Neoadjuvant chemotherapy followed by chemoradiation and surgery with and without cetuximab in patients with resectable esophageal cancer: a randomized, open-label, phase III trial (SAKK 75/08).

Background: This open-label, phase III trial compared chemoradiation followed by surgery with or without neoadjuvant and adjuvant cetuximab in patients with resectable esophageal carcinoma. Patients and methods: Patients were randomly assigned (1 : 1) to two cycles of chemotherapy (docetaxel 75 mg/m2, cisplatin 75 mg/m2) followed by chemoradiation (45 Gy, docetaxel 20 mg/m2 and cisplatin 25 mg/m2, weekly for 5 weeks) and surgery, with or without neoadjuvant cetuximab 250 mg/m2 weekly and adjuvant cetuximab 500 mg/m2 fortnightly for 3 months. The primary end point was progression-free survival (PFS). Results: In total, 300 patients (median age, 61 years; 88% male; 63% adenocarcinoma; 85% cT3/4a, 90% cN+) were assigned to cetuximab (n = 149) or control (n = 151). The R0-resection rate was 95% for cetuximab versus 97% for control. Postoperative treatment-related mortality was 6% in both arms. Median PFS was 2.9 years [95% confidence interval (CI), 2.0 to not reached] with cetuximab and 2.0 years (95% CI, 1.5-2.8) with control [hazard ratio (HR), 0.79; 95% CI, 0.58-1.07; P = 0.13]. Median overall survival (OS) time was 5.1 years (95% CI, 3.7 to not reached) versus 3.0 years (95% CI, 2.2-4.2) for cetuximab and control, respectively (HR, 0.73; 95% CI, 0.52-1.01; P = 0.055). Time to loco-regional failure after R0-resection was significantly longer for cetuximab (HR 0.53; 95% CI, 0.31-0.90; P = 0.017); time to distant failure did not differ between arms (HR, 1.01; 95% CI, 0.64-1.59, P = 0.97). Cetuximab did not increase adverse events in neoadjuvant or postoperative settings. Conclusion: Adding cetuximab to multimodal therapy significantly improved loco-regional control, and led to clinically relevant, but not-significant improvements in PFS and OS in resectable esophageal carcinoma. Clinical trial information: NCT01107639.

Quaternary cytoreductive surgery in ovarian cancer: does surgical effort still matter?

BACKGROUND: To evaluate surgical outcome and survival benefit after quaternary cytoreduction (QC) in epithelial ovarian cancer (EOC) relapse. METHODS: We systematically evaluated all consecutive patients undergoing QC in our institution over a 12-year period (October 2000-January 2012). All relevant surgical and clinical outcome parameters were systematically assessed. RESULTS: Forty-nine EOC patients (median age: 57; range: 28-76) underwent QC; in a median of 16 months (range:2-142) after previous chemotherapy. The majority of the patients had an initial FIGO stage III (67.3%), peritoneal carcinomatosis (77.6%) and no ascites (67.3%). At QC, patients presented following tumour pattern: lower abdomen 85.7%; middle abdomen 79.6% and upper abdomen 42.9%. Median duration of surgery was 292 min (range: a total macroscopic tumour clearance could be achieved. Rates of major operative morbidity and 30-day mortality were 28.6% and 2%, respectively.Mean follow-up from QC was 18.41 months (95% confidence interval (CI):12.64-24.18) and mean overall survival (OS) 23.05 months (95% CI: 15.5-30.6). Mean OS for patients without vs any tumour residuals was 43 months (95% CI: 26.4-59.5) vs 13.4 months (95% CI: 7.42-19.4); P=0.001. Mean OS for patients who received postoperative chemotherapy (n=18; 36.7%) vs those who did not was 40.5 months (95% CI: 27.4-53.6) vs 12.03 months (95% CI: 5.9-18.18); P<0.001.Multivariate analysis indentified multifocal tumour dissemination to be of predictive significance for incomplete tumour resection, higher operative morbidity and lower survival, while systemic chemotherapy subsequent to QC had a protective significant impact on OS. No prognostic impact had ascites, platinum resistance, high grading and advanced age. CONCLUSION: Even in this highly advanced setting of the third EOC relapse, maximal therapeutic effort combining optimal surgery and chemotherapy appear to significantly prolong survival in a selected patients 'group'.

