Differences in the treatment of young gastric cancer patients: patients under 50 years have better 5-year survival than older patients.

PURPOSE: In the literature, the manifestations of gastric cancer have been described based on all patients. In recent times, interest has focused on the subgroup of young patients. In the following analysis, the subgroup of young patients (< 50y) is compared with an older reference group (≥ 50y). MATERIAL AND METHODS: Between 01.01.1995 and 31.12.2005, 482 patients with a previously untreated gastric cancer underwent surgery. Fifty-six patients in this group were under 50 years of age, and the remaining 367 patients constituted the reference group. All data were recorded prospectively and analyzed retrospectively from the clinical cancer registry of the University of Erlangen. RESULTS: The analysis showed that the young patients had a similar tumor stage distribution. Diffuse tumor stages in the Laurén classification occurred significantly more often. The postoperative complication rate was similar, but the hospital mortality rate was significantly lower. The young patients had an obvious, but not significant, 5-year survival advantage in all tumor stages. CONCLUSIONS: Younger patients can be operated on with greater confidence as they have a significantly lower hospital mortality rate. They exhibit markedly better 5-year survival at all tumor stages. According to our data, there is nothing to support the general belief that young patients have a poorer disease course. Further clinical and experimental studies are necessary to investigate this group more precisely.

[Scientific acquisition of knowledge in operative medicine. The importance of intensive care medicine]. / Wissenschaftlicher Erkenntnisgewinn in der operativen Medizin. Die Bedeutung der Intensivmedizin.

The forms of treatment in intensive care medicine and the medicinal and instrumental equipment for maintaining the circulation, pulmonary and renal functions as well as surveillance for recognition of life-threatening arrhythmias or multiorgan failure have experienced an enormous development in recent decades. Survival of traumatized or critically ill patients has been substantially improved. Due to these developments surgeons are confronted with new patterns of diseases which necessitate the development of new operative measures. This article gives a review of the most important changes in operative medicine (e.g. traumatology and vascular surgery) which can essentially be attributed to experience and success in intensive care medicine.

Protein binding capacity in vitro changes metabolism of substrates and influences the predictability of metabolic pathways in vivo.

UNLABELLED: Large numbers of lipophilic molecules are attached to fractions of serum protein, e.g. albumin, in vivo. Cell culture medium of most in vitro hepatocyte models for the prediction of metabolism does not contain albumin. Consequently, in vitro availability and metabolism of substrates could differ significantly from the in vivo situation. The influence of albumin on the in vitro metabolism was tested on a new lipophilic compound. METHODS: Primary human and rat hepatocytes were cultured in a collagen sandwich configuration and incubated with (14)C-labeled compound X127 that is known to exhibit a high propensity to bind to plastic surfaces. Groups contained either 1% (w/v) BSA or none. Substrates as well as metabolism products were determined with radio-HPLC and radioactivity levels in the medium were recorded. RESULTS: Quantitative differences were seen in the distribution of the compound in BSA and non BSA containing groups, thus indicating a substantial binding of the compound to polystyrol surfaces of cell culture dishes. Metabolic radio-HPLC profiles showed different patterns after 24 h of incubation between the two species as well as between the BSA- and non-BSA groups within the species. CONCLUSIONS: With addition of albumin the adherance of lipophilic substrates and metabolites to cell culture dish surfaces can be neutralized and in vitro systems can more closely mimic the in vivo situation.

Laparoscopic diaphragmatic plication: long-term results of a novel surgical technique for postoperative phrenic nerve palsy.

