These latter deposits are regarded as distant metastases (pM1). These peritoneal deposits may involve the surface of the colon away from the region of the tumour.
• Cases showing perforation through the tumour should be classified as pT4a, but not cases where perforation is at a site distant to the tumour.
S3.04
Involvement of the proximal or distal resection margins (‘cut-end’ margins) by tumour must be recorded. If the margin is less than 10 mm, the clearance must be recorded.
CS3.04a
See commentary relating to this in Chapter 2 (Macroscopic findings S2.07).
S3.05
The status of the nonperitonealised circumferential margin in rectal tumours must be recorded.
CS3.05a
In rectal tumours, the minimum distance in millimetres between the tumour and the nonperitonealised (circumferential, radial) margin must be recorded from the histological slides.
CS3.05b
Rectal tumours frequently (5–36%) involve the nonperitonealised surgical circumferential resection margin (CRM) and this is
27
associated with significantly higher rates of local recurrence and cancer-related death.44-51
CS3.05c
The frequency of involvement of the CRM depends on the quality of surgery, advancing TNM stage and whether the patient has undergone preoperative neoadjuvant therapy. The closer the tumour is to the CRM, the worse the prognosis.52 The vast majority of studies, including clinical trials and population studies, have used a cutoff of 1 mm or less to define margin involvement.
CS3.05d
CRM involvement may be through direct continuity with the main tumour, by tumour deposits discontinuous from the main tumour, or by tumour in veins, lymphatics or lymph nodes (Figure S3.05). All types of involvement confer a poor prognosis.45,48
Figure S3.05 Measurement of the distance of tumour to the circumferential resection margin (CRM)
CS3.05e
Confusingly, the residual tumour status (R) used in the TNM staging system requires that tumour be identified at the actual resection margin for the margin to be considered involved.35 Thus, in TNM staging if tumour is not actually seen at this margin it is coded as R0. Therefore, recording the distance between the tumour and the CRM will alert the clinician to those patients who may benefit from being treated as though they were margin positive.
S3.06
Results of lymph node histopathology must be recorded.
CS3.06a
The finding of positive lymph nodes is a major determinant of whether the patient receives adjuvant therapy. The probability of finding a positive node increases with the number of nodes found.53-54 Although this probability curve flattens out after finding
x = minimum clearance in mm of primary tumour, extramural or nodal deposit or tumour in vessel etc, whichever is the closest.
28
12–15 nodes54, all identified lymph nodes must be microscopically examined. In general, a minimum of 10-12 lymph nodes should be identified and examined.7 35
CS3.06b
The AJCC recommendations state that if the examined lymph nodes are negative, even if only a small number of nodes has been found, the case should nevertheless be classified as pN0 rather than pNX.35
CS3.06c
Direct extension of a colorectal tumour into a lymph node is considered nodal metastasis. Metastasis in any lymph nodes other than regional nodes is classified as distant metastasis.35
CS3.06d
There is no consensus that occult metastatic disease detected by immunohistochemistry or other methods discriminates between high- and low-risk groups of patients. Data are thus insufficient to recommend routine use of tissue levels or ancillary special techniques.31-32
CS3.06e
Recording small tumour deposits in lymph nodes needs to take account of the following issues:
• Isolated tumour cells are defined as “single malignant cells or a few tumour cells in microclusters”, not more than 0.2 mm in diameter, present within a lymph node. They may be single or multiple. They may be visible in H&E stained sections or detected by immunohistochemistry. The literature suggests that the finding of such cells is not a marker of an adverse prognosis for the patient.55-57
• The AJCC TNM 7th edition recommends that cases in which isolated tumour cells are the only form of nodal involvement should be classified as pN0, although the presence of the isolated tumour cells should be noted.9 Optional designation as pN0(i+) may be used in this situation,41although a free-text description might provide clearer communication.
• It has been argued that very small nodal deposits that show evidence of growth, for example glandular differentiation, distension of the sinus or a stromal reaction, should be regarded as metastases irrespective of size.31
CS3.06f
The assessment of isolated deposits of tumour within the mesocolic and mesorectal fat, in particular whether they represent nodal metastases, can be difficult.
Isolated tumour deposits may derive from nodes, vascular invasion, perineural invasion or a combination of these within a single case. Such deposits are conveniently described as discontinuous extramural tumour deposits or satellite nodules. Most examples occur in situations where there are unequivocally involved nodes anyway (in a literature review of 1520 patients, only 8% of cases were not associated with lymph node deposits). However even where present without definite nodal metastasis, they are associated with an adverse prognosis.58
This difficulty has been neatly addressed in the AJCC TNM 7th
29
edition by the placing of cases with extramural tumour deposits within the N category. In the absence of co-existent definite lymph node metastases (defined in the 7th edition as having identifiable residual lymph node tissue), these cases are categorised as N1c.9
G3.01
Involvement of the apical lymph node should be recorded, if required where staging systems additional to TNM staging are in use.
CG3.01a
Both the Australian Clinicopathological Staging System and the Dukes staging system are in use in some institutions in Australasia. These require the status of the apical lymph node to be recorded.59
S3.07
For all tumours, venous and small vessel invasion must be reported and its anatomic location specified as intramural or extramural.
CS3.07a
Venous invasion by tumour has been repeatedly shown by multivariate24,60-61 and univariate analyses to be a stage independent adverse prognostic factor. However some studies identifying venous invasion as an adverse factor on univariate analysis have failed to confirm its independent impact on prognosis on multivariate breakdown.61-63 Similar disparate results have also been reported for lymphatic invasion.63 In other reports, vascular invasion as a general feature was prognostically significant, but no distinction between lymphatic and venous vessels was made. In a few studies the location as well as the type of the involved vessels (eg extramural veins) were both considered strong determinants of prognostic impact.32,64 Data from the many studies are difficult to amalgamate but nevertheless, the importance of venous and small vessel (lymphovascular) invasion by tumour is generally accepted, and it is considered that venous and small vessel invasion must be sought and separately recorded.
CS3.07b
Some groups have recommended that only extramural venous invasion be recorded,21 while others have recommended that the site of any venous invasion should be recorded, along with its location, intra or extramural.32 In one study, intramural and extramural vascular invasion were shown to have similar prognostic value.22 It is recommended that extramural and intramural venous invasion be recorded separately.
