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

Colorectal Adenocarcinoma in East Africa: A Narrative Literature Review

This paper is a review of work done on colorectal adenocarcinomain East Africa showing geographic spread, age and sex ratios, clinical presentation, management and predominant histopathology. A steady increased incidence of CRC in East African countries is currently being documented however this is associated with a higher CRC-associated morbidity and mortality. Whilst the male: Female ratio varies between 1.2:1 to 1.88:1, up to 38% of CRC diagnosis are in patients younger than 40 years, in contrast to only 1.9% of CRC patients in Western developed countries such as the USA. Generally rectal carcinoma is more common than colon carcinoma and abdomino-perineal resections are commonly performed in up to between 54% -71% due to the advanced stage of presentation of rectal tumours in East Africa. The late stage presentationand delayed effective treatment in East Africa may result in a higher morbidity in CRC patients. Interestingly there is a significant incidence of mucinous adenocarcinoma sub-groups compared to Western developed countries which carry a poor prognosis. A significant proportion of CRC patients have been found to have histological and demographic features which suggest that MSI-tumours and these tumours are more common in younger patients. However only a few authors have looked at the possibility of mismatch repair mutations in the genetic aetiopathogenesis of colorectal adenocarcinoma in East Africa.

Extensive colectomy in colorectal cancer and hereditary nonpolyposis colorectal cancer - long-term results / Colectomia extensa em cancro colorretal e cancro colorretal hereditário sem polipose - resultados a longo prazo

ABSTRACT Background: Colorectal cancer survival is better in hereditary nonpolyposis colorectal cancer patients than in sporadic colorectal cancer patients and even for hereditary nonpolyposis colorectal cancer with colorectal cancer is not consensual that extensive colectomy is preferable to partial colectomy. This study analyzes and compares the long-term results of these two groups of patients submitted to curative subtotal colectomy or total colectomy. Methods: Between 2002 and 2018, 68 patients with colorectal cancer without familial adenomatous polyposis were submitted to a total or subtotal colectomy in a single tertiary center. The patients were divided in two groups: hereditary nonpolyposis colorectal cancer patients (with Amsterdam criteria) and sporadic colorectal cancer patients (the others). The presence of Amsterdam criteria for hereditary nonpolyposis colorectal cancer and germline mutation for mismatch repair genes was confirmed by clinical records. Results and survival were analyzed following surgery. Results: We obtained a sporadic colorectal cancer group with 31 patients and a hereditary nonpolyposis colorectal cancer group with 37 patients. The two groups differ in age but not in gender, tumor stage or surgical morbidity. The overall survival and disease-free survival were good in both groups but even better for hereditary nonpolyposis colorectal cancer group with statistical significance when comparing the two groups. Conclusion: Total or subtotal colectomy for colorectal cancer provides a good survival. These surgical procedures should be considered the first option for colorectal cancer in young hereditary non polyposis colorectal cancer patients. In those cases, they provide good long-term results, avoiding the risk of metachronous colorectal cancer and the surveillance is restricted only to the remaining need for rectum.

RESUMO Introdução: A sobrevivência do cancro colorretal é melhor em pacientes com cancro colorretal hereditário não associado a polipose do que em pacientes com cancro colorretal esporádico. Mesmo em casos de cancro colorretal hereditário sem polipose, a preferência pela colectomia total em relação à parcial não é consensual na literatura. Este estudo analisa e compara os resultados a longo prazo destes dois grupos de pacientes submetidos à colectomia curativa subtotal ou total. Métodos: Entre 2002 e 2018, 68 pacientes com cancro colorretal sem polipose adenomatosa familiar foram submetidos a colectomia total ou subtotal em um único centro terciário. Os pacientes foram divididos em dois grupos: aqueles com cancro colorretal hereditário sem polipose (de acordo com os critérios de Amsterdão) e os com cancro colorretal esporádico (os demais). Os critérios de Amsterdão para cancro colorretal hereditário sem polipose e a presença de mutação germinativa para os genes de reparação de ADN foram confirmados por consulta dos registros clínicos. Os resultados e a sobrevivência foram analisados após a cirurgia. Resultados: No presente estudo, 31 pacientes foram incluídos no grupo de cancro colorretal esporádico e 37 no grupo de cancro colorretal hereditário sem polipose. Diferenças significativas foram observadas em relação à idade, mas não ao gênero, estadio do tumor ou morbilidade cirúrgica. A sobrevivência global e a sobrevivência livre de doença foram boas em ambos os grupos, mas os resultados foram ainda melhores no grupo de cancro colorretal hereditário sem polipose, com significado estatístico. Conclusão: A colectomia total ou a colectomia subtotal para o cancro colorretal proporcionam uma boa sobrevivência e devem ser consideradas a primeira opção de tratamento em pacientes jovens com cancro colorretal hereditário sem polipose. Nestes pacientes, uma cirurgia cólica mais extensa permite a obtenção de bons resultados a longo prazo; reduz o risco de cancro colorretal metácrono e restringe a vigilância endoscópica ao reto remanescente.

