Surgical Repair of a Traumatic Gastrobronchial Fistula.

BACKGROUND Gastrobronchial fistulas mostly occur as a result of postoperative complications, including those of bariatric, esophageal, and spleno-pancreatic surgery. Other causes are pneumonia, neoplasm, gastric ulcer, and subphrenic abscess. Traumatic fistulous communications between the stomach and the lung tissue are rare, with only 8 cases reported in the English-language literature (PubMed search) until now. CASE REPORT We report a 49-year-old female patient with a gastrobronchial fistula secondary to diaphragm rupture 7 years prior, with intrathoracic herniation of the gastric fundus. She underwent thoracotomy for surgical repair. She presented in our Emergency Department with recurrent hemoptysis and painful cough. The diagnosis of the gastrobronchial fistula was confirmed by computed tomography and simultaneous bronchoscopy and esophagogastroscopy, with injection of toluidine blue. As a multidisciplinary team, we opted for surgical repair owing to the fistula extent and severity and the need of repair of the diaphragm hernia. The patient underwent left-sided thoracoscopy. However, owing to dense adhesions and chronic inflammation, we converted to an open procedure. The herniated gastric fundus was repaired by wedge resection. The affected lung tissue was debrided and reconstructed by suture repair. The diaphragmatic defect was closed by sutures with mesh augmentation. The patient's postoperative course was uncomplicated, and she was discharged in good clinical condition on postoperative day 7. CONCLUSIONS Owing to the scarcity of the disease, the management of a gastrobronchial fistula is not standardized. The establishment of the diagnosis of the disease is often challenging. Therapeutic options include conservative measures, endoscopic options, and surgical repair. Our case showed that a multidisciplinary workup is essential for successful treatment.

A novel human gastric primary cell culture system for modelling Helicobacter pylori infection in vitro.

BACKGROUND AND AIMS: Helicobacter pylori is the causative agent of gastric diseases and the main risk factor in the development of gastric adenocarcinoma. In vitro studies with this bacterial pathogen largely rely on the use of transformed cell lines as infection model. However, this approach is intrinsically artificial and especially inappropriate when it comes to investigating the mechanisms of cancerogenesis. Moreover, common cell lines are often defective in crucial signalling pathways relevant to infection and cancer. A long-lived primary cell system would be preferable in order to better approximate the human in vivo situation. METHODS: Gastric glands were isolated from healthy human stomach tissue and grown in Matrigel containing media supplemented with various growth factors, developmental regulators and apoptosis inhibitors to generate long-lasting normal epithelial cell cultures. RESULTS: Culture conditions were developed which support the formation and quasi-indefinite growth of three dimensional (3D) spheroids derived from various sites of the human stomach. Spheroids could be differentiated to gastric organoids after withdrawal of Wnt3A and R-spondin1 from the medium. The 3D cultures exhibit typical morphological features of human stomach tissue. Transfer of sheared spheroids into 2D culture led to the formation of dense planar cultures of polarised epithelial cells serving as a suitable in vitro model of H. pylori infection. CONCLUSIONS: A robust and quasi-immortal 3D organoid model has been established, which is considered instrumental for future research aimed to understand the underlying mechanisms of infection, mucosal immunity and cancer of the human stomach.

High Impact of Histopathological Remission for Prognosis after Perioperative Chemotherapy with ECF and ECF-Like Regimens for Gastric and Gastroesophageal Adenocarcinoma.

BACKGROUND: Perioperative chemotherapy with epirubicin, cisplatin and 5-fluorouracil (5-FU) (ECF)-like regimens is the European standard for patients with adenocarcinoma of the gastroesophageal junction (GEJ) or gastric body (GaCa) stage UICC II/III (staged according to the Union for International Cancer Control). However, limited data exist on the histopathological response and relevance of prognosis for patients homogeneously treated with ECF(-like) therapies. METHODS: All patients with GEJ/GaCa treated from September 2004 to September 2008 by perioperative ECF(-like) chemotherapy were retrospectively analyzed. Cisplatin and 5-FU were substituted with oxaliplatin or capecitabine when indicated. The histopathological response was assessed using the Becker score. RESULTS: Seventy-seven patients were analyzed with a median follow-up of 72.3 months. R0 resection was achieved in 53 of 68 operated patients. Recurrence was observed in 25 (32.5%) of these curatively treated patients, whereas 53/77 patients (68.8%) died, 39 (50.6%) of whom tumor related. The 5-year overall survival (OS) for the intention-to-treat population was 36.3%, and the 5-year tumor-specific survival was 42.2%. Pathological complete response (pCR) was seen in 10 patients (13.0%) and near pCR in 3 patients (3.9%). Patients with pCR had a significantly prolonged 5-year OS of 80.0 versus 29.7% compared to the nonhistopathological complete remission group (p = 0.01). CONCLUSION: In our retrospective analysis, ECF(-like) pretreatment resulted in a (near) pCR rate of 16.9%. In line with other regimens, our data suggest that histopathological response predicts the OS in patients treated with ECF(-like) regimens.