BACKGROUND: Paralysis of the diaphragm is a severe complication of cardiothoracic surgery carrying significant morbidity and mortality. This study demonstrates a novel minimally invasive technique for treatment of phrenic nerve injuries presenting with symptomatic eventration of the diaphragm. It also presents long-term results of three patients treated with this operation. METHODS: Chest x-ray proved eventration of the left diaphragm in all patients. Two patients required treatment due to prolonged respirator therapy/assisted ventilation for 4 weeks after cardiac surgery. One patient suffered from progressive dyspnea caused by increasing left-sided diaphragmatic elevation and underwent surgery 2 years after cardiac surgery. In all cases, a minimally invasive abdominal approach was chosen. During surgery the dome of the diaphragm was pulled down via three percutaneously inserted retention stitches. This resulted in two or three folds of the diaphragm located within the abdomen. These diaphragmatic folds were subsequently tightened using 12 to 15 unresorbable sutures with extracorporally prepared knots. Surgical as well as long-term follow-up results are presented of all patients and a review of the current literature is provided. RESULTS: Mean operating time was 203 min; mean intraoperative blood loss was 130 ml. No major complications occurred during surgery or the postoperative period. At a median follow-up of 72 months no recurrence was observed. CONCLUSIONS: Laparoscopic diaphragmatic plication provides excellent relief of symptoms caused by diaphragmatic paralysis. There is no perioperative morbidity, and hospital stay is short. The laparoscopic approach, therefore, is an attractive surgical alternative for the treatment of phrenic nerve palsy and should be considered in all suitable patients.

Efficacy and tolerance of a new gentamicin collagen fleece (Septocoll) after surgical treatment of a pilonidal sinus.

OBJECTIVE: Pilonidal sinus is common. It causes substantial loss of working hours. The major disadvantage of open wound treatment is the long time required for healing. Primary wound closure is on the other hand often followed by infection. A controlled, multicentre trial was carried out to evaluate the efficacy of a new gentamicin collagen fleece (Septocoll) combined with primary closure. PATIENTS AND METHODS: One hundred and three patients (88 men, 15 women, median age 30 years) were included. Fifty-one were randomised to gentamicin fleece plus primary closure (Genta Group), and 52 patients to open treatment alone (Open Group). RESULTS: The median interval to wound healing was 17 days in the Genta group and 68 days in the Open group (P = 0.0001, log-rank test). Two patients in Group 1 developed infection within the first two weeks, requiring reopening of the wound, with primary wound healing occurring in 73%. Failure of primary healing (27%) was usually due to seroma or spontaneous dehiscence which subsequently healed. CONCLUSION: The combination of gentamicin collagen fleece (Septocoll) with primary closure resulted in a shorter period to healing than the open technique without unwanted effects.

A new bioassay including a small scale hepatocyte bioreactor for hepato-mediated toxicity testing in a target cell line.

New approaches for in vitro testing of hepato-mediated toxicity are undertaken to offer alternatives to in vivo animal testing. The described bioassay for hepato-mediated toxicity testing is based on a small scale hepatocyte-bioreactor with pig hepatocytes connected to a silicon sensor based microphysiometer system for monitoring of the extracellular acidification rate (EAR) of cells and the microphysiometer alone. EAR represents the metabolic activity of tested cells (hepatocytes and ZR 751 cells) under the influence of perfused media, compared to controls, which were set to 100%. Cyclophosphamide (CYCL), whose cytostatic effect is dependent on CYP 450 biotransformation was used as a model substrate. CYCL showed decrease of EAR in hepatocytes, but not in ZR 751 cells. Bioreactor supernatant including CYCL was pumped into the microphysiometer and EARs of the target ZR 751 cell line were recorded. After 7 h of bioreactor supernatant perfusion the ZR 751 cell line showed an EAR decrease of 18.68% +/- 10.18, as compared to controls (bioreactor supernatant from the identical set-up without CYCL). Thus the presented model of hepato-activated toxicity showed an EAR decrease in the ZR 751 cell line that reflected the toxic activation of CYCL by the bioreactor. This new bioassay serves as an example of future applications for hepatocyte bioreactors in automated toxicity testing devices, e.g. in preclinical drug studies or evaluation of hepato-mediated toxicity, not depending on cell destruction or further assays.

Recent advances in minimally invasive colorectal cancer surgery.