CS3.07c
There should be a high index of suspicion of involvement of a vein if an isolated elongated deposit of tumour is seen alongside an artery. Examination of multiple levels in blocks showing features suspicious of vascular invasion can be helpful and there may be a role for the use of immunohistochemical stains for endothelium and smooth muscle. An elastic tissue stain such as an orcein histochemical stain is also useful to aid detection of venous invasion.65 Assessment should be concentrated at the invasive edge of the tumour. It is an observation of the Royal College of Pathologists colorectal reporting database that extramural venous invasion should be detected in at least 25% of colectomy specimens.66
30
CS3.07d
The prognostic importance of involvement of small (thin-walled, presumably lymphatic) vessels in the submucosa has been well documented with respect to polypectomies of malignant polyps. Such involvement has been shown to be associated with an increased risk of regional lymph node metastasis.67
G3.02
Perineural invasion should be assessed using routine histology and reported.
CG3.02a
There is some evidence that perineural infiltration by tumour is an important indicator of spread, particularly in rectal tumours where it may involve the sacral plexus and this may be an indication for radiotherapy.68
S3.08
The presence of histologically confirmed distant metastases and their site must be recorded.
CS3.08a
Disease classifiable as distant metastasis may sometimes be present within the primary tumour resection specimen (eg a serosal or mesenteric or greater omental deposit that is distant from the primary tumour mass).
CS3.08b
Metastatic deposits in lymph nodes distant from those surrounding the main tumour or its main artery in the specimen will usually be submitted separately by the surgeon. Metastatic deposits in lymph nodes distant from the tumour or its main artery (ie nonregional nodes) may be seen in extended colectomy specimens and are regarded as distant metastases (pM1).41
S3.09
The presence of any relevant coexistent pathological abnormalities in the bowel must be recorded.
CS3.09a
The presence of polyps (type, number, and whether having the criteria of a polyposis syndrome), presence and type of chronic inflammatory bowel disease, with or without dysplasia, and any other clinically relevant pathology is important information that needs to be recorded.
S3.10
The microscopic residual tumour status must be recorded (ie the completeness of resection).
CS3.10a
As the assessment of residual tumour status requires the input of the surgeon, as well as macroscopic and microscopic assessment; it is further dealt with in Chapter 5 (Synthesis and overview).
S3.11
The response of the tumour to neoadjuvant treatment must be recorded.
CS3.11a
Chemotherapy and/or radiotherapy before resection is associated with significant downstaging, and improved prognosis. These specimens require close gross examination and additional blocking to demonstrate tumour. The degree of tumour regression has been shown to correlate with prognosis. The classification of the AJCC, based on that of Ryan et al, is recommended:69
• Grade 0: (complete response): No viable cancer cells
• Grade 1: (moderate response): Single cells or small groups
31
of cancer cells.
• Grade 2: (minimal response): Residual cancer outgrown by fibrosis
• Grade 3: (poor response): Minimal or no tumour kill; extensive residual cancer
CS3.11b
Note that acellular mucin pools seen in patients after therapy are regarded as indicators of complete regression. They do not contribute to T staging, and when seen in lymph nodes do not count as positive nodes. It is advisable to comment upon their presence in a free text comment for the purpose of correlation with pre-operative imaging.
CS3.11c
If neoadjuvant chemotherapy or radiotherapy has been given, the prefix ‘yp’ should be used to indicate that the original p stage may have been modified by therapy. Tumour remaining in a resection specimen following neoadjuvant therapy should always be classified by ypTNM to distinguish it from untreated tumour.41
G3.03
Any additional relevant information should be recorded.
CG3.03a
There must be a free text field so that the pathologist can add any essential information that is not addressed by the above points.
32
4 Ancillary studies findings
Ancillary studies of colorectal carcinoma are being increasingly used as prognostic biomarkers, to aid detection of an underlying genetic basis and to indicate the likelihood of patient response to specific biologic therapies.
G4.01
Immunohistochemistry tests should be performed to test mismatch repair deficiency status and the results recorded in the pathology report.
CG4.01a
Mismatch repair enzymes are important proteins that fix small errors in the gene code following DNA synthesis. The four most common enzymes are MLH1, MSH2, PMS2, MSH6. Defects in the genes coding for these enzymes can result in loss of the protein, as well as loss of this important function. Tumours showing this loss are said to be mismatch repair deficient (MMRD). MMRD cancers occur either sporadically (~12% of all colorectal cancers, usually as a result of methylation of the MLH1 gene), or less commonly (~2%) associated with Lynch syndrome (hereditary nonpolyposis colorectal cancer or HNPCC syndrome) because of changes in the DNA sequence of the genes.
CG4.01b
Immunohistochemical analysis of mismatch repair proteins is used to detect MMRD in colorectal cancer, with an absence of one or more of the mismatch repair proteins considered an abnormal result.70-71 The absence should be a complete absence of nuclear staining of all the carcinomatous epithelium with unequivocal positive staining of the nuclei of non-neoplastic epithelium and intratumoral lymphocytes. As PMS2 is an obligate partner of MLH1 and MSH6 is an obligate partner of MSH2, it is adequate to screen for MMRD by using only MSH6 and PMS2 in the first instance. MLH1 and MSH2 can be studied subsequently if either MSH6 or PMS2 is absent.72-73 This limited approach may not be adequate for archival tissue where the intensity of immunoreactions is often reduced.
CG4.01c
Certain histological features suggest the presence of MMRD, including:
• increased tumour infiltrating lymphocytes
• medullary or micro-glandular morphology
• mucinous or signet ring cell morphology in 50% or more of the tumour.
Intraepithelial lymphocytes (IELs) are those that are in direct contact with tumour cells or are located directly between tumour cell clusters. Only a high density of lymphocytes (≥5 per high-powered field) (× 40 objective) should be considered significant. While the extent of lymphocytic infiltrates at the margins of the tumour (peritumoural lymphocytes) and the prominence of lymphoid follicles (Crohn’s-like reaction) in adjacent tissues are also features of MMRD tumours, most studies have found the strongest correlation between IELs and MMRD.74-75 IEL counts are not necessary if MMR deficiency status is to be assessed formally, by MMRD immunohistochemistry or microsatellite instability (MSI)
33
testing (see CG4.01d).
Medullary carcinomas have a strong association with MMRD, and both medullary and mucinous carcinomas with MMRD have been shown to have a more favourable prognosis. Most mucinous carcinomas however, are not MMRD and these tend to have a poorer prognosis. Thus the prognostic significance of a mucinous carcinoma diagnosis is uncertain without knowledge of MMRD status.
