Epstein-Barr virus and mismatch repair deficiency status differ between oesophageal and gastric cancer: A large multi-centre study.

BACKGROUND: Oesophageal (OeC) and gastric (GC) cancer patients are treated with similar multimodal therapy and have poor survival. There remains an urgent clinical need to identify biomarkers to individualise patient management and improve outcomes. Therapy with immune checkpoint inhibitors has shown promising results in other cancers. Proposed biomarkers to predict potential response to immune checkpoint inhibitors include DNA mismatch repair (MMR) and/or Epstein-Barr virus (EBV) status. The aim of this study was to establish and compare EBV status and MMR status in large multi-centre series of OeC and GC. METHODS: EBV was assessed by EBV-encoded RNA (EBER) in situ hybridisation and MMR protein expression by immunohistochemistry (IHC) in 988 OeC and 1213 GC from multiple centres. In a subset of OeC, microsatellite instability (MSI) was tested in parallel with MMR IHC. RESULTS: Frequency of MMR deficiency (MMRdef) and MSI was low in OeC (0.8% and 0.6%, respectively) compared with GC (10.3%). None of the OeCs were EBER positive in contrast to 4.8% EBER positive GC. EBV positive GC patients were younger (p = 0.01), more often male (p = 0.001) and had a better overall survival (p = 0.012). MMRdef GC patients were older (p = 0.001) and showed more often intestinal-type histology (p = 0.022). CONCLUSIONS: This is the largest study to date indicating that EBV and MMRdef do not play a role in OeC carcinogenesis in contrast to GC. The potential clinical usefulness of determining MMRdef/EBV status to screen patients for eligibility for immune-targeting therapy differs between OeC and GC patients.

Impact of the Weekday of Surgery on Outcome in Gastric Cancer Patients who Underwent D2-Gastrectomy.

BACKGROUND: The impact of the weekday of surgery in major elective cases of the upper-GI has been discussed controversially. The objective of this study was to assess whether weekday of surgery influences outcome in patients undergoing D2-gastrectomy. MATERIALS AND METHODS: Patients who underwent D2-gastrectomy for gastric adenocarcinoma between 1996 and 2016 were included. Weekday of surgery was recognized, and subgroups were analyzed regarding clinical and histopathological differences. Survival analysis was performed based on weekday of surgery, and early weekdays (Monday-Tuesday) were compared with late weekdays (Wednesday-Friday). RESULTS: In total, 460 patients, 71% male and 29% female, were included into analysis. The median age was 65 years. Distribution to each weekday was equal and ranged from 86 cases (Wednesday) to 96 cases (Tuesday). The pT, pN and M category and the rate of patients who underwent neoadjuvant treatment did not show significant differences (p = 0.641; p = 0.337; p = 0.752; p = 0.342, respectively). The subgroups did not differ regarding the number of dissected lymph nodes and rate of R-1/2 resections (p = 0.590; p = 0.241, respectively). Survival analysis showed a median survival of 43 months (95% CI 31-55 months), and there was no single weekday or a combination of weekdays (Mon/Tue vs Wed/Thu/Fri) with a significant favorable or worse outcome (p = 0.863; p = 0.30, respectively). The outcome did not differ regarding mortality within the first 90 days after surgery (p = 0.948). CONCLUSIONS: The present study does not show any evidence for a significant impact of weekday of surgery on short- and long-term outcome of patients undergoing gastrectomy for gastric adenocarcinoma.

Neoadjuvant chemotherapy or chemoradiation for patients with advanced adenocarcinoma of the oesophagus? A propensity score-matched study.

