Fit-for-Discharge Criteria after Esophagectomy: An International Expert Delphi Consensus.

There are no internationally recognized criteria available to determine preparedness for hospital discharge after esophagectomy. This study aims to achieve international consensus using Delphi methodology. The expert panel consisted of 40 esophageal surgeons spanning 16 countries and 4 continents. During a 3-round, web-based Delphi process, experts voted for discharge criteria using 5-point Likert scales. Data were analyzed using descriptive statistics. Consensus was reached if agreement was ≥75% in round 3. Consensus was achieved for the following basic criteria: nutritional requirements are met by oral intake of at least liquids with optional supplementary nutrition via jejunal feeding tube. The patient should have passed flatus and does not require oxygen during mobilization or at rest. Central venous catheters should be removed. Adequate analgesia at rest and during mobilization is achieved using both oral opioid and non-opioid analgesics. All vital signs should be normal unless abnormal preoperatively. Inflammatory parameters should be trending down and close to normal (leucocyte count ≤12G/l and C-reactive protein ≤80 mg/dl). This multinational Delphi survey represents the first expert-led process for consensus criteria to determine 'fit-for-discharge' status after esophagectomy. Results of this Delphi survey may be applied to clinical outcomes research as an objective measure of short-term recovery. Furthermore, standardized endpoints identified through this process may be used in clinical practice to guide decisions regarding patient discharge and may help to reduce the risk of premature discharge or prolonged admission.

[Surgical strategy for early stage carcinoma of the esophagus]. / Chirurgische Strategie bei Frühkarzinomen des Ösophagus.

Early stage carcinomas of the esophagus are histologically differentiated into adenocarcinomas and squamous cell carcinomas and subdivided into mucosal (m1-3) and submucosal (sm1-3) carcinomas depending on the infiltration depth. While the prevalence of lymph node metastases in mucosal carcinomas is very low, the probability of lymph node metastases increases from submucosal infiltration with increasing depth. According to the current German S3 guidelines endoscopic resection is the recommended treatment strategy for mucosal adenocarcinoma without histological risk factors (lymphatic invasion [L1], venous invasion [V1], poorly differentiated [>G2], microscopic residual disease [R1] at the deep resection margin). For superficial submucosal infiltration (sm1) without histological risk factors endoscopic resection can also be carried out, whereby in this case the guidelines make a stronger recommendation for esophagectomy. For squamous cell carcinoma endoscopic resection is indicated for an infiltration depth up to middle layer mucosal carcinoma (m2) without histological risk factors. Outside of these criteria an esophageal resection should always be carried out. The surgical gold standard is a subtotal abdominothoracic esophagectomy with two-field lymphadenectomy. Alternative procedures are total esophagectomy in proximal esophageal carcinoma and transhiatal extended gastrectomy for carcinoma of the cardia. Limited proximal or distal esophageal resections can be performed in proximal or distal mucosal carcinoma without the possibility of endoscopic resection; however, partial resections are not superior in terms of functional results and are not oncologically equivalent due to limited lymphadenectomy. Minimally invasive procedures show good oncological results and reduce the morbidity of radical esophagectomy. Reduced morbidity might be an argument for surgical resection in borderline cases between endoscopic and surgical resection.

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.

[Therapeutic approach in oligometastatic gastric and esophageal cancer]. / Therapeutisches Vorgehen beim oligometastasierten Magen- und Ösophaguskarzinom.

The therapeutic approach to patients with oligometastatic gastric cancer and esophageal cancer is currently undergoing a shift towards a more aggressive therapy including surgical resection. In the current German S3 guidelines surgical treatment of metastatic disease is not recommended; however, nowadays interdisciplinary tumor boards have to evaluate such patients increasingly more often. On an individual basis a radical surgical resection of the primary tumor and the metastases is considered and performed in patients who respond well to multimodal chemotherapy concepts. In this review article the currently available data from the literature are discussed and a foundation for individually extended surgical approaches is presented. Together with the currently available results of the FLOT 3 study and the mostly retrospective studies, it seems to be possible to identify patients who would profit from such an aggressive treatment. In the future randomized prospective studies, such as the RENAISSANCE/FLOT 5 study and the GASTRIPEC study will have to evaluate whether an aggressive surgical therapy within multimodal therapy concepts of metastatic gastric and esophageal carcinomas is warranted.