CG4.01d
Tumours that show loss of MMR proteins are almost always characterised by MSI. Although microsatellite analysis, which involves the amplification and analysis of selected microsatellite loci within the genome of the tumour cells, is used less commonly in the diagnostic pathology setting, it continues to have a role in problematic cases.
CG4.01e
The finding of MMRD and/or MSI is important in colorectal cancer for the following reasons:
• MMRD has been shown to be a favourable prognostic factor in colorectal cancer, in terms of both recurrence-free survival and overall survival.74,76-77
• There is increasing evidence to support the observations that MMRD tumours are less responsive to 5FU-based adjuvant chemotherapy30,78-79 although this has not been shown conclusively in all studies.58,80-81
• In ~20% of cases with MMRD, this abnormality will be associated with underlying Lynch syndrome, which raises cancer issues for all family members.
CG4.01f
For the purposes of detecting individuals with Lynch syndrome (HNPCC), MMR testing is currently recommended as the initial screening procedure. At a minimum all cases of colorectal cancer arising in individuals less than 50 years of age should be tested. In addition, all cases meeting the revised Bethesda guidelines (below) should be tested.
• patients with synchronous, metachronous colorectal, or other HNPCC-associated tumours regardless of age
• colorectal cancer with MSI-H histology in patients under age of 60
• colorectal cancer diagnosed in one or more first-degree relatives with an HNPCC-related tumour, with one of the cancers being diagnosed under age 50 years
• colorectal cancer diagnosed in two or more first or second-degree relatives with HNPCC-related tumours, regardless of age
NB HNPCC-associated tumours include endometrial, gastric, ovarian, pancreatic, upper urinary tract, biliary, small bowel, and brain tumours, and sebaceous adenomas and keratoacanthomas in Muir-Torre syndrome.
It is increasingly recognised that many patients with Lynch syndrome fall outside of the Bethesda screening guidelines. This is mainly because as many as 50% of patients with Lynch syndrome develop their first colorectal carcinoma >50 years of
34
age.82 and because a family history is often not evident. In view of this, at least some laboratories now perform routine testing of all colorectal carcinomas. There is also good data to support extending routine MMRD testing at least to a patient age of 70 years.82
MMRD staining can be performed on either biopsy or resection specimen material. Biopsy material has been shown to be as reliable as resection specimen material in detecting a defect in MMR expression.83 Biopsy material has the added advantage of allowing preoperative decision making if Lynch syndrome is suspected.
The following situations deserve further commentary:
1) Lynch syndrome arising due to MSH6 deficiency typically occurs at a later age (median, 56 y) at diagnosis and is found in larger proportion (25%) of rectal cancers than the other MMRD enzymes. However, MMRD testing of rectal cancers post adjuvant chemo/radiotherapy will typically reveal a loss of MSH-6 staining which is an effect of the treatment and does not indicate underlying MMRD.84 In post chemo/radiotherapy cases displaying MSH6 loss, it is advisable that the MMR stains are performed on the pre-treatment biopsy.
2) Recently it has been discovered that a subset of MSH2 deficiency related Lynch syndrome is due to an inherited epigenetic defect of EPCAM. While not routinely available at present, pathologists may be able to perform immunohistochemical testing for this protein in the future.85
3) Loss of expression of all mismatch repair markers (‘null pattern’)
- Sporadic methylation of MLH-1 promotor region with secondary mutation related loss of MSH-2 can rarely occur.86
Pathologists should be aware that preservation of staining for MMR does not exclude Lynch syndrome since truncating mutations of MMR genes may produce a protein that is immunoreactive but non functional.87 MSH6 gene defects may be particularly prone to this phenomonen.88
CG4.01g
Testing for somatic mutations of the BRAF gene may be used in conjunction with MMRD tests as a surrogate indicator for Lynch syndrome. Mutations of the BRAF gene are rare in tumours arising from a Lynch syndrome background, yet are very common in MMRD tumours that occur sporadically because of methylation of MLH1.61-64,67-68,70-71,74-75,80,89-90 As a consequence, when present, BRAF mutations can be useful in helping to distinguish between sporadic tumours arising through hypermethylation, and Lynch syndrome-associated tumours arising from a germline mutation. As the test results may indicate possible familial cancer cases, there are ethical implications that need to be taken into account before BRAF testing. Note: The usefulness of the BRAF V600E test is in tumours exhibiting loss of MLH1 expression – the presence of the mutation effectively excludes Lynch syndrome, whereas its absence is unhelpful (ie could be either sporadic or
35
familial). An immunohistochemical stain for detection of BRAF V600E has recently become commercially available and may supplant the need for PCR based testing.
G4.02
The result of KRAS mutation testing should be recorded.
CG4.02a
Testing for the presence of mutations in the KRAS gene is typically requested by the clinician when metastatic disease is present. Therefore, such testing will most often be performed after the colorectal resection. In this situation, the result should be appended to the initial pathology report.
CG4.02b
Some studies suggest that individuals with KRAS mutant colorectal cancers have a reduced progression-free survival and overall survival. More recently KRAS mutation status has been shown to predict response to drugs that specifically target the epidermal growth factor receptor (EGFR).91-93 Tumours that harbour mutations in KRAS are resistant to the effects of these medications. Thus, testing for KRAS mutations will become increasingly important as the activity of anti EGFR compounds is confined to only those patients with wild type KRAS. Anti-EGFR treatments are often used in individuals with metastatic disease, but the status of KRAS in the primary tumour is usually the same as that of metastases, and thus the findings from the primary tumour block can be used to predict treatment response in metastatic settings.
CG4.02c
KRAS mutation status is currently determined by a variety of genetic methods that are not routine in most diagnostic laboratory settings. The majority of these tests can be performed on formalin fixed paraffin embedded tissue and requests for blocks containing tumour for KRAS testing may be received many years after the primary cancer has been resected. For this reason, for possible subsequent mutation testing, it is desirable to designate a block from all colorectal cancer resections that contains a high proportion (preferably over 70%) of cancer.
36
5 Synthesis and overview
Information that is synthesized from multiple modalities and therefore cannot reside solely in any one of the preceding chapters is described here. For example, tumour stage is synthesized from multiple classes of information – clinical, macroscopic and microscopic. Overarching case comment is synthesis in narrative form. Although it may not necessarily be required in any given report, the provision of the facility for overarching commentary in a cancer report is essential.