BACKGROUND: Multimodal therapies are the standard of care for advanced adenocarcinomas of the oesophagus and gastro-oesophageal junction (AEG Types I and II). Only three randomised trials have compared preoperative chemotherapy with and without radiation. The results showed a small benefit for combined chemoradiation. In the meantime, newer therapy protocols are available. AIM: In a propensity-score matched study, we analysed patients with locally advanced AEG type I or II, treated with chemotherapy (FLOT-protocol) or chemoradiation (CROSS-protocol), followed by oesophagectomy, in a single high-volume centre. PATIENTS AND METHODS: Between 2011 and 2015, 137 patients with advanced (cT3NxcM0) adenocarcinoma received pre-operative therapy; 70% had chemoradiation (CROSS-protocol) and 30% had chemotherapy (FLOT-protocol). After propensity-score matching, 40 patients from the CROSS-group were selected for analysis. Postoperative histopathological response and prognosis were analysed. RESULTS: The two groups were comparable according to the matching criteria age, gender, tumour location, and year of surgery. R0-resection was achieved in 97% of patients in the CROSS-group and 85% of the FLOT-group (p = 0.049). Major response of the primary tumour was evident more often in the CROSS-group (17/40 pts. 43%) versus FLOT-group (11/40 pts. 27%) as well no lymph node metastasis (ypN0 = 68% versus ypN0 = 40%) (p = 0.014). Prognosis were not significantly different between the two groups. In multivariate analysis, only ypN-category was an independent prognostic factor. CONCLUSION: Compared to FLOT-chemotherapy, neoadjuvant chemoradiotherapy with the CROSS-protocol in locally advanced adenocarcinoma AEG types I and II resulted in better response by the primary tumour and less lymph node metastasis but without superior survival.

Preoperative airway colonization prior to transthoracic esophagectomy predicts postoperative pulmonary complications.

PURPOSE: Respiratory complications are responsible to a high degree for postoperative morbidity and mortality after Ivor-Lewis esophagectomy. The etiology of respiratory failure is known to be multifactorial with preoperative impaired lung function being the most important one. The aim of this study was to investigate the correlation between preoperative airway colonization (PAC) and postoperative respiratory complications. METHODS: In this observational study, 64 patients with esophageal cancer were included. All patients underwent Ivor-Lewis esophagectomy with laparoscopic or open gastric mobilization. After induction of anesthesia and intubation with a double-lumen tube, bronchial exudate was collected by random endoluminal suction for further microbiological work-up. Length of postoperative mechanical ventilation (<24 h, 24-72 h, >72 h), re-intubation, and tracheostomy were recorded as primary and secondary study endpoints. RESULTS: In 13 of 64 study patients (20.3 %), pathological colonization of the bronchial airways could be proved prior to esophagectomy. Haemophilus species was the most frequently identified pathogen. PAC was associated with a longer history of smoking (p = 0.025), a lower preoperative forced expiratory volume (FEV1, p = 0.009) or vital capacity (VC, p = 0.038), a prolonged postoperative mechanical ventilation (p < 0.001), and a higher frequency of re-intubation (p < 0.001) and tracheostomy (p = 0.017). In the multivariate analysis, PAC was identified as an independent predictor of respiratory failure (hazard ratio 11.4, 95 % confidence interval 2.6-54, p = 0.002). Mortality in the PAC group was 30.8 % compared to 0 % in patients without PAC (p < 0.0001). CONCLUSION: PAC is a significant risk factor for postoperative respiratory failure. A routine bronchoscopy and bronchoalveolar lavage as part of preoperative management prior to esophagectomy need to be discussed.

[Quality of life and visceral surgery]. / Lebensqualität nach viszeralchirurgischen Operationen.

Quality of life (QOL) is becoming more and more relevant in clinical research. An increasing number of publications each year confirmed this. The aim of this review is to summarize current data of QOL after surgical procedures. The results are represented by two examples each of malignant and benign diseases. The evaluation of QOL for patients with cancer is only possible with respect to the prognosis. Prospective randomized trials comparing laparoscopic and open surgery for early gastric cancer are only available from Asia. Data from the USA show that the QOL after gastrectomy was worse regardless of the surgical procedure. During the next 6 months the QOL improved but about one third of the patients had severe impairment during longer follow-up periods. Patients with R1 resection of pancreatic cancer showed only a slightly better prognosis but significantly better QOL compared to patients without resection. The results for the various procedures of cholecystectomy or hernia repair are not always consistent.

MicroRNA profiling in locally advanced esophageal cancer indicates a high potential of miR-192 in prediction of multimodality therapy response.