Minimally invasive accessory splenectomy for recurrent gastric variceal bleeding due to left-sided portal hypertension: report of the first case.

Upper gastrointestinal bleeding from esophagogastric varices is a common scenario, especially in patients with portal hypertension induced by liver cirrhosis or other diseases with thrombosis of the splenic vein. However, accessory spleen as pathophysiological cause of a regional, left-sided portal hypertension and consecutive development of isolated gastric varices is rare. We report a case of recurrent gastric variceal bleeding resulting from sinistral portal hypertension associated with an accessory spleen in a patient who had traumatic splenectomy many decades before. The accessory spleen is an extremely rare cause for the development of regional, left-sided portal hypertension leading to isolated gastric varices. Minimally invasive splenectomy is a safe and efficient treatment option.

The impact of carbon dioxide pneumoperitoneum on liver regeneration after liver resection in a rat model.

BACKGROUND: In recent years, laparoscopic hepatic resection is performed by an increasing number of surgeons. Despite many advantages of the laparoscopic procedure, it is unclear whether the pneumoperitoneum affects the postoperative liver regeneration after liver resection. The current study aimed to investigate the influence of a carbon dioxide (CO(2)) pneumoperitoneum on liver regeneration in a rat model. METHODS: In this study, 60 male Wistar rats were subjected to 70% partial hepatic resection. Of these 60 animals, 30 underwent preoperative pneumoperitoneum at 9 mmHg for 60 min. After hepatic resection, the rats were killed at 12, 24, and 48 h, and on days 4 and 7. The outcome parameters were hepatocellular injury (plasma aminotransferases), oxidative stress (plasma malondialdehyde), interleukin-6 (IL-6), and liver regeneration (mitotic index, KI-67; regenerating liver mass). RESULTS: The mitotic index was significantly lower in the pneumoperitoneum group than in the group without pneumoperitoneum at all time points (p < 0.05). In the pneumoperitoneum group, KI-67 was significantly lower on day 4 (p < 0.05). The liver regeneration rate was significantly lower for the animals with pneumoperitoneum on days 2 and 4 (p < 0.05). The postoperative hepatocellular injury was significantly greater after pneumoperitoneum at 12, 24, and 48 h (p < 0.05). Plasma malondialdehyde and IL-6 were significantly higher in the pneumoperitoneum group at 24 h and on day 4 (p < 0.05). CONCLUSION: This study showed that pneumoperitoneum before extended liver resection impaired postoperative liver regeneration. Oxidative stress reaction and hepatocellular damage was markedly higher after pneumoperitoneum. Further investigations, especially with patients that have impaired liver function, are necessary for clinical consequences to be drawn from these results.

Advances in image guided conventional and minimal invasive liver surgery.

Technological developments, advances in perioperative medicine and ongoing scientific research have led to reduced rates of mortality and morbidity in patients undergoing major liver surgery. Under these conditions, the frontier of resectability is constantly in movement towards more complex cases with extended tumor spread and potentially minimized remnant liver volume. A promising technique to support oncological correct and safe liver surgery is the introduction of preoperative computer based planning models and intraoperative navigation systems. Whereas three-dimensional (3D) liver models are commercially available and have been clinically implemented, the use of navigation systems is currently under evaluation by different groups using a variety of techniques. This manuscript is meant to give the reader an overview on current developments, difficulties and future aspects of image guided liver surgery.

Imaging sequences for intraoperative MR-guided laparoscopic liver resection in 1.0-T high field open MRI.

The aim of this study was to identify suitable interactive (dynamic) magnetic resonance (MR) sequences for real-time MR-guided liver dissection in a 1.0-T high field open MRI system. Four dynamic sequences encompassing balanced steady state free precession (bSSFP), T1W gradient echo (GRE), T2W GRE and T2W fast spin echo (FSE) were analysed regarding the image quality, artefact susceptibility and the performance of SNR and CNR. The T2W FSE sequence (1.5 s/image) was considered superior because of an intraoperative SNR of 6.9 (+/-0.7) and CNR (vessel to parenchyma) of 5.6 (+/-1.7) in the interventional setting. As a proof of concept, MR-guided laparoscopic liver resection was performed in two healthy domestic pigs by using the T2W FSE sequence. The additional MR images offered simultaneous multiplanar real-time visualisation of the liver vessels during the intervention and thereby increased the anatomical orientation of the surgeon.

