João Pinto-de-Sousa

c-erb B-2 Expression Is Associated with Tumor Location and Venous Invasion and Influences Survival of Patients with Gastric Carcinoma:

The HER-2/neu gene or c-erb B-2, localized on chromosome 17q, belongs to a family of tyrosine kinase receptors and shares extensive homology with the epidermal growth factor receptor. c-erb B-2 gene amplification and protein overexpression have been reported in several human cancers. The prognostic value of this genetic alteration in gastric carcinoma is far from being established. In the present study, formalin-fixed, paraffin-embedded gastric carcinoma tissues from 157 patients were evaluated for c-erb B-2 overexpression, by immunohistochemistry using a polyclonal antibody. c-erb B-2 expression was evaluated according to clinical and pathological parameters, and to the survival of the patients. Our results show that: (1) c-erb B-2 was overexpressed in 15.3% of gastric carcinoma cases; (2) c-erb B-2 overexpression was significantly more frequent in cardia (23.8%) and fundus/body (25.0%) carcinomas than in antrum (7.2%) carcinomas; (3) c-erb B-2 overexpression was significantly associated with venous invasion; (4) c-erb B-2 is a prognostic factor for gastric carcinoma.

Glycoproteomic Analysis of Serum from Patients with Gastric Precancerous Lesions

Gastric cancer is preceded by a carcinogenesis pathway that includes gastritis caused by Helicobacter pylori infection, chronic atrophic gastritis that may progress to intestinal metaplasia (IM), dysplasia, and ultimately gastric carcinoma of the more common intestinal subtype. The identification of glycosylation changes in circulating serum proteins in patients with precursor lesions of gastric cancer is of high interest and represents a source of putative new biomarkers for early diagnosis and intervention. This study applies a glycoproteomic approach to identify altered glycoproteins expressing the simple mucin-type carbohydrate antigens T and STn in the serum of patients with gastritis, IM (complete and incomplete subtypes), and control healthy individuals. The immunohistochemistry analysis of the gastric mucosa of these patients showed expression of T and STn antigens in gastric lesions, with STn being expressed only in IM. The serum glycoproteomic analysis using 2D-gel electrophoresis, Western blot, and MALDI-TOF/TOF mass spectrometry led to the identification of circulating proteins carrying these altered glycans. One of the glycoproteins identified was plasminogen, a protein that has been reported to play a role in H. pylori chronic infection of the gastric mucosa and is involved in extracellular matrix modeling and degradation. Plasminogen was further characterized and showed to carry STn antigens in patients with gastritis and IM. These results provide evidence of serum proteins displaying abnormal O-glycosylation in patients with precursor lesions of gastric carcinoma and include a panel of putative targets for the non-invasive clinical diagnosis of individuals with gastritis and IM.

Expression of UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase-6 in gastric mucosa, intestinal metaplasia, and gastric carcinoma.

Aberrant mucin O-glycosylation is often observed in cancer and is characterized by the expression of immature simple mucin-type carbohydrate antigens. UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase-6 (ppGalNAc-T6) is one of the enzymes responsible for the initial step in O-glycosylation. This study evaluated the expression of ppGalNAc-T6 in human gastric mucosa, intestinal metaplasia, and gastric carcinomas. Our results showed that ppGalNAc-T6 is expressed in normal gastric mucosa and in intestinal metaplasia. A heterogeneous expression and staining pattern for this enzyme was observed in gastric carcinomas. ppGalNAc-T6 was expressed in 79% of the cases, and its expression level was associated with the presence of venous invasion. Our results provide evidence that ppGalNAc-T6 is an IHC marker associated with venous invasion in gastric carcinoma and may contribute to the understanding of the molecular mechanisms that underlie aberrant glycosylation in gastric carcinogenesis and in gastric carcinoma.

Clinicopathologic profiles and prognosis of gastric carcinomas from the cardia, fundus/body and antrum.

