Standardizing terminology for minimally invasive pancreatic resection.

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.

Worldwide survey on opinions and use of minimally invasive pancreatic resection.

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.

Proceedings of the first international state-of-the-art conference on minimally-invasive pancreatic resection (MIPR).

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.

Liver resection for the treatment of post-cholecystectomy biliary stricture with vascular injury.

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/E4 injuries, 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 long-term 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.

Adjuvant chemoradiotherapy after d2-lymphadenectomy for gastric cancer: the role of n-ratio in patient selection. results of a single cancer center.

BACKGROUND: Adjuvant chemoradiotherapy is part of a multimodality treatment approach in order to improve survival outcomes after surgery for gastric cancer. The aims of this study are to describe the results of gastrectomy and adjuvant chemoradiotherapy in patients treated in a single institution, and to identify prognostic factors that could determine which individuals would benefit from this treatment. METHODS: This retrospective study included patients with pathologically confirmed gastric adenocarcinoma who underwent surgical treatment with curative intent in a single cancer center in Brazil, between 1998 and 2008. Among 327 patients treated in this period, 142 were selected. Exclusion criteria were distant metastatic disease (M1), T1N0 tumors, different multimodality treatments and tumors of the gastric stump. Another 10 individuals were lost to follow-up and there were 3 postoperative deaths. The role of several clinical and pathological variables as prognostic factors was determined. RESULTS: D2-lymphadenectomy was performed in 90.8% of the patients, who had 5-year overall and disease-free survival of 58.9% and 55.7%. The interaction of N-category and N-ratio, extended resection and perineural invasion were independent prognostic factors for overall and disease-free survival. Adjuvant chemoradiotherapy was not associated with a significant improvement in survival. Patients with node-positive disease had improved survival with adjuvant chemoradiotherapy, especially when we grouped patients with N1 and N2 tumors and a higher N-ratio. These individuals had worse disease-free (30.3% vs. 48.9%) and overall survival (30.9% vs. 71.4%). CONCLUSION: N-category and N-ratio interaction, perineural invasion and extended resections were prognostic factors for survival in gastric cancer patients treated with D2-lymphadenectomy, but adjuvant chemoradiotherapy was not. There may be some benefit with this treatment in patients with node-positive disease and higher N-ratio.

TP53 mutation p.R337H in gastric cancer tissues of a 12-year-old male child: evidence for chimerism involving a common mutant founder haplotype: case report.

BACKGROUND: 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. CASE PRESENTATION: 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. CONCLUSION: 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.

Prognostic implications of altered human epidermal growth factor receptors (HERs) in gastric carcinomas: HER2 and HER3 are predictors of poor outcome.

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Ileal loop interposition: an alternative biliary bypass technique.

BACKGROUND: Obstructive jaundice is a common condition in advanced digestive cancer. Palliative procedures can improve quality of life and allow patients to attempt a systemic treatment. Bilioenteric anastomosis is still the procedure of choice for patients in many centers. When a surgical bypass is not possible, biliary drainage can be done by placing endoscopic or transparietal stents, which are less durable methods even when an expandable stent is employed. METHODS: A 47-year-old male with an excellent clinical status and a previous cholecystectomy and an exploratory laparotomy for advanced gastric cancer was referred with obstructive jaundice. A preoperative CT scan showed a dilated bile duct and a small mass at the distal hepatic hilum. No other signs of metastasis were found. A surgical bilioenteric anastomosis was indicated. At surgery, a distal choledochal obstruction and a mesenteric retraction by a lymph node mass prevented the jejunum to ascend for a bilioenteric anastomosis. Surgically, an alternative bilioenteric bypass was performed by means of an ileal loop interposition between the bile duct and the jejunum. RESULT: The recovery of the patient was uneventful and his bilirubin levels normalized after one week. The patient was then referred for systemic chemotherapy. CONCLUSIONS: This alternative biliary bypass can be safely and easily performed, and may be a good alternative for patients already referred for surgery because of a better life expectancy and when the jejunum is not an alternative.

Cadherin-catenin adhesion system and mucin expression: a comparison between young and older patients with gastric carcinoma.

BACKGROUND: Young patients are thought to develop gastric carcinomas with a molecular genetic profile that is distinct from that of gastric carcinomas occurring at a later age. The aim of this study was to compare the clinicopathological features and expression patterns of the markers E-cadherin and beta-catenin, and mucins (MUC1, MUC2, MUC5AC, and MUC6) in young and older patients. METHODS: The clinicopathological features and overall survival data of 62 young patients (age 40 years). A tissue microarray method and immunohistochemistry were used in order to analyze marker expression in paraffin-embedded tissue blocks obtained from both groups. RESULTS: The young group presented a higher percentage of diffuse-type tumors in comparison to the older group (P<0.01). The rates of positivity for E-cadherin and beta-catenin membranous expression patterns and mucin (MUC2, MUC5AC and MUC6) positivity were higher in the young group (P<0.01). Although young patients showed a lower frequency of alterations in marker expression and had significantly better survival rates than the older patients, neither age nor the marker expression pattern were found to be independent prognostic factors of survival. Only stage, tumor size, and tumor location persisted as prognostic factors for patients with gastric cancer. CONCLUSION: Biological markers of cellular adhesion and gastric differentiation were differently expressed in young and older patients. Our findings support the hypothesis that young patients develop carcinomas with a different genetic pathway compared to the pathway of tumors occurring at a later age, and we suggest further investigations to assess the prognostic relevance of the markers to specific subgroups.

Synchronous adenocarcinoma of the major and minor duodenal papilla.

A 50-year-old woman presented with pancreatitis, fluctuant jaundice, weight loss, and abdominal pain. Contrast-enhanced computed tomography and abdominal ultrasound showed slight dilatation of the biliary tree and gallbladder without calculi. Endoscopy demonstrated a tumor protruding from the papilla of Vater. First endoscopically biopsy diagnosed no tumor, and a second biopsy diagnosed as papillary adenocarcinoma. The patient underwent duodenopancreatectomy. The specimen was fixed in formalin (10%). The tissue was processed routinely, and paraffin sections were stained with hematoxylin-eosin and periodic acid Schiff. Gross examination showed two tumors seen as prolapsed nodules growing isolated from the minor and major duodenal papillae measuring 1.5 and 1.0 cm, respectively, both covered by duodenal mucosa and the histologic study of both lesions demonstrated a moderately differentiated tubular adenocarcinoma, which invaded duodenal wall. After surgery, she is alive 24 months without evidence of recurrence.

Differential expression of apoptosis related proteins and nitric oxide synthases in Epstein Barr associated gastric carcinomas.

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.

[Laparoscopic distal pancreatectomy for pancreatic cystadenomas]. / Pancreatectomia distal videolaparoscópica em pacientes com cistadenoma de pâncreas.

BACKGROUND: Cystic neoplasms are an uncommon group among pancreatic tumors. These lesions are seen more frequently in recent surgical practice, probably because of advances in diagnostic and surgical techniques. Total tumor resection provides the best chance of cure and may remove the risk of malignant transformation of the cystadenomas, particularly of the mucinous type. Minimally invasive techniques have been revolutionary and provide clinical evidence of decreased morbidity and comparable efficacy to traditional, open surgery. However, laparoscopic pancreatic resection is not an established treatment for tumors of the pancreas. AIM: The authors present their initial experience with laparoscopic distal pancreatectomy for pancreatic cystadenomas. MATERIAL AND METHODS: Three female patients (mean age, 55 years) underwent laparoscopic pancreatic resection between September 2001 and December 2003. RESULTS: Laparoscopic pancreatic resection was successfully performed in all patients. Operative time varied between 4 and 6 hours. Intraoperative bleeding was minimal. Due to a thick pancreas, the application of vascular endoscopic stapler was difficult in one patient. Two patients presented postoperative pancreatic leakage with spontaneous resolution. CONCLUSIONS: Resection of the pancreas can be safely performed via the laparoscopic approach with all the potential benefits to the patients of minimally invasive surgery.

Pancreatectomia distal videolaparoscópica em pacientes com cistadenoma de pâncreas / Laparoscopic distal pancreatectomy for pancreatic cystadenomas

RACIONAL: O diagnóstico de tumores císticos do pâncreas vem aumentando nos últimos anos. Estes tumores acometem geralmente pacientes do sexo feminino e apresentam poucos sintomas. Sua remoção por videolaparoscopia está indicada em pacientes selecionadas, principalmente quando localizados na região distal do pâncreas. OBJETIVOS: É apresentada a experiência inicial de um grupo de cirurgiões na realização de pancreatectomia distal por videolaparoscopia em pacientes com cistadenoma pancreático. MATERIAL E MÉTODOS: Três pacientes do sexo feminino (idade média, 55 anos) foram submetidas a ressecção pancreática por videolaparoscopia entre setembro de 2001 e dezembro de 2003. RESULTADOS: A ressecção pancreática por videolaparoscopia foi realizada com sucesso nas três doentes. O tempo cirúrgico variou de 4 a 6 horas. O sangramento operatório foi mínimo em todos os casos. A aplicação do grampeador endoscópico foi difícil em uma paciente devido à espessura do pâncreas. As três pacientes evoluíram bem, recebendo alta entre o 2° e o 5° dia pós-operatório. Duas apresentaram fístula pancreática com resolução após tratamento conservador. CONCLUSÃO: A pancreatectomia laparoscópica é factível, pode trazer benefícios aos pacientes portadores de neoplasia cística da porção distal do pâncreas, com pouca dor pós-operatória, curto tempo de permanência hospitalar, baixo índice de complicações e melhor resultado estético.

Non-Oriental primary intrahepatic lithiasis: experience with 48 cases.

An experience with the diagnosis and treatment of patients with non-Oriental primary intrahepatic lithiasis (PIHL) is described. A group of 48 native Brazilian patients with symptomatic PIHL were studied, and the patients' characteristics, diagnoses, treatment protocols based on the presentation of the disease, prognostic factors, and late results were analyzed. Liver resection was performed in patients with an irreversible lesion, such as parenchymal atrophy or biliary stenosis; and biliary drainage procedures were employed in patients with bilateral disease. Late results were considered good when no postoperative symptoms were observed and poor if there was pain recurrence or cholangitis. Overall good results were observed in 73.4% of the patients. Good late results were observed in 94.1% and 62.1% of the patients with unilateral and bilateral stones, respectively. None of the analyzed parameters (gender, age, previous biliary surgery, bilirubin level, serum leukocyte counts, prothrombin activity, previous history of cholangitis, stone location) predicted poor late results, but the risk for patients with bilateral stones to develop late complications was 7.2 times higher than for those with unilateral disease. Non-Oriental PIHL is a rare disease, and the patients' characteristics are similar to those of patients with Oriental PIHL. We believe that personalized treatment based on the presentation of the disease led to the high incidence of good late results in this series.

A new test to avoid arterial complications during pancreaticoduodenectomy.

Celiac trunk or superior mesenteric artery stenosis are usually innocuous conditions. In such patients, arterial blood supply to the stomach, spleen, liver and bowel is sustained through extraordinarily well-developed pathways through the pancreas. If division of these collateral vessels is necessary during a surgical procedure such as pancreaticoduodenectomy, life-threatening celiac organ or bowel ischemia may occur. The authors describe a new test, using pancreatic inflow occlusion, to reliably identify celiac trunk or superior mesentery artery stenosis. The authors describe two cases of celiac axis occlusion and one case of superior mesenteric artery stenosis. In all three presented cases the gastroduodenal artery clamping test was negative and ischemia was only noticed after pancreatic section, suggesting that in severe occlusions this test may fail in diagnosing the vascular abnormality. All patients were successfully treated by revascularization with no operative mortality. If the diagnosis is unsuspected and in cases where appropriate angiographic studies have not been obtained before pancreatic resection, a test occlusion of the gastroduodenal artery should always precede its ligation. However, this test may not be effective in all cases and in instances where high suspicion of celiac axis or mesenteric stenosis is present, other maneuvers, such as pancreatic inflow test, could be helpful for the diagnosis of these rare and morbid situations.

Exposure of splenic hilum increases safety of laparoscopic splenectomy.

Laparoscopic splenectomy is becoming the gold standard technique for the treatment of hematological disorders of the spleen. Hemostasis is a fundamental step during laparoscopic splenectomy leading some authors to develop several techniques to control splenic vessels such as hand assistance, preoperative splenic artery embolization, and the use of vascular linear staplers. However, intraoperative bleeding is usually due to inadequate exposure of the hilar splenic vessels itself. The authors describe a standardized technique for the exposure of splenic pedicle using an endoscopic triangular retractor. We have been used this technique in 16 consecutive laparoscopic splenectomies with minimal blood loss. The present technique may increase the safety of laparoscopic splenectomy with adequate exposure of the splenic hilum reducing the conversion rate and intraoperative blood loss.

Molecular classifiers for gastric cancer and nonmalignant diseases of the gastric mucosa.

High incidence of gastric cancer-related death is mainly due to diagnosis at an advanced stage in addition to the lack of adequate neoadjuvant therapy. Hence, new tools aimed at early diagnosis would have a positive impact in the outcome of the disease. Using cDNA arrays having 376 genes either identified previously as altered in gastric tumors or known to be altered in human cancer, we determined expression signature of 99 tissue fragments representing normal gastric mucosa, gastritis, intestinal metaplasia, and adenocarcinomas. We first validated the array by identifying molecular markers that are associated with intestinal metaplasia, considered as a transition stage of gastric adenocarcinomas of the intestinal type as well as markers that are associated with diffuse type of gastric adenocarcinomas. Next, we applied Fisher's linear discriminant analysis in an exhaustive search of trios of genes that could be used to build classifiers for class distinction. Many classifiers could distinguish between normal and tumor samples, whereas, for the distinction of gastritis from tumor and for metaplasia from tumor, fewer classifiers were identified. Statistical validations showed that trios that discriminate between normal and tumor samples are powerful classifiers to distinguish between tumor and nontumor samples. More relevant, it was possible to identify samples of intestinal metaplasia that have expression signature resembling that of an adenocarcinoma and can now be used for follow-up of patients to determine their potential as a prognostic test for malignant transformation.

Alternative treatment for gallbladder stones in portal venous thrombosis.

BACKGROUND/AIMS: Cholecystectomy for treatment of gallbladder stones in patients with portal vein thrombosis can be a hazardous procedure. Dissection into an area of thin-walled collateral vessels can trigger troublesome bleeding and consequent blood coagulation disorders. METHODOLOGY: In order to avoid dissection, cholecysto-jejunostomy was used as the treatment of choice in three patients with symptomatic gallbladder stones and portal vein thrombosis. RESULTS: Surgical procedure was uneventful, blood or plasma transfusions were not required either at surgery or afterwards. Pre- and postoperative hematocrit evaluations showed no difference, as well as liver function tests. The procedure was well tolerated and patients were discharged from day 5 to 7. Follow-up ranged from 2 to 3 years, no biliary complications were found during this period. CONCLUSIONS: Choleysto-jejunostomy is a safe procedure and can be used as an effective treatment of symptomatic gallbladder stones in patients with portal vein thrombosis.

Pylorus-preserving pancreatoduodenectomy associated with longitudinal pancreatojejunostomy for treatment of chronic pancreatitis.

Patients with chronic pancreatitis presenting with lesions at the head of the pancreas and in the uncinate process associated with duct dilatation at the body and tail of the gland are inadequately treated by partial pancreatic head resection or by standard pancreatic drainage procedures. A new technique for the surgical treatment of this form of chronic pancreatitis, based on the performance of a pylorus-preserving pancreaticoduodenectomy associated with a longitudinal pancreatojejunostomy, is proposed herein. Nine patients with chronic pancreatitis were operated on according to this technique with no postoperative complications or mortality. Complete symptom control was achieved in all patients. Follow-up periods varied from one month to five years.