Surgical results of patients after esophageal resection or extended gastrectomy for cancer of the esophagogastric junction.

Precise classification of cancers of the esophagogastric junction according to Siewert may be difficult for the presence of Barrett's esophagus or hiatal hernia, which subsequently leads to a difficult choice of the surgical procedure of esophagectomy or gastrectomy. Ninety-six patients with such cancers were operated on in our department in 7 years. Twenty-nine patients (30.2%), classified as type I (group 1), underwent a transthoracic esophagectomy with gastric pull up. Sixty-seven patients (69.8%) classified as type II or III (group 2) underwent an extended gastrectomy. We compared the patients of both groups retrospectively for disease-free survival and postoperative complications. The general performance status of most patients was comparable in both groups and was assigned to the American Society of Anesthesiologists class II or III. Statistically significant differences between the groups were seen for the postoperative reintubation rate [group 1: 31.0% vs. group 2: 9.0% (P = 0.009)], median time for surgery [group 1: 6 (3.5-8.5) hours vs. group 2: 4.7 (2.2-11.5) hours (P = 0.001)], time in the intensive care unit [group 1: 6 (3-85) days vs. group 2: 3 (1-54) days (P = 0.001)], median hospitalization time [group 1: 23 (14-105) days vs. group 2: 18 (10-63) days (P = 0.018)]. No statistical difference was observed for the recurrence-free survival of 40% after 3 years (P = 0.311), the mortality rate, the morbidity rate (P = 0.108), surgical and respiratory complications, and the incidence of anastomotic leakage (P = 0.645). We conclude that in selected cases it may be possible to perform an extended gastrectomy for small type I cancers.

[Clinical and pathological prognostic factors for cancers of the esophagogastric junction]. / Klinisch-pathologische Prognosefaktoren des Adenokarzinoms des gastroösophagealen Ubergangs.

INTRODUCTION: Adenocarcinoma of the esophagogastric junction (AEG) is a particular tumour entity because two substantially different surgical procedures are required according to the location. There is no difference in long-term prognosis between the tumour types in spite of the different surgical procedures. We were interested to evaluate the clinical and pathological prognostic factors of the AEGs which were operated in our department. PATIENTS AND METHODS: 108 patients were operated for AEG between 1.1.2000 and 1.4.2006 in our institution. 32 (29.6 %) patients with distal esophageal cancer (type I according to Siewert) underwent a transthoracic esophagectomy with gastric pull-up and two-field lymphadenectomy. 57 (52.8 %) patients with type II and 19 (17.6 %) patients with type III cancers received an extended gastrectomy with D2 lymphadenectomy. The retrospective analysis was focused on clinical and pathological parameters. Possible differences between the tumour types were also evaluated. Median follow-up was 11.4 months (range: 1-57 months). RESULTS: Follow-up data were complete for 107 patients. A median survival of 17.4 +/- 3.25 months and a cumulative survival of 30 % were independent of the tumour location and the surgical procedure. Overall hospital mortality was 3.7 %. The univariate analysis showed that survival was significantly associated with the T category, lymph node status, lymphangio- and angioinvasion and tumour grading. In the multivariate analysis, only lymph node status was identified as an independent prognosis factor for survival. Where-as the R status was not a prognostic factor per se, how-ever, patients with an R0 situation without lymphangio- and angioinvasion had a significantly better survival compared to all other patients (p = 0.001). An increased angioinvasion rate was observed in type III tumours (52.6 %) in comparison to type I (21.9 %) and type II (21.1 %) tumours. CONCLUSION: The prognostic factors of our patients determined substantially the prognosis of the patients. Patients with lymph- or haemangioinvasion should regarded as high-risk patients independent of the R status. Close oncological follow-up including potential adjuvant treatment in these patients is recommended.

Initial experience with the use of fibrin sealant for the fixation of the prosthetic mesh in laparoscopic transabdominal preperitoneal hernia repair.