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.

[Resection of advanced esophagogastric adenocarcinoma : Extended indications]. / Resektion beim fortgeschrittenen Adenokarzinom des Magens und des Ösophagus : Erweiterung der Indikation.

In the current German S3 guidelines surgical treatment is not recommended for metastatic gastric cancer or metastatic adenocarcinoma of the esophagogastric junction; however, in routine practice the indications can be extended so that there may be occasions in which radical surgical intervention for specific individuals may be appropriate as part of a multimodal therapy with curative intent. This article presents the scientific rationale of such an approach based on the available literature considering modern, multimodal therapy concepts including criteria to be met for radical surgery. Currently only retrospective trials and limited current meta-analysis data are available for justifying surgical treatment for metastatic adenocarcinoma. The recently published initial results of the FLOT-3 study identified a patient subgroup that benefits from a resection even though metastasis has occurred. Whether surgical therapy will become an integral part of the treatment of limited metastatic adenocarcinoma of the stomach and esophagus in the future, has to be demonstrated by large prospective randomized studies, such as the RENAISSANCE/FLOT-5 study.

Description and analysis of clinical pathways for oesophago-gastric adenocarcinoma, in 10 European countries (the EURECCA upper gastro intestinal group - European Registration of Cancer Care).

AIMS: Outcomes for patients with oesophago-gastric cancer are variable across Europe. The reasons for this variability are not clear. The aim of this study was to describe and analyse clinical pathways to understand differences in service provision for oesophageal and gastric cancer in the countries participating in the EURECCA Upper GI group. METHODS: A questionnaire was devised to assess clinical presentation, diagnosis, staging, treatment, pathology, follow-up and service frameworks across Europe for patients with oesophageal and gastric cancer. The questionnaire was issued to experts from 14 countries. The responses were analysed quantitatively and qualitatively and compared. RESULTS: The response rate was (10/14) 71.4%. The approach to diagnosis was similar. Most countries established a diagnosis within 3 weeks of presentation. However, there were different approaches to staging with variable use of endoscopic ultrasound reflecting availability. There has been centralisation of treatments in most countries for oesophageal surgery. The most consistent area was the approach to pathology. There were variations in access to specialist nurse and dietitian support. Although most countries have multidisciplinary teams, their composition and frequency of meetings varied. The two main areas of significant difference were research and audit and overall service provision. Observations on service framework indicated that limited resources restricted many of the services. CONCLUSION: The principle approaches to diagnosis, treatment and pathology were similar. Factors affecting the quality of patient experience were variable. This may reflect availability of resources. Standard pathways of care may enhance both the quality of treatment and patient experience.

[Spectrum of laparoscopic surgery for gastric tumors]. / Spektrum der laparoskopischen Chirurgie bei Magentumoren.

Minimally invasive operative procedures are increasingly being used for treating tumors of the upper gastrointestinal tract. While minimally invasive surgery (MIS) has become established as a standard procedure for benign tumors and gastrointestinal stromal tumors (GIST) based on current studies, the significance of MIS in the field of gastric cancer is the topic of heated debate. Until now the majority of studies and meta-analyses on gastric cancer have come from Asia and these indicate the advantages of MIS in terms of intraoperative blood loss, minor surgical complications and swifter convalescence although without any benefits in terms of long-term oncological results and quality of life. Unlike in Germany, gastric cancer in Asia with its unchanged high incidence rate, 50 % frequency of early carcinoma and predominantly distal tumor localization is treated at high-volume centres. Due to the proven marginal advantages of MIS over open resection described in the published studies no general recommendation for laparoscopic surgery of gastric cancer can currently be given.

[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.

[Effects of endovascular therapy for renal artery stenosis on blood pressure and renal function: retrospective analysis of an unselected patient collective from 1994 to 2007]. / Auswirkungen der endovaskulären Therapie von Nierenarterienstenosen auf Blutdruck und Nierenfunktion : Retrospektive Auswertung bei einem nicht-selektierten Patientenkollektiv von 1994-2007.

