Synchronous colorectal cancer

Synchronous carcinomas of the colon and rectum are of considerable clinical significance because of their frequency, the number of extra tumours missed and the difficulty of preoperative diagnosis. A retrospective evaluation of 283 patients with primary colorectal adenocarcinomas was performed. There were 6 patients with 12 synchronous adenocarcinomas (2.12%). Colonoscopy and double-contrast barium enema revealed the synchronous cancer in 66.6% of the cases. In two cases the second cancer was found intraoperatively. In one patient an urgent laparotomy was performed because of acute abdomen caused by perforation of the ascending colon. Typical colectomies, depending upon the segment of the location of the lesion, were performed. Second cancers had a significantly more favourable stage than index colorectal adenocarcinomas. The index and the secondary cancers of synchronous colorectal adenocarcinomas showed a better histologic grade (well differentiated type) than the single cancers. Full clinical and radiological investigation is essential, before any operation is undertaken for colorectal cancer.     

Colonic and anal metastases from pancreato-biliary malignancies

Pancreato-biliary malignancies often present with locally advanced or metastatic disease.Surgery is the mainstay of treatment although less than 20%of tumours are suitable for resection at presentation.Common sites for metastases are liver,lungs,lymph nodes and peritoneal cavity.Metastatic disease carries poor prognosis,with median survival of less than 3 mo.We report two cases where metastases from pancreato-biliary cancers were identified in the colon and anal canal.In both cases specific immunohistochemical staining was utilised in the diagnosis.In the first case,the pre-senting complaint was obstructive jaundice due to an ampullary tumour for which a pancreato-duodenectomy was carried out.However,the patient re-presented 4wk later with an atypical anal fissure which was found to be metastatic deposit from the primary ampullary adenocarcinoma.In the second case,the patient presented with obstructive jaundice due to a biliary stricture.Subsequent imaging revealed sigmoid thickening,which was confirmed to be a metastatic deposit.Distal colonic and anorectal metastases from pancreatobiliary cancers are rare and can masquerade as primary colorectal tumours.The key to the diagnosis is the specific immunohistochemical profile of the intestinal lesion biopsies.     

Introduction of evidence-based medicine into an ambulatory clinical clerkship

Evidence-based medicine (EBM) has emerged has a critical clinical competency in the 21st century. Medical schools usually introduce students to critical appraisal in the preclinical years, but there have been few evaluated interventions in teaching EBM in the clinical years. We describe a strategy to encourage students to practice EBM during a required ambulatory medicine clerkship. During this clerkship, our students are required to submit an EBM report, which is prompted by an individual case, and structured with a 5-step approach. One small-group session is devoted to modeling this approach with a case of chest pain. Using a checklist to grade 216 consecutive EBM reports, we found that students were quite successful with the exercise, achieving on average 89.6% of possible checklist points. Students who followed the structure of the exercise closely were more likely to extend their discussions beyond that required and to suggest potential further areas of investigation or design.     

Giant gastrointestinal stromal tumour of rare sarcomatoid epithelioid subtype:Case study and literature review

Gastrointestinal stromal tumours(GISTs) are the most common mesenchymal tumours of the gastrointestinal tract,but they represent less than 3% of all gastrointestinal tract malignancies.This is a detailed case study of a 52-yearold male patient treated for very uncommon histological subtype of gastric GIST with atypical clinical presentation,asymptomatic progress and late diagnosis.The resected tumour,giant in diameters,was confirmed to represent the most rare histopathologic subtype of GISTs- sarcomatoid epithelioid GIST.We report this case and review the literature with a special focus on pathomorphological evaluation,biological aggressiveness and prognostic factors.To our knowledge this is the first report of giant GIST of very uncommon sarcomatoid epithelioid subtype.It is concluded that clinicians should pay attention to the fact that initial diagnosis may be delayed due to mildly asymptomatic and non-specific clinical presentation.Asymptomatic tumours diagnosed at a late stage,which is often the case,can be large on presentation.Prognosis for patients diagnosed with GIST depend on tumour size,mitotic rate,histopathologic subtype and tumour location.That is why early diagnosis and R0 resection,which is usually feasible and safe even in giant gastric sarcomatoid epithelioid subtype of GISTs,are the key factors for further treatment and good prognosis.     