By definition, synthetic elements are inferential rather than observational, often representing high-level information that is likely to form part of the ‘Diagnostic summary’ section in the final formatted report (see G5.01).
S5.01
The tumour stage and stage grouping must be recorded, incorporating clinical and pathological data, based on the TNM staging system of the AJCC Cancer Staging Manual (7th Edition).9 (See Tables S5.01a and S5.01b below.)
Table S5.01a
AJCC/UICC colorectal cancer TNM classification. Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer Science and Business Media LLC, www.springerlink.com.
T classification
Primary tumour
TX
Primary tumour cannot be assessed
T0
No evidence of primary tumour
Tis
Carcinoma in situ: intraepithelial or invasion of lamina propria
T1
Tumour invades submucosa
T2
Tumour invades muscularis propria
T3
Tumour invades through the muscularis propria into pericolorectal tissues
T4a
Tumour penetrates to the surface of the visceral peritoneum
T4b
Tumour directly invades or is adherent to other organs or structures
N classification
Regional lymph nodes
NX
Regional lymph nodes cannot be assessed
N0
No regional lymph node metastasis
N1
Metastasis in 1-3 regional lymph nodes
N1a
Metastasis in one regional lymph node
N1b
Metastasis in 2-3 regional lymph nodes
N1c
Tumour deposit(s) in the subserosa, mesentery, or nonperitonealised pericolic or perirectal tissues without regional nodal metastasis
N2
Metastasis in 4 or more regional lymph nodes
N2a
Metastasis in 4-6 regional lymph nodes
N2b
Metastasis in 7 or more regional lymph nodes
M classification
Distant metastasis
M0
No distant metastasis
37
M1
Distant metastasis
M1a
Metastasis confined to one organ or site (e.g., liver, lung, ovary, nonregional node)
M1b
Metastases in more than one organ/site or the peritoneum
Table S5.01b
AJCC/UICC pathological stage grouping for colorectal cancer9 Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer Science and Business Media LLC, www.springerlink.com.
Stage
T
N
M
0
Tis
N0
M0
I
T1
N0
M0
T2
N0
M0
IIA
T3
N0
M0
IIB
T4a
N0
M0
IIC
T4b
N0
M0
IIIA
T1-T2
N1/N1
M0
T1
N2a
M0
IIIB
T3-T4a
N1/N1
M0
T2-T3
N2a
M0
T1-T2
N2b
M0
IIIC
T4a
N2a
M0
T3-T4a
N2b
M0
T4b
N1-N2
M0
IVA
Any T
Any N
M1a
IVB
Any T
Any N
M1b
CS5.01a
The allocation of the TNM stage relies upon synthesis of information provided in the clinical request form and following macroscopic and microscopic examination.
CS5.01b
The y prefix must be used if there has been prior chemotherapy or radiotherapy.
CS5.01c
The terminology pM1 (distant metastases present) should only be used by pathologists on the basis of pathological assessment of a relevant tissue sample. However, pathologists are strongly encouraged to use clinical terminology (cM0, cM1) in their final report on the basis of information provided to them on the surgical request form. It may advisable to make this clear in a comment (ie cM1 – based on clinical evidence of liver metastases). Under this scenario, the hierarchy of M stage reports available to the pathologist would be as follows:
• pM1 in the presence of pathologically proven metastatic disease
• cM1 where clinical information stated metastases were present but where there was no pathological evidence of this
38
• cM0 where there was a clinical statement of no metastases and no pathological evidence of metastases.
S5.02
The year of publication and/or edition of the cancer staging system used in S5.01 must be included in the report.
S5.03
The residual tumour status must be recorded according to the AJCC Cancer Staging Manual (7th Edition)9
CS5.03a
The R codes are as follows. (Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer Science and Business Media LLC, www.springerlink.com.)
• R0: Complete resection, margins histologically negative, no residual tumour left after resection (primary tumour, regional nodes)
• R1: Incomplete resection, margins histologically involved, microscopic tumour remains after resection of gross disease (primary tumour, regional nodes)
• R2: Incomplete resection, margins macroscopically involved or gross disease remains after subtotal resection (eg primary tumour, regional nodes, or liver metastasis).
CS5.03b
Residual tumour classification (R status) is not limited to the primary tumour. The R classification not only considers locoregional residual tumour, but also distant residual tumour in the form of unresected or incompletely resected metastases (R2)94 For example, a metastasis in the liver from a primary colorectal carcinoma would be M1 and R0 if the metastasis was solitary and resected with tumour-free margins. This case would be M1 and R2 if the metastasis was not resected.
CS5.03c
The resection status rule also applies to lymph nodes. If a positive lymph node is left behind it is classified as R2.
CS5.03d
Tumour cells that are confined to the lumen of blood vessels or lymphatics at the resection margin are classified as R0.94
CS5.03e
Peritoneal involvement alone is not a reason to categorise the tumour as incompletely excised.
G5.01
The ‘Diagnostic summary’ section of the final formatted report should include:
a. specimen type (S1.02)
b. tumour site (S2.02)
c. tumour type (S3.01)
d. tumour stage (S5.01)
e. completeness of excision (S5.03).
39
S5.04
Record if this is a new primary cancer or a recurrence of a previous cancer, if known.
CS5.04a
The term recurrence defines the return, reappearance or metastasis of cancer (of the same histology) after a disease free period.
Recurrence should be classified as distant metastasis or regional (local) recurrence.
Regional (local) recurrence refers to the recurrence of cancer cells at the same site as the original (primary) tumour or the regional lymph nodes.
Distant metastasis refers to the spread of cancer of the same histologic type as the original (primary) tumour to distant organs or distant lymph nodes.
CS5.04b
This information will provide an opportunity for previous reports to be reviewed during the reporting process, which may provide valuable information to the pathologist. This information also has implications for recording cancer incidence and evidence based research.
S5.05
A field for free text or narrative in which the reporting pathologist can give overarching case comment must be provided.
CS5.05a
This field may be used, for example, to:
• list any relevant ancillary tests
• document any noteworthy adverse gross and/or histological features
• express any diagnostic subtlety or nuance that is beyond synoptic capture
• document further consultation or results still pending.
CS5.05b
Use of this field is at the discretion of the reporting pathologist.
40
6 Structured checklist
The following checklist includes the standards and guidelines for this protocol which must be considered when reporting, in the simplest possible form. The summation of all ‘standards’ is equivalent to the ‘minimum dataset’ for colorectal cancer. For emphasis, standards (mandatory elements) are formatted in bold font.
S6.01
The structured checklist provided may be modified as required but with the following restrictions:
a. All standards and their respective naming conventions, definitions and value lists must be adhered to.
b. Guidelines are not mandatory but are recommendations and where used, must follow the naming conventions, definitions and value lists given in the protocol.
G6.01
