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4 result(s) for "Wohnrath, Durval R."
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Profile of esophageal squamous cell carcinoma mutations in Brazilian patients
Esophageal cancer is an aggressive tumor that has a high rate of incidence and mortality worldwide. It is the 10th most frequent type in Brazil, being squamous cell carcinoma (ESCC) the predominant subtype. There is currently an incessant search to identify the frequently altered genes associated with esophageal squamous cell carcinoma biology that could be druggable. This study aimed to analyze the somatic mutation profile of a large panel of cancer-related genes in Brazilian ESCC. In a series of 46 ESCC diagnoses at Barretos Cancer Hospital, DNA isolated from paired fresh-frozen and blood tissue, a panel of 150 cancer-related genes was analyzed by next-generation sequencing. The genes with the highest frequency of mutations were TP53 (39/46, 84.8%), followed by NOTCH1 (7/46, 15.2%), NFE2L2 (5/46, 10.8%), RB1 (3/46, 6.5%), PTEN (3/46, 6.5%), CDKN2A (3/46, 6.5%), PTCH1 (2/46, 4.3%) and PIK3CA (2/46, 4.3%). There was no significant association between molecular and patients’ clinicopathological features. Applying an evolutionary action score of p53 (EAp53), we observed that 14 (35.9%) TP53 mutations were classified as high-risk, yet no association with overall survival was observed. Concluding, this the largest mutation profile of Brazilian ESCC patients, which helps in the elucidation of the major cancer-related genes in this population.
Prognostic value of epidermal growth factor receptors in gastric cancer: a survival analysis by Weibull model incorporating long-term survivors
Background There is no consensus about the prognostic role of HER2 expression and that of other members of the EGFR family in gastric cancer patients. The aim of this study was to evaluate the prognostic value of the EGFR family in gastric cancer. Methods This retrospective study included 201 patients with gastric and esophagogastric junction adenocarcinoma stages 0–IV (AJCC 6th edition) who underwent primary tumor resection. Tissues from primary tumors were analyzed by tissue microarray technology and immunohistochemistry. Correlations between receptor expression and clinicopathological characteristics were performed according to the chi-square test. Survival analysis was calculated according to the Weibull model with a mixture model incorporating long-term survivors. Multivariate analysis of prognostic factors was performed by a regression model incorporating long-term survivors with the Weibull distribution. Results Membrane expression of HER1, HER2, and HER4 were 9, 17, and 15 %, respectively. No membrane expression of HER3 was observed. Cytoplasmic expression of HER1, HER3, and HER4 were 45, 62, and 24 %, respectively. HER2 and HER3 expression were correlated ( p  < 0.001) and associated with intestinal-type histology ( p  = 0.001 and p  < 0.001, respectively) and advanced age ( p  = 0.011 and p  = 0.008, respectively). According to a regression model adjusted for age, surgical radicality, surgical modality, Laurén histology, adjuvant therapy, TNM stage, and receptor expressions, only TNM stage showed prognostic influence. Conclusions According to analysis by a parametric model, the EGFR family did not have prognostic influence in the gastric cancer population studied. The data presented showed a correlation between HER2 and HER3 expression, which might suggest a potential role for HER2–HER3 heterodimerization inhibitors.
Effect of adjuvant chemoradiotherapy on overall survival of gastric cancer patients submitted to D2 lymphadenectomy
Background Adjuvant chemoradiotherapy (CRT) is the standard treatment in Western countries for gastric cancer patients submitted to curative resection. However, the role of adjuvant CRT in gastric cancer treated with D2 lymphadenectomy has not been well defined. Methods We conducted a retrospective study in patients with stage II to IV gastric adenocarcinoma with no distant metastases, who underwent curative resection with D2 lymphadenectomy between January 2002 and December 2007. The present study compared the 3-year overall survival of two treatments (adjuvant CRT according to the INT 0116 trial versus resection alone). Survival curves were estimated by the Kaplan–Meier method and compared with a log-rank test. Multivariate analysis of prognostic factors was performed by the Cox proportional hazards model. Results A total of 185 patients were included, 104 patients (56 %) received adjuvant CRT and 81 received resection alone. The 3-year overall survival was 64.4 % in the CRT group and 61.7 % in the resection-alone group ( p : 0.415). However, according to the Cox proportional hazards model, adjuvant CRT was a prognostic factor for 3-year overall survival (hazard ratio [HR] 0.46, 95 % confidence interval [CI] 0.26–0.82, p : 0.008). Conclusions In the present study, adjuvant CRT was associated with a lower risk of death over a 3-year period in gastric cancer patients treated with D2 lymphadenectomy.
Robotic left lateral sectionectomy as stepwise approach for cirrhotic liver
Laparoscopy is considered the gold standard approach to perform left lateral sectionectomy (LLS). Furthermore, laparoscopy for cirrhotic patients can reduce intraoperative bleeding and postoperative morbidity when compared to open surgery. Although robotic surgery is feasible for both minor and major liver resections, it remains a work in progress and only few series reported this approach for cirrhotic patients. We reported two cases of 62-year-old men, both with hepatitis C virus and alcoholic cirrhosis, but with compensated liver functions (MELD 9–10 and Child–Pugh A5–A6). The patients were diagnosed with a single lesion in the left lobe. Robotic LLS was performed using intraoperative ultrasound to confirm findings of pre-operative image, and linear staplers were used to control left lobe inflow and outflow. The specimens were removed through Pfannenstiel incision in both patients. Both procedures followed the same standardization. The total operative time was 250 and 151 min with estimated blood loss of 100 and 70 ml, respectively, for cases 1 and 2. The procedures were made without Pringle maneuver and postoperative course was uneventful with hospital discharge at third and fourth postoperative day, respectively. The pathology examination confirmed a 2.5- and 4.5-cm hepatocellular carcinoma, respectively; both presented negative margins and cirrhosis. Robotic LLS seems to be as feasible as conventional laparoscopic approach as a stepwise procedure in a robotic learning curve for liver resection. Its benefits can also be offered to selected cirrhotic patients.