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Introduction The only curative treatment for most gastric cancer is radical gastrectomy with D2 lymphadenectomy (LAD). Minimally invasive total gastrectomy (MIG) aims to reduce postoperative morbidity, but its use has not yet been widely established in Western countries. Minimally invasivE versus open total GAstrectomy is the first Western multicentre randomised controlled trial (RCT) to compare postoperative morbidity following MIG vs open total gastrectomy (OG). Methods and analysis This superiority multicentre RCT compares MIG (intervention) to OG (control) for oncological total gastrectomy with D2 or D2+LAD. Recruitment is expected to last for 2 years. Inclusion criteria comprise age between 18 and 84 years and planned total gastrectomy after initial diagnosis of gastric carcinoma. Exclusion criteria include Eastern Co-operative Oncology Group (ECOG) performance status >2, tumours requiring extended gastrectomy or less than total gastrectomy, previous abdominal surgery or extensive adhesions seriously complicating MIG, other active oncological disease, advanced stages (T4 or M1), emergency setting and pregnancy. The sample size was calculated at 80 participants per group. The primary endpoint is 30-day postoperative morbidity as measured by the Comprehensive Complications Index. Secondary endpoints include postoperative morbidity and mortality, adherence to a fast-track protocol and patient-reported quality of life (QoL) scores (QoR-15, EUROQOL EuroQol-5 Dimensions-5 Levels (EQ-5D), EORTC QLQ-C30, EORTC QLQ-STO22, activities of daily living and Body Image Scale). Oncological endpoints include rate of R0 resection, lymph node yield, disease-free survival and overall survival at 60-month follow-up. Ethics and dissemination Ethical approval has been received by the independent Ethics Committee of the Medical Faculty, University of Heidelberg (S-816/2021) and will be received from each responsible ethics committee for each individual participating centre prior to re

Aims Neoadjuvant chemoradiation reduces tumour volume and improves the R0 resection rate, followed by extended survival for patients with advanced oesophageal cancer. The degree of tumour regression has high prognostic relevance. To date, there is still no generally accepted tumour regression grading system. The aim of this study was to compare the prognostic discrimination power of different histological regression grading systems: (i) the fibrosis/tumour ratio within the primary tumour (Mandard classification), (ii) the percentage of residual vital tumour cells (VTC) compared to the original primary tumour (Cologne Regression) and (iii) the ypT category, in patients with cT3 carcinoma of the oesophagus after neoadjuvant chemoradiation. Methods and results This study included 216 patients with oesophageal cancer clinically staged as cT3NxM0 and treated from 2009 to 2012 with standardised chemoradiation followed by oesophagectomy [median age 62 years, 176 (81%) male and 138 (64%) adenocarcinoma patients]. The subgroup frequencies of the three classification systems were ypT category: ypT0 = 18%, ypT1 = 14%, ypT2 = 23%, ypT3 = 44%, ypT4 = 1%; Mandard classification: TRG1 = 18%, TRG2 = 26%, TRG3 = 24%, TRG4 = 30%, TRG5 = 2%; and Cologne Regression Scale: no tumour = 18%, 1-10% VTC = 27%, 10-50% VTC = 26% and >50% VTC = 29%. The Mandard and Cologne Regression classifications showed better prognostic differentiation for the subgroups than the ypT category. The four-tiered Cologne Regression system had a good prognostic relevance. Comparing results of the re-evaluated Cologne Regression classification with the classification by routine pathological report showed very good inter-rater agreement, with kappa value 0.891. Conclusion Compared to the original primary tumour, the tumour regression grading system using the percentage of residual vital tumour has prognostic relevance.

History and findings upon admission A 50-year-old man presented at the emergency unit with abdominal pain in the right lower quadrant and dysuria. He described an increase in pain during micturition. Examinations After multiple examinations (CT-scan, MR-scan, ileocolonoscopy) were performed to no avail, a toothpick was detected in the terminal ileum during an ultrasound scan of the small intestine. Prompted elevation of intra-abdominal pressure led to migration of the radiolucent sharp foreign body into the wall of the urinary bladder, inducing pain. Treatment Median laparotomy revealed a two-sided perforation of the terminal ileumwith ileosigmoidal fistula, which was induced by an ingested toothpick. The patient underwent en-bloc resection of the infectious tumor by segmental ileal resection and sigma resection. Anastomoses were performed as hand-sewn end-to-end ileoileostomy and end-to-end stapled colorectal anastomosis, respectively. Conclusion Ingested foreign bodies and perforation of the gastrointestinal tract by foreign bodies are rare events but may cause serious gut injuries. The ingestion of foreign bodies should be kept in mind as an important differential diagnosis in patients with acute abdomen or chronic abdominal pain of unknown origin, especially in children. Abdominal ultrasound can be a useful diagnostic tool in identifying ingested foreign bodies.

