Publications by authors named "Durval R Wohnrath"

9 Publications

  • Page 1 of 1

Profile of esophageal squamous cell carcinoma mutations in Brazilian patients.

Sci Rep 2021 10 18;11(1):20596. Epub 2021 Oct 18.

Molecular Oncology Research Center, Barretos Cancer Hospital, Antenor Duarte Villela, 1331, Barretos, São Paulo, 14784 400, Brazil.

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.
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http://dx.doi.org/10.1038/s41598-021-00208-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523676PMC
October 2021

BRAZILIAN GASTRIC CANCER ASSOCIATION GUIDELINES (PART 2): UPDATE ON TREATMENT.

Arq Bras Cir Dig 2021 14;34(1):e1563. Epub 2021 May 14.

Hospital das Clinicas HCFMUSP, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil.

Background: : The II Brazilian Consensus on Gastric Cancer of the Brazilian Gastric Cancer Association BGCA (Part 1) was recently published. On this occasion, countless specialists working in the treatment of this disease expressed their opinion in the face of the statements presented.

Aim: : To present the BGCA Guidelines (Part 2) regarding indications for surgical treatment, operative techniques, extension of resection and multimodal treatment.

Methods: To formulate these guidelines, the authors carried out an extensive and current review regarding each declaration present in the II Consensus, using the Medline/PubMed, Cochrane Library and SciELO databases initially with the following descriptors: gastric cancer, gastrectomy, lymphadenectomy, multimodal treatment. In addition, each statement was classified according to the level of evidence and degree of recommendation.

Results: : Of the 43 statements present in this study, 11 (25,6%) were classified with level of evidence A, 20 (46,5%) B and 12 (27,9%) C. Regarding the degree of recommendation, 18 (41,9%) statements obtained grade of recommendation 1, 14 (32,6%) 2a, 10 (23,3%) 2b e one (2,3%) 3.

Conclusion: : The guidelines complement of the guidelines presented here allows surgeons and oncologists who work to combat gastric cancer to offer the best possible treatment, according to the local conditions available.
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http://dx.doi.org/10.1590/0102-672020210001e1563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121052PMC
May 2021

BRAZILIAN GASTRIC CANCER ASSOCIATION GUIDELINES (PART 1): AN UPDATE ON DIAGNOSIS, STAGING, ENDOSCOPIC TREATMENT AND FOLLOW-UP.

Arq Bras Cir Dig 2020 18;33(3):e1535. Epub 2020 Dec 18.

Hospital das Clinicas HCFMUSP, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil.

Background: The II Brazilian Consensus on Gastric Cancer by the Brazilian Gastric Cancer Association (ABCG) was recently published. On this occasion, several experts in gastric cancer expressed their opinion before the statements presented.

Aim: To present the ABCG Guidelines (part 1) regarding the diagnosis, staging, endoscopic treatment and follow-up of gastric cancer patients.

Methods: To forge these Guidelines, the authors carried out an extensive and current review regarding each statement present in the II Consensus, using the Medline/PubMed, Cochrane Library and SciELO databases with the following descriptors: gastric cancer, staging, endoscopic treatment and follow-up. In addition, each statement was classified according to the level of evidence and degree of recommendation.

Results: Of the 24 statements, two (8.3%) were classified with level of evidence A, 11 (45.8%) with B and 11 (45.8%) with C. As for the degree of recommendation, six (25%) statements obtained grade of recommendation 1, nine (37.5%) recommendation 2a, six (25%) 2b and three (12.5%) grade 3.

Conclusion: The guidelines presented here are intended to assist professionals working in the fight against gastric cancer with relevant and current information, granting them to be applied in the daily medical practice.
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http://dx.doi.org/10.1590/0102-672020200003e1535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747489PMC
December 2020

Positive node-ratio in curative-intent treatment for gastric cancer is a strong independent prognostic factor for 5-year overall survival.

J Surg Oncol 2020 Apr 5;121(5):777-783. Epub 2019 Nov 5.

Department of Upper Gastrointestinal and Hepato-Pancreato-Billiary Surgery, Barretos Cancer Hospital, Barretos, SP, Brazil.

Introduction: This study addressed whether the positive node-ratio (N-ratio) for patients who underwent curative-intent treatment was an independent prognostic factor of overall survival (OS) for gastric adenocarcinoma (GA).

Methods: Consecutive patients who underwent gastrectomy for GA with at least 15 harvested nodes were evaluated for 5-year OS. The best threshold was determined using the area under an receiver operating characteristic (ROC) curve. Univariate and multivariate models were assessed looking for independent prognostic factors for OS.

Results: From 1994 to 2015, 398 consecutive patients were evaluated. The N-ratio ≥11% had an accuracy of 0.764, the sensitivity of 71.1%, the specificity of 81.7%, positive predictive value (PPV) of 91.7%, and odds ratio (OR) of 11. After multivariate analysis for OS, age ≥70 years (HR 1.44), need for total gastrectomy (HR 1.45), need for extended resection (HR 1.7), and N-ratio ≥11% (HR 3.7) were unfavorable prognostic factors. D2 lymphadenectomy (HR 0.53) was a protective factor. The median OS according to N-ratio was 14 months for N-ratio >11 vs 58 months for N-ratio <11%.

Conclusion: The N-ratio ≥11% was an independent negative prognostic factor for patients who underwent treatment for GA with curative intent. The N-ratio ≥11% presented high specificity, high PPV and high OR for risk of death for 5 years after surgery.
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http://dx.doi.org/10.1002/jso.25755DOI Listing
April 2020

Robotic Surgery as an Alternative Approach for Reoperation of Incidental Gallbladder Cancer.

J Gastrointest Cancer 2020 Mar;51(1):332-334

Department of Upper Gastrointestinal and Hepato-pancreato-biliary Surgery, Barretos Cancer Hospital, Rua Antenor Duarte Villela, 1331, Barretos, SP, 14784-400, Brazil.

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http://dx.doi.org/10.1007/s12029-019-00264-3DOI Listing
March 2020

D2 lymphadenectomy for gastric cancer as an independent prognostic factor of 10-year overall survival.

Eur J Surg Oncol 2019 03 30;45(3):446-453. Epub 2018 Oct 30.

Department of Upper Gastrointestinal and Hepato-pancreato-biliary Surgery, Barretos Cancer Hospital, Barretos, SP, Brazil; IRCAD (Research Institute Against Cancer of the Digestive System) Latin America, Barretos, SP, Brazil; Department of Digestive Surgery, Escola Paulista de Medicina - UNIFESP, São Paulo, SP, Brazil. Electronic address:

Background: The extension of lymphadenectomy for GA remains on debate even after Eastern and Western clinical trials. The main concern is if morbidity of extended lymphadenectomy could be justified based on benefits in oncologic outcomes. This study addressed the extension of lymphadenectomy as a prognostic factor of overall survival (OS) for gastric adenocarcinoma (GA).

Methods: Consecutive patients who underwent gastrectomy for GA were retrospectively evaluated. Univariate and multivariate models assessed determinants of OS.

Results: From 1994 to 2015, 656 consecutive patients who underwent gastrectomy were evaluated. Briefly, 455 (69.4%) were male, 397 (60.5%) underwent total gastrectomy, Roux-en-Y reconstruction was done in 483 (73.6%), and R0 resection was achieved in 632 patients (96.3%). According to multivariate analysis, the risk of death was increased with older age (≥70-y), high-grade tumors, lesions ≥ 5 cm, positive nodes ≥ 3, and extra-gastric resections. Otherwise, D2 lymphadenectomy improved median OS (37 versus 16 months), 3-y (51.1 versus 32.2%), 5-y (43.2 versus 26), and 10-y OS (30.6 versus 9.4%), with HR of 0.48 (95% CI 0.34-0.67, p < 0.001). The general median OS was 31 months and 3-, 5-, and 10-y were 47.6, 40, and 27%, respectively. The median follow-up for all patients was 26 months, and for survivors was 65 months.

Conclusion: This study showed D2 lymphadenectomy for GA as an independent prognostic factor for OS, even after 5-y and until 10-y. Our study suggests that D2 should be offered as the curative-intent treatment for all patients with GA that fit to undergo surgery.
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http://dx.doi.org/10.1016/j.ejso.2018.10.538DOI Listing
March 2019

Robotic left lateral sectionectomy as stepwise approach for cirrhotic liver.

J Robot Surg 2018 Sep 21;12(3):549-552. Epub 2017 Jul 21.

Department of Upper Gastrointestinal and Hepato-pancreato-biliary Surgery, Barretos Cancer Hospital, Rua Antenor Duarte Villela, 1331, Barretos, SP, CEP 14784-400, Brazil.

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.
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http://dx.doi.org/10.1007/s11701-017-0730-0DOI Listing
September 2018

Prognostic value of epidermal growth factor receptors in gastric cancer: a survival analysis by Weibull model incorporating long-term survivors.

Gastric Cancer 2014 Jan 28;17(1):76-86. Epub 2013 Feb 28.

Department of Medical Oncology, Barretos Cancer Hospital, Str. Antenor Duarte Villela, 1331, Barretos, SP, 14784-400, Brazil,

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.
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http://dx.doi.org/10.1007/s10120-013-0236-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3889290PMC
January 2014

Effect of adjuvant chemoradiotherapy on overall survival of gastric cancer patients submitted to D2 lymphadenectomy.

Gastric Cancer 2013 Apr 29;16(2):233-8. Epub 2012 Jun 29.

Department of Gastrointestinal Medical Oncology, Barretos Cancer Hospital, Str Antenor Duarte Villela 1331, Barretos, SP, 14784-400, Brazil.

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.
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http://dx.doi.org/10.1007/s10120-012-0171-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627041PMC
April 2013
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