Background/Aims: The putative influence of tumor location on the biologic behavior of gastric carcinomas remains controversial. The aim of this study was to investigate if carcinomas arising in the three types of gastric mucosa (cardia, fundus/body and antrum) have different clinical and pathologic profiles and carry a different prognosis. Methods: Three hundred and two patients with cardia or gastric carcinoma resected between 1984 and 1996 were retrospectively studied. Cases were divided in three groups according to tumor location: cardia (n = 80); fundus/body (n = 60); antrum (n = 162). The three groups were crosstabulated with clinic and pathologic parameters, such as age, sex, macroscopy, histology, desmoplasia, tumor size, depth of tumor wall penetration, nodal status, venous invasion and stage. Survival rates were calculated for the three locations according to the aforementioned parameters. Univariate survival analysis and Cox regression were performed for each location. Results: Cases from the cardia and fundus/body were similar and distinct from antrum cases according to macroscopy, tumor size, depth of wall penetration, venous invasion, nodal status and stage. Cases from fundus/body were similar to antrum cases and distinct from cardia cases according to gender and Laurén’s classification. An overall difference in survival between the three locations was observed (p = 0.006). Cumulative survival was better for patients with carcinomas in the antrum than in the cardia (p = 0.04) and in the fundus/body (p = 0.003); no significant differences were observed in survival between cardia and fundus/body carcinoma cases. Cox regression identified stage and venous invasion as prognostic factors for patients with carcinomas in the three locations. In the group of cardia tumors, older patients had a worse outcome and in the group of fundus/body carcinomas, large tumors were associated with a poorer survival. Conclusions: Our results show that cardia carcinoma and antrum carcinoma are distinct gastric carcinoma entities whereas fundus/body carcinoma shares some characteristics from both entities.

Acute diverticulitis in younger patients: any rationale for a different approach?

AIM To compare the natural history and course of acute diverticulitis in a younger age group with an older population and to evaluate whether younger patients should be managed differently. METHODS This study was a retrospective review of 157 patients treated with acute diverticulitis between January 1, 2004 and December 31, 2007. Diverticulitis was stratified according to the Hinchey classification. Patients were divided into 2 populations: group A ≤ 50 years (n = 31); group B > 50 years (n = 126). Mean patient follow-up was 15 mo. RESULTS The median age was 60 years. A significantly higher proportion of patients in group B presented with complicated diverticulitis (36.5% vs 12.9%, P = 0.01). Recurrence was more frequent in group A (25.8% vs 11.1%, P = 0.03) and the mean time-to-recurrence was shorter (12 mo vs 28 mo, P = 0.26). The most severe recurrent episodes of acute diverticulitis were classified as Hinchey stage I and none of the patients required emergency surgery. In multivariate analysis, only age (P = 0.024) was identified as an independent prognostic factor for recurrence. CONCLUSION Based on the results of this study, the authors recommend that diverticulitis management should be based on the severity of the disease and not on the age of the patient.

Early Onset Gastric Cancer No Longer Presents as an Advanced Disease with Ominous Prognosis

Background: This study aimed to characterize the clinicopathological features and prognosis of early onset gastric carcinomas (EOGCs) in a sample of young Portuguese adults. Material and Methods: A subset of 415 patients submitted to gastric resection was divided into 2 groups: A – patients aged 45 years or less (n = 108), and B – patients older than 45 years (n = 307). The groups were compared for several clinicopathological features and the survival of the patients was analyzed by uni- and multivariate analysis. Results: The surgical resection rate was higher in young patients, in whom tumors more frequently displayed an ulcerative shape (p < 0.001) and diffuse/isolated cell-type histology (p < 0.001). In the elderly, the rate of vascular invasion was significantly higher (p = 0.002). Overall, the survival of young patients was higher than in the elderly (p < 0.001). Survival curves were higher in young patients, except for pT4 and pM1 cases. In the multivariate survival analysis, age (p < 0.001), depth of tumor invasion (p < 0.001), nodal status (p < 0.001), vascular invasion (p = 0.011) and distant metastases (p = 0.007) emerged as independent prognostic factors for gastric carcinoma. Conclusion: Young gastric cancer patients no longer present with more advanced disease than the elderly and, overall, survival is better in young patients.

Immunohistochemical molecular phenotypes of gastric cancer based on SOX2 and CDX2 predict patient outcome.