The order of information and design of the checklist may be varied according to the laboratory information system (LIS) capabilities and as described in Functional Requirements for Structured Pathology Reporting of Cancer Protocols.{Royal College of Pathologists of Australasia, 2011 #790}
CG6.01a
Where the LIS allows dissociation between data entry and report format, the structured checklist is usually best formatted to follow pathologist workflow. In this situation, the elements of synthesis or conclusions are necessarily at the end. The report format is then optimised independently by the LIS.
CG6.01b
Where the LIS does not allow dissociation between data entry and report format, (for example where only a single text field is provided for the report), pathologists may elect to create a checklist in the format of the final report. In this situation, communication with the clinician takes precedence and the checklist design is according to principles given in Chapter 7.
G6.02
Where the checklist is used as a report template (see G6.01), the principles in Chapter 7 and Appendix 2 apply.
CG6.02a
All extraneous information, tick boxes and unused values should be deleted.
G6.03
Additional comment may be added to an individual response where necessary to describe any uncertainty or nuance in the selection of a prescribed response in the checklist. Additional comment is not required where the prescribed response is adequate.
41
Values in italics are conditional on previous responses.
Values in all caps are headings with sub values.
S/G
Item description
Response type
Conditional
Pre-analytic
S1.01
Demographic information provided
S1.02
Clinical information provided on request form
Text
OR
Structured entry as below:
Operating surgeon name & contact details
Text
Perforation
Single selection value list:
• Absent
• Present
If present, record the nature of perforation
Nature of perforation
Multi select value list (select all that apply):
• Through tumour prior to surgery
• Through tumour during surgery mobilisation
• Away from tumour
42
S/G
Item description
Response type
Conditional
Clinical obstruction
Single selection value list:
• Absent
• Present
Tumour location
Single selection value list:
• Caecum
• Ascending colon
• Hepatic flexure
• Transverse colon
• Splenic flexure
• Descending colon
• Sigmoid colon
• Rectosigmoid junction
• Rectum
For synchronous tumours indicate each other site
Text
Note
: Synchronous tumours should be reported separately – this serves only to identify the presence of other synchronous tumours for which separate reports will be submitted.
Distance from the anal verge
Numeric: ___cm
Note
Conditional on rectum being selected : Measured in cm by longstanding surgical convention
43
S/G
Item description
Response type
Conditional
Type of operation
Single selection value list:
• Right hemicolectomy
• Extended right hemicolectomy
• Transverse colectomy
• Left hemicolectomy
• Anterior resection
• Abdominoperineal resection
• Proctocolectomy
• Total colectomy with ileorectal anastomosis
• Hartmann’s procedure
• Other procedure(s)
If other procedure(s) is selected, record type of procedure.
If anterior resection is selected, record anterior resection type.
Type of procedure
Text
Anterior resection type
Single selection value list:
• High
• Low
• Ultralow
Pre-operative radiotherapy
Single selection value list:
• No
• Yes
If yes, record type of course
44
S/G
Item description
Response type
Conditional
Type of course
Single selection value list:
• Short course
• Long course
Surgeon’s opinion on the existence of local residual cancer postsurgery
Text
Involvement of adjacent organs
Text
New primary cancer or recurrence
Single selection value list:
• New primary
• Regional (local) recurrence
• Distant metastases
If regional (local) recurrence or distant metastasis describe.
Describe
Text
S1.03
Pathology accession number
Alpha-numeric
G1.01
Other relevant details
Text
Macroscopic findings
S2.01
Specimen length
Numeric:___mm
45
S/G
Item description
Response type
Conditional
S2.02
Tumour site
Single selection value list:
• Caecum
• Ascending colon
• Hepatic flexure
• Transverse colon
• Splenic flexure
• Descending colon
• Sigmoid colon
• Rectosigmoid junction
• Rectum
S2.03
Maximum tumour diameter
Numeric: ___mm
S2.04
Distance of tumour to the nearer proximal or distal ‘cut end’
Numeric: ___mm
S2.05
Distance of tumour to the nonperitonealised circumferential margin
Numeric: ___mm
S2.06
Tumour perforation
Single selection value list:
• Absent
• Present
46
S/G
Item description
Response type
Conditional
S2.07
Relationship to anterior peritoneal reflection
Single selection value list:
• Entirely above
• Astride
• Entirely below
Conditional on rectum being selected in S2.02
S2.08
Intactness of mesorectum
Single selection value list:
• Incomplete (grade 1)
• Nearly complete (grade 2)
• Complete (grade 3)
Conditional on rectum being selected in S2.02
G2.01
Peritoneum
Single selection value list:
• Tumour invades to the peritoneal surface
• Tumour has formed nodule(s) discrete from the tumour mass along the serosal surface
G2.02
Lymph nodes
Single selection value list:
• Not received
• Received
If received, record the number of nodes
Number of lymph nodes per cassette
Numeric: ___ in cassette: ___
Note
: repeat for each cassette with lymph nodes.
G2.03
Polyps
Single selection value list:
• Absent
• Present
If present, provide a polyp summary.
47
S/G
Item description
Response type
Conditional
Polyp summary
Text
Note
: the polyp summary should include the numbers, diameter range and gross appearance
G2.04
Other macroscopic comments
Text
S2.09
Nature and site of blocks
Text
Microscopic findings
S3.01
Tumour type
Single selection value list from WHO Classification of Tumours. Pathology and Genetics of Tumours of the Digestive System (2010).
S3.02
Histological grade
Single selection value list:
• Low grade – well and moderately differentiated
• High grade - poorly and undifferentiated
48
S/G
Item description
Response type
Conditional
S3.03
Maximum degree of local invasion into or through the bowel wall
Single selection value list:
• pT1 Tumour invades submucosa
• pT2 Tumour invades muscularis propria
• pT3 Tumour invades through muscularis propria into pericolorectal tissues
• pT4a Tumour penetrates to the surface of the visceral peritoneum
• pT4b Tumour directly invades or is adherent to other organs or structures
S3.04
Involvement of the proximal or distal resection (‘cut-end’) margins
Single selection value list:
• Not involved
• Involved
If involved is selected, record involved margin(s)
If not involved is selected, record microscopic clearance.
Involved margin(s)
Multi select value list (select all that apply):
• Distal
• Proximal
Microscopic clearance
Numeric: ___mm (if the margin is less than 10 mm)
OR Clearance is ≥10mm
49
S/G
Item description
Response type
Conditional
S3.05
Status of the nonperitonealised circumferential margin (rectal tumours)
Single selection value list:
• Not involved
• Involved
Conditional on rectum being selected in S2.02
If not involved is selected, record microscopic clearance.
Microscopic clearance
Numeric: ___mm
S3.06
Lymph node involvement
Single selection value list:
• Absent
• Present
Conditional on nodes being received in G2.02. If G2.02 has been recorded as “not received” this standard is not required.
If present, record site(s) and number of lymph nodes
Site(s) and numbers of lymph nodes
Text: Site of lymph node
AND
Numeric: ____/_____
(Number of positive nodes/ Total number of nodes from this site)
Site is the LN drainage relevant to the site of tumour being reported.
