New founding mutation in MSH2 associated with hereditary nonpolyposis colorectal cancer syndrome on the Island of Tenerife.

Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC) is a hereditary syndrome with genetic heterogeneity. The disease is caused by mutations or epigenetic silencing in DNA mismatch repair genes, MLH1, MSH2, MSH6, PMS2 and MLH3, although the vast majority of cases correspond to mutations of MLH1 and MSH2. We herein describe a nucleotide change, c.2063T>G in exon 13 of the MSH2 gene, present in families that fulfill the Amsterdam criteria for Lynch syndrome and originate from northern Tenerife (Canary Islands-Spain). This mutation is expected to result in a nonconservative amino acid change, M688R, at the ATPase domain of the MSH2 protein. We found five large families with this mutation, and about half the individuals heterozygous for M688R developed malignancies by the sixth decade of life. In many cases analyzed, their tumors revealed loss of the normal allele, being homozygous for M688R. There is an evidence of historical isolation for the population studied, which could have favored a considerable genetic drift. The presence of the same mutation and the disease associated-haplotype conservation in families not directly related can be probably the consequence of a bottleneck in the founding of this population (rather than a relatively recent founding of the mutation).

Mucinous cystic neoplasm of the pancreas during pregnancy: the importance of proper management.

We describe a case of huge mucinous cystic tumor of the pancreas in a 26-year-old woman during pregnancy. Ultrasonography demonstrated a well-delimited cystic mass in the left upper abdominal quadrant, suggestive of benignity. Magnetic resonance imaging showed a large cystic mass resembling a mucinous cystic tumor of the pancreas. After this assessment the patient underwent surgical exploration and a huge cystic tumor of the pancreas was discovered. The tumor was enucleated and distal pancreatectomy was performed. The resected margin of the specimen was free of tumor. In this case report we discuss the management of mucinous pancreatic tumors during pregnancy and we briefly review the previously reported cases of mucinous pancreatic tumors in pregnant patients. We conclude that surgical resection of these tumors should be strongly considered in pregnancy. Removal of the tumor appears to be a safe procedure without harmful effects to the fetus.

Coeliac axis ligation in a case of unmanageable upper gastrointestinal haemorrhage.

Upper gastrointestinal haemorrhage (UGH) is a frequent reason for referral in gastroenterologic practice. It consists of bleeding that originates in the upper gastrointestinal tract, between the oesophagus and Treitz's angle. Gastroduodenal peptic ulceration, severe lesions of gastric or duodenal mucosa, and esophageal varicose rupture are the most frequently reported causes of UGH. Clinically, it manifests as rectal bleeding or haematemesis. Regardless of the causal lesion, UGH is differentiated by the degree of haemodynamic instability. Thus, initial management of UGH with haemodynamic instability does not depend on the lesion that produces it but rather on controlling the hypovolaemia in all cases. Subsequent therapeutic measures, which in certain cases are defined in early stages of this picture, depend on the aetiology of the lesion causing the UGH and its treatment. We present a case of unmanageable UGH of unknown aetiology despite multiple diagnostic and therapeutic measures, where final successful treatment required an exceptional surgical intervention--celiac axis ligation.

Can early diagnosis of symptomatic colorectal cancer improve the prognosis?

Patients with colorectal cancer continue to present with relatively advanced tumors. Delay in diagnosis is often believed to have been a contributing factor, and the validity of this hypothesis has seldom been questioned. The aim of this study was to establish whether a delay in diagnosis is related to long-term survival and if the most frequent symptoms were related to the stage or time at which the carcinoma was diagnosed. Data from 660 patients surgically treated for uncomplicated colorectal carcinoma in our institution between 1985 and 2000 were analyzed retrospectively. Age, sex, initial symptoms, duration of symptoms, neoplasm location, curative surgery, TNM stage, and survival time were the variables recorded. Patients were classified into two groups according to symptom duration: < 3 months versus >/= 3 months. Comparative statistical analysis was performed for the two groups as well as the initial symptom, TNM stage, and survival time. Also, the initial symptoms most frequently reported were compared with the TNM stage. The two groups were found to be equal with regard to distribution of age, gender, location of the neoplasm, type of surgery performed, and TNM stage. We found that symptom duration was shortened in the presence of abdominal pain ( p = 0.002) [odds ratio (OR) 0.53; 95% confidence interval (CI) 0.35-0.80] and was delayed in the presence of an anemic syndrome ( p = 0.006) (OR 2.4; 95% CI 1.27-4.56). Also, the stage of the neoplasm was related to rectal bleeding ( p < 0.001) and abdominal pain ( p = 0.008). The log-rank test indicated that duration of symptoms was not related to long-term survival ( p = 0.90). We concluded that the duration of colorectal cancer symptoms is not related to the stage or prognosis of tumors.

Genetic alterations and MSI status in primary, synchronous, and metachronous tumors in a family with hereditary nonpolyposis colorectal cancer (HNPCC).

In colorectal cancer, different levels of microsatellite instability (MSI) have been described: high-frequency MSI, low-frequency MSI, and stable microsatellites. MSI-H characterizes a unique clinical and pathologic phenotype known as hereditary nonpolyposis colorectal cancer syndrome (HNPCC). In this case, an increased incidence of synchronous and metachronous tumors has been reported, but there are few reports with standardized criteria of MSI in HNPCC-associated tumors. The authors attempted to establish whether tumors of the HNPCC spectrum with different levels of MSI could predict the development of metachronous carcinomas. We have examined the levels of MSI at loci frequently affected in colorectal cancers in primary, synchronous, and metachronous tumors in a family that fulfils the Amsterdam criteria for HNPCC. This family presents colorectal cancers, HNPCC-extracolonic tumors (endometrial and ureter), and tumors (breast and bladder) not described in the HNPCC spectrum. The tumors exhibited MSI-H, irrespective of their location and regardless whether they were primary, synchronous, or metachronous, with the only exception of both endometrial tumors that showed low-frequency MSI tumors (MSI-L). Our results suggest that not only colorectal tumors with MSI-H result in a potential marker for the determination of high-risk individuals for metachronous and synchronous tumors, but also MSI-L endometrial tumors might be considered as indicative of high-risk individuals.