Vicente Medina-Arana

Adrenocortical carcinoma, an unusual extracolonic tumor associated with Lynch II syndrome

Lynch syndrome (LS) is an autosomal dominant condition that predisposes to colorectal cancer and specific other tumors. Extracolonic tumors occur mainly in the endometrium, stomach, ovary, small intestine and urinary tract. The presence of rare tumors in patients belonging to families who have Lynch syndrome is always interesting, because the question arises whether these tumors should be considered as a coincidence or are related with the syndrome. In this last case, they are also the result of the defect in the mismatch repair system, opening the possibility of extending the tumor spectrum associated with the syndrome. Here we describe a patient from a Lynch syndrome family with a germline mutation c.2063T>G (p.M688R) in the MSH2 gene, who developed an adrenal cortical carcinoma, a tumor not usually associated with LS. We analyzed the adrenocortical tumour for microsatellite instability (MSI), LOH and the presence of the germline c.2063T>G (M688R) mutation. The adrenal cortical carcinoma showed the MSH2 mutation, loss of heterozygosity of the normal allele in the MSH2 gene and loss of immunohistochemical expression for MSH2 protein, but no microsatellite instability. Additionally, the adrenal cortical carcinoma did not harbour a TP53 mutation. The molecular study indicates that this adrenal cortical cancer is probably due to the mismatch repair defect.

Impact of the MTHFR C677T polymorphism on colorectal cancer in a population with low genetic variability

PurposesMethylenetetrahydrofolate reductase (MTHFR) plays a key role in folate metabolism, and folate is implicated in carcinogenesis by its role in DNA methylation, repair, and synthesis. We analyzed the impact of MTHFR C677T polymorphism in colorectal cancer in a region of the Tenerife Island whose population has a history of genetic isolation and a low genetic variability. This allows analyzing the effects of the polymorphism that are not due to interactions with different genetic variants.MethodsGenomic DNA of 50 Spanish sporadic colorectal cancer (CRC) patients and 103 controls was analyzed by PCR/RFLP and sequencing.ResultsThe T allele is more frequent in controls than in patients (P < 0.01). The variant (T) carriers displayed significant odds ratio values for the CT heterozygotes (P = 0.026) and even when grouping heterozygote (CT) and homozygotes (TT) (P = 0.015). Patients carriers of the variant T (CT y TT) show a higher survival rate after chemotherapy than the CC homozygotes (log rank; P = 0.001).ConclusionsThe MTHRF C677T variant has a protective effect on CRC development in a population with low allelic variability and an optimal intake of folic acid. Moreover, patients carrying the variant (T) show a better prognosis after 5-fluorouracil/folinic acid-based chemotherapy.

El íleo biliar como causa de abdomen agudo. Importancia del diagnóstico precoz para el tratamiento quirúrgico

Gallstone ileus is an uncommon type of mechanical intestinal obstruction caused by an intraluminal gallstone, and preoperative diagnosis is difficult in the Emergency department. This study is a retrospective analysis of the clinical presentation of 5 patients with gallstone ileus treated between 2000-2010. Clinical features, diagnostic testing, and surgical treatment were analyzed. Five patients were included: 2 cases showed bowel obstruction; 2 patients presented a recurrent gallstone ileus with prior surgical intervention; and one patient presented acute peritonitis due to perforation of an ileal diverticula. In all cases CT confirmed the preoperative diagnosis. In our experience, gallstone ileus may present with clinical features other than intestinal obstruction. In suspicious cases CT may be useful to decrease diagnostic delay, which is associated with more complications.

Tumor spectrum in lynch syndrome, DNA mismatch repair system and endogenous carcinogens

Inactivation of Mismatch Repair genes in Lynch Syndrome, caused by inherited mutations, decreases the ability to repair DNA errors throughout life. This deficit may allow the development of any tumor type. Nevertheless, the Syndrome develops a specific tumor spectrum associated with the disease. We think that such spectrum of tumors would be related to the action of certain endogenous carcinogens such as bile acids and estrogens that aggravate the inherited defect. J. Surg. Oncol. 2012; 106:10–16.

The hMSH2(M688R) Lynch syndrome mutation may function as a dominant negative

The hMSH2(M688R) mismatch repair (MMR) gene mutation has been found in five large families from Tenerife, Spain, suggesting it is a Lynch syndrome or hereditary non-polyposis colorectal cancer (LS/HNPCC) founder mutation. In addition to classical LS/HNPCC tumors, these families present with a high incidence of central nervous system (CNS) tumors normally associated with Turcot or constitutional mismatch repair deficiency (CMMR-D) syndromes. Turcot and CMMR-D mutations may be biallelic, knocking out both copies of the MMR gene. The hMSH2(M688R) mutation is located in the ATP hydrolysis (ATPase) domain. We show that the hMSH2(M688R)-hMSH6 heterodimer binds to mismatched nucleotides but lacks normal ATP functions and inhibits MMR in vitro when mixed with the wild-type (WT) heterodimer. Another alteration that has been associated with LS/HNPCC, hMSH2(M688I)-hMSH6, displays no identifiable differences with the WT heterodimer. Interestingly, some extracolonic tumors from hMSH2(M688R) carriers may express hMSH2-hMSH6, yet display microsatellite instability (MSI). The functional analysis along with variability in tumor expression and the high incidence of CNS tumors suggests that hMSH2(M688R) may act as a dominant negative in some tissues, while the hMSH2(M688I) is most likely a benign polymorphism.

Metastatic lymphs nodes and lymph node ratio as predictive factors of survival in perforated and non-perforated T4 colorectal tumors.