Notes:
50
S/G
Item description
Response type
Conditional
Isolated extra-mural tumour deposits
Single selection value list:
• Absent
• Present
G3.01
Apical node involvement
Single selection value list:
• Not applicable
• Absent
• Present
S3.07
VENOUS AND SMALL VESSEL INVASION
Intramural vein invasion
Single selection value list:
• Not identified
• Present
Extramural vein invasion
Single selection value list:
• Not identified
• Present
Small vessel invasion
Single selection value list:
• Not identified
• Present
• Present and extensive
51
S/G
Item description
Response type
Conditional
G3.02
Perineural invasion
Single selection value list:
• Not identified
• Present
• Present and extensive
S3.08
Histologically confirmed distant metastases
Single selection value list:
• Absent
• Present
If present, record sites
Site(s)
Text
S3.09
Relevant coexistent pathological abnormalities
Multi select value list (select all that apply):
• None noted
• Polyps
• Ulcerative colitis
• Crohn’s disease
• Other
If Polyps is selected provide details
If Ulcerative colitis or Crohn’s disease is selected record dysplasia
If other is selected, provide details in “other abnormality”
Polyp details (type, number, polyposis syndrome criteria met etc)
Text
Dysplasia
Single selection value list:
• With dysplasia
• Without dysplasia
Other abnormality
Text
52
S/G
Item description
Response type
Conditional
S3.10
Microscopic residual tumour status (completeness of resection)
Text
S3.11
Response to neoadjuvant therapy
Single selection value list:
• No prior treatment
• Grade 0 (complete response) No viable cancer cells
• Grade 1 (moderate response) Single cells or small groups of cancer cells
• Grade 2 (minimal response) Residual cancer outgrown by fibrosis
• Grade 3 (poor response) Minimal or no tumour kill; extensive residual cancer.
G3.03
Microscopic comments
Text
Ancillary test findings
G4.01
MISMATCH REPAIR ENZYMES
MLH-1
Single selection value list:
• Not tested
• Normal staining
• Loss of staining
53
S/G
Item description
Response type
Conditional
PMS-2
Single selection value list:
• Not tested
• Normal staining
• Loss of staining
MSH-2
Single selection value list:
• Not tested
• Normal staining
• Loss of staining
MSH-6
Single selection value list:
• Not tested
• Normal staining
• Loss of staining
Comments
Text
Microsatellite instability (MSI)
Single selection value list:
• Unstable
• Stable
• Not tested
If unstable or stable, record laboratory performing test and report number
Comments
Text
Laboratory performing test and report number
Text
54
S/G
Item description
Response type
Conditional
BRAF (V600E mutation)
Single selection value list:
• Mutated
• Wild type
• Not tested
If mutated or wild type, record laboratory performing test and report number
Comments
Text
Laboratory performing test and report number
Text
G4.02
KRAS gene mutation (codons 12 and 13)
Single selection value list:
• Mutated
• Wild type
• Not tested
If mutated or wild type, record laboratory performing test and report number
Comments
Text
Laboratory performing test and report number
Text
Synthesis and overview
S5.01
TUMOUR STAGE
T
Single selection value list:
TX Primary tumour cannot be assessed
T0 No evidence of primary tumour
Tis Carcinoma in situ: intraepithelial or invasion of lamina propria
T1 Tumour invades submucosa
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S/G
Item description
Response type
Conditional
T2 Tumour invades muscularis propria
T3 Tumour invades through the muscularis propria into pericolorectal tissues
T4a Tumour penetrates to the surface of the visceral peritoneum
T4b Tumour directly invades or is adherent to
other organs or structures
N
Single selection value list:
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in 1-3 regional lymph nodes
N1a Metastasis in one regional lymph node
N1b Metastasis in 2-3 regional lymph nodes
N1c Tumour deposit(s) in the subserosa, mesentery, or nonperitonealised pericolic or perirectal tissues without regional nodal metastasis
N2 Metastasis in 4 or more regional lymph nodes
N2a Metastasis in 4-6 regional lymph nodes
N2b Metastasis in 7 or more regional lymph nodes
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S/G
Item description
Response type
Conditional
M
Single selection value list:
M0 No distant metastasis
M1 Distant metastasis
M1a Metastasis confined to one organ or site (e.g. liver, lung, ovary, nonregional node)
M1b Metastases in more than one organ/site or the peritoneum
Stage grouping
Single selection value list:
Stage T N M
0 Tis N0 M0
I T1 N0 M0
T2 N0 M0
IIA T3 N0 M0
IIB T4a N0 M0
IIC T4b N0 M0
IIIA T1-T2 N1/N1c M0
T1 N2a M0
IIIB T3-T4a N1/N1c M0
T2-T3 N2a M0
T1-T2 N2b M0
IIIC T4a N2a M0
T3-T4a N2b M0
T4b N1-N2 M0
IVA Any T Any N M1a
IVB Any T Any N M1b
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S/G
Item description
Response type
Conditional
S5.02
Year and/or edition of staging system
Numeric: year
AND/OR
Text: Edition eg 1st, 2nd etc
S5.03
Residual tumour status
Single selection value list:
R0: Complete resection, margins histologically negative, no residual tumour left after resection (primary tumour, regional nodes)
R1: Incomplete resection, margins histologically involved, microscopic tumour remains after resection of gross disease (primary tumour, regional nodes)
R2: Incomplete resection, margins macroscopically involved or gross disease remains after subtotal resection (eg primary tumour, regional nodes, or liver metastasis).
G5.01
Diagnostic summary
Include:
a. specimen type
b. tumour site
c. tumour type
d. tumour stage
e. completeness of excision
Text
58
S/G
Item description
Response type
Conditional
S5.04
New primary cancer or recurrence
Single selection value list:
• New primary
• Regional (local) recurrence
• Distant metastases
• Indeterminate
If regional (local) recurrence or distant metastasis describe.
Describe
Text
S5.05
Overarching comment
Text
59
7 Formatting of pathology reports
Good formatting of the pathology report is essential for optimising communication with the clinician, and will be an important contributor to the success of cancer reporting protocols. The report should be formatted to provide information clearly and unambiguously to the treating doctors, and should be organised with their use of the report in mind. In this sense, the report differs from the structured checklist, which is organised with the pathologists’ workflow as a priority.
Uniformity in the format as well as in the data items of cancer reports between laboratories makes it easier for treating doctors to understand the reports; it is therefore seen as an important element of the systematic reporting of cancer. For guidance on formatting pathology reports, please refer to Appendix 2.
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Appendix 1 Pathology request information and surgical handling procedures
This appendix describes the information that should be collected before the pathology test. Some of this information can be provided on generic pathology request forms; any additional information required specifically for the reporting of colorectal cancer may be provided by the clinician on a separate request information sheet. An example request information sheet is included below. Elements which are in bold text are those which pathologists consider to be required information. Those in non-bold text are recommended.
Also included in this appendix are the procedures that are recommended before handover of specimens to the laboratory.
Patient information