Laparoscopy has improved surgical treatment of various diseases due to its limited surgical trauma and has developed as an interesting therapeutic alternative for the resection of colorectal cancer. Despite numerous clinical advantages (faster recovery, less pain, fewer wound and systemic complications, faster return to work) the laparoscopic approach to colorectal cancer therapy has also resulted in unusual complications, i.e. ureteral and bladder injury which are rarely observed with open laparotomy. Moreover, pneumothorax, cardiac arrhythmia, impaired venous return, venous thrombosis as well as peripheral nerve injury have been associated with the increased intraabdominal pressure as well as patient's positioning during surgery. Furthermore, undetected small bowel injury caused by the grasping or cauterizing instruments may occur with laparoscopic surgery. In contrast to procedures performed for nonmalignant conditions, the benefits of laparoscopic resection of colorectal cancer must be weighed against the potential for poorer long-term outcomes of cancer patients that still has not been completely ruled out. In laparoscopic colorectal cancer surgery, several important cancer control issues still are being evaluated, i.e. the extent of lymph node dissection, tumor implantation at port sites, adequacy of intraperitoneal staging as well as the distance between tumor site and resection margins. For the time being it can be assumed that there is no significant difference in lymph node harvest between laparoscopic and open colorectal cancer surgery if oncological principles of resection are followed. As far as the issue of port site recurrence is concerned, it appears to be less prevalent than first thought (range 0-2.5%), and the incidence apparently corresponds with wound recurrence rates observed after open procedures. Short-term (3-5 years) survival rates have been published by a number of investigators, and survival rates after laparoscopic surgery appears to compare well with data collected after conventional surgery for colorectal cancer. However, long-term results of prospective randomized trials are not available. The data published so far indicate that the oncological results of laparoscopic surgery compare well with the results of the conventional open approach. Nonetheless, the limited information available from prospective studies leads us to propose that minimally invasive surgery for colorectal cancer surgery should only be performed within prospective trials.

Techniques and results of esophageal cancer surgery in Germany.

AIMS: This study evaluated the techniques and short-term results of surgical treatment for esophageal cancer in Germany by a nationwide representative survey. METHODS: In 2000 a questionnaire including 63 structured items concerning indication, technique, number of procedures, complications, and hospital mortality was sent to 308 randomly selected general, gastrointestinal, and thoracic surgeons and all university hospitals in Germany (20% of all surgeons). The response rate was 76% ( n=234). RESULTS: In 1999 the 56 participating hospitals performed approximately 370,000 procedures, including 1,677 operations for esophageal diseases, including 891 esophagectomies, 706 for esophageal cancer, 285 for cancer of the cardia. Gastric interposition was the most common technique to restore alimentary tract continuity (86%). Interposition of the colon (ascending colon 64%) is a common procedure only in 22 centers, indicating that experience with this means of esophageal reconstruction is limited. There were no significant differences in complication and mortality rates between gastric transposition and colon interposition. The overall complication rate was 61%, with 36% after gastric interposition and 42% after colon interposition. Anastomotic leakages occurred in 12% and 15%, respectively, and the rate of graft necrosis was 3% in both groups. Hospital mortality was 8% with gastric transposition and 11% with colon interposition. Mean postoperative hospital stay was 24 days. CONCLUSIONS: This study indicates that gastric transposition is frequently used for reconstruction after esophageal resection for malignant disease. It appears that the colon is not as accepted as the stomach for reconstruction, although the reported complication rates compare well with those reported after gastric transposition. This study allows a realistic evaluation of the overall risk of these surgical techniques.

Impact of epidermal growth factor (EGF) radioreceptor analysis on long-term survival of gastric cancer patients.

BACKGROUND: The EGF receptor/ligand system seems to be involved in the regulation of gastric mucosa proliferation and progression of gastric carcinomas. PATIENTS AND METHODS: EGF receptor levels were quantitatively determined in 47 gastric carcinomas by 125J [EGF] radioreceptor assays in membrane preparations of tumor samples or corresponding adjacent mucosa. Specific receptor binding was determined by the analysis of displacement curves by non-linear least-square regression analysis using an estimated model of 'goodness of fit'. RESULTS: Increased EGF receptor binding was observed in gastric carcinomas (mean +/- SEM: 11.87 +/- 1.9 fmol/mg protein) in comparison to adjacent normal gastric mucosa ( 5.28 +/- 1.0 fmol/mg protein, p = 0.003). Elevated EGF receptor levels were especially found in more invasive T3/4 carcinomas, tumors with positive lymph nodes, advanced UICC III carcinomas, undifferentiated tumors, carcinomas of the diffuse-type according to Lauren's classification and gastric carcinomas localized distal from the cardia. In histopathologically normal appearing gastric mucosa, EGF-receptor levels were significantly decreased relative to corresponding tumor samples from advanced UICC stages (UICC I vs UICC I/II: p = 0.008) or tumors with low levels of differentiation (G2 vs G3: p = 0.028). Overall survival was significantly reduced in patients with advanced gastric carcinomas according to UICC classification (UICC III vs UICC I/II: 18.8 vs 45.5 months, p = 0.016). A subgroup analysis of gastric carcinomas localized distal from the cardia indicated, that increased EGF-receptor levels were an independent indicator of poor prognosis as determined by univariate (p = 0.020) and multivariate analysis (p = 0.042). CONCLUSION: Gastric carcinomas with increased EGF receptors might be a possible target for anticancer strategies blocking the EGF receptor/ligand pathway.