Management of gastroesophageal junction (GEJ) adenocarcinoma is a controversial topic. The rising incidence of this cancer requires a clear consensus to ensure proper management. Application of oncological principles for tumors of the esophagus or stomach is not possible because of comparative differences in the biology of GEJ adenocarcinoma, leading to different therapeutic options. Staging work-up with endoscopy, endosonography, and PET is essential to inform the choice of neoadjuvant treatment and surgical approach to GEJ adenocarcinoma. Surgery remains the only curative treatment and should be undertaken in specialized centers.

Introduction: Esophageal cancer is the eighth most common cancer globally and has the sixth worst prognosis because of its aggressiveness and poor survival. Data regarding cancer treatment in older patients is limited because the elderly have been under-represented in clinical trials. Therefore, we reviewed the existing literature regarding treatment results for elderly patients (70+ years).Areas covered: We used pubmed to analyze the actual literature according to elderly esophageal cancer patients with subheading of incidence, esophagectomy, chemoradiation or chemotherapy. The main points of interest were treatment options for patients with Barrett's esophagus or early carcinoma, advanced tumor stages, and inoperable cancer.Expert opinion: The incidence of esophageal cancer has been increasing over the past thirty years, with a rapid increase of esophageal adenocarcinoma in Western industrialized nations. Patients aged over 60years have been particularly affected. In this review, we have shown that elderly patients with esophageal cancer have various alternatives for adequate treatment. Clinical evaluation of comorbidity is necessary to make treatment decisions. Therapeutic options for early carcinomas are endoscopic or surgical resection. For elderly patients with advanced carcinomas, preoperative chemoradiation or chemotherapy should be discussed.

Background Due to proliferation and increased metabolism, cancer cells have high glucose requirements. The glucose uptake of cells is influenced by a group of membrane proteins denoted the glucose transporter family (Glut-1 to -12). Whereas increased expression and a negative correlation with survival have been described for Glut-1 in several types of cancer, the impact of other glucose transporters on tumor biology is widely unknown. In this retrospective study, gastric cancer specimens of 150 patients who underwent total gastrectomy between 2005 and 2010 were stained for Glut-1, -3, -6, and -10 by immunohistochemistry. Expression of Glut-1, -3, -6, and 10 was correlated to prognosis as well as clinical and pathological parameters. Glut-1, Glut-3, Glut-6, and Glut-10 were expressed in 22.0, 66.0, 38.0, and 43.3 % of the analyzed samples. Whereas Glut-1, -6, and -10 did not show a correlation with prognosis, positive staining for Glut-3 was associated with higher UICC stage and inferior prognosis. The mean overall survival was 38.6 months for Glut-3 positive patients, as compared to 51.2 months for Glut-3 negative patients (p < 0.05). Coexpression of two or more of the analyzed glucose transporters was correlated to inferior prognosis. Glut-3 and UICC stage were significant prognostic factors in multivariate analysis. All of the analyzed glucose transporters were expressed in a significant proportion of the gastric cancer samples. Glut-3 was associated with higher UICC stage and inferior prognosis. These findings are relevant to therapeutic approaches that target glucose metabolism as well as to imaging using radioactively labeled glucose.

Epidemiologically, around 15,500 persons per year contract gastric cancer with continuously decreasing incidence and a 5-year survival rate of only 30% to 35%. Contrary to the Asian countries, there are no prevention programs for gastric cancer in Germany, which leads to the disease frequently being diagnosed in locally advanced stages and predominantly being treated with multimodal therapy concepts. Complete (R0) resection is the therapy of choice for resectable gastric cancer. Special forms of gastric cancer that are limited to the mucosa can be endoscopically resected with a curative intent. Systematic D2 lymphadenectomy (LAD) plays a decisive role in the management of local advanced tumors because it significantly contributes to the reduction of tumor-related death and both local and regional relapse rates. Perioperative chemotherapy improves prognosis in the advanced stages, whereas palliative chemotherapy is normally indicated for metastatic diseases. Standardized resection procedures and the use of individualized multimodal therapy concepts have led to improvement in the 5-year survival rate.