Adequate demographic and request information should be provided with the specimen.

Items relevant to cancer reporting protocols include:
• patient name
• date of birth
• sex
• identification and contact details of requesting doctor
• date of request

The patient’s ethnicity should be recorded, if known. In particular whether the patient is of aboriginal or Torres Strait islander origin. This is in support of a government initiative to monitor the health of indigenous Australians particularly in relation to cancer.

The patient’s health identifiers should be provided.

The patient’s health identifiers may include the patient’s Medical Record Number as well as a national health number such as a patient’s Medicare number (Australia), Individual Healthcare Identifier (IHI) (Australia) or the National Healthcare Identifier (New Zealand).
Clinical Information

The surgeon’s identity and contact details should be recorded.

Name of operating surgeon, contact details, and date of operation.

Perforation and/or obstruction should be recorded.

Perforation may be more easily appreciated by the surgeon than the pathologist. Tumour perforation is a prognostic factor in determining postoperative mortality and long-term survival.
61
Perforation away from the tumour, related to colonic obstruction by the tumour, should be distinguished from perforation through the tumour. Perforation occurring during the course of surgery should be differentiated from the above and should be identified as such by the surgeon on the surgical request form.

The tumour location should be recorded.

Choose from one of the following:
• caecum
• ascending colon
• hepatic flexure
• transverse colon
• splenic flexure
• descending colon
• sigmoid colon
• rectosigmoid junction
• rectum.

For synchronous tumours indicate each other site for which a separate report will be submitted.

The distance from the anal verge should be recorded (for rectal tumours only).

This should be measured in centimetres (by longstanding surgical convention) using the best available information; rigid sigmoidoscopy measurements are preferred over digital rectal examination, operative findings or colonoscopy measurements.

This measurement allows for the classification of rectal cancers into upper, mid- and lower third categories, which has a significant impact on case management.

The type of operation performed should be recorded.

Choose from one of the following:
• right hemicolectomy
• extended right hemicolectomy
• transverse colectomy
• left hemicolectomy
• anterior resection (specify whether high, low or ultralow)
• abdominoperineal resection
• proctocolectomy
• total colectomy with ileorectal anastomosis
• Hartmann’s procedure
• other (specify).

If pre-operative radiotherapy has been administered, this should be recorded.
62

In general, this applies to rectal cancer only. Pre-operative radiotherapy significantly alters the gross and microscopic appearance of the tumour.

Short-course and long-course radiotherapy regimes need to be differentiated because the effects in the resected specimens are quite different.

The surgeon’s opinion on the existence of local residual cancer following the operative procedure should be recorded.