BackgroundGastric cancer remains a serious health concern worldwide. Patients would greatly benefit from the discovery of new biomarkers that predict outcome more accurately and allow better treatment and follow-up decisions. Here, we used a retrospective, observational study to assess the expression and prognostic value of the transcription factors SOX2 and CDX2 in gastric cancer.MethodsSOX2, CDX2, MUC5AC and MUC2 expression were assessed in 201 gastric tumors by immunohistochemistry. SOX2 and CDX2 expression were crossed with clinicopathological and follow-up data to determine their impact on tumor behavior and outcome. Moreover, SOX2 locus copy number status was assessed by FISH (N = 21) and Copy Number Variation Assay (N = 62).ResultsSOX2 was expressed in 52% of the gastric tumors and was significantly associated with male gender, T stage and N stage. Moreover, SOX2 expression predicted poorer patient survival, and the combination with CDX2 defined two molecular phenotypes, SOX2+CDX2- versus SOX2-CDX2+, that predict the worst and the best long-term patients’ outcome. These profiles combined with clinicopathological parameters stratify the prognosis of patients with intestinal and expanding tumors and in those without signs of venous invasion. Finally, SOX2 locus copy number gains were found in 93% of the samples reaching the amplification threshold in 14% and significantly associating with protein expression.ConclusionsWe showed, for the first time, that SOX2 combined with CDX2 expression profile in gastric cancer segregate patients into different prognostic groups, complementing the clinicopathological information. We further demonstrate a molecular mechanism for SOX2 expression in a subset of gastric cancer cases.

Gastric Stump Cancer: More Than Just Another Proximal Gastric Cancer and Demanding a More Suitable TNM Staging System

Background. Considerable controversy persists about the biological behavior of gastric stump cancer (GSC). The aim of this study is to clarify if this cancer is just another proximal gastric cancer or if it emerges as a distinctive clinicopathologic entity. Methods. This review of a prospectively collected gastric cancer database identified 73 patients with GSC in a single institution between January 1980 and June 2012 and compared them with 328 patients with proximal gastric cancer (PGC) and 291 patients with esophagogastric junction cancer (EGJC). Results. Patients with GSC were predominantly males. Eighty-three percent of GSC penetrated the subserosal or the serosal layers. The median number of lymph nodes retrieved in GSC patients was significantly lower than in PGC patients or in EGJC patients. Cumulative survival curves were not different between GSC, PGC, or EGJC patients. Unlike that observed in PGC and in EGJC, no significant differences in cumulative survival according to the TNM staging system were observed in GSC cases. Conclusions. The outcome of patients with GSC displayed significant differences when compared to those with other proximal gastric cancers concerning the lack of survival association with the TNM staging system. Therefore a more suitable staging system should be designed for these unique cancers.

Gastric wall ischemia following massive gastric distension due to peptic pyloric stenosis: a case report

Gastric necrosis is a rare entity mainly due to the rich collateral blood flow the stomach is supplied by. Acute gastric dilation is one of the described underlying causes, and although not fully understood, many potential alterations, such as vascular compression, herniation, volvulus, acute necrotizing gastritis, complications after abdominal surgery, anorexia, bulimia nervosa, trauma, exposure to caustic materials, diabetes, medications, infections, debilitating chronic illness, gastric outlet obstruction, aerophagia and acute pancreatitis have been described. In this report, we present a case of partial gastric ischemia with necrosis and consequent perforation of the lesser curvature of the stomach, as a result of gastric outlet obstruction due to pyloric stenosis. The patient underwent an emergency laparotomy. An atypical gastrectomy and a Heineke–Mikulicz pyloroplasty were performed. We emphasize the need for the quick recognition of this condition and for the urgent management because of the high mortality rate associated with undiagnosed gastric necrosis.

Mesenteric inflammatory pseudotumor: A difficult diagnosis. Case report

Highlights • Inflammatory pseudotumor is a very rare benign neoplasm.• Definitive diagnosis is usually made only after surgery.• Mesenteric location is rare.• Surgical resection can cure the disease.• Close follow-up is advised to identify recurrences.