IMPORTANCE Surgical resection has a potential benefit for patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. OBJECTIVE To evaluate outcome in patients with limited metastatic disease who receive chemotherapy first and proceed to surgical resection. DESIGN, SETTING, AND PARTICIPANTS The AIO-FLOT3 (Arbeitsgemeinschaft Internistische Onkologie-fluorouracil, leucovorin, oxaliplatin, and docetaxel) trial is a prospective, phase 2 trial of 252 patients with resectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Patients were enrolled from 52 cancer care centers in Germany between February 1, 2009, and January 31, 2010, and stratified to 1 of 3 groups: resectable (arm A), limited metastatic (arm B), or extensive metastatic (arm C). Data cutoff was January 2012, and the analysis was performed in March 2013. INTERVENTIONS Patients in arm A received 4 preoperative cycles of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) followed by surgery and 4 postoperative cycles. Patients in arm B received at least 4 cycles of neoadjuvant FLOT and proceeded to surgical resection if restaging (using computed tomography and magnetic resonance imaging) showed a chance of margin-free (RO) resection of the primary tumor and at least a macroscopic complete resection of the metastatic lesions. Patients in arm C were offered FLOT chemotherapy and surgery only if required for palliation. Patients received a median (range) of 8 (1-15) cycles of FLOT. MAIN OUTCOMES AND MEASURES The primary end point was overall survival. RESULTS In total, 238 of 252 patients (94.4%) were eligible to participate. The median (range) age of participants was 66 (36-79) years in arm A(n = 51), 63 (28-79) years in arm B (n = 60), and 65 (23-83) years in arm C (n = 127). Patients in arm B (n = 60) had only retroperitoneal lymph node involvement (27 patients [45%]), liver involvement (11 [18.3%]), lung involvement (10 [16.7%]), localized peritoneal invol

Background: Historical data indicate that surgical resection may benefit select patients with metastatic gastric and gastroesophageal junction cancer. However, randomized clinical trials are lacking. The current RENAISSANCE trial addresses the potential benefits of surgical intervention in gastric and gastroesophageal junction cancer with limited metastases. Methods: This is a prospective, multicenter, randomized, investigator-initiated phase III trial. Previously untreated patients with limited metastatic stage (retroperitoneal lymph node metastases only or a maximum of one incurable organ site that is potentially resectable or locally controllable with or without retroperitoneal lymph nodes) receive 4 cycles of FLOT chemotherapy alone or with trastuzumab if Her2+. Patients without disease progression after 4 cycles are randomized 1: 1 to receive additional chemotherapy cycles or surgical resection of primary and metastases followed by subsequent chemotherapy. 271 patients are to be allocated to the trial, of which at least 176 patients will proceed to randomization. The primary endpoint is overall survival; main secondary endpoints are quality of life assessed by EORTC-QLQ-C30 questionnaire, progression free survival and surgical morbidity and mortality. Recruitment has already started; currently (Feb 2017) 22 patients have been enrolled. Discussion: If the RENAISSANCE concept proves to be effective, this could potentially lead to a new standard of therapy. On the contrary, if the outcome is negative, patients with gastric or GEJ cancer and metastases will no longer be considered candidates for surgical intervention.

Presently, there is no scientific evidence supporting a definite role for follow-up after gastrectomy for cancer, and clinical practices are quite different around the globe. The aim of this consensus conference was to present an ideal prototype of follow-up after gastrectomy for cancer, based on shared experiences and taking into account the need to rationalize the diagnostic course without losing the possibility of detecting local recurrence at a potentially curable stage. On June 19-22, 2013 in Verona (Italy), during the 10th International Gastric Cancer Congress (IGCC) of the International Gastric Cancer Association, a consensus meeting was held, concluding a 6-month, Web-based, consensus conference entitled Rationale of oncological follow-up after gastrectomy for cancer. Forty-eight experts, with a geographical distribution reflecting different health cultures worldwide, participated in the consensus conference, and 39 attended the consensus meeting. Six statements were finally approved, displayed in a plenary session and signed by the vast majority of the 10th IGCC participants. These statements are attached as an annex to the Charter Scaligero on Gastric Cancer. After gastrectomy for cancer, oncological follow-up should be offered to patients; it should be tailored to the stage of the disease, mainly based on cross-sectional imaging, and should be discontinued after 5 years.