BACKGROUND: A retrospective analysis of the long-term success rates of endoluminal therapy of renal artery stenosis in a university hospital was carried out. MATERIAL AND METHODS: Preinterventional and postinterventional data contained in the clinical records of all 104 patients who underwent percutaneous transluminal angioplasty (PTA, 25 patients) or stent PTA (79 patients) from 01 January 1994 to 31 December 2007, were documented using an electronically structured questionnaire and a time period classification. Subgroup analyses and statistical calculations were done using t-tests for joint random samples. RESULTS: At day 1 postintervention all patients showed a statistically significant decrease in mean systolic blood pressure (all patients: p=0.002, stent PTA group: p=0.023, PTA group: p=0.022). The significant decrease in mean systolic blood pressure persisted in years 1 and 2 postintervention (all patients: p=0.009 and 0.007, stent PTA group: p=0.039 and 0.015, respectively). Mean blood pressure values remained constant during the other time periods analyzed. In patients with a stent PTA carried out between 2001 and 2007 there was no significant reduction of prescribed antihypertonic drugs (p=0.023 and p=0.046, respectively). Mean serum creatinine concentrations decreased during years 1 and 2 postintervention and increased starting in year 3. In patients with elevated serum creatinine levels prior to the intervention the increase in mean serum creatinine level started in year 5. CONCLUSIONS: Endoluminal therapy of arteriosclerotic renal artery stenosis delays further deterioration of renal function and stabilizes blood pressure as well as the number of prescribed antihypertonic drugs. This can be considered a response to treatment in view of the mostly chronic progressive course of the disease.

[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.

[Current S3 guidelines on surgical treatment of gastric carcinoma]. / Aktuelle S3-Leitlinie zur Chirurgie des Magenkarzinoms.

The current S3 guidelines on the diagnosis and treatment of gastric carcinoma including those of the esophagogastric junction describe optimal clinical practice based on a high level of evidence and expert consensus from different medical disciplines. Endoscopy and performance of multiple biopsies is the standard approach to detect malignant tumors in the upper gastrointestinal tract. Further diagnostic procedures are necessary to evaluate the tumor stage. With the exception of mucosal carcinomas, surgical therapy is the cornerstone of curative treatment in all potentially resectable stages. In locally advanced carcinomas perioperative chemotherapy should be carried out and in high-seated tumors preoperative radiochemotherapy might be an alternative option. Palliative surgical resection should be avoided in disseminated asymptomatic stages. In a palliative situation complications of the tumor should primarily be treated by interventional or conservative procedures.

Lymph node size and metastatic infiltration in adenocarcinoma of the pancreatic head.

BACKGROUND: Preoperative lymph node staging of pancreatic cancer by CT relies on the premise that malignant lymph nodes are larger than benign nodes. In imaging procedures lymph nodes >1 cm in size are regarded as metastatic nodes. The extend of lymphadenectomy and potential application of neoadjuvant therapy regimens could be dependent on this evaluation. PATIENTS AND METHODS: In a morphometric study regional lymph nodes from 52 patients with pancreatic cancer were analyzed. The lymph nodes were counted, the largest diameter of each node was measured, and each node was analyzed for metastatic involvement by histopathological examination. The frequency of metastatic involvement was calculated and correlated with lymph node size. RESULTS: A total of 636 lymph nodes were present in the 52 specimens examined for this study (12.2 lymph nodes per patient). Eleven patients had a pN0 status, whereas 41 patients had lymph nodes that were positive for cancer. Five-hundred-twenty (82%) lymph nodes were tumor-free, while 116 (18%) showed metastatic involvement on histopathologic examination. The mean (±SD) diameter of the nonmetastatic nodes was 4.3 mm, whereas infiltrated nodes had a diameter of 5.7 mm (p = 0.001). Seventy-eight (67%) of the infiltrated lymph nodes and 433 (83%) of the nonmetastatic nodes were ≤5 mm in diameter. Of 11 pN0 patients, 5 (45%) patients had at least one lymph node ≥10 mm, in contrast only 12 (29%) out of 41 pN1 patients had one lymph node ≥10 mm. CONCLUSION: Lymph node size is not a reliable parameter for the evaluation of metastatic involvement in patients with pancreatic cancer.

[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.

[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.

GNAS1 T393C polymorphism is associated with histopathological response to neoadjuvant radiochemotherapy in esophageal cancer.