To identify possible predictive markers, our study aimed to characterize microRNA (miRNA) profiles of responder and nonresponder in the multimodality therapy of locally advanced esophageal cancer. Initially, a microarray-based approach was performed including eight patients with esophageal cancer. Patients received neoadjuvant chemoradiation followed by surgical resection. Major histopathological response was defined if resected specimens contained less than 10% vital tumor cells (major/minor response: 4/4 patients). Intratumoral RNA was isolated from both, pretherapeutic tissue biopsies in addition to corresponding surgical specimens. The profile of 768 miRNAs was analyzed in 16 specimens (preneoadjuvant and postneoadjuvant therapy). Selected miRNAs were than analyzed on pretherapeutic and post-therapeutic biopsies of 80 patients with esophageal cancer, who underwent multimodality therapy (major/minor response: 30/50 patients). Comprehensive miRNA profiling identified miRNAs in pretherapeutic biopsies that were significantly different between major/minor responders. Based on the microarray results, miR-192, miR-194 and miR-622 were selected and the dysregulated miRNAs were studied on an extended series of esophageal cancer patients. The expression of miR-192, miR-194 and miR-622 was significantly reduced after neoadjuvant therapy confirming the array profiling data. Importantly, the pretherapeutic intratumoral expression of miR-192 and miR-194 was significantly associated with the histopathologic response of esophageal squamous cell carcinoma to multimodal therapeutic treatment. Therefore, in patients with locally advanced esophageal cancer undergoing neoadjuvant chemoradiation followed by esophagectomy, miR-192 and miR-194 in pretherapeutic biopsies are considered as indicators of major histopathologic regression.

Health-related quality of life after Ivor Lewis esophagectomy.

PURPOSE: Transthoracic Ivor Lewis esophagectomy is a surgical standard therapy for esophageal carcinoma. The aim of this study was to assess health-related quality of life (HRQL) in mid- and long-term survivors. METHODS: Patients with cancer-free survival of at least 12 months after esophageal resection for cancer were identified from a prospectively maintained database. EORTC questionnaires were sent out to assess health-related general (QLQ-C30) and esophageal cancer-specific (QLQ-OES18) quality of life (QOL). A numeric score was calculated in each conceptual area and compared with reference data. RESULTS: One hundred forty-seven patients completed the self-rated questionnaires. They were 121 men and 26 women with a mean age of 63.4 (21-83) years; median FU was 39 (12-139) months. Global health status, functional scales, and symptom scores were significantly reduced compared with healthy reference populations. Also, there was no significant impact of tumor histology, neoadjuvant treatment, minimally invasive approach, or duration of follow-up on HRQL. However, more than half of the patients reported a HRQL similar to that of the healthy reference population. CONCLUSIONS: Despite the major psychosocial and physiological impacts of the disease, more than 50 % of mid- and long-term survivors of the Ivor Lewis procedure for esophageal cancer have a HRQL similar to that of the healthy reference population.

Vascular endothelial growth factor expression following ischemic conditioning of the gastric conduit.

The partial devascularization of the stomach, necessary for esophageal reconstruction with a gastric conduit, impairs microcirculation in the anastomotic region of the gastric fundus. Ischemic conditioning of the gastric tube is considered as a possible approach to improve microcirculation in the gastric mucosa. The aim of this study was to investigate whether ischemic conditioning induces neo-angiogenesis in the gastric fundus by expression of vascular endothelial growth factor (VEGF). Twenty patients with an esophageal carcinoma scheduled for esophagectomy and gastric reconstruction were included. To compare VEGF expression before and after ischemic conditioning, preoperative endoscopic biopsies were taken from the gastric fundus. The surgical procedure consisted of two separate steps, the complete gastric mobilization including partial devascularization of the stomach and after a delay of 4-5 days high transthoracic esophagectomy with intrathoracic gastric reconstruction (Ivor-Lewis procedure). The second tissue sample was obtained from the donut of the stapled esophagogastrostomy. For further work-up, preoperative biopsies and the gastric donuts were fixed in liquid nitrogen. Preoperative and intraoperative VEGF expression was measured by quantitative real-time reverse transcription-polymerase chain reaction (VEGF×100/ß-actin) and results were compared using Wilcoxon test for paired samples. In all 40 specimens, a distinct expression of VEGF could be detected. Comparing the level of VEGF expression of the preoperative biopsies and postoperative tissue sample, no significant difference could be demonstrated following ischemic conditioning. In this model of ischemic conditioning with delayed reconstruction of 4-5 days, no induction of neo-angiogenesis could be demonstrated by measurement of VEGF expression.

Choosing the best treatment for esophageal cancer : criteria for selecting the best multimodal therapy.