Comparative analysis of clinical features and survival rate of HNPCC and sporadic colon cancer / 医学研究生学报

Objective Different types of colon cancer have a big difference in their clinical features and prognosis.The article aimed to provide theoretical basis for the diagnosis and treatment of colon cancer patients by analyzing the differences of clinical features and survival rates between hereditary non-polyposis colorectal cancer (HNPCC) and sporadic colon cancer.Methods Retrospective analysis was made on 22 HNPCC cases and 105 cases of sporadic colon cancer in our hospital from January 2007 to January 2012 to get the clinical features and prognosis by comparative analysis.Results Compared with sporadic group, the early onset(under 40 years) (36.37％ vs 9.52％), mucinous adenocarcinoma (59.09％ vs 17.14％), low differentiation (45.45％ vs 16.19％), TNM stage (III+IV) (54.55％ vs 26.66％), lymph node metastasis (81.82％ vs 57.14％), multiple primary carcinoma (36.36％ vs 7.62％) and parenteral tumor (22.73％ vs 5.71％) were higher in HNPCC group, but the 5 year survival rate was lower in HNPCC group, and there were significant differences between two groups(P0.05) between two groups.Multiple primary tumors were independent risk factors for survival in HNPCC group (P<0.05), lymph node metastasis and TNM stage were independent risk factors for survival sporadic group (P<0.05).Conclusion Compared with sporadic colon cancer, HNPCC is characterized by early onset, low differentiation, high incidence of multiple primary tumors and poor prognosis, which is of great importance to find HNPCC patients or suspicious HNPCC patients.

R659X mutation in the MLH1 gene in hereditary non-polyposis colorectal cancer (HNPCC) in an Indian extended family.

Background & objective: Hereditary non-polyposis colorectal cancer (HNPCC or Lynch syndrome), is a genetically heterogeneous disorder that is believed to account for 2–10 per cent of all the colorectal cancer cases. The disease follows autosomal dominant inheritance pattern with high penetrance (85%) and younger age of onset when compared to patients with sporadic tumours. HNPCC is associated with germ-line mutations in the DNA mismatch repair (MMR) genes namely MLH1, MSH2, MSH6, and PMS2. The present study was aimed at analyzing mismatch repair gene(s) in an extended Indian family satisfying the Amsterdam criteria, and extending the analysis to general population to estimate frequency of the mutations/polymorphisms observed. Methods: A total 12 members of the HNPCC family were studied for genetic investigation. Ethnically matched 250 normal individuals were also included as controls to study the observed mutations/ polymorphisms at population level. Results: The analysis resulted in identification of a 1975C>T mutation in exon 17, resulting in substitution of arginine residue with stop codon at codon 659. 655A>G substitution was also observed, resulting in replacement of isoleucine with valine at codon 219. Similar analysis on 250 ethnically matched control subjects revealed complete absence of R659X mutation, while I219V variant was found in 9.8 per cent of the controls. Interpretation & conclusion: R659X mutation correlates with disease phenotype, and 655A>G locus is highly polymorphic. Our study suggested that R659X substitution was prime cause for the disease phenotype in this family. I219V substitution is a polymorphism having no association with the disease onset or segregation. The family members harbouring this mutation were advised to be under regular medical surveillance.

Identification of nonfamilial MSI-H colorectal cancer based on clinicopathological features / 基础医学与临床

Objective To identify clinicopathological features of high MSI (MSI-H).Methods We enrolled 150 patients,standard microsatellite loci (BA T25,BA T26,D2S123,D5S346,D17S250) were amplified by polymerase chain reaction(PCR) with fluorescent primers,and the PCR products were analyzed by GeneMapper software;age at diagnosis,gender and site were obtained;various pathological features were observed by light microscopy;the expression of tumor infiltrating lymphocytes (CD4~+ and CD8~+) was detected by immunohistochemistry.Using a stepwise logistic regression model,a formula was generated that could be used to calculate the probability of a colorectal carcinoma being MSI-H based on pathological features.Results Among 150 cancers,MSI-H was 13.33%.Independent identifiers inclucle poor differentiation,histologic heterogeneity,Crohn's-like reaction and tumor-infiltrating lymphocytes,logistic regression formula shows a sensitivity of 70.0% and a specificity of 99.2% and a accurate ratio of 95.3% for MSI-H.Conclusion MSI-H phenotype cancer is a type of nonfamilial colorectal cancer with specific pathological features,Clinicopathological features can efficiently identify MSI-H colorectal cancers.

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.

One case of Lynch type II syndrome / 대한산부인과학회지

Lynch syndrome is also called Hereditary nonpolyposis colorectal cancer (HNPCC). It is characterized by a risk of colorectal cancer and other cancers of the endometrium, ovary, stomach, small intestine etc. The increased risk is due to inherited mutations that impaired DNA mismatch repair. Two to three percentage of colon cancer is caused by Lynch syndrome. A family history of colon cancer occurs at a young age. We experienced one case of Lynch syndrome who had had stomach cancer, endometrial cancer and colon cancer recently. Hence we report this case with a brief review of literature.