Significance of a fall in serum CEA concentration in patients treated with cytotoxic chemotherapy for disseminated colorectal cancer.

'Tumour response', defined as clinical or radiological evidence of tumour shrinkage is frequently regarded as an objective of chemotherapy, rather than as a predictor of prolonged survival. This study has assessed whether a fall in the serum CEA concentration after chemotherapy for disseminated colorectal cancer is a predictor of prolonged survival and compared it with tumour response as a predictor of survival. There was a 37% improvement in median survival among patients whose serum CEA concentration fell after chemotherapy (70% of patients treated) compared with patients whose serum CEA did not fall. The use of greater than 25% clinical or radiological tumour shrinkage as a predictor of prolonged survival identified a smaller proportion (36%) of patients in whom there was a 52% prolongation in median survival compared with patients whose tumours shrank less than 25%, or did not shrink. Proportional hazards regression analysis suggested that tumour shrinkage was a stronger predictor of survival. A fall in serum CEA concentration, however, identified a group of patients whose tumours did not shrink, but who had a 27% improvement in median survival compared with those whose tumours did not shrink and whose serum CEA concentration did not fall. Monitoring of the serum CEA during the first two months of treatment appears to provide a sensitive and economical means of identifying those patients whose survival is likely to be prolonged by chemotherapy for colorectal cancer.     

Serum carcinoembryonic antigen and DNA ploidy in colorectal carcinoma. A prospective study.

We have analysed the relationship between carcinoembryonic antigen (CEA) and DNA ploidy prospectively in 130 colorectal carcinoma patients. CEA was elevated preoperatively significantly more often in patients with DNA-aneuploid tumours than in DNA-diploid or DNA-tetraploid tumours--that is, in 48% (36 of 75) of patients with aneuploid tumours, in 34% (14 of 41) of patients with diploid tumours, but only in 14% (2 of 14) of patients with tetraploid tumours (p less than 0.05). Aneuploid tumours had an elevated CEA level in 38% of stage A-B disease and in 61% of stage C-D disease. The elevated CEA values (greater than or equal to 5.0 micrograms/l) correlated with tumour stage in patients with aneuploid tumours but not in patients with diploid tumours. Whereas CEA is a suitable marker for aneuploid carcinomas, other more sensitive tumour markers should be sought for diploid and also for tetraploid tumours. If such markers are found, flow cytometry could provide the most important information in selecting individual follow-up programmes for colorectal cancer patients.     

Gastric and colorectal cancer in the rural Indian subcontinent: a survey of patients attending mission hospitals.

37 missionaries working in India, Nepal, Pakistan, Bangladesh and Bhutan completed questionnaires regarding their clinical practice during the year 1980. Information was collected on the frequency of both gastric and colorectal cancers. More than 500,000 out-patients were reviewed and over 100,000 inpatients treated. A total of 291 gastric tumours and 169 colorectal carcinomas were diagnosed. Surgery was performed in 82% of the hospitals but only 36% had a histology service. In India and Pakistan there was no significant difference between the incidence of gastric and colorectal neoplasms. The relative risk of developing gastric rather than colorectal cancer in Bangladesh was 8 (95% confidence limits 4.5-14.2) and in Nepal the relative risk was 4 (95% confidence limits 2.0-7.0). A significant variation in the occurrence of cancer was observed between countries. Nepal had the highest and Pakistan the lowest numbers of both gastric and colorectal tumours. It seems likely that local environmental factors, such as diet, play a significant role in the development of these tumours.     

Expression of inducible nitric oxide synthase in colorectal cancer and its association with prognosis

BACKGROUND: The expression of inducible nitric oxide synthase (iNOS) has been reported to be altered in a number of tumours, but its role in tumour biology is still unclear. METHODS: iNOS was studied in a series of 157 colorectal carcinoma patients and its relation to tumour grade, stage, cell cycle regulators, cell proliferation as well as survival was assessed. RESULTS: iNOS intensity was moderate or intense in 37% of the tumours. iNOS intensity and percentage of positive cells were higher in Dukes A and B tumours than in Dukes C and D tumours, and low iNOS expression intensity was related to high histological grade. iNOS expression correlated positively with cell cycle regulators p21 and AP-2. There was also a high iNOS expression intensity and high fraction of iNOS positive cells in tumours with a high amount of tumour infiltrating lymphocytes (TILs). The cancer related survival was significantly lower among patients with a low signal for iNOS and low iNOS percentage in tumour epithelium. In multivariate analysis iNOS was not an independent prognostic factor. CONCLUSIONS: These results suggest that iNOS has a protective role in colorectal carcinogenesis, but further studies are required to establish the clinical significance of iNOS in colorectal cancer.     