The best multimodal therapy in esophageal cancer comprises neoadjuvant radiochemotherapy in patients with adenocarcinoma or squamous cell carcinoma whereas neoadjuvant chemotherapy is only appropriate for patients with adenocarcinoma. However, the 2-year survival benefit by this induction therapy compared to surgery alone is only 5-9 %. Targeted drugs seem to be promising in order to improve the response rate. The choice of the best multimodal therapy by response prediction seems only to be possible in patients during chemotherapy for adenocarcinoma, whereas during neoadjuvant radiochemotherapy a response prediction by FDG-PET is not possible. The principle item of multimodal therapy is still transthoracic en bloc esophagectomy which should be performed in high volume centers in order to guarantee stable and good results.

The prognostic impact of extracapsular lymph node involvement in rectal cancer patients: Implications for staging and adjuvant treatment strategies.

Limited data suggest that extracapsular lymph node involvement (LNI) has a negative prognostic impact in gastrointestinal malignancies. The aim of this study was to assess the prevalence and prognostic impact of LNI in patients with primary resected rectal cancer. Between 1997 and 2007, 243 rectal cancer patients underwent surgical therapy without neoadjuvant treatment at our Department. Of these, 12 (5%) patients received transanal endoscopic microsurgery and were not included for further analyses. In the remaining patients, a (low) anterior resection was performed in 79% and an abdominoperineal rectal amputation in 21%. The total number of analyzed lymph nodes and the number of metastatic lymph nodes with/without extracapsular LNI were determined and the prognostic impact of LNI was assessed. The median number of analyzed lymph nodes was 14. In total, 59% of patients were node-negative, 18% of patients were node-positive without extracapsular LNI and 23% of patients were node-positive with extracapsular LNI. A positive lymph node status with extracapsular LNI was significantly correlated with a poorer T-, N- and M-category, grading and more frequent lymphatic vessel infiltration compared with node-negative or node-positive without extracapsular LNI patients (p<0.001). The overall 5-year survival rate of node-negative patients was 75%, for node-positive without extracapsular LNI patients 69% and for node-positive with extracapsular LNI patients 36% (p<0.001). By multivariate analysis, the N-category with extracapsular LNI was characterized as an independent prognostic factor. Extracapsular lymph node involvement reveals an independent negative prognostic impact in patients with rectal cancer undergoing surgical therapy. Staging systems for rectal cancer should include the implementation of extracapsular lymph node involvement.

Evaluation of histological regression grading systems in the neoadjuvant therapy of rectal cancer: do they have prognostic impact?

PURPOSE: Neoadjuvant treatment options have been developed to improve survival of patients with locally advanced rectal cancer. As only patients with a major histopatholocial response benefit from this preoperative therapy, several tumor regression grading systems have been developed. However, currently no accepted comprehensive grading system for clinical use is available. Therefore, we studied the impact of four histological regression grading systems in the neoadjuvant therapy of rectal cancer. METHODS: In this retrospective study, 85 patients with locally advanced rectal cancer were included. All patients received a neoadjuvant radiochemotherapy followed by surgical resection. The histological regression grading was evaluated using four classification systems: (1) grading system by the Japanese society of colorectal cancer, (2) grading system by Junker-Müller, (3) grading system by Dworak, (4) Cologne grading system. The four classification systems were analyzed for their prognostic impact. RESULTS: The following significant correlations were detected between the four classification systems and the ypTNM categories: (1) patients with a ypT3/4 category had significantly more often a worse histopathologic response in all four grading systems (p = 0.001); (2) a ypN0 category was significantly correlated with good histopathologic response only in the Cologne grading system; (3) in the Junker-Müller and Dworak grading systems, a ypM0 category was significantly correlated with a good histopathologic response (p = 0.046; p = 0.03). However, none of the used classification systems had a prognostic impact on survival. CONCLUSIONS: Currently, none of the analyzed histological regression grading systems is effective for clinical use.

[Experience with an interdisciplinary surgical handbook for medical students]. / Erfahrungen mit einem fächerübergreifenden Logbuch für Medizinstudenten im Chirurgischen Tertial des Praktischen Jahres am Uniklinikum Köln.