Promoter Methylation in the Genesis of Gastrointestinal Cancer

Colorectal cancers (CRC)-and probably all cancers-are caused by alterations in genes. This includes activation of oncogenes and inactivation of tumor suppressor genes (TSGs). There are many ways to achieve these alterations. Oncogenes are frequently activated by point mutation, gene amplification, or changes in the promoter (typically caused by chromosomal rearrangements). TSGs are typically inactivated by mutation, deletion, or promoter methylation, which silences gene expression. About 15% of CRC is associated with loss of the DNA mismatch repair system, and the resulting CRCs have a unique phenotype that is called microsatellite instability, or MSI. This paper reviews the types of genetic alterations that can be found in CRCs and hepatocellular carcinoma (HCC), and focuses upon the epigenetic alterations that result in promoter methylation and the CpG island methylator phenotype (CIMP). The challenge facing CRC research and clinical care at this time is to deal with the heterogeneity and complexity of these genetic and epigenetic alterations, and to use this information to direct rational prevention and treatment strategies.

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.

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.

Four Cases of HNPCC Including Two Cases with Synchronous Stomach Cancer

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disease characterized by early manifestation of colorectal cancer (CRC), occurrence of multiple colorectal tumors and high frequencies of extracolonic malignancies. Evaluation of clinical findings in concert with a well-documented and extended pedigree and genetic studies of colorectal cancer can identify person who are at high risk and who thereby might benefit from targeted early detection and primary prevention programs. Here we report 4 cases of HNPCC including 2 cases with synchronous gastric cancers.

Clinical Aspect of Suspected HNPCC in Korea

PURPOSE: The criteria for Suspected hereditary nonpolyposis colorectal cancer(Suspected HNPCC) has been devised by the Korean Hereditary Tumor Registry for families who do not fulfill Amsterdam criteria, but hereditary background is strongly suggested. This study was performed to define the clinical characteristics of 'Suspected HNPCC'. METHODS: The 'Suspected HNPCC' criteria include the followings: a) vertical transmission of colorectal cancer or at least two siblings affected with colorectal cancer in a family and b) development of multiple colorectal tumors (including adenoma) or at least one colorectal cancer case diagnosed before the age of 50 years or development of extracolonic cancers (endometrium, urinary tract, small intestine, stomach, hepatobiliary system, ovary) in family members. We analysed the clinical characteristics of 93 patients from 39 Suspected HNPCC families and compared these characteristics with 176 HNPCC familes and with 1,204 non-hereditary colorectal cancer patients. RESULTS: The mean age of Suspected HNPCC patients at the time of diagnosis (49.0 years) was significantly lower than that of non-hereditary colorectal cancer patients (56.1 years), but higher than that of the HNPCC patients (44.5 years). Tumors were more frequently located in the right colon (34%) in Suspected HNPCC compared to non-hereditary colorectal cancer (23%). Dukes' A and B cancers were more frequent in the Suspected HNPCC as compared to non-hereditary colorectal cancer (55% vs. 48%, p<0.05), but tumor differentiation was not statistically different between the two groups. Among the Suspected HNPCC, 24.0% of the patients had synchronous adenomatous polyps and 20.0% had synchronous colorectal cancers and 15.6% had metachronous polyps or cancers. These findings were similar to HNPCC, but significantly higher than non-hereditary colorectal cancers (p<0.05). In Suspected HNPCC families, 42 patients had extracolonic malignancies with the stomach cancer being the most common (n=22). CONCLUSION: These data indicate that the clinical characteristics of Suspected HNPCC are similar to those of HNPCC and may suggest that the management principles of the HNPCC should also be applied to the Suspected HNPCC.

Hereditary Nonpolyposis Colorectal Cancer

Hereditary nonpolyposis colorectal cancer(HNPCC) is an autosomal dominantly inherited disease associated with a marked increase in cancer susceptibility, especially cancer of the colorectum. The frequency of HNPCC in the general population is yet to be determined, but HNPCC may account for as much as 2% to 5% of colorectal cancer, Colorectal cancer in HNPCC differs from sporadic colorectal cancer by an early age of cancer onset, proximal predominance of colorectal cancer, an excess of synchronous and metachronous colorectal cancer, and excess extra-colonic cancers. We have found 5 HNPCC families since 1992 when we reported first HNPCC family (KHU-Hl) In order to register the patients of HNPCC and to review the clinicopathologic feature and appropriate management, we have analysed 5 HNPCC families. Five HNPCC families included 16 colorectal cancer patients(14 males and 2 females). The average age of first diagnosis was 39. Among 16 patients, 8 patient were operated at the KyungHee University hospital and their operative and pathologic records were available. Two synchronous and seven metachronous cancers were founded, so that eight patients had 15 colorectal cancer lesions. Ten cancers were located proximal to splenic flexure and five were distal. Partial resection of colon was performed in seven cases except one when the first diagnosis was made and recurrence was founded in 5 patients. Recurrence was treated by total colectomy in 3 cases and subtotal colectomy in two. In conclusion, we re-confirmed that HNPCC patient should be treated by no less than a subtotal colectomy because of high multiplicity and high recurrence rate of partial resection.