Esophagectomy with gastric tube reconstruction and extended transhiatal gastrectomy with Roux-en-Y reconstruction are alternative procedures in current therapeutic concepts for adenocarcinoma of the esophagogastric junction (AEG). The impact of these operations on long-term health-related quality of life (HRQL) is incompletely understood. Patients with cancer-free survival of at least 24 months after esophagectomy (ESO) or extended gastrectomy (GAST) for AEG were identified from a prospectively maintained database. EORTC questionnaires were sent out to assess health-related general (QLQ-C30) and cancer-specific (OG-25) quality of life. Numeric scores were calculated for each conceptual area and compared with those of healthy reference populations. 123 patients (ESO n = 71; GAST n = 52) completed the self-rated questionnaires. HRQL was consistently lower in surgical patients (GAST and ESO) compared with healthy reference populations. Also, there was a general trend for a better HRQL in GAST compared with ESO patients. This trend was statistically significant for physical function (p = 0.04), dyspnea (p = 0.02), and reflux (p = 0.03). Subgroup analysis revealed no significant differences between patients with or without prior neoadjuvant therapy. After mid- and long-term follow-up, HRQL after extended gastrectomy with Roux-en-Y reconstruction is superior to that after esophagectomy and gastric tube reconstruction. Improved HRQL after gastrectomy is mainly due to less pulmonary and reflux-related symptoms. Our findings may influence the choice of the surgical strategy for patients with AEG.

Zusammenfassung Nach der durch das Leitlinienprogramm Onkologie geforderten deutschen S3-Leitlinie Palliativmedizin fur Patienten mit einer nicht-heilbaren Krebserkrankung erfordert das haufige Auftreten einer Obstipation bei Palliativpatienten eine konsequente Prophylaxe und Therapie. Als Ursachen der Verstopfung finden sich haufig Immobilitat, ein reduzierter Allgemeinzustand, ein geringer Volumenstatus bzw. eine ballaststoffarme Ernahrung oder auch eine vorbestehende chronische Obstipation. Obstipierende Pharmaka wie z. B. Opioide oder Substanzen mit anticholinergen Eigenschaften stellen weitere wichtige Ursachen dar. Die Diagnose einer Obstipation erfolgt pragmatisch uberwiegend durch subjektive Parameter wie das Gefuhl einer unvollstandigen Entleerung, die Notwendigkeit vermehrten Pressens bzw. stuhlgangabhangige Beschwerden. Objektive Parameter sind eine harte Stuhlkonsistenz bzw. eine verminderte Stuhlmenge und -frequenz. Zur Therapie der Obstipation wird ein standardisiertes stufenformiges Vorgehen mit ausreichender Flussigkeitszufuhr, ballaststoffreicher Ernahrung und Laxanzien empfohlen. Neue prokinetische Substanzen, Sekretagoga oder Opioidantagonisten konnen als Reservemedikamente eingesetzt werden. Abstract According to the German S3-guideline Palliative Medicine' which has been supported by the German Guideline Program in Oncology, constipation in palliative patients requires a consistent prophylaxis and therapy. Constipation is caused by immobilisation, poor health, exsiccosis, a low-fiber diet or a preexisting functional constipation. Further important causes are substances with constipating side effects, such as opioids or anticholinergic drugs. Pragmatically, constipation should be assessed by subjective parameters such as the feeling of incomplete evacuation, straining, or other complaints. Objective parameters are hard stool or reduced number of bowel movements. For the early detection of constipation the amount of the stool mass and the stool fr