INTRODUCTION: Laparoscopic inguinal hernia repair offers more rapid recovery and less pain than with the traditional open approach. However, injury to the nerves of the lumbar plexus with subsequent chronic pain or neuralgia has a reported incidence of 2% during laparoscopic hernia repair, particularly when the transabdominal preperitoneal technique (TAPP) is used. These complications are inherent to the use of staples for fixation of the mesh. To avoid nerve irritation, we considered the use of fibrin sealant for the fixation of the mesh instead of staples. The aim of this study was to evaluate this technique and to compare the short-term follow-up of these patients with patients who underwent the staple repair technique. This is the first reported use of fibrin sealant in laparoscopic TAPP hernia repair. METHOD: Between September and November 2004, we performed 17 consecutive laparoscopic hernia repairs (TAPP) in 14 patients (3 bilateral hernias) with primary hernias. The prosthetic mesh was fixed (10 x 15 cm) with 1 ml fibrin. The fibrin was applied using a special laparoscopic applicator. The peritoneum was closed with absorbable sutures. The postoperative course of these patients was compared with a cohort of matched patients who received the traditional staple fixation of the prosthetic mesh. RESULTS: Patients were evaluated at a median follow-up of 10.4 months (3.8-16.0 months). All patients underwent postoperative physical examinations. No recurrent hernia was found. There were 2 seromas and one hematoma in the stapled group. In the stapled group, one patient had pain in the area of the lateral femoral cutaneous nerve. There was no postoperative complication in the non-stapled group. CONCLUSION: Fibrin fixation of the mesh during laparoscopic transabdominal preperitoneal inguinal hernia repair is feasible without higher risk of recurrences. In addition the fibrin fixation method may decrease postoperative neuralgia and reduce the incidence of postoperative seromas and hematomas.

[Treatment of iatrogenic bile duct lesions from laparoscopic cholecystectomy]. / Behandlung von iatrogenen Gallengangverletzungen im Rahmen der laparoskopischen Cholecystektomie.

Injuries of the biliary tract following laparoscopic cholecystectomy have increased with the widespread use of the procedure. Compared to the conventional open choelycstectomy, the incidence of bile duct injuries is at least twofold higher after the laparoscopic procedure. A number of risk factors for the occurrence of bile duct injuries have been well described, including severe inflammation, bleeding, anatomical variations and lack of surgical experience. The appropriate management of bile duct injuries depends on the time of diagnosis after the injury and the type of injury. While peripheral leakages and short strictures can be treated endoscopically, extended injuries and long strictures require surgical reconstruction. The best long-term results are achieved with a tension-free, end-to-side mucosa-to-mucosa Roux-Y hepaticojejunostomy.

Continuous versus conventional tissue expansion: experimental verification of a new technique.

Historically, tissue expansion is a prolonged process, typically requiring at least 6 weeks to complete. Recently, interest has increased in shortening this time period. In the current study, a continuous infusion device maintaining constant expander pressure less than capillary filling pressure was used in a canine model in seven dogs to minimize the time period needed to achieve significant expansion. There were no complications, except one device malfunction, corrected by changes in design. The process was shown to be a safe and effective means of producing amounts of expansion similar to traditional methods in approximately 72 hours, with expansion of 28 percent (n = 6) for continuous tissue expansion (CTE) versus 34 percent (n = 6) for a 2-week rapid expansion protocol. This expansion was derived from either stretch of preexisting tissue (46 percent for CTE, 35 percent for 2-week expansion) or recruitment of adjacent tissue. The clinical application of continuous tissue expansion could permit the advantages of tissue expansion to be obtained in many more situations than are currently available to traditional tissue expansion techniques.

Low malignant epithelioid peritoneal mesothelioma: successful treatment with surgical therapy alone.

A 31-year-old man presented with malignant peritoneal mesothelioma. His past medical history was uneventful, specifically there was no personal or environmental asbestos exposure. The patient was treated by complete tumor resection including peritonectomy. Because of the histologic diagnosis of a low malignant, unusual highly differentiated epithelioid tumor with very low proliferative activity a postoperative chemotherapy was not administered. After a follow-up of 20 months, the patient is in excellent clinical condition and there is no evidence of disease by computed tomography. The present paper reports a case of this rare variant of malignant peritoneal mesothelioma.

Cocaine use in pregnancy in Amsterdam.