[Antireflux surgery in Germany. Results of a representative survey with analysis of 2,540 antireflux operations]. / Antirefluxchirurgie in Deutschland. Ergebnisse einer repräsentativen Umfrage mit Analyse von 2.540 Antirefluxoperationen.

INTRODUCTION: Aim of this study was the evaluation of antireflux surgery in Germany. METHODS: An anonymous questionnaire including 288 structured items about diagnostic and therapeutic approaches, complications and mortality was sent to 33% randomly selected German general surgeons (n = 546) at the end of 2000. RESULTS: A total of 2,540 antireflux procedures was reported, 81% were performed laparoscopically; 65% were total, 31% partial fundoplications. The number of surgeons offering laparoscopic antireflux surgery increased from 0.3% in 1990 to 5% in 1995 and to 32% in 2000. Numerous modifications regarding esophageal mobilisation, crural repair, kind and extension of the wrap, use and size of a bougie, as well as an additional gastropexy were observed. Morbidity rates were significantly higher for open than for laparoscopic procedures (15.0% vs. 7.7%), mainly caused by wound healing problems (4.4% vs. 0.8%) and splenic lesions (3.1 vs. 0.6%). Gastric and esophageal perforations were similar in both groups (1.1 vs. 0.9%). Hospital mortality rate was 0.1%. We observed a frequency dependent learning curve regarding complication rates after laparoscopic antireflux surgery (< 11 fundoplication p.a.: 14.0%; 11-30 fundoplications: 7.3% (p = 0.05); > 30 fundoplications: 4.2% (p = 0.05%). Long-term-dysphagia occurred more often after 360 degrees-versus partial fundoplications (6.6% vs. 2.4%; p < 0.001) and after Nissen/Nissen-Rossetti--than after Floppy-Nissen-procedures (6.6% vs. 3.6%, p = 0.1). The recurrency rate was 9.3% without significant differences between the procedures. CONCLUSION: Laparoscopy has replaced the open technique. Different technical approaches significantly affect the outcome after laparoscopic antireflux surgery in Germany.

[Indications, techniques and results of laparoscopic surgery for diaphragmatic diseases]. / Indikation, Technik und Ergebnisse der laparoskopischen Zwerchfellchirurgie.

Eleven patients with congenital, traumatic and functional extrahiatal diaphragmatic lesions are reported. Since 1991 two patients with acute, two patients with old ruptures of the diaphragm and one patient with a Morgagni-Larrey-hernia were successfully treated by laparoscopic direct suturing. In two other patients with Morgagni hernias we used a polypropylene mesh for closure of the defect. One procedure was performed in a patient with symptomatic congenital dysplasia of the diaphragm with aplasia of the pericard. Laparoscopic plication of the diaphragm was performed in three symptomatic patients with phrenic nerve palsy after cardiac surgery. The intra- and postoperative course was uneventful in all cases. During a median follow-up of 60 months there was no recurrence. Therefore the laparoscopic technique is an effective and attractive alternative for treatment of these diseases.

[Management of common bile duct stones--Results of a nationwide survey with analysis of 8 433 common bile duct explorations in Germany]. / Management der Choledocholithiasis - Umfrageergebnisse und Analyse von 8 433 Gallengangsrevisionen in Deutschland, Germany.