Remarkable efficacy of immune checkpoint inhibition has been reported for several types of solid tumors and early studies in gastric adenocarcinoma are promising. A detailed knowledge about the natural biology of immune checkpoints in gastric adenocarcinoma is essential for clinical and translational evaluation of these drugs. This study is a comprehensive analysis of cytotoxic T lymphocyte associated molecule 4 (CTLA-4) and programmed death 1 ligand 1 (PD-L1) expression in gastric adenocarcinoma. PDL1 and CTLA-4 were stained on tumor sections of 127 Caucasian patients with gastric adenocarcinoma by immunohistochemistry (IHC) and somatic mutation profiling was performed using targeted next-generation sequencing. Expression of PD-L1 and CTLA-4 on lymphocytes in tumor sections, tumor-draining lymph nodes (TDLN) and peripheral blood were studied by flow-cytometry and immune-fluorescence microscopy in an additional cohort. PD-L1 and CTLA-4 were expressed in 44.9% (57/ 127) and 86.6% (110/127) of the analyzed gastric adenocarcinoma samples, respectively. Positive tumor cell staining for PD-L1 or CTLA-4 was associated with inferior overall survival. Somatic mutational analysis did not reveal a correlation to expression of PD-L1 or CTLA-4 on tumor cells. Expression of PD-1 (52.2%), PD-L1 (42.2%) and CTLA-4 (1.6%) on tumor infiltrating T cells was significantly elevated compared to peripheral blood. Of note, PD-1 and PD-L1 were expressed far higher by tumor-infiltrating lymphocytes than CTLA-4. In conclusion, specific immune checkpoint-inhibitors should be evaluated in this disease and the combination with molecular targeted therapies might be of benefit. An extensive immune monitoring should accompany these studies to better understand their mode of action in the tumor microenvironment.

Clinical guidelines are essential in implementing and maintaining nationwide stage-specific diagnostic and therapeutic standards. In 2011, the first German expert consensus guideline defined the evidence for diagnosis and treatment of early and locally advanced esophagogastric cancers. Here, we compare this guideline with other national guidelines as well as current literature. The German S3-guideline used an approved development process with de novo literature research, international guideline adaptation, or good clinical practice. Other recent evidence-based national guidelines and current references were compared with German recommendations. In the German S3 and other Western guidelines, adenocarcinomas of the esophagogastric junction (AEG) are classified according to formerly defined AEG I-III subgroups due to the high surgical impact. To stage local disease, computed tomography of the chest and abdomen and endosonography are reinforced. In contrast, laparoscopy is optional for staging. Mucosal cancers (T1a) should be endoscopically resected en-bloc to allow complete histological evaluation of lateral and basal margins. For locally advanced cancers of the stomach or esophagogastric junction (a parts per thousand yenT3N+), preferred treatment is preoperative and postoperative chemotherapy. Preoperative radiochemotherapy is an evidence-based alternative for large AEG type I-II tumors (a parts per thousand yenT3N+). Additionally, some experts recommend treating T2 tumors with a similar approach, mainly because pretherapeutic staging is often considered to be unreliable. The German S3 guideline represents an up-to-date European position with regard to diagnosis, staging, and treatment recommendations for patients with locally advanced esophagogastric cancer. Effects of perioperative chemotherapy versus chemoradiotherapy are still to be investigated for adenocarcinoma of the cardia and the lower esophagus.

Background. The role of glucose transporter 14 (GLUT-14/SLC2A14) in tumor biology is entirely unknown, and the significance of hypoxia inducible factor 1-alpha (HIF1-alpha) for gastric adenocarcinoma is controversial. The impact of GLUT-1/SLC2A1 has never been confirmed in a Caucasian cohort. Methods. Between 1996 and 2007, 124 patients underwent gastrectomy for gastric adenocarcinoma. Tumor sections were incubated with GLUT-1, GLUT-14, and HIF1-alpha antibodies. Expression was analyzed for correlations with histopathology, marker coexpression, and patient survival by uni- and multivariate analyses. Results. Expressions of GLUT-1, GLUT-14, and HIF1-alpha were detectable in 50, 77.4, and 27.1 %, respectively. Expression of GLUT-1 was associated with pT-category (p = 0.019), pN-category (p = 0.019), tubular (WHO, p = 0.008), and intestinal (Lauren classification; p = 0.002) histologic subtypes. Expression of GLUT-14 was correlated with pT category (p = 0.043), whereas HIF1-alpha did not show any correlation with histopathology or survival. The median survival period was 14 months (95 % confidence interval [CI] 9.2-18.8 months) for GLUT-1-positive patients and 55 months (95 % CI 25.8-84.2; p = 0.01) for GLUT-1-negative patients. An inferior prognosis also was seen for GLUT-14-positive cases compared with GLUT-14-negative cases (p = 0.004). Thus, worst survival was seen with both GLUT-1- and GLUT-14-positive expression followed by single-positive and then double-negative cases (p = 0.004). In multivariate analysis including International Union Against Cancer (UICC) stages, R category, Lauren classification, surgery alone versus neoadjuvant/perioperative chemotherapy, and marker expression as covariates, GLUT-1 (p = 0.011) and GLUT-14 (p = 0.025) kept their prognostic independence. Conclusions. The study findings suggest that detection of GLUT-1 and GLUT-14 is of high prognostic value. It gives additional information to UICC stages and identifies patients with inferior p