To study the effects of cocaine use in pregnancy in Amsterdam, clinical data on cocaine-using pregnant women (n = 21) and their offspring (n = 23) were obtained retrospectively (1987-1994) at the Academic Medical Center, Amsterdam. Infants exposed to cocaine had a median gestational age of 39 weeks and a median birth weight of 3090 g. There were six preterm infants, two small-for-gestational-age infants and five infants with a small head circumference. Three infants had a congenital malformation. One infant (Potter's syndrome) died shortly before birth. One infant had congenital syphilis, four had intracerebral abnormalities on ultrasound and four had abnormal neurologic symptoms in the neonatal period. One infant died after 21 days of life. At follow-up four infants showed abnormal development. In 12 of the 23 infants (52%), one or more possible effects of cocaine were found.

[Partial hepatectomy after post-traumatic liver abscess]. / Leberteilresektion nach posttraumatischem Leberabscess.

Post-traumatic pyogenic liver abscess is a rare disease. We present the case of a 38-year-old man with multilocular liver abscess and pleural empyema following blunt abdominal trauma. The patient had a prodrome lasting 3 months before presenting in our department. The therapy included partial hepatectomy and pleural drainage. Clinical signs, diagnosis and possible therapy are discussed in this case report.

[Classification and treatment of bile duct injuries after laparoscopic cholecystectomy]. / Einteilung und Behandlung von Gallengangverletzungen nach laparoskopischer Cholecystektomie.

Iatrogenic bile duct lesions are serious complications during laparoscopic cholecystectomy and include biliary leakage and major bile duct injury. The incidence of biliary lesions following laparoscopic cholecystectomy is up to threefold higher than that of the open procedure. A total of 108 patients with bile duct lesions after laparoscopic cholecystectomy were treated at our institution. Endoscopic treatment was successful in 68 cases, 6 patients were treated by external drainage, and 34 patients required surgical therapy. Selection criteria for the type of treatment included the etiology, anatomical situation, and diagnostic interval of the biliary lesion. We suggest a classification of bile duct injury and a proposal for diagnosis and treatment of these complications.

APACHE III score is superior to King's College Hospital criteria, MELD score and APACHE II score to predict outcomes after liver transplantation for acute liver failure.

OBJECTIVES: The Model for End-Stage Liver Disease score and King's College Hospital (KCH) criteria are accepted prognostic models acute liver failure (ALF), while the use of (APACHE) scores predict to outcomes of emergency liver transplantation is rare. MATERIALS AND METHODS: The present study included 87 patients with ALF who underwent liver transplantation. We calculated (KCH) criteria, as well as MELD, APACHE II, and APACHE III scores at the listing date for comparison with 3-month outcomes. RESULTS: According to the Youden-Index, the best cut-off value for the APACHE II score was 8.5 with 100% sensitivity, 49% specificity, 24% positive predictive value (PPV), and 100% negative predictive value (NPV). Patients with <8.5 points had a significantly higher survival rate (P < .05). The proposed APACHE III cut-off was 80. The APACHE III score demonstrated the highest specificity and PPV (90% specificity, 50% PPV). The NPV was 92%. With a 90-point threshold the specificity increased to 98% with 75% PPV and 89% NPV. Only 1 of 4 patients with a score >90 survived transplantation (P = .001). MELD score and KCH criteria were not significant (P > .05). According to the Hosmer-Lemeshow test, only the APACHE III score adequately describe the data. CONCLUSIONS: The APACHE III score was superior to KCH criteria, MELD score, and APACHE II score to predict outcomes after transplantation for ALF. It is a valuable parameter for pretransplantation patient selection.

Laparoscopic fenestration of non-parasitic liver cysts and health-related quality of life assessment.

Although laparoscopic fenestration has become an established treatment in symptomatic liver cyst patients in the recent years, the success of surgical treatment cannot only be evaluated by post-operative morbidity and mortality. Therefore, the aim of this study was to analyze the safety of laparoscopic fenestration of non-parasitic liver cysts and to assess the impact of this therapy on patients' quality of life. A total of 43 patients who underwent laparoscopic fenestration of non-parasitic liver cysts at our center were included in this study. Post-operative course was assessed and patients' quality of life was evaluated before surgery and at present time using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ C-30). The results were that, post-operative morbidity and mortality rates were 0%. After a median follow-up of 49 months (19-97 months) the recurrence rate was 11.1% for simple liver cysts (SLC) and 42.9% for polycystic liver disease (PCLD). Thirty-one out of 43 patients (72.1%) completed the EORTC C-30 questionnaire. There was highly significant post-operative improvement in global health status (p < 0.001) as well as in physical (p = 0.002), role (p = 0.004), emotional (p = 0.003) and social (p = 0.001) functioning. Furthermore, a significant reduction of symptoms could be shown for pain (p < 0.001), nausea and vomiting (p = 0.001), appetite loss (p = 0.006), insomnia (p = 0.04) and fatigue (p = 0.025). To conclude, laparoscopic fenestration of symptomatic non-parasitic liver cysts is a safe procedure with good long-term results and the patients' benefit of this intervention is excellent as shown by highly significant improvement in patients' quality of life.

