Mucinous Adenocarcinoma of the Colon in Uganda: A Case Report and Literature Review

Introduction:In Uganda, the Kampala Cancer Registry has reported a steady increase in the incidence of colorectal carcinoma(CRC) over the last few decades. The author reports a case of a 25 year old gentlemanpresenting with bowel obstruction and found to have mucinous adenocarcinoma of the colon. This is followed by a literature review of the clinical and pathological characteristics of young age sporadic colorectal carcinoma (YSCC) and hereditary nonpolyposis colorectal carcinoma (HNPCC).Presentation of Case:This patient presented with a family history of colorectal carcinoma (CRC) and with bowel obstruction. An emergency laparotomy involving a right hemicolectomy was carried out. The postoperative course of this patient was uneventful. Discussion:The typical histological features of mucinous adenocarcinoma of the colon were seen on the resected colon specimen. In addition this study reviews the literature regarding the clinical presentation, pathological characteristics, histology and prognosis of mucinous and medullary carcinoma of the colon.Conclusions:Mucinous adenocarcinoma happens to be the most common histological type of colorectal carcinoma in young adults. In Uganda, low risk young patients withsymptoms should be screened for colorectal lesions. A high index of suspicion should therefore be taken in the diagnosis of colorectal malignancy in these patients

Adherence to colonoscopy recommendations for first-degree relatives of young patients diagnosed with colorectal cancer

OBJECTIVES:Colorectal cancer is the third leading cause of cancer death in the United States. The American College of Gastroenterology recommends screening for first-degree relatives of patients diagnosed with colorectal cancer before the age of 50. A colonoscopy is one of the most commonly recommended exams due to its specificity and the possibility to resect pre-malignant lesions. Nevertheless, the rate of physician adherence to this recommendation is unknown.METHODS:This transversal study was performed at a major cancer center in Brazil with 62 patients, aged 18 to 50, who completed a questionnaire on information received from their physicians regarding screening their first-degree relatives. We used the answers from patients who provided explicit consent.RESULTS:Two hundred and three patients were eligible to participate and 93 (45.8%) agreed to complete the questionnaire. Twenty-three questionnaires (24.73%) were returned and 39 were completed by telephone. Of the patients who answered the questionnaire, 39 (62.9%) had received a colonoscopy recommendation for their first-degree relatives and 23 (37.1%) were not informed of the recommendation. Among the patients who received the recommendations, 20.51% affirmed that all relatives completed the exam and 51.28% stated that no relatives completed the exam.DISCUSSION:The adherence rate of our physicians to the ACG guideline recommendations was 62.9%. Considering that our study was performed at a leading center for cancer treatment in Latin America, we had expected better adherence. The results show that adherence to the colorectal cancer screening recommendations for high-risk patients must be improved.

Síndrome de Lynch: selección de pacientes para el estudio genético mediante análisis de inestabilidad microsatelital e inmunohistoquímica / Lynch syndrome: selection of families by microsatellite instability and immunohistochemistry

Background: Selection of patients with Lynch Syndrome (LS) for a genetic study involves the application of clinical criteria. To increase the rate of identification of mutations, the use of molecular studies as Microsatellite Instability (MSI) and Im-munohistochemistry (IHC) in the tumor has been proposed. Aim: To demonstrate the usefulness of MSI and IHC in the detection of mutations in patients with LS. Material and Methods: From our Familial Colorectal Cancer Registry, families suspected of LS were selected according to Amsterdam or Bethesda clinical criteria. Screening of germline mutations of MLH1, MSH2 and MSH6 genes was performed. In addition, analysis of MSI and IHC were performed in colorectal tumors. Results: A total of 35 families were studied (19 met Amsterdam and 16 met Bethesda criteria). Twenty one families harbored a germline alteration in MLH1, MSH2 or MSH6 (18 Amsterdam and 3 Bethesda). In these families, eighteen different alterations were found, 15 of which were mutations and 3 corresponded to variants of uncertain pathogenicity. On the other hand, 80% of the tumors showed positive microsatellite instability (27 MSI-high and 1 MSI-low), and immunohistochemical testing showed that 77% of tumors had the loss of a protein. Correlation between results of tumor molecular studies and the finding of germline nucleotide change showed that IHC and MSI predicted mutations in 81 and 100% of patients, respectively. Conclusions: MSI and IHC can efficiently select patients with a high probability of carrying a mutation in DNA repair genes.

Clinical approach of hereditary cancer in gynecology / 대한산부인과학회지

Hereditary cancer syndrome is a genetic condition that causes and increases the risk for specific type of cancers. Recent advances in genetics have identified a number of genes associated with inherited susceptibility to cancer, and this rapid development of knowledge about cancer genetics have implications for all aspects of cancer management, including prevention, screening, and treatment. Hereditary patterns of cancer are often characterized by early age at onset, high penetrance, bilaterality in paired organs, vertical transmission through either parent, and an association with other types of tumors. Most representative hereditary cancer syndromes in gynecologic field are hereditary breast/ovarian cancer syndrome (HBOC), hereditary non-polyposis colorectal cancer (HNPCC), Li-Fraumeni syndrome, and Cowden syndrome. Several familial mutations of specific genes, such as BRCA1, 2, TP53, PTEN, MMR, CHEK2, are linked to hereditary cancer syndrome, which are responsible for hereditary gynecologic cancers. It would be very important for gynecologic doctors to know the inclusion criteria for the genetic assessment, taking family history, clinical evaluation, genetic testing, screening guideline and risk reduction strategies for women with hereditary high risk factor. The morbidity and mortality of gynecologic malignancies related to these syndromes could be reduced by the adequate clinical approach, although recent guidelines were developed with an acute awareness of the preliminary nature of much of our knowledge regarding the clinical application of the rapidly emerging field of molecular genetics, and with an appreciation for the need for flexibility when applying these guidelines to individual families.

Four Synchronous Colorectal Cancers and One Small Bowel Cancer in a Patient with HNPCC

The frequency of multiple synchronous carcinomas of the colon and rectum have varied in different reports from 3~4% to more than 10% of all tumors of the large bowel. Especially, the frequency is higher in hereditary non-polyposis colorectal cancer (HNPCC) patients. There are a few reported cases of five simultaneous cancers in a patient at the same time. We report here on a case of five synchronous cancers arising from the terminal ileum and colon in a patient with a strong familial tendency for colon cancer. The patient was a 43-year-old-female who presented with intermittent abdominal pain and diarrhea for one month. Colonoscopic examination revealed four adenocarcinomas at the proximal ascending, the proximal transverse, the distal descending and the sigmoid colon; the cancer in the sigmoid colon was at 30 cm above the anal verge. During the operation, another 3 cm sized ulcerative lesion was noted at the terminal ileum. Total colectomy, including the lesion of the terminal ileum, and ileorectal anastomosis were performed. Histologic evaluation revealed that all those lesions were adenocarcinomas invading the pericolic fat and three out of 126 lymph nodes were invaded by the cancer cells. It was a MSI-high cancer; 5 markers of MSI (BAT25, BAT26, D5S346, D17S250 and D2S123) were all unstable. We revealed a point mutation of the 67th base (GaT) of the 1st exon of hMLH1.

Hereditary Colorectal Cancer / 대한소화기학회지

Hereditary syndromes cause approximately 5 to 15% of overall colorectal cancer (CRC) cases. Hereditary CRC is conventionally divided into two major categories: hereditary non-polyposis colorectal cancer (HNPCC) and those related to polyposis syndromes including familial adenomatous polyposis (FAP), Peutz-Jegher syndrome (PJS), and juvenile polyposis (JP). The screening for the cancer and methods of treatment applied to patients with hereditary CRC are quite different from those applied to the general population. The genes responsible for these syndromes has recently identified, as a result, genetic testing has become the most important determining factor in clinical decisions. Germ-line mutation of the APC gene induces FAP, an autosomal dominant disorder, characterized by the development of hundreds to thousands of colonic adenomas. CRC appears in almost all affected individuals by the time they are 50 years of age. An affected individual should undergo colectomy by his/her late teens. Furthermore, according to the findings of genetic testing, at-risk family members also need endoscopic surveillance and surgery. Recently, a mutation on the MYH gene is increasingly being investigated in patients with multiple polyps, and autosomal recessive MYH polyposis is considered to be a new category of polyposis. More common than FAP, HNPCC is caused by germ-line mutations in DNA mismatch repair genes, mainly MLH1 and MSH2. Although there is no polyposis, polyps seem to be more villous and dysplastic and appear to grow rapidly into CRCs. The aggregate lifetime risk of CRC is about 80% for mutation carriers. The risk for other types of cancer, such as endometrial, ovarian, small bowel, and transitional cell cancer, is also increased. The Amsterdam criteria and Bethesda guidelines are the best-known tools for diagnosis and genetic testing, and colectomy followed by endoscopic follow-up is the standard treatment. PJS and JP are reported to be characterized by hamartomatous polyps throughout the GI tract and germ-line mutations in the STK11 gene (PJS) and the DPC4/BMPR1A gene (JP).

A Case of Endometrial Cancer with Hereditary Non-Polyposis Colorectal Cancer (HNPCC) / 대한산부인과학회지

Endometrial cancer is the most common malignant disorder that can be associated with hereditary non-polyposis colorectal cancer (HNPCC), which is known as Lynch II syndrome. HNPCC is a polyposis of the colon which is inherited in an autosomal dominant pattern and can cause cancer in other organs, especially in the endometrium. The overall risk of a women with HNPCC to develop endometrial cancer is 40-60%, much higher than the 3% of the general population of women. The average age of developing endometrial cancer of a women with HNPCC is 45 years of age and is often found before development of colon cancer. We have recently experienced a case of de novo type of hereditary non-polyposis colorectal cancer associated with endometrial cancer, hence we are reporting this case with a brief review of literatures.

Mechanism of Genomic Instability and Its Clinical Applications

Multiple genetic alterations are common prerequisite for carcinogenesis including colorectal cancers (CRCs). Recently, mutations within microsatellites have been described as a result of defective DNA mismatch repair (MMR) mechanisms, resulting in the phenomenon of microsatellite instability (MSI). This has been implicated in the etiology of hereditary non-polyposis colorectal cancer (HNPCC) and significant portions of sporadic colorectal cancers. However, the mechanisms underlying the MSI are different from hereditary CRCs and sporadic CRCs. While the germline mutation of MMR genes is responsible for HNPCC, the hypermethylation of MLH1 gene promoter regions, an epigenetic, not inherited alteration is responsible for most sporadic CRCs showing MSI. MSI tumors exhibit characteristic clinco- pathologic features, i.e, tumors are preferentially located to proximal to splenic flexure, poorly differentiated, mucinous cell type, frequently showing peritumoral lymphocytic infiltration, and, of importance, showing better survival in stage- matched cases. In this article, the results of recent investigations about MSI and its clinical applications are comprehensively reviewed. Knowledge of these biochemical mechanisms are likely to lead to more effective diagnosis and therapy of CRCs in the future