Background: This review depicts surgical treatment strategies in the management of esophageal cancer under the focus of evidence-based medicine. The main emphasis lies on technical details, i.e. surgical approach, lymphadenectomy, and current techniques of anastomosis. Methods: The current literature on operative details in esophageal cancer treatment was reviewed. Surgical approaches and different techniques of anastomotic reconstruction utilizing a gastric tube were compared. The grade of evidence regarding the necessity and extent of lymphadenectomy was discussed. Results: There is no level-1 evidence-based difference regarding the surgical approach for esophagectomy. The preferred anastomosis site is intrathoracic compared to the neck. Extended lymphadenectomy is still imperative in esophagectomy although neoadjuvant protocols might also result in a downstaging effect of lymph nodes. Neoadjuvant regimens have no negative influence on complication rate and anastomotic integrity. Conclusion: A tailored interdisciplinary approach to the patients' physiology and esophageal cancer stage is the most important factor that influences operative outcome and oncological results after esophagectomy. (C) 2015 S. Karger GmbH, Freiburg

Objective The aim of this study was to analyze the incidence and impact of extracapsular lymph node spread (ELNS) in pancreatic cancer (PC) and cancer of the papilla of Vater (CPV). Methods Between 2004 and 2009, 148 patients underwent surgical therapy for PC (n = 112) and CPV (n = 36). The resected lymph nodes (LNs) were further analyzed for ELNS. Results In 95 (64.2%) patients, LN metastasis was present. In 45 (47.3%) of these patients, an ELNS was present on histopathology. The patients' survival was negatively affected by ELNS. For PC, the 5-year survival rate was 37% for patients with no LN metastasis compared with 4% and 0% for patients with LN metastasis (pN1) but without extracapsular LN involvement and patients with pN1 disease with extracapsular LN involvement of at least 1 LN, respectively (P < 0.001). In patients with CPV, the 5-year survival rate was 56% for patients with no LN metastasis and 44% and 0% for patients with pN1 disease but without extracapsular LN involvement and patients with pN1 disease with extracapsular LN involvement of at least 1 LN, respectively (P = 0.006). Multivariate analysis revealed ELNS as an independent prognostic factor of survival for both tumor types. Conclusions Extracapsular LN spread is an independent negative prognostic factor in PC and CPV. In future staging systems, ELNS should be included.

Background/Aim: Tissue Microarray (TMA) is a widely used method to perform high-throughput immunohistochemical analyses on different tissues by arraying small sample cores from paraffin-fixed tissues into a single paraffin block. TMA-technology has been validated on numerous cancer tissues and also for gastric cancer studies, although it has not been validated for this tumor tissue so far. The objective of this study was to assess, whether the 2-mm TMA-technology is able to provide representative samples of gastric cancer tissue. Materials and Methods: TMA paraffin blocks were constructed by means of 220 formalin-fixed and paraffin-embedded gastric cancer samples with a sample diameter of 2 mm. The agreement of immunohistochemical stainings of Glut-1 and Hif-1 alpha in TMA sections and the original full sections was calculated using kappa statistics and direct adjustment. Results: The congruence was substantial for Glut-1 (kappa 0.64) and Hif-1 alpha (kappa 0.70), but with an agreement of only 71% and 52% within the marker-positive cases of the full-section slides. Conclusion: Due to tumor heterogeneity primarily, the TMA technology with a 2-mm sample core shows relevant limitations in gastric cancer tissue. Although being helpful for tissue screening purposes, the 2-mm TMA technology cannot be recommended as a method equal to full-section investigations in gastric cancer.

Several pathohistological classification systems exist for the diagnosis of gastric cancer. Many studies have investigated the correlation between the pathohistological characteristics in gastric cancer and patient characteristics, disease specific criteria and overall outcome. It is still controversial as to which classification system imparts the most reliable information, and therefore, the choice of system may vary in clinical routine. In addition to the most common classification systems, such as the Lauren and the World Health Organization (WHO) classifications, other authors have tried to characterize and classify gastric cancer based on the microscopic morphology and in reference to the clinical outcome of the patients. In more than 50 years of systematic classification of the pathohistological characteristics of gastric cancer, there is no sole classification system that is consistently used worldwide in diagnostics and research. However, several national guidelines for the treatment of gastric cancer refer to the Lauren or the WHO classifications regarding therapeutic decision-making, which underlines the importance of a reliable classification system for gastric cancer. The latest results from gastric cancer studies indicate that it might be useful to integrate DNA-and RNA-based features of gastric cancer into the classification systems to establish prognostic relevance. This article reviews the diagnostic relevance and the prognostic value of different pathohistological classification systems in gastric cancer. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