BACKGROUND: There is a lack of well-trained surgeons in Germany. The medical students get their last contact to a surgical discipline in the final year of their medical education. The student's decision for a medical discipline is surely influenced by bad experiences during the last practical training in surgery. The aim of our project was to give the medical students an engaged and structured understanding of surgery with the aid of a logbook. It was tested in a pilot phase and should increase the number of final year students and their interest in surgery in the long-term. METHODS: From 5 / 2009 the structure of the surgical part of the final year was worked over by the Clinics for General, Visceral und Tumour Surgery, Vascular Surgery, Heart and Thoracic Surgery and Trauma Surgery. A logbook was developed which includes the rotation through the 4 different surgical departments, lists the targets of study and the practical exercises in obligatory and optional schedules, defines one patient care per rotation and introduces a mentoring system. The logbook is clearly represented and the required signatures of the senior doctors are minimized. After the surgical term the students filled out a questionnaire and were interviewed about the pros and cons of the logbook. RESULTS: In December 2009 the new logbook was distributed for the first time. Until now 113 final year students have used it. The first evaluation of 45 students showed a positive rating of the clinical organization and structure of the clinic, the list of the learning targets and the practical skills. The implementation of the mentoring system and the required signatures were still incomplete. The final year students wished for more training time for the doctors. The positive response of the final year students results in an increasing number of final year students chosing a career in surgery. CONCLUSION: The new logbook for the surgical part of the final year at the University of Cologne helps the students with the daily routine of the surgical departments, gives a review of the learning targets and emphasizes a good surgical training.

Prognostic impact of nodal micrometastasis in early esophageal cancer.

INTRODUCTION: Nodal micrometastasis is a negative prognosticator for esophageal cancer. There is a trend toward endoscopic resection for early cancer of the esophagus without lymphadenectomy. Frequency and prognostic impact of nodal micrometastasis in early cancer of the esophagus have not been investigated so far. PATIENTS AND METHODS: This study includes 69 patients with a pT1-stage cancer of the esophagus (SCC: n = 26, AC: n = 43), who underwent transthoracic en-bloc esophagectomy with D2-lympadenectomy between 1996 and 2004. On routine histopathological analysis 48 patients were diagnosed as pN0. Lymph nodes (n = 1344) of these patients were further examined for the presence of isolated tumor cells with the monoclonal anti-epithelial antibody AE1/AE3. RESULTS: In lymph nodes of 7 (14.6%) out of 48 pN0-patients a positive staining for AE1/AE3 as a sign for nodal micrometastasis was found. In these patients the tumor has infiltrated the submucosal layer. In patients with tumors restricted to mucosal layer (n = 20) no nodal micrometastasis was present. 5-year survival of pN0-patients with nodal micrometastasis was inferior compared to pN0-patients (57% vs. 82%; p = 0.002). CONCLUSION: Almost 15% of patients with pT1 N0 M0 carcinoma of the esophagus and only those with submucosal infiltration show nodal micrometastasis. It has a significant negative impact on survival already in early esophageal cancer.

[Value of distal gastrectomy as a remedial operation for failed fundoplication]. / Stellenwert der distalen Magenresektion mit Rekonstruktion nach Roux-Y zur Behandlung des Refluxrezidivs nach Fundoplikatio.

BACKGROUND: Failure of conventional antireflux surgery is a challenging problem. This study aims at defining the role of distal gastrectomy with Roux-en-Y diversion in the treatment of failed fundoplication. MATERIAL AND METHODS: This report reviews the indications and results of 26 patients who underwent revisional antireflux surgery in our department. Distal gastrectomy and Roux-en-Y reconstruction were performed in 6 patients (group a), refundoplication in 15 (group b), and re-hiatoplasty in 5 patients (group c). RESULTS: Group a patients had the longest history (p = 0.001) and the highest number of previous operative procedures (p = 0.001). In contrast, hospital stay was longer and postoperative morbidity was higher after distal gastrectomy (p = n. s.). At follow-up, symptom improvement was achieved most reliably after distal gastrectomy (groups a-c: 100%, 78.6%, and 60% of patients; p = n. s.). CONCLUSION: Distal gastrectomy with Roux-en-Y diversion is a safe and reliable surgical option for selected patients after failed fundoplication. Distal gastrectomy with Roux-en-Y diversion is a reliable surgical option for selected patients after failed fundoplication. Despite a higher morbidity, this procedure represents an important addition to the surgical armamentarium, particularly in patients with a history of multiple previous interventions.

A multicenter study of survival after neoadjuvant radiotherapy/chemotherapy and esophagectomy for ypT0N0M0R0 esophageal cancer.