BACKGROUND: Aim of this study was the evaluation of the management of choledocholithiasis and outcome of laparoscopic as well as open cholecystectomy in Germany. METHODS: A written questionnaire was sent to 449 randomly selected German surgeons annually from 1991 to 1994 and additionally to all German university hospitals until 1998. RESULTS: A total of 98 482 operations for gallstone disease including 86 485 cholecystectomies (non-university hospitals 1991-1993: n = 60 246, university hospitals 1991-1996: n = 26 239) and 8 433 common bile duct (CBD) explorations (non-university hospitals: n = 6 919, university hospitals: n = 1 514) with or without cholecystectomy were reported. The overall complication rate for CBD explorations was 13.2 % (non-university hospitals) and 15.1 % (university hospitals), the overall hospital mortality rate was 0.64 % (non-university hospitals) and 0.58 % (university hospitals, n. s.). When choledocholithiasis was suspected, in 1998 all university hospitals used a two-stage management with preoperative ERC. In case of diagnosed isolated choledocholithiasis 93 % usually chose an endoscopic approach. When simultaneous cholecysto-choledocholithiasis was diagnosed preoperatively 86 % of the university hospitals used a two-stage management with preoperative ERC and stone extraction and secondary cholecystectomy (1991: 45 %). The percentage of CBD explorations decreased continuously from 7.4 % in 1991 to 3.8 % in 1996 (p < 0.01). CONCLUSION: These results allow for the estimation of frequency and overall risks in surgical therapy of CBD stones. At the moment, laparoscopic CBD exploration does not play a significant role in Germany. Data show a trend to the two-stage "therapeutical splitting" with lower complication rates.

[Postoperative endoscopy for the diagnosis and therapy of complications]. / Postoperative Endoskopie zur Diagnose und Therapie von Komplikationen.

A variety of endoscopic methods are available as the main tools in the diagnostics and therapy of various complications after visceral and thoracic surgery. Indications for endoscopic interventions are anastomotic leaks, stenoses, Gl-tract bleedings, biliary lesions and functional problems after surgical procedures. The most common are fibrin sealing of fistulas, dilatation and bougienage, injection therapy for bleeding, bile duct interventions and stent implantations. In most cases operative revisions can be avoided by using endoscopic methods with an overall good success rate. No disadvantages are foreseen following conventional operative interventions if the endoscopic treatment is not successful.

[Surgical therapy of locally advanced and primary inoperable pancreatic carcinoma after neoadjuvant preoperative radiochemotherapy]. / Chirurgische Therapie des lokal fortgeschrittenen und primär inoperablen Pankreaskarzinoms nach neoadjuvanter präoperativer Radiochemotherapie.

INTRODUCTION: So far, surgery represents the only prospect for cure in patients with pancreatic cancer. Most patients, however, present with locally advanced pancreatic cancer at primary diagnosis. Recently, novel therapeutic regimens with preoperative radiochemotherapy have been developed that may improve long-term survival and resectability rates of patients with locally advanced pancreatic cancer. METHODS: This feasibility study evaluates the preliminary results of neoadjuvant therapy with gemcitabine and 5-fluorouracil (5-FU) or cisplatin. Twenty-six patients suffering from locally advanced pancreatic cancer were considered for preoperative radiochemotherapy. They received radiation (45 Gy) and chemotherapy with simultaneous or sequential gemcitabine and 5-FU (n = 15) or gemcitabine and cisplatin (n = 11) administration prior to surgical resection. RESULTS: Mean patient age was 62.4 +/- 2.6 years and 62% (n = 16) were male. The response rate was 69%, and 11 patients underwent curative surgical resection of the pancreatic cancer. Nine Whipple procedures and two complete pancreatectomies were carried out. In five patients a total of eight surgical complications were observed. Median overall survival was 9.8 months after primary cancer diagnosis (mean 12.0 +/- 1.2). During follow-up no local recurrent disease was detected. CONCLUSIONS: Our findings lead us to conclude that preoperative chemoradiation with 45 Gy, gemcitabine and 5-FU or cisplatin is a powerful therapeutic tool in patients with locally advanced non-resectable pancreatic cancer. Major resections, including vascular reconstructions, are nonetheless associated with increased mortality. Preoperative chemoradiation contributes to improved survival in patients with primary non-resectable pancreatic cancer.

Laparoscopic repair of an extrahiatal hernia caused by congenital dysplasia: a case report.

A 40-year-old woman with complaints of relapse in the upper abdomen and dysphagia was referred for laparascopic hiatal hernia repair. Chest radiograph, barium-swallow, and upper endoscopy revealed a paraesophageal hernia. Esophageal manometry and 24-h-pH study showed no pathological findings. A laparoscopic gastropexy was planned. Intraoperatively, in contradiction to the preoperative findings, an extrahiatal hernia containing most of the stomach was found. After resection of the hernia sac, the beating heart without covering pericardium was seen. These findings were confirmed by an additional thoracoscopy at the end of the operation. The defect was closed by direct suturing. The postoperative course and 2-month follow-up were uneventful. The resected parts of the hernia sac showed an embryonic and dysgenetic etiology. This rare malformation has been reported in combination with complex syndromes, which appear with serious clinical and morphological signs in the neonatal period. In adults, the pericardial aplasia can be observed during diagnostic or surgical interventions. In these patients, complaints are usually not caused by the malformation but may be due to the occasional herniation of abdominal organs. We consider laparoscopic repair to be a gentle and safe procedure for the treatment of extrahiatal hernias.

Improvement of lung preservation -- from experiment to clinical practice.

BACKGROUND: Reperfusion injury represents a severe early complication following lung transplantation. Among the pathogenetic factors, the high potassium content of Euro-Collins(reg) solution is discussed. MATERIAL AND METHODS: In a pig model of orthotopic left-sided lung transplantation we investigated the effect of Euro-Collins solution (EC: n = 6) versus low potassium dextran (LPD: Perfadex: n = 6). Sham-operated (n = 6) animals served as control. Transplant function, cellular energy metabolism and endothelial morphology served as parameters. In a clinical investigation, 124 patients were evaluated following single (EC: n = 31; LPD n = 37) or double (EC: n = 17; LPD n = 39) lung transplantation, whose organs where preserved with EC (n = 48) or LPD (n = 76). Duration of ischemia, duration of ventilation and stay on ICU were registered. Primary transplant function was evaluated according to AaDO(2) values. Cause of early death (30 days) was declared. RESULTS: Experimental results: After flush with EC and 18 h ischemia, a reduction of tissue ATP content (p < 0.01 vs inital value and LPD) was noted. Endothelial damage after ischemia was severe (p < 0.05 vs control), paO(2) was significantly decreased. CLINICAL RESULTS: In the LPD group, duration of ischemia was longer for the grafts transplanted first (SLTx and DLTx: p = 0.0009) as well as second (2. organ DLTx: p = 0.045). Primary transplant function was improved (day 0: SLTx: p = 0.0015; DLTx: p = 0.0095, both vs EC). Duration of ventilation and stay on ICU were shorter (n.s.). Reperfusion injury-associated death was reduced from 8% (EC) to 0 (LPD). CONCLUSION: In experimental lung preservation, LPD lead to an improved graft function. These results were confirmed in clinical lung transplantation. Clinical lung preservation, therefore, should be carried out by use of LPD.

[Surgical therapy of advanced gallbladder carcinoma]. / Die chirurgische Therapie des fortgeschrittenen Gallenblasen--Karzinoms.

The use of surgery for the treatment of advanced gall bladder cancer is controversially discussed. This retrospective study included 204 patients who were subjected to surgery due to advanced gall bladder cancer at the Klinikum Grosshadern. Mean survival time of all patients was 4.5 months. Advancement of the tumor stage resulted in a decreased percentage of possible R0 resections (T3 n = 48, R0 31%, T4 n = 87, R0 13%). Nonetheless, R0 resections of T3 tumors significantly increased the survival rate compared to R1 and R2 resections (mean survival 20.2 vs. 4.5 months). R0 resections of T4 tumors also significantly attenuated the survival rate (18.1 vs. 2.4 months compared to R1 and R2 resections). Thus, diagnostic procedures have to focus on identifying patients with possible R0 resections and perform extensive resections on those patients.