Results of liver resection in combination with radiofrequency ablation for hepatic malignancies.

INTRODUCTION: Liver tumors should be surgically treated whenever possible. In the case of bilobar disease or coexisting liver cirrhosis, surgical options are limited. Radiofrequency ablation (RFA) has been successfully used for irresectable liver tumors. The combination of hepatic resection and RFA extends the feasibility of open surgical procedures in patients with liver metastases and hepatocellular carcinoma (HCC). PATIENTS AND METHODS: RFA was performed with two different monopolar devices using ultrasound guidance. Intraoperative use of RFA for the treatment of liver metastases or HCC was limited to otherwise irresectable tumors during open surgical procedures including hepatic resections. Irresectability was considered if bilobar disease was treated, the functional hepatic reserve was impaired or appraised marginal for allowing further resection. RESULTS: Ten patients with both liver metastases and HCC, and two patients with cholangiocellular carcinoma were treated. Complete initial tumor clearance was achieved in all patients. Two patients of the metastases group and five patients of the HCC group suffered from local recurrence after a median of 12 months (1-26) (local recurrence rate 32%). Five patients of the metastases group and six patients of the HCC group developed recurrent tumors in different areas of the ablation site after a median time of 4 months (2-18) (distant intrahepatic recurrence in 55%). Survival at 31 months was 36%. CONCLUSION: RFA extends the scope of surgery in some candidates with intraoperatively found irresectability.

Can complete tumor resection be predicted in advanced primary epithelial ovarian cancer? A systematic evaluation of 360 consecutive patients.

BACKGROUND: Postoperative tumor-residual-mass is the most important prognostic factor in epithelial ovarian cancer (EOC). Aim of our study was to define risk factors for incomplete tumor resection in advanced primary EOC. PATIENTS & METHODS: A validated intraoperative documentation tool ("Intraoperative-Mapping of Ovarian-Cancer" = "IMO") was applied to systematically evaluate intraabdominal tumor dissemination pattern, maximal tumor load, tumor residuals and operative morbidity for all EOC-patients who underwent primary surgery in our institution during 09/2000-08/2009. Univariate- and multivariate analysis were performed to identify independent risk factors of incomplete tumor resection and operative complications. RESULTS: We evaluated 360 consecutive EOC-patients of FIGO-stage-III/IV. In 221(61%) patients a complete tumor resection could be obtained. In 50(14%) patients tumor residuals were <0.5 cm. Sixty (17%) patients developed a major (14%) complication. Multivariate analysis identified intestinal resection (OR:2.0; 95%CI:1.14-3.4; p = 0.01) and macroscopical tumor residuals (OR:0.5; 95%CI:0.2-1.2; p = 0.05) as independent predictors of major operative morbidity. Tumor dissemination pattern and maximal tumor load were significantly different between tumor-free and not-tumor-free operated patients, with less extrapelvic tumor involvement in the tumor-free group (p < 0.001). More than 4 IMO-fields of tumor involvement (OR:3.3; 95%CI:1.5-7.0; p = 0.002) were identified to be of predictive significance for incomplete tumor resection. FIGO-stage, histology, age, CA125-levels, bowel resection and ascites did not affect optimal tumor resectability. CONCLUSIONS: Tumor expanding in multiple (>4) abdominal quadrants was the major negative predictors for complete tumor resection in primary EOC-patients. Bowel resection and macroscopical tumor residuals were of predictive value for a higher operative major morbidity. Identifying high-risk patients for suboptimal tumor resection and operative complications may improve surgical outcome in advanced primary EOC.