Expression of Inducible Nitric Oxide Synthase in Colorectal Cancer and Its Association with Prognosis

Background: The expression of inducible nitric oxide synthase (iNOS) has been reported to be altered in a number of tumours, but its role in tumour biology is still unclear. Methods: iNOS was studied in a series of 157 colorectal carcinoma patients and its relation to tumour grade, stage, cell cycle regulators, cell proliferation as well as survival was assessed. Results: iNOS intensity was moderate or intense in 37% of the tumours. iNOS intensity and percentage of positive cells were higher in Dukes A and B tumours than in Dukes C and D tumours, and low iNOS expression intensity was related to high histological grade. iNOS expression correlated positively with cell cycle regulators p21 and AP-2. There was also a high iNOS expression intensity and high fraction of iNOS positive cells in tumours with a high amount of tumour infiltrating lymphocytes (TILs). The cancer related survival was significantly lower among patients with a low signal for iNOS and low iNOS percentage in tumour epithelium. In multivariate analysis iNOS was not an independent prognostic factor. Conclusions: These results suggest that iNOS has a protective role in colorectal carcinogenesis, but further studies are required to establish the clinical significance of iNOS in colorectal cancer.     

Colorectal carcinoma: histopathological diagnosis and staging

It is possible to make a histopathological diagnosis of colorectal carcinoma from ulcerating lesions by means of forceps biopsy, but this presents problems in polypoid tumours. In order to make the diagnosis of invasive carcinoma, evidence of invasive growth into the submucosa is necessary. In polypoid tumours, this can be done usually only by endoscopic or surgical polypectomy. In addition to histopathological diagnosis, one of the most important tasks for the contemporary pathologist is the exact classification of colorectal tumours. The most important parameters are typing, grading, staging and the R classification, i.e. the assessment of presence or absence of residual tumour following treatment. Typing and grading is done according to the WHO recommendations; the great majority of colorectal carcinomas are adenocarcinomas or mucinous adenocarcinomas. In grading, one can differentiate into either four grades (G1 to 4) or between low and high grade. The internationally accepted TNM/pTNM system, as described in the 4th edition, is used for staging. This system has considerable advantages over the traditional, but often misused Dukes' classification. After treatment, the surgeons and the pathologists must work together to determine the R classification. Typing, grading and staging are of great importance in deciding on the indication for either a limited surgical procedure or a radical resection. Together with the R classification, they decisively influence the indications for post-treatment after surgical therapy. R classification is the most important factor for prognosis after surgical removal of tumours. Following resection for cure, the prognosis is especially affected by the pTNM classification and its corresponding stages. The independent prognostic significance of other clinical, macroscopic and histological findings cannot yet be definitively determined.     

Simplified identification of Lynch syndrome: a prospective, multicenter study

BackgroundRecommended strategies to screen for Lynch syndrome in colorectal cancer are not applied in daily practice and most of Lynch cases remain undiagnosed.AimsWe investigated in routine conditions a strategy that uses simplified clinical criteria plus detection of MisMatch Repair deficiency in tumours to identify Lynch carriers.MethodsColorectal cancer patients that met at least one of three clinical criteria were included: (1) colorectal cancer before 50 years, (2) personal history of colorectal or endometrial cancer, (3) first-degree relative history of colorectal or endometrial cancer. All tumours underwent an MisMatch Repair test combining microsatellite instability analysis and MisMatch Repair immunohistochemistry. Patients with an MisMatch Repair-deficient tumour were offered germline testing.ResultsOf the 307 patients fulfilling the clinical criteria, 46 (15%) had a MisMatch Repair-deficient tumour. Amongst them 27 were identified as Lynch carriers (20 with germline mutation: 12 MLH1, 7 MSH2, 1 MSH6; 7 highly suspected cases despite failure of genetic testing). The simplified clinical criteria selected a population whose MisMatch Repair-deficient status was highly predictive (59%) of Lynch syndrome.ConclusionThis bio-clinical strategy based on simplified clinical criteria combined with an MisMatch Repair test efficiently detected LS cases and is easy to use in clinical practice, outside expert centres.     

