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Hereditary Non-Polyposis Colorectal Cancer
 

Hereditary Non-Polyposis Colorectal Cancer

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case prentation and review of Literature

case prentation and review of Literature

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    Hereditary Non-Polyposis Colorectal Cancer Hereditary Non-Polyposis Colorectal Cancer Presentation Transcript

    • The Lebanese UniversityFaculty of medical sciencesGeneral surgery training programmeThe central military hospitalgeneral surgery department
      Clinical case, surgical technique and review of literature.
      Hippocrates (460 B.C. – 377 B.C.) -
      The father of medicine.
      20 April 2010
    • Clinical Case
      Attended by: Dr. Ali Khalil.
      Prepared by: Mohomad Chour, PGY II, general surgery.
      Dungeness crab (Cancer magister).
    • Case presentation
      25 y old male with lower GI bleeding .
      HPI: rectal bleeding, alteration of bowel mvt and weight loss of 5 Kg over the last year .
      PMHx:neg
      PSHx:Hemorrhoidectomy 3 y ago
      FHx: - mother DMII
      - father colorectal cancer at age 37 treated surgically and with chemo-radiotherapy with apparent recovery.
    • Physical exam
      Abd: non tender, soft, no mass, no organomegaly
      DRE: no abnormalities
      Left axillary mass (fibrotic related to previous trauma)
    • labs
      Hb 11.9
      Ht 36.6
      MCV 75
      WBC 9100
      PLT 264000
      INR 1.35
      Electr ,BUN , creat: normal
      Tumor markers : negative
    • Colonoscopy report(2/3/10)
      Anus: normal
      Rectum: at the rectosigmoidjuction ( 14 cm from AM) presence of a friable and infiltrating tumor, and reaching 20 cm from AM compatible with adenoca multiple bx taken .
      Left and transverse colon: normal
      Right colon: normal
      Cecum: normal
    • pathology
      Evidence of malignant cells suggestive of Adenocarcinoma
    • Abd and pelvic CT scan 16/3/10
      Thickening of the sigmoid wall .
      No adenopathies .
    • decision
      Laparoscopic sigmoid + upper rectum colectomy
    • Operative report(24/3/10)…
      DD, modified lithotomy position, routine S&D.
      Pneumoperitoneum: Veress, umbilical trocar (10mm), 2 R midclavicular 5mm trocars ,PCO2 14 mmHg
      Evidence of an upper rectal tumor(adhesions or invasion of the posterior wall of the bladder) with narrow pelvic inlet converted to open .
    • Operative report…
      Midline laparotomy incision
      Identification of a tumor (some 6 cm in length) extending from just above the peritoneal reflection proximally.
      Mobilisation of the sigmoid starting laterally to proximal with minimal liberation of the splenic flexure .
      Identification of the left ureter.
      Further dissection of sigmoid and distal descending colon
      Identifiation of IMA ligation & section at its origin .
      Dissection continuing distally to the peritoneal reflection after sectioning the bowel 20 cm away from the tumor using GIA 60 .
    • Operative report
      Opening of the peritoneal reflection ,dissection through mesorectum around the upper and midrectum reaching almost the seminal vesicle : section using endoGIA 60.
      Perineal part: using CEEA 31 completing the colorectal anastomosis, checked for tightness.
      1 drain
      Closure ,transferred to ICU .
    • The specimen
    • The specimen
    • Final pathology report
      Adenocarcinoma, Mucinous type, moderately differentiated, Duke’s stage C, with :
      • Tumor measuring 5.5x2.8x5 cm
      • Infiltrating through the wall into serosa and pericolic fat
      • Evidence of vascular invasion
      • Metastasis to 10/18 pericolic lymph nodes
      • Free surgical margins (with distal 2 cm free margins in the colon and 1.5 cm in frozen sections specimen)
      • Anastomotic edges: no evidence of malignancy
    • Staging
      -Stage III C
      -Duke’s stage C
    • Counseling
      Patient was counseled to attend a geneticist for DNA mapping.
      Possible HNPCC.
    • Hereditary Non-Polyposis Colorectal Cancer(HNPCC)
      A Review of Literature
      Plato and Aristotle, from School of Athens.
      Raphael, 1508-1511.
    • Introduction.
      Inherited colorectal carcinoma:
      Hereditary non-polyposis colorectal cancer (5-7% of cases of CRC)
      Familial adenomatouspolyposis and attenuated FAP(1%)
      Familial colorectal cancer (10-15%)
      Peutz-Jeghers syndrome (<1%)
      Juvenile polyposis syndrome (<1%)
    • Introduction.
      Inherited colorectal carcinoma:
      Hereditary non-polyposis colorectal cancer (5-7% of cases of CRC)
      Familial adenomatouspolyposis and attenuated FAP(1%)
      Familial colorectal cancer (10-15%)
      Peutz-Jeghers syndrome (<1%)
      Juvenile polyposis syndrome (<1%)
    • Historical perspectives.
      In 1985, the chairman of pathology at the University of Michigan, Dr. Alder Warthin, recognised this syndrome.
      Dr. Warthin’s seamstress prophesied that she would die of cancer because of her strong family history of endometrial, gastric and colon cancer.
      Dr. Warthin’s investigations of her family’s medical records revealed a pattern of autosomal dominant transmission of cancer risk.
      Dr. Henry Lynch fully investigated this entity in the early 1990’s and 2 hereditary syndromes were described: Lynch I and Lynch II.
    • Lynch syndromes.
      Lynch I
      Cancer of the colon
      occurring at a relatively young age (mean, 44 years),
      with proximal distribution (70% of cancers located in the right colon),
      predominance of mucinous or poorly differentiated (signet cell) adenocarcinoma, and the presence of tumour-infiltrating and peritumoural lymphocytes
      increased number of synchronous and metachronous cancers
      despite all the these poor prognostic indicators, a relatively good outcome after surgery.
    • Lynch syndromes.
      Lynch II
      Families are at increased risk for colorectal cancer and extracolonic cancers,
      endometrial
      ovarian
      gastric
      small intestinal
      pancreatic
      ureteral
      renal pelvic.
    • Lynch syndromes.
      Before genetic mechanisms underlying the Lynch syndromes were understood, the syndromes were defined by Amsterdam Criteria that were soon modified.
      Further modifications have affected the criteria and the Bethesda criteria emerged.
      Amsterdam, the Netherlands
    • Bethesda Criteria.
      Modified Amsterdam Criteria
      At least 3 relatives with HNPCC-associated cancer (colon, endometrium, small bowel, ureter, renal pelvis) and all of the following:
      One affected person is a first-degree relative of the other 2 affected persons
      2 successive generations affected
      At least one case of cancer diagnosed before age 50 years
      FAP excluded
      Bethesda Criteria
      The Amsterdam criteria or one of the following:
      2 cases of HNPCC-associated cancer in one patient, including synchronous or metachronous cancer
      Colon cancer and a first-degree relative with HNPCC-associated cancer and/or colonic adenoma (one case diagnosed before age 45 years and adenoma diagnosed before 40 years)
      Colon or endometrial cancer diagnosed before 45 years
      Right-sided colon cancer that has an undifferentiated pattern (solid-cribriform) or signet-cell histopathologic features diagnosed before 45 years
      Adenomas diagnosed before age 40 years
      Lynch HT, Riley BD, Weissman SM, et al; Hereditary nonpolyposis colorectal carcinoma (HNPCC) and HNPCC-like families: problems in diagnosis, surveillance, and management. Cancer 100:53, 2004.
    • Introduction.
      HNPCC is inherited in an autosomal dominant fashion
      HNPCC accounts for 5-7% of colorectal cancers, it is the most frequent inherited CRC syndrome in the West.
      Results from a mutation in one of the DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS1, PMS2, MLH3, MSH3).
      Lynch HT, de la Chapelle A: Hereditary colorectal cancer. N Engl J Med 348:919, 2003.
    • Genetics.
      Only 50-70% of patients meeting clinical criteria for HNPCC have an identifiable germline MMR mutation which suggests that one or more unidentifiable genes or other genetic events (e.g., large germline deletions) may be involved that result in microsatellite instability in 80-90% of cases.
      20% of newly discovered cases have a spontaneous germline mutation, with no evident family history.
      Lynch HT, de la Chapelle A: Hereditary colorectal cancer. N Engl J Med 348:919, 2003.
    • Clinical features.
      Early-onset CRC.
      Predominance of lesions proximal to the splenic flexure (60-70%).
      Benign and malignant extracolonic tumours.
      Predilection for synchronous and metachronous colorectal tumours.
      The lifetime risk of CRC in HNPCC patients is approx. 80%.
      A better prognosis for cancer patients with HNPCC than for non-HNPCC patients with cancer of the same stage!!!
    • Clinical features.
      ACS Surgery: Principles & Practice, 2007.
    • Investigations.
      Colorectal cancer, or an HNPCC-related cancer, arising in a person < 50 years should raise the suspicion of this syndrome.
      The mainstay of the diagnosis of HNPCC is a detailed family history, yet 20% of newly discovered cases are caused by spontaneous germline mutations.
      CRC patients who belong to known HNPCC kindreds, who have a pedigree suggestive of HNPCC, or who meet the Bethesda criteria should be offered screening by MSI testing.
      Patients with MSI-high tumours should undergo testing for germline MMR mutations. If a mutation is identified then other family members can be tested after obtaining genetic counselling.
      Lynch HT, de la Chapelle A: Hereditary colorectal cancer. N Engl J Med 348:919, 2003.
    • Screening and surveillance.
      If a family member has tested negative for a specific MMR mutation identified in an index case => an average risk subject.
      If no genetic counselling, or positive for a given MMR mutation => screening recommendation as follows:
    • Management.Surgical therapy: When? What? Who?
      Prophylactic surgical intervention is considered for the following reasons:
      80% lifetime risk of developing CRC
      45% rate of metachronous tumours
      The possibility of an accelerated adenoma-carcinoma sequence.
      Candidates are HNPCC patients as defined by:
      their genotype
      Amsterdam or Bethesda criteria
      colon cancer and more than one advanced adenoma.
      Options include:
      Prophylactic total abdominal colectomy with ileo-rectal anastomosis
      Total proctocolectomy with ileal pouch-anal anastomosis (restorative proctocolectomy)
      Segmental colectomy with yearly colonoscopy.
    • Prophylactic surgical intervention.Mutation-positive patients with a normal colorectum?
      Normal rectal reservoir function
      Normal anal sphincter function
      A survival benefit of 1.8 years evident if performed at age 25 years.
      No survival benefit if performed at time of cancer development.
      1- to 3-yearly colonoscopy, optimal < 2 year surveillance intervals.
      Quality of life benefit.
      Total abdominal colectomy with ileo-rectal anastomosis
      Colonoscopic surveillance
      Factors affecting the decision:
      Penetrance of disease in family
      The age of cancer onset in family members
      Functional and QoL considerations
      Likelihood of patient compliance to surveillance.
    • Management.Surgical therapy
      A coronal view of the anal canal and rectum.
      Rectosigmoid junction
      10-12 cm
      The upper limit of the surgical anal canal.
      The pelvic floor.
      8 cm
      The upper limit of the anatomical anal canal.
      (Dentate line).
      4-5 cm
      2-3 cm
    • Management.Surgical therapy
      Total abdominal colectomy with ileo-rectal anastomosis.
      This option is open only to patients with:
      Normal rectal reservoir function
      Normal anal sphincter function
      No evidence of rectal involvement.
      Lifelong surveillance is necessary because:
      the risk of developing a metachronous rectal cancer is 12 % at 10-12 years after the operation
      this risk is evidently less than among patients who have undergone segmental colectomy.
      Lynch HT, Lynch JF, Fitzgibbons R Jr: Role of prophylactic colectomy in Lynch syndrome. Clin Colorectal Cancer 3:99, 2003.