This item relates to the overall completeness of resection of the tumour, including evidence of residual disease at surgical margins or within regions in which resection has not been attempted. It allows for residual tumour status (R) to be assessed (see Chapters 2 and 3).

The involvement of adjacent organs should be recorded.

With regard to extension of disease into areas which either have or have not been resected (ie involvement of other organs or tissues by direct spread), it is the responsibility of the surgeon to report these deposits and, if indicated, mark these areas with a suture or other marker.

Record if this is a new primary cancer or a recurrence of a previous cancer, if known.

The term recurrence defines the return, reappearance or metastasis of cancer (of the same histology) after a disease free period.
Recurrence should be classified as distant metastases or regional (local) recurrence.
Regional (local) recurrence refers to the recurrence of cancer cells at the same site as the original (primary) tumour or the regional lymph nodes.
Distant metastasis refers to the spread of cancer of the same histologic type as the original (primary) tumour to distant organs or distant lymph nodes.

The reporting of metastatic deposits, either resected or not resected, is required for assessment of the metastatic (M) stage of the tumour.

The presence of involved nonregional lymph nodes stages the tumour as M1.

This information will provide an opportunity for previous reports to be reviewed during the reporting process, which may provide valuable information to the pathologist. This information also has implications for recording cancer incidence and evidence based research.
63

Any additional relevant information should be recorded.

A free text field should be completed by the referring doctor to communicate anything that is not addressed by the above points, such as previous cancers, risk factors, investigations, treatments and family history.
64
Example Request Information Sheet
The above Request Information Sheet is published to the RCPA website.
65
Appendix 2 Guidelines for formatting of a pathology report
Layout
Headings and spaces should be used to indicate subsections of the report, and heading hierarchies should be used where the LIS allows it. Heading hierarchies may be defined by a combination of case, font size, style and, if necessary, indentation.
Grouping like data elements under headings and using ‘white space’ assists in rapid transfer of information.95
Descriptive titles and headings should be consistent across the protocol, checklist and report.
When reporting on different tumour types, similar layout of headings and blocks of data should be used, and this layout should be maintained over time.
Consistent positioning speeds data transfer and, over time, may reduce the need for field descriptions or headings, thus reducing unnecessary information or ‘clutter’.
Within any given subsection, information density should be optimised to assist in data assimilation and recall. The following strategies should be used:
• Configure reports in such a way that data elements are ‘chunked’ into a single unit to help improve recall for the clinician.95
• Reduce ‘clutter’ to a minimum.95 Thus, information that is not part of the protocol (eg billing information or Snomed codes) should not appear on the reports or should be minimised.
• Reduce the use of formatting elements (eg bold, underlining or use of footnotes) because these increase clutter and may distract the reader from the key information.
Where a structured report checklist is used as a template for the actual report, any values provided in the checklist but not applying to the case in question must be deleted from the formatted report.
Reports should be formatted with an understanding of the potential for the information to ‘mutate’ or be degraded as the report is transferred from the LIS to other health information systems.
As a report is transferred between systems:
• text characteristics such as font type, size, bold, italics and colour are often lost
• tables are likely to be corrupted as vertical alignment of text is lost when fixed font widths of the LIS are rendered as proportional fonts on screen or in print
• spaces, tabs and blank lines may be stripped from the report, disrupting the formatting
• supplementary reports may merge into the initial report.
66
Appendix 3 Example of a pathology report
67
68
Appendix 4 WHO Classificationa of tumours of the colon and rectum 4th edition.
Epithelial tumors Premalignant lesions Adenoma, NOS 8140/0 Tubular adenoma, NOS 8211/0 Villous adenoma, NOS 8261/0 Tubulovillous adenoma, NOS 8263/0 Glandular intraepithelial neoplasia, low grade 8148/0 Glandular intraepithelial neoplasia, high grade 8148/2 Serrated lesions Sessile serrated adenoma/polyp 8213/0 Serrated polyposis 8213/0 Traditional serrated adenoma 8213/0 Carcinomas Adenocarcinoma, NOS 8140/3 Cribriform comedo-type adenocarcinoma 8201/3 Medullary carcinoma, NOS 8510/3 Micropapillary carcinoma 8265/3 Colloid carcinoma 8480/3 Serrated adenocarcinoma 8213/3 Signet ring cell carcinoma 8490/3 Adenosquamous carcinoma 8560/3 Spindle cell carcinoma, NOS 8032/3 Squamous cell carcinoma, NOS 8070/3 Undifferentiated carcinoma 8020/3 Neuroendocrine neoplasms Neuroendocrine tumor G1 (NET G1) / Carcinoid 8240/3 Neuroendocrine tumor G2 (NET G2) 8249/3 Neuroendocrine carcinoma, NOS 8246/3 Large cell neuroendocrine carcinoma 8013/3 Small cell neuroendocrine carcinoma 8041/3 Mixed adenoneuroendocrine carcinoma 8244/3 Enterochromaffin cell (EC), serotonin-producing
neuroendocrine tumour (NET) 8241/3 L cell, Glucagon-like peptide-producing and
PP/PYY-producing NETs 8152/1 Mesenchymal tumors Leiomyoma, NOS 8890/0 Lipoma, NOS 8850/0 Angiosarcoma 9120/3 Gastrointestinal stromal tumor, malignant 8936/3 Kaposi sarcoma 9140/3 Leiomyosarcoma, NOS 8890/3 Schwannoma, NOS 9560/0 Perineurioma, NOS 9571/0 Ganglioneuroma 9490/0 Granular cell tumor, NOS 9580/0
69
Malignant lymphomas Extranodal marginal zone lymphoma of
mucosa-associated lymphoid tissue
(MALT lymphoma) 9699/3 Mantle cell lymphoma 9673/3 Diffuse large B-cell lymphoma (DLBCL), NOS 9680/3 Burkitt lymphoma, NOS 9687/3 B-cell lymphoma, unclassifiable, with features
intermediate between diffuse large B-cell
lymphoma and Burkitt lymphoma 9680/3
© International Agency for Research on Cancer (IARC). Reproduced with permission.
70
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