Incidence, risk factors and management of incisional hernia in a high volume liver transplant center.

BACKGROUND: Incisional hernia after liver transplantation is a common complication with an incidence between 5% and 34%. This prospective study analyzed risk factors, surgical management and long-term results after hernia repair. MATERIAL AND METHODS: From February 2002 until August 2009, 810 liver transplantations were performed. 77 patients (9.5%) underwent incisional hernia repair after a median time of 21.1 months (4.6-76.7) following transplant. These patients were compared to patients without hernia (n=733). RESULTS: No statistically significant differences between the groups were observed with respect to gender, underlying liver disease, Child-Pugh classification, MELD-Score and preoperative renal failure (p=NS). Multivariate analysis revealed advanced age (p=0.014), body mass index (p=0.016), and re-laparotomies (p<0.001) as independent risk factors for incisional hernias. Pre-existing diabetes mellitus and immunosuppression with mycophenolate mofetil reached significance only in the univariate analysis (p<0.001). Recurrent hernia was observed in 12 of 77 patients (15.6%) at a median time of 7.9 months (4.8-46.8) after primary surgical repair. The recurrence rate after intraperitoneal onlay mesh implantation was lower compared to other mesh techniques (7.7% vs. 21.4%). CONCLUSIONS: The risk factors for the development of incisional hernias in liver transplant patients are similar to patients with prior abdominal surgery for other reasons. Intraperitoneal onlay mesh implantation may lead to a decrease of hernia recurrences. The role of immunosuppression in the genesis of incisional hernias requires further elucidation.

Postoperative immunosuppression after open and laparoscopic liver resection: assessment of cellular immune function and monocytic HLA-DR expression.

BACKGROUND AND OBJECTIVES: Major abdominal procedures are strongly associated with postoperative immunosuppression and subsequent increased patient morbidity. It is believed that laparoscopic surgery causes less depletion of the systemic immune function because of the reduced tissue trauma. Various cytokines and monocytic HLA-DR expression have been successfully implemented to assess postoperative immune function. The aim of our study was to show the difference in immunologic profiles after minimally invasive versus conventional liver resection. METHODS: Ten animals underwent either laparoscopic or conventional open left lateral liver resection. Flow cytometric characteristics of HLA-DR expression on monocytes and lipopolysaccharide-stimulated cellular secretion of tumor necrosis factor α, interferon γ, interleukin 6, and interleukin 8 were measured and analyzed in ex vivo whole blood samples. Intraoperative and postoperative clinical outcome parameters were also documented and evaluated. RESULTS: All animals survived the procedures. Postoperative complications were fever (n = 3), wound infections (n = 2), and biloma (n = 1). Open surgery showed a morbidity rate of 80% compared with 40% after laparoscopic surgery. Laparoscopic liver resection showed no postoperative immunoparalysis. Major histocompatibility complex class II expression in this group was elevated, whereas the open surgery group showed decreased major histocompatibility complex class II expression on postoperative day 1. Postoperative secretion of tumor necrosis factor , interleukin 6, and interferon was lower in the open surgery group. Elevated transaminase levels after laparoscopy might have resulted from an ischemia/reperfusion injury caused by the capnoperitoneum. CONCLUSION: Major immunoparalysis depression was not observed in either group. Laparoscopic surgery shows a tendency to improve immunologic recovery after liver resection.

The APACHE III score as preoperative indicator of patient outcome in liver transplantation after fulminant hepatic failure.

BACKGROUND: Given the current organ shortage, an accurate assessment of the patient's outcome after orthotopic liver transplantation (OLTX) for fulminant hepatic failure (FHF) is crucial in order to determine the suitability for transplantation. The purpose of this study was to assess whether APACHE II and III scores would provide prognosis of posttransplant mortality. MATERIAL/METHODS: The study included 129 patients with FHF who underwent OLTX between 1988 and 2008. APACHE II and III scores were calculated one day before transplantation and correlated with postoperative mortality. The cohort consisted of 42 males and 87 females with a mean age of 32 ± 17 years. RESULTS: Gender, age and etiology of FHF did not correlate with posttransplant survival (p=NS). The APACHE II score was not significantly higher amongst 30-day non-survivors (p = NS). Both patients who died during this period had a significantly higher APACHE III score compared to survivors (82 ± 19.4 vs. 62 ± 18, p<0.01). Patients with an APACHE III score > 68 had a significantly higher mortality rate (p<0.01). Cox regression analysis revealed the APACHE III score as a significant predictor of death (p<0.001). Each additional point in the APACHE III system raises the postoperative mortality by 3.1%. CONCLUSIONS: The major advantage of the APACