The human epidermal growth factor receptor (HER) family consists of four members: ErbB-1 (HER1), ErbB-2 (HER2), ErbB-3 (HER3), and ErbB-4 (HER4). These receptors activate numerous downstream pathways ...in response to extracellular ligands, regulating diverse processes that include differentiation, migration, proliferation, and survival. Alterations in these genes play a role in the development and progression of many human cancers. In gastric carcinomas (GCs), expression of HER1 and HER2 is thought to be a prognostic factor and target of novel biologic agents. The effect of HER3 or HER4 expression in GC has not been sufficiently studied. In this study, we explored the gene and protein expression of the HER family in GC to establish new potential prognostic factors.
Immunohistochemistry and fluorescence in situ hybridization were performed in 221 patients with GC using tissue microarray. Correlation between the expression or amplification of HER genes and the clinicopathologic parameters was statistically analyzed.
Alterations of members of the HER family were significantly associated with the parameters involved in tumor progression, including depth of tumor invasion, involved lymph nodes, and tumor stage. In addition, HER2 amplification and HER3 expression were significantly related to worse survival.
These results reveal that all members of the HER family are expressed in GC. Furthermore, expression of HER2 and HER3 is a significant predictor of poor survival in GC. Therefore, the development of HER-targeted agents and agents targeting downstream signaling pathways provides new possibilities in the treatment of GC.
Abstract Background The introduction of minimally invasive pancreatic resection (MIPR) into surgical practice has been slow. The worldwide utilization of MIPR and attitude towards future perspectives ...of MIPR remains unknown. Methods An anonymous survey on MIPR was sent to the members of six international associations of Hepato-Pancreato-Biliary (HPB) surgery. Results The survey was completed by 435 surgeons from 50 countries, with each surgeon performing a median of 22 (IQR 12–40) pancreatic resections annually. Minimally invasive distal pancreatectomy (MIDP) was performed by 345 (79%) surgeons and minimally invasive pancreatoduodenectomy (MIPD) by 124 (29%). The median total personal experience was 20 (IQR 10–50) MIDPs and 12 (IQR 4–40) MIPDs. Current superiority for MIDP was claimed by 304 (70%) and for MIPD by 44 (10%) surgeons. The most frequently mentioned reason for not performing MIDP (54/90 (60%)) and MIPD (193/311 (62%)) was lack of specific training. Most surgeons (394/435 (90%)) would consider participating in an international registry on MIPR. Discussion This worldwide survey showed that most participating HPB surgeons value MIPR as a useful development, especially for MIDP, but the role and implementation of MIPD requires further assessment. Most HPB surgeons would welcome specific training in MIPR and the establishment of an international registry.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract The application of minimally-invasive techniques to major pancreatic resection (MIPR) has occurred steadily, but slowly, over the last two decades. Questions linger regarding its safety, ...efficacy, and broad applicability. On April 20th, 2016, the first International State-of-the-Art Conference on Minimally Invasive Pancreatic Resection convened in Sao Paulo, Brazil in conjunction with the International Hepato-Pancreato-Biliary Association's (IHPBA) 10th World Congress. This report describes the genesis, preparation, execution and output from this seminal event. Major themes explored include: (i) scrutiny of best-level evidence outcomes of both MIPR Distal Pancreatectomy (DP) and pancreatoduodenectomy (PD), (ii) Cost/Value/Quality of Life assessment of MIPR, (iii) topics in training, education and credentialing, and (iv) development of best approaches to analyze results of MIPR – including clinical trial design and registry development. Results of a worldwide survey of over 400 surgeons on the practice of MIPR were presented. The proceedings of this event serve as a platform for understanding the role of MIPR in pancreatic resection. Data and concepts presented at this meeting form the basis for further study, application and dissemination of MIPR.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
AIM:To report experience with liver resection in a select group of patients with postoperative biliary stricture associated with vascular injury.METHODS:From a prospective database of patients ...treated for benign biliary strictures at our hospital,cases that underwent liver resections were reviewed.All cases were referred after one or more attempts to repair bile duct injuries following cholecystectomy(open or laparoscopic).Liver resection was indicated in patients with Strasberg E3/E4(hilar stricture)bile duct lesions associated with vascular damage(arterial and/or portal),ipsilateral liver atrophy/abscess,recurrent attacks of cholangitis,and failure of previous hepaticojejunostomy.RESULTS:Of 148 patients treated for benign biliary strictures,nine(6.1%)underwent liver resection;eight women and one man with a mean age of 38.6 years.Six patients had previously been submitted to open cholecystectomy and three to laparoscopic surgery.The mean number of surgical procedures before definitive treatment was 2.4.All patients had Strasberg E3/E4injuries,and vascular injury was present in all cases.Eight patients underwent right hepatectomy and one underwent left lateral sectionectomy without mortality.Mean time of follow up was 69.1 mo and after longterm follow up,eight patients are asymptomatic.CONCLUSION:Liver resection is a good therapeutic option for patients with complex postoperative biliary stricture and vascular injury presenting with liver atrophy/abscess in which previous hepaticojejunostomy has failed.
Abstract Background There is a growing body of literature pertaining to minimally invasive pancreatic resection (MIPR). Heterogeneity in MIPR terminology, leads to confusion and inconsistency. The ...Organizing Committee of the State of the Art Conference on MIPR collaborated to standardize MIPR terminology. Methods After formal literature review for “minimally invasive pancreatic surgery” term, key terminology elements were identified. A questionnaire was created assessing the type of resection, the approach, completion, and conversion. Delphi process was used to identify the level of agreement among the experts. Results A systematic terminology template was developed based on combining the approach and resection taking into account the completion . For a solitary approach the term should combine “approach + resection” ( e.g . “laparoscopic pancreatoduodenectomy); for combined approaches the term must combine “first approach + resection” with “second approach + reconstruction” ( e.g. “laparoscopic central pancreatectomy” with “open pancreaticojejunostomy”) and where conversion has resulted the recommended term is “first approach” + “converted to” + “second approach” + “resection” ( e.g. “robot-assisted” “converted to open” “pancreatoduodenectomy”) Conclusions The guidelines presented are geared towards standardizing terminology for MIPR, establishing a basis for comparative analyses and registries and allow incorporating future surgical and technological advances in MIPR.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
AIM： To determine the incidence of Epstein Barr virus associated gastric carcinoma （GC） in Brazil and compare the expressions of apoptosis related proteins and nitric oxide synthases between EBV ...positive and negative gastric carcinoma. METHODS： In situ hybridization of EBV-encoded small RNA-1 （EBER-1） and PCR was performed to identify the presence of EBV in GCs. Immunohistochemistry was used to identify expressions of bcl-2, bcl-xl, bak, bax, p53, NOS-1, NOS-2, and NOS-3 proteins in 25 EBV positive GCs and in 103 EBV negative GCS. RESULTS： 12% of the cases of GC （25/208） showed EBER-1 and EBNA-1 expression. The cases were preferentially of diffuse type with intense lymphoid infiltrate in the stroma. EBV associated GCs showed higher expression of bcl-2 protein and lower expression of bak protein than in EBV negative GCs. Indeed, expressions of NOS-1 and NOS-3 were frequently observed in EBV associated GCs. CONCLUSION： Our data suggest that EBV infection may protect tumor cells from apoptosis, giving them the capacity for permanent cell cycling and proliferation. In addition, EBV positive GCs show high expression of constitutive NOS that could influence tumor progression and aggressiveness.
The diagnosis of benign hepatic tumors as hepatic adenoma (HA) and focal nodular hyperplasia (FNH) remains a challenge for clinicians and surgeons. The importance of differentiating between these ...lesions is based on the fact that HA must be surgically resected and FNH can be only observed. A series of 23 female patients with benign liver tumors (13 FNH, 10 HA) were evaluated, and a radiologic diagnostic algorithm was employed with the aim of establishing preoperative criteria for the differential diagnosis. All patients were submitted to surgical biopsy or hepatic resection to confirm the diagnosis. Based only on clinical and laboratory data, distinction was not possible. According to the investigative algorithm, the diagnosis was correct in 82.6% of the cases; but even with the development of imaging methods, which were used in combination, the differentiation was not possible in four patients. For FNH cases scintigraphy presented a sensitivity of 38.4% and specificity of 100%, whereas for HA the sensitivity reached 60% and specificity 85.7%. Magnetic resonance imaging, employed when scintigraphic findings were not typical, presented sensitivities of 71.4% and 80% and specificities of 100% and 100% for FNH and HA, respectively. Preoperative diagnosis of FNH was possible in 10 of 13 (76.9%) patients and was confirmed by histology in all of them. In one case, FNH was misdiagnosed as HA. The diagnosis of HA was possible in 9 of 10 (90%) adenoma cases. Surgical biopsy remains the best method for the differential diagnosis between HA and FNH and must be performed in all doubtful cases. Surgical resection is the treatment of choice for all patients with adenoma and can be performed safely. With the evolution of imaging methods it seems that the preoperative diagnosis of FNH may be considered reliable, thereby avoiding unnecessary surgical resection.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Background Increased incorporation of minimally invasive pancreatic resections (MIPR) has emerged into hepato-pancreato-biliary practice, however, no standardization exists for its safe ...adoption. Novel strategies are presented for dissemination of safe MIPR. Methods An international State-of-the-Art conference evaluating multiple aspects of MIPR was conducted by a panel of pancreas experts in Sao Paulo, Brazil on April 20, 2016. Training and education issues were discussed regarding the introduction of novel strategies for safe dissemination of MIPR. Results The low volume of pancreatic resections per institution poses a challenge for surgeons to overcome their MIPR learning curve without deliberate training. A mastery-based simulation and biotissue curriculum can improve technical proficiency and allow for training of surgeons before the operating room. Video-based platforms allow for performance reporting and feedback necessary for coaching and surgical quality improvement. Centers of excellence with training involving a standardized approach and proctorship are important concepts that can be utilized in various formats internationally. Discussion Surgical volume is not sufficient to ensure quality and patient safety in MIPR. Safe adoption of these complex procedures should consider innovative mastery-based training outside of the operating room, novel video based coaching techniques and prospective reporting of patient data and outcomes using standardized definitions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Gastric adenocarcinoma is rare in children and adolescents, with about 17 cases under age 21 in the world's literature. We report a case of invasive well-differentiated metastatic gastric cancer in a ...Brazilian 12-year-old boy without documented familial history of cancer.
The patient, diagnosed with metastatic disease, died seven months after surgery. DNA from intra-surgical specimens revealed a TP53 mutation at codon 337 (p.R337H) in samples with neoplastic cells (dysplasia, tumor and metastasis) but not in non-transformed cells (incomplete intestinal metaplasia and non-involved celiac lymph node). In all mutation-positive tissues, p.R337H occurred on the same background, a founder allele identified by a specific haplotype previously described in Brazilian Li-Fraumeni syndrome patients. The same mutant haplotype, corresponding to a founder mutation present in 0.3% of the general population in Southern Brazil, was found in the genome of the father. Presence of this inherited haplotype in the tumor as well as in the father's germline, suggests a rare case of microchimerism in this patient, who may have harbored a small number of mutant cells originating in another individual, perhaps a dizygotic twin that died early in gestation.
This case represents one of the earliest ages at diagnosis of gastric cancer ever reported. It shows that cancer inheritance can occur in the absence of an obvious germline mutation, calling for caution in assessing early cancers in populations with common founder mutations such as p.R337H in Southern Brazil.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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