    • Management.Surgical therapy
      Total abdominal colectomy with ileo-rectal anastomosis.
      A -> K: Total abdominal colectomy.
    • Management.Surgical therapy
      Total proctocolectomy with ileal pouch-anal anastomosis
      (Restorative proctocolectomy).
      Indicated in patients with rectal cancer that is amenable to sphincter-preserving resection.
      The risk of developing a metachronous lesion in the remaining colon with an index rectal cancer in HNPCC patients is 17-45% at 10-12 years.
      The patient’s will to undergo extensive surveillance and concern on bowel function is decisive.
      Lynch HT, Lynch JF, Fitzgibbons R Jr: Role of prophylactic colectomy in Lynch syndrome. Clin Colorectal Cancer 3:99, 2003.
    • Management.Surgical therapy
      Total proctocolectomy with ileal pouch-anal anastomosis
      (Restorative proctocolectomy).
      A -> L: Total proctocolectomy.
    • Management.Surgical therapy
      Segmental colectomy with yearly colonoscopic surveillance.
      This option is the standard of care in terms of quality of life and preserved bowel function.
      The need for extensive surveillance on a one-yearly basis cannot be overemphasised.
      An accelerated adenoma-carcinoma sequence and microsatellite instability may lead cancers to develop in less than one-year intervals.
      Lynch HT, Lynch JF, Fitzgibbons R Jr: Role of prophylactic colectomy in Lynch syndrome. Clin Colorectal Cancer 3:99, 2003.
    • Management.Extracolonic disease.
      Endometrial and ovarian cancer.
      Female patients with a family history of uterine cancer should be offered prophylactic total abdominal hysterectomy + oophorectomy (TAHBSO) if childbearing is complete or if undergoing abdominal surgery for other conditions.
      43% rate of endometrial cancer in mutation-positive patients.
      Inefficacy of screening for uterine cancers.
      The optimal timing is unclear yet cases < 35 years have been reported.
      Recommendation: begin surveillance at 25 years and delay prophylactic surgery until childbearing is complete.
      Lynch HT, Riley BD, Weissman SM, et al; Hereditary nonpolyposis colorectal carcinoma (HNPCC) and HNPCC-like families: problems in diagnosis, surveillance, and management. Cancer 100:53, 2004.
    • Inherited colorectal carcinoma.
      Hereditary non-polyposis colorectal cancer (5-7% of cases of CRC)
      Familial adenomatouspolyposis and attenuated FAP(1%)
      Familial colorectal cancer (10-15%)
      Peutz-Jeghers syndrome (<1%)
      Juvenile polyposis syndrome (<1%)
    • Inherited colorectal carcinoma.
      Hereditary non-polyposis colorectal cancer (5-7% of cases of CRC)
      Familial adenomatouspolyposis and attenuated FAP(1%)
      Familial colorectal cancer (10-15%)
      Peutz-Jeghers syndrome (<1%)
      Juvenile polyposis syndrome (<1%)
    • Familial colorectal cancer.
      Non-syndromic familial colorectal cancer accounts for 10-15% of CRC cases.
      The lifetime risk of developing CRC increases with a family history of the disease and the age of onset in family.
      Average risk in USA: 6%
      If one first-degree relative affected: 12%
      If two first-degree relatives affected: 35%
      Screening colonoscopy is recommended every 5 years beginning at age 40 years or 10 years earlier than the index case.
      No specific genetic abnormalities are associated with familial CRC.
    • The take-home message.
      Every patient presenting with a malignant tumor involving the colon, rectum, stomach, uterus, ovaries, renal pelvis or ureters under the age of 50 years is to be screened or at least counseled for a possible inherited carcinoma syndrome.
      He/she and their first-degree relatives are to be counseled appropriately with the aid of a geneticist, if possible.
    • “There is a tremendous literature on cancer, but what we know for sure about it can be printed on a calling card.” - August Bier
      (Ger., 1861-1949).
      Thank you.