The incidence rate of gastric cancer is much higher in Asia than in the Western industrial nations. According to the different screening programs in Japan and Korea about fifty percent of treated patients had an early tumor stage. In contrast, European and American patients with gastric cancer had an advanced tumor stage. Therefore, the experience for the various therapeutic options for gastric cancer may be different between these regions. In this review we tried to point out the treatment modalities in Western industrial countries for early gastric cancer. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Currently, patients with locally advanced esophageal cancer receive neoadjuvant chemoradiotherapy but only about half of these patients benefit from this treatment. GNAS T393C has been shown to predict the postoperative course in solid tumors and may therefore be useful for treatment stratification. The aim of the present study was to determine if the single-nucleotide polymorphism GNAS T393C can be used for treatment stratification in esophageal cancer patients. A total of 596 patients underwent surgical resection for esophageal carcinoma from 1996 to 2008; 279 patients received chemoradiotherapy prior to surgery (RTX-SURG group). All patients and a reference group of 820 healthy White individuals were genotyped for GNAS T393C. The 5-year-survival rate for the 317 patients who underwent esophagectomy as initial treatment (SURG group) was 57 % for homozygous C-allele carriers (n = 99) and 43 % for T-allele carriers (n = 218; log- rank test p = 0.025). Multivariate analysis revealed the GNAS T393C genotype (p = 0.034), pT (p < 0.001), pN (p < 0.001) and age (p < 0.001) as prognostic of survival. Homozygous C-allele carriers with a locally advanced tumor stage (cT3/T4, n = 129) in the SURG group had a 5-year survival rate of 37 %, which, remarkably, exceeded the 5-year survival rate of 30 % for the entire RTX-SURG group (n = 279). In the RTX-SURG group, the GNAS T393C genotype did not show any prognostic significance. Patients with a locally advanced esophageal cancer and an homozygous GNAS 393C genotype do not benefit from platinum-based neoadjuvant chemoradiotherapy, indicating that these patients should be treated by alternative treatment strategies.

Background Neoadjuvant treatment strategies have been developed to improve survival of patients with advanced rectal cancer. Since mainly patients with major histopathological response benefit from this therapy, predictive and prognostic markers are needed. We examined the association of beta-catenin and Her2/neu protein expression with histopathologic response to neoadjuvant radiochemotherapy and prognosis in patients with locally advanced rectal cancer. Methods Fifty-four patients (33 male; 21 female; median age 60.4 years) with locally advanced rectal cancer were included in this study. All patients received a neoadjuvant radiochemotherapy (50.4 Gy, 5-FU) followed by surgical resection. Histomorphologic regression was evaluated by Dworak and Cologne staging system. Major response was defined by Dworak classification when resected specimens contained less than 50% vital tumor cells (n=14) and by Cologne grading system when resected specimens contained less than 10% vital tumor cells (n=15). Intratumoral beta-catenin (nuclear/membranous) and Her2/neu (cytoplasmatic/membranous) expression was determined by immunohistochemistry in pre- and post-therapeutic specimens and correlated with clinicopathologic parameters. Results A significant association was detected between pretherapeutic membranous beta-catenin levels and response: patients with a lower beta-catenin protein expression showed significantly more often a major response compared with patients having high intratumoral protein levels (p=0.011). In addition, patients with a higher Her2/neu protein expression showed a significant survival benefit compared with patients having low intratumoral protein levels (5-year survival rate: 81% vs. low 41%; p=0.023). Conclusions The pre-therapeutic beta-catenin and Her2/neu protein expression seem to be valuable predictive and prognostic markers in the multimodality treatment of advanced rectal cancer.