Recent studies have shown an association between the GNAS1 T393C polymorphism and clinical outcome for various solid tumors. In this study, we genotyped 51 patients from an observational trial on cisplatin/5-FU-based neoadjuvant radiochemotherapy of locally advanced esophageal cancer (cT2-4, Nx, M0) and genotyping was correlated with histomorphological tumor regression. The C-allele frequency in esophageal cancer patients was 0.49. Pearson's chi(2)-test showed a significant (P<0.05) association between tumor regression grades and T393C genotypes. Overall, 63% of the patients in the T-allele group (TT+CT) were minor responders with more than 10% residual vital tumor cells in resection specimens, whereas T(-) genotypes (CC) showed a major histopathological response with less than 10% residual vital tumor cells in 80%. The results support the role of the T393C polymorphism as a predictive molecular marker for tumor response to cisplatin/5-FU-based radiochemotherapy in esophageal cancer.

[The prognostic relevance of age and comorbidity in patients with resected gastric cancer]. / Einfluss von Alter und Begleiterkrankungen auf die Prognose von Patienten mit operiertem Magenkarzinom.

BACKGROUND: In spite of decreasing incidence rates, gastric carcinomas still belong to the top ten causes of tumour death in Germany. The aim of our study was to analyse the influence of age and comorbidity on the prognosis in patients with gastric cancer. MATERIAL AND METHODS: One-hundred and seventy-five consecutive patients with gastric cancer resected under curative intentions were included in this study. The comorbidity (Com) was evaluated with the Charlson comorbidity index (CCI) classifying four different grades of severity (CCI grade 0 = no Com, I = light Com, II = middle Com, III = severe Com). For each decade more than fifty years of age, one point was added for the calculation of the age-adjusted CCI grade. The prognosis was analysed with uni- and multivariate methods. RESULTS: Sixty-two percent of the 175 patients were males. The median age of all patients was 67 years; 18 % were younger than 50 years, 40 % between 51 and 70 years and 42 % were older than 70 years. The frequencies of comorbidity were as follows: CCI grade 0 = 32 %, I = 46 %, II = 18 % and III = 4 %. The 5-years survival rate (5y-SR) for all patients was 39 %. The univariate analysis of the prognosis showed a significant -influence (p < 0.001) of pT, pN, pM and R categories, but no significant results for age and comorbidity. However, the age-adjusted CCI grades demonstrated significantly different prognoses both in the univariate (p < 0.05) and in the multivariate analyses (p < 0.001) including the UICC stages. Patients between 50 and 70 years -without or with only minor comorbidity had the best prognosis (5y-SR = 55 %). In contrast, young patients without comorbidity had a worse prognosis comparable with that of older patients with comorbidity. CONCLUSION: The combination of high age and comorbidity are -together with the UICC stage the most relevant prognostic factors in patients with resected gastric cancer.

Clinicopathological significance of MMP-2 and its specific inhibitor TIMP-2 in gastric cancer.

Matrix metalloproteinases (MMPs) can degrade type IV collagen of extracellular matrices and basal membranes and thus play a key role in the migration of malignant cells. In vivo, MMPs are inhibited by tissue inhibitors of metalloproteinases (TIMPs). Since in a previous study we showed that the expression of MMP-2 correlates with clinicopathological parameters in gastric cancer, we have now investigated a possible correlation of MMP-2 and TIMP-2 expression with survival in gastric cancer, as well as the possible association of TIMP-2 with clinicopathological parameters. Tissue samples were obtained from 116 gastric cancer patients who underwent gastrectomy with extended lymphadenectomy. MMP-2 and TIMP-2 expression was analysed using immunohistochemical staining and was graded semiquantitatively (score 0 - 3). High epithelial MMP-2 immunoreactivity was significantly associated with tumor stage and poor survival using the Kaplan-Meier log-rank statistical method (log-rank statistics). However, using Cox regression analysis, high epithelial MMP-2 immunoreactivity was not an independent prognostic factor. TIMP-2 showed no association with survival in gastric cancer, but the intensity of TIMP-2 staining in tumor cells correlated significantly with tumor differentiation based on the WHO and Lauren and Ming classifications, as well as with presence of distant metastasis. Our results show that high epithelial MMP-2 expression in gastric cancer is associated with poor survival, although it is not an independent prognostic factor, and that aggressive forms of gastric cancer are associated with low TIMP-2 expression.