Recently it has been hypothesized that perforation of colorectal cancer (CRC) itself is not a predictor of poor prognosis. The aim of this study was to analyze the prognostic impact, of the spontaneous perforation of the tumour, metastatic lymph nodes and lymph node ratio (LNR) after potentially curative surgery.

Predictive factors of years of potential life lost by colorectal cancer

Objective To evaluate the impact of colorectal cancer (CRC) by estimating the years of potential life lost (YPLL) by this neoplasm in a cohort of patients, as well as to define the predictive factors of YPLL. Methods A descriptive cross-sectional study of 980 consecutive patients diagnosed and treated because of CRC in our institution between 1985 and 2002 was carried out. Demographic, clinical, pathological, surgical, hospital stay, complications, and mortality variables were recorded. The primary endpoint of this study was to calculate individual YPLL. Univariate analysis was performed to compare each independent variable with the variable YPLL. All clinically relevant variables significantly associated with YPLL were included in an ordinal regression model to identify independent factors prognostic of YPLL. Results The final study sample was 794 patients, 413 (52%) men and 381 (48%) women, mean age 65.3 years [confidence interval (CI) 95%: 64.4–66.2 years; SD: 12.8]. The mean global YPLL for the 351 patients who died of CRC was 15.2 years (SD: 10.7; CI 95%: 14.1–16.3). Lower age [odds ratio (OR)=0.98; CI 95%: 0.97–0.98], male sex (OR=1.19; CI 95%: 1.00–1.43), lower tumor, nodes, metastasis (TNM) stage (OR=0.29; CI 95%: 0.24–0.35), and rectum localization of the tumor (OR=1.37; CI 95%: 1.14–1.64) were independent prognostic factors for YPLL. Conclusion In our community, the mean number of YPLL by CRC exceeds 15 years. Lower age, male sex, higher TNM stage, and rectum localization are negative predictors of YPLL.

Enterolitotomía más colecistectomía precoz, una aplicación de cirugía de control de daños para pacientes con íleo biliar

BACKGROUND Recurrent gallstone ileus is an uncommon mechanical intestinal obstruction secondary to occlusion of the intestine by an intraluminal biliary calculus. CLINICAL CASE Female, 75 years old, ischaemic heart disease (stent), arrived in our department complaining of abdominal pain and vomiting. Computed tomography showed gallstone ileus. The patient underwent an enterotomy with gallstone removal. Three months later, the patient came back with the same clinical symptoms and signs. A new computed tomography highlighted a gallstone ileus again. Enterolithotomy and gallstone removal, cholecystectomy and closure of cholecystoduodenal fistula were performed. The patient had a prolonged hospital stay due to the development of congestive heart failure. Case 2. Male, 71 years old, ischaemic heart disease and aortocoronary bypass, seen in our department complaining of vomiting. Computed tomography showed aerobilia and gallstone ileus. The patient underwent an urgent enterolithotomy. Seven months later, the patient came back with the same clinical symptoms and signs. Computed tomography showed a new gallstone ileus. An enterotomy and gallstone removal, cholecystectomy and closure of cholecystoduodenal fistula were performed. The patient died due to multi-organ failure in post-surgery period. CONCLUSION In the elderly patients with concomitant medical illnesses with the risk of a second laparotomy, it is justifiable to reconsider the definitive repair in the treatment of gallstone ileus. The enterolithotomy in acute phase followed by early cholecystectomy (4-8 weeks) may be a safe method for eliminating, not only the possibility of recurrent gallstone ileus, and probably the need for a second laparotomy, but also the exceptional possibility of developing a gallbladder carcinoma.

Genealogical tree study as screening method in the Lynch syndrome prior to genetic test.

Objectives:Despite genetic advances in the study of Lynch syndrome (LS), difficulties remain in the diagnosis of the syndrome. The aim of this study was to assess the usefulness of a detailed genealogical tree as a screening method to identify Tenerife island families with a high probability of LS. Methods:We elaborated complete genealogical trees of the families. According to the degree of fulfillment of the Amsterdam Criteria II, the genealogical trees were classified as high or low probability of LS. Additionally, we analyzed the level of tumor microsatellite instability (MSI+) and identified a mutation in exon 13 of the MSH2 gene by single-strand conformation polymorphism, sequencing, and PCR-RFLP. Results:According the genealogical trees, we found 10 families with high probability of LS and 30 families with low probability of LS. The families with high probability of LS showed high MSI+ in all cases. Conversely, families with low probability were MSS (microsatellite stable). In 5 of the 10 families with high probability, we discovered a T→G mutation in position 688 of exon 13 of MSH2, which appeared in all the family members with the tumor, except 1 patient with a retinoblastoma. Conclusions:Our results indicate that genealogical tree is a highly effective tool for classifying families with a high probability of Lynch Syndrome prior to genetic test.

Carbón activado en la cavidad peritoneal

We completely agree with the statements by Nogué et al. Our case seems to have originated with the placement of a nasogastric tube, a previously injured gastric cavity and an attempt at decontamination in a therapeutic interval that was a priori out of range. For years, our group has been advising against both the indication as well as the use of routine decontamination measures due to potential iatrogenesis, which is probably underreported. In any event, given the possibility that similar unfortunate episodes may continue to occur, we feel the need to insist to surgeons that, in spite of a thorough initial surgical abdominal lavage, these patients require strict monitoring after the surgical intervention, as new episodes of peritonitis are foreseeable given the extensive diffusion of AC in the peritoneal cavity.