Background. Along with primary tumor response, lymph node (LN) status after radiochemotherapy is one of the most important prognostic factors for advanced esophageal carcinoma. We investigated the influence of neoadjuvant radiochemotherapy on histomorphologic parameters of LNs. Methods. One hundred ninety-two patients with esophageal carcinoma underwent surgery after preoperative radiochemotherapy. Response of primary tumor was graded as minor or major. Two matched subgroups were chosen: 20 patients with minor response and 20 patients with major response. Histomorphologic criteria of LNs underwent univariate and multivariate analyses and correlated with tumor response and prognosis statistics. Results. The LNs from 40 patients (N = 1276) were examined (median number of LNs per patient, 31). Of patients with minor response, 65% showed LN metastasis; of those with major response, 20% did so (p = 0.011). Major responders had significantly lower rates of capsular and central fibrosis and vascular transformation and had more sarcoidlike lesions. Logistic regression analysis did not distinguish these parameters between major and minor responders. The 5-year survival rate was 55% for major responders and 10% for minor responders (p = 0.025), 47% for patients with LN metastasis (LNM) and 18% for patients with LNM (p = 0.041). An optimal prognostic factor, LN morphologic grading, was defined as follows: low risk, no LNM and less than 3 LNs with central fibrosis; medium risk, no LNM and central fibrosis in 3 or more LNs or LNM with an LN ratio of less than 0.05; high risk, all other cases. The 5-year survival rate was 56%, 25%, and 0% for patients considered to have low, medium, and high risk, respectively, according to LN morphologic grading (p < 0.003). With the inclusion of this classification in the Cox regression analysis, no other factors showed prognostic relevance. Conclusions. Grading of LN morphology after neoadjuvant radiochemotherapy is the most important prognost

Background Recent studies suggest that single-nucleotide polymorphisms (SNPs) within matrix metalloproteinase (MMP) genes and genes of tissue inhibitors of metalloproteinases (TIMPs) have an impact on the expression of these genes and on the prognosis for gastric cancer. Methods Genomic DNA was extracted from paraffin-embedded tissues of 135 patients who were treated surgically for primary gastric carcinoma. Genotyping was performed for MMP-2(-1306C>T), TIMP-2(303C>T), and MMP-7(-181A>G). MMP-2 and TIMP-2 antigen expression in resected tumor tissues was detected immunohistochemically. Genotyping was correlated with antigen expression, histopathologic parameters, and prognosis. Results The SNPs did not correlate with tumor differentiation, pT, R category, or the classifications according to the International Union Against Cancer (UICC), the World Health Organization (WHO), and Lauren and Ming. A significant correlation was observed for TIMP-2(303C>T) with higher pN stages (p = 0.01) and more distant metastasis (p = 0.02) for patients with the CC genotypes. In univariate analysis, patients with the TIMP-2(303C>T) CC genotype had an inferior survival, that was not significant (p = 0.2). However, among the gastric cancer patients in the present study, MMP-2(-1306C>T) significantly correlated with gender, with men having more CC genotypes than women (p = 0.025). There were no significant correlations between genotype and protein levels of MMP-2 (p = 0.766) and TIMP-2 (p = 0.684). Conclusions The TIMP-2(303C>T) CC genotype is associated with higher pN and pM categories and, in contrast to previous studies, with worse survival in gastric cancer.

Studies have shown that along with primary tumor response, lymph node status after RTx/CTx is one of the most important prognostic factors for advanced esophageal carcinoma. The goal of our study was to investigate the influence of neoadjuvant radiochemotherapy (RTx/CTx) on lymph nodes (LN). From 1997 until 2006, 297 patients underwent surgery for advanced esophageal carcinoma. Of these, 192 received preoperative chemoradiation (5-FU, cisplatin, 36 Gy). The following matched subgroups were chosen: Group I, 20 with surgery alone: 10 adenocarcinoma (AC), 10 squamous cell carcinoma (SCC); Group II, 20 with minor response (10 AC, 10 SCC); Group III, 20 with major response (10 AC, 10 SCC). Tumor response was graded as minor or major according to the Cologne Regression Scale, the LN size determined by the largest measured diameter. A total of 1967 LNs from 60 patients were examined. Of these, 161 LNs showed metastasis. The median number of LNs examined per patient was not significantly higher in group I compared with the group with pretreatment (32 vs 31). Group I and group II showed LN metastasis (LNM) in 65% of cases, and group III in only 20% (p = 0.011). LNMs after pretreatment had significantly smaller median diameters (5.0 mm) than those without (7.0 mm) (p < 0.02). Nonmetastatic LN size did not vary between the three groups. LN size with and without metastasis did not differ between AC and SCC or between major and minor responders. With good response to neoadjuvant radiochemotherapy, the size and the number of metastatic LNs is significantly reduced regardless of histologic cancer type.