Hereditary non-polyposis colorectal cancer: clinical and molecular evidence for a new entity of hereditary colorectal cancer

BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is clinically defined by familial clustering of colorectal cancer and other associated tumours. METHODS: By thorough molecular and clinical evaluation of 41 families, two different groups were characterised: group 1, 25 families with truncating mutations in MLH1 or MSH2 (12 novel mutations); and group 2, 16 Amsterdam positive families without mutations in these genes and without microsatellite instability in their corresponding tumours. RESULTS: Significant clinical differences between these two groups were found. Firstly, earlier age of onset for all colorectal cancers (median 41 v 55 years; p < 0.001) and all tumours (median 43 v 56 years; p = 0.022) was observed, comparing groups 1 and 2. Secondly, 68% of the index colorectal cancers were localised proximally of the splenic flexure in group 1 compared with 14% in group 2 (p < 0.010). Thirdly, more synchronous and metachronous colorectal (p = 0.017) and extracolorectal tumours (p < 0.001) were found in group 1. Fourthly, a higher colorectal adenoma/carcinoma ratio (p = 0.030) and a tendency towards more synchronous or metachronous adenomas in group 2 (p = 0.084) was observed, indicating a slower progression of adenomas to carcinomas. As three mutation negative tumours revealed chromosomal instability after comparative genomic hybridisation, these tumours may be caused by one or more highly penetrant disease alleles from the chromosomal instability pathway. CONCLUSION: These data show that HNPCC includes at least two entities with clinical and molecular differences. This will have implications for surveillance programmes and for cancer research.     

Evidence-based medicine in HBP surgery: Is there any?

BACKGROUND: Evidence-based medicine (EBM) has become widely accepted as a basis for clinical decision in many fields of medicine. This review examines the specific role of EBM in hepato-biliary and pancreatic (HBP) surgery. EBM relies on four main sources, including clinical guidelines, meta-analyses, primary information and clinical experience. Randomized controlled trials (RCTs) constitute the cornerstone of EBM and a recent study reported that there are relatively few RCTs evaluating the effectiveness of surgical therapies and procedures (1,530 out of 45,342 or 3.4% in five leading surgical journals) and only a few in HBP surgery. Although the effort must be to implement EBM as far as possible in HBP surgery, there are several obstacles to conducting RCTs in HBP surgery, including problems associated with standardization of surgical skills, sham-operations often impossible to perform, and the general applicability of specific findings may be uncertain. DISCUSSION: This paper will provide two relevant examples of EBM in HBP surgery in patients with hepatic metastases and pancreatic adenocarcinoma, illustrating some problems but also the potential of introducing EBM in HBP surgery. In the future, our effort must be devoted to implementing EBM in applicable areas of HBP surgery but also remembering that in certain areas accumulated knowledge from observational studies, including drainage of abscesses and surgical treatment of intestinal obstruction, may have similar or even higher clinical value than RCTs.     

Endosonography and endoscopic magnetic resonance imaging.

Endosonography is an important modality for the diagnosis and staging of oesophageal, gastric, colorectal and pancreatobiliary malignancy. It is also recognized as a reliable method for the evaluation of submucosal tumours of the gastrointestinal tract, for differentiating benign lesions from giant gastric folds, and for the localization of pancreatic endocrine tumours. The latest development, that of endosonographic fine-needle aspiration, provides for the cytological diagnosis of gastrointestinal tumours. This new technique may also be used for endoscopic therapy. High-frequency probes can be used to make a more accurate diagnosis of superficial carcinoma of the gastrointestinal tract, for three-dimensional imaging of gastrointestinal tumours and for intraductal ultrasonography of the bile duct and pancreatic duct. Endoscopic magnetic resonance imaging provides information not obtainable with endosonography or other modalities. It has high potential in the diagnosis and staging of gastrointestinal and pancreatobiliary tumours.     

Microsatellite instability and the clinicopathological features of sporadic colorectal cancer

BACKGROUND AND AIMS: In this study, we prospectively examined the clinical significance of the microsatellite instability (MSI) phenotype in sporadic colorectal cancer, and investigated methods for effective identification of these tumours in routine pathology practice. METHODS: DNA was extracted from 310 tumours collected from 302 consecutive individuals undergoing curative surgery for sporadic colorectal cancer. Microsatellite status was determined by polymerase chain reaction amplification using standard markers, while immunostaining was used to examine expression of MLH1, MSH2, and p53. RESULTS: Eleven per cent of tumours showed high level instability (MSI-H), 6.8% had low level instability (MSI-L), and the remainder were stable. MSI-H tumours were significantly more likely to be of high histopathological grade, have a mucinous phenotype, and to harbour increased numbers of intraepithelial lymphocytes. They were also more likely to be right sided, occur in women, and be associated with improved overall survival. In total, 25 (8%) tumours showed loss of staining for MLH1 and a further three tumours showed absence of staining for MSH2. The positive and negative predictive value of immunohistochemistry in the detection of MSI-H tumours was greater than 95%. CONCLUSIONS: We conclude that the MSI-H phenotype constitutes a pathologically and clinically distinct subtype of sporadic colorectal cancer. Immunohistochemical staining for MLH1 and MSH2 represents an inexpensive and accurate means of identifying such tumours.     

Hereditary nonpolyposis colorectal cancer (Lynch syndrome). Clinical case

Colorectal cancer is an important neoplasm in general population, about 90% of the cases are sporadical, but near of 5% are due to hereditary non polyposis colorectal cancer. Early detection is imperative due to genetic linkage and association to other neoplasms diagnosed an early age. This case report is about a young man diagnosed with colorectal cancer that presented multiple recurrences and had at least two affected generations. The most important aspects of diagnosis, management and genetic counseling are discussed.     

Hereditäres nichtpolypöses kolorektales Karzinom

Colorectal cancer (CRC) is the 2nd most common cancer in Germany (incident cases >70,000 persons each year). In 15–25% of all cases, a positive family history is present, and in 2–5% there is a monogenetic background. The most common form of hereditary CRC is hereditary nonpolyposis colorectal cancer (HNPCC) syndrome (also called Lynch syndrome). The cumulative lifetime risk for the development of tumours is 80%. In addition to an increased CRC risk, patients have an increased risk of developing extracolonic cancers. Through identification of the genetic background, at-risk individuals have the chance nowadays to learn their individual risk before they develop malignancies. This article reviews the clinical characteristics, genetics, diagnostic criteria, differential diagnosis, tumour risk, surveillance programmes, and distinct therapeutic aspects.     

遗传性非息肉病性大肠癌6家系临床分析

目的总结遗传性非息肉病性大肠癌(HNPCC)的临床特征,提高其早期诊断和治疗水平。方法对我院6个HNPCC家系进行调查,记录患者性别、发病年龄、肿瘤部位等。结果6个家系有大肠癌患者19例,占同期所有大肠癌的2.7%。其中男性10例,女性9例;发病年龄为26～74岁,中位年龄为53.4岁;共有大肠癌病灶23处,60.9%位于右半结肠,多原发大肠癌有4例。另有大肠腺瘤患者2例,白血病患者1例,原发性肝癌患者1例。结论HNPCC有明显的临床特征,利用这些特征有助于早期诊断和提高防治效果。     

Genetics of colorectal polyps

Currently, genetic investigation of human tumours starts from the analysis of advanced cancers. Once a given genetic alteration has been found in advanced tumours, this same alteration is investigated in the pre-neoplastic lesions. The aim of this approach is to assess the significance of the genetic alteration during the carcinogenic process. This review is focused on alterations that have proven to be present in pre-neoplastic lesions that are associated to colorectal cancer (ACF and early adenoma). Alterations that are present at the early stages are likely to play a crucial role in colorectal tumorigenesis. Colorectal tumorigenesis is extremely heterogeneous from a genetic point of view: tumours follow alternative molecular pathways and show different phenotypes (CIN, MIN and CIMP). Tumours are genetically heterogeneous from their early stages: the sequence of genetic events that accumulate within cells during progression to malignancy appears to be determined by the first events. These events have been investigated in ACF and in early adenomas. The understanding of the molecular mechanisms underlying genesis and progression of colorectal tumours will allow the development of new tools for cancer prevention and early diagnosis, as well as for therapeutic approaches specific for different molecular targets.