OBJECTIVE: To evaluate 5-year survival of patients with locally advanced esophageal cancer (LAEC) who have undergone multimodality treatment with complete histopathologic response. BACKGROUND: Patients with LAEC may obtain excellent local-regional response to multimodality therapy. The overall benefit of a complete histopathologic response, when no viable tumor is present in the surgical specimen, is incompletely understood and existing data are limited to single-center studies with relatively few patients. The aim of this multicenter study was to define the outcome of patients with complete histopathologic response after multimodality therapy for LAEC. METHODS: The study population included 299 patients (229 male, 70 female; median age: 60 years) with LAEC (cT2N1M0, T3-4N0-1M0; 181 adenocarcinomas, 118 squamous carcinomas) who underwent either neoadjuvant radiochemotherapy (n = 284) or chemotherapy (n = 15) followed by esophagectomy at 6 specialized centers: Europe (3) and United States (3). All patients in the study had stage ypT0N0M0R0 after resection. RESULTS: Esophagectomy with thoracotomy (n = 255) was more frequent than with a transhiatal approach (n = 44). The median number of analyzed lymph nodes in the surgical specimens was 20 (minimum-maximum: 1-77). Thirty-day mortality rate was 2.4% and 90-day mortality rate was 5.7%. Overall 5-year survival rate was 55%. The disease-specific 5-year survival rate was 68%, with a recurrence rate of 23.4% (n = 70; local vs distant recurrence: 3.3% vs 20.1%). Cox regression analysis identified age as the only independent predictor of survival, whereas gender, histology, type of esophagectomy, type of neoadjuvant therapy, and the number of resected lymph nodes had no prognostic impact. CONCLUSION: Patients with histopathologic complete response at the time of resection of LAEC achieve excellent survival.

[18F]-fluorodeoxyglucose-positron emission tomography for the assessment of histopathologic response and prognosis after completion of neoadjuvant chemotherapy in gastric cancer.

BACKGROUND AND OBJECTIVES: Neoadjuvant chemotherapy is applied to improve the prognosis of patients with advanced gastric cancer. However, only a major histopathological response will provide a benefit. Recent studies suggest that [(18)F]-fluorodeoxyglucose-positron-emission-tomography (FDG-PET) correlates with response and survival in patients with gastroesophageal adenocarcinomas undergoing neoadjuvant chemotherapy. We evaluated the potential of FDG-PET for the assessment of response and prognosis in the multimodality treatment of gastric cancer. METHODS: Study patients were recruited from a prospective observation trial. Forty two patients with advanced gastric cancer received neoadjuvant chemotherapy and subsequently 40 patients underwent standardized gastrectomy (2 patients with tumor progression had therapy limited to palliative chemotherapy without surgery). Histomorphologic regression was defined as major response when resected specimens contained <10% vital tumor cells. FDG-PET was performed before and 2 weeks after the end of neoadjuvant chemotherapy with assessment of the intratumoral FDG-uptake [pre-treatment standardized uptake value (SUV1); post-treatment SUV (SUV2); percentage change (SUVDelta%)]. RESULTS: Histomorphological tumor regression was confirmed as a prognostic factor (P = 0.039). No significant correlations between SUV1, SUV2, or SUVDelta% and response or prognosis were found. CONCLUSION: FDG-PET seems not to be an imaging system that effectively characterizes major/minor response and survival in patients with gastric cancer following multimodality treatment.

Options in the management of esophageal perforation: analysis over a 12-year period.

Controversies exist about the management of esophageal perforation in order to eliminate the septic focus. The aim of this study was to assess the etiology, management, and outcome of esophageal perforation over a 12-year period, in order to characterize optimal treatment options in this severe disease. Between May 1996 and May 2008, 44 patients (30 men, 14 women; median age 67 years) with esophageal perforation were treated in our department. Etiology, diagnostic procedures, time interval between clinical presentation and treatment, therapeutic management, and outcome were analyzed retro- or prospectively for each patient. Iatrogenic injury was the most frequent cause of esophageal perforation (n= 28), followed by spontaneous (n= 9) and traumatic (n= 4) esophageal rupture (in three patients, the reasons were not determinable). Eight patients (18%) underwent conservative treatment with cessation of oral intake, antibiotics, and parenteral nutrition. Twelve (27%) patients received an endoscopic stent implantation. Surgical therapy was performed in 24 (55%) patients with suturing of the lesion in nine patients, esophagectomy with delayed reconstruction in 14 patients, and resection of the distal esophagus and gastrectomy in one patient. In case of iatrogenic perforation, conservative or interventional therapy was performed each in 50% of the patients; 89% of the patients with a Boerhaave syndrome underwent surgery. The hospital mortality rate was 6.8% (3 of 44 patients): one patient with an iatrogenic perforation after conservative treatment, and two patients after surgery (one with Boerhaave syndrome, one with iatrogenic rupture). No death occurred in the 25 patients with a diagnostic interval less than 24 hours, whereas the mortality rate in the group (n= 16 patients) with a diagnostic interval of more than 24 hours was 19% (P= 0.053). In three patients, the diagnostic interval was not determinable retrospectively. An individualized therapy depending on etiology, diagnostic delay, and septic status leads to a low mortality of esophageal perforation.

[Diagnosis of and therapy for gastric cancer--work-flow]. / Diagnostik und Therapie des Magenkarzinoms--Workflow.

AIM: This review comments on the diagnosis and treatment of gastric cancer in the classical meaning--excluding adenocarcinoma of the -oesophagogastric junction. Algorithms of diagnosis and care with respect to tumour stage are presented. PREOPERATIVE DIAGNOSIS: Besides oesophagogastroduodenoscopy, endoscopic ultrasonography is necessary for the accurate diagnosis of T categories and as a selection criterion for neoadjuvant chemotherapy. Computed tomography is recommended for preoperative evaluation of tumours > T1, laparoscopy has become an effective stag-ing tool in T3 and T4 tumours avoiding unnecessary laparotomies and improving the detection of small -liver and peritoneal metastases. TREATMENT: Endoscopic mucosal resection and submucosal dissection are indicated in superficial cancer confined to the mucosa with special characteristics (T1 a / no ulcer / G1, 2 / Laurén intestinal / L0 / V0 / tumour size < 2 cm). In all other cases total gastrectomy or distal subtotal gastric resection are indicated, the latter in cases of tumours located in the distal two-thirds of the stomach. Standard lymphadenectomy (LAD) is the D2 LAD without distal pancreatectomy and splenectomy. The Roux-en-Y oesophagojejunostomy is still the preferred type of reconstruction. An additional pouch reconstruction should be considered in -patients with favourable prognosis, this also -applies for the preservation of the duodenal passage by jejunum interposition. Extended organ resections are only indicated in cases where a R0-resection is possible. Hepatic resection for metachronous or synchronous liver metastases is rarely advised since 50 % of patients with liver metastases show concomitant peritoneal dissemination of the disease. DISCUSSION AND CONCLUSIONS: Undergoing gastrectomy at a high-volume centre is associated with lower in-hospital mortality and a better prognosis, however, clear thresholds for case load cannot be given. Perioperative chemotherapy and postoperative chemoradiotherapy are based on the MAGIC and MacDonald trials. Perioperative chemotherapy should be performed in patients with T3 and T4 tumours with the aim to increase the likelihood of curative R0-resection by downsizing the tumour. Adjuvant postoperative chemotherapy cannot be recommended since its benefit has so far not been proven in randomised trials. In selected patients with incomplete lymph-node dissection and questionable R0-resection postoperative chemoradiotherapy may be debated.

Survivin expression in gastric cancer: Association with histomorphological response to neoadjuvant therapy and prognosis.

BACKGROUND AND OBJECTIVES: Neoadjuvant therapy is applied to improve the prognosis associated with advanced gastric cancer. Only patients with a major response seem to have a survival benefit. Predictive markers to allow individualisation of treatment could be helpful. We examined the association of survivin protein expression with histopathologic response to neoadjuvant chemotherapy and prognosis in patients with gastric cancer. METHODS: Forty patients with gastric cancer received neoadjuvant chemotherapy. Afterwards, 38 patients underwent total gastrectomy, while 2 patients received definitive chemotherapy because of tumour progression. Histomorphologic regression was defined as major response when resected specimens contained <10% tumour cells. Intratumoural survivin expression was determined by immunohistochemistry in pre- and post-therapeutic specimens and correlated with clinicopathologic parameters. RESULTS: The pre- and post-therapeutic intratumoural survivin protein expression was not associated with histomorphologic regression. Post-therapeutic survivin expression did not have prognostic impact. A significant association was detected between pre-therapeutic survivin levels and prognosis: patients with a higher survivin protein expression showed a significant survival benefit. In multivariate analysis pre-therapeutic survivin expression was characterised as an independent prognostic marker, besides pN-status and histopathologic regression. CONCLUSIONS: The pre-therapeutic survivin protein expression seems to be an independent prognostic marker in the multimodality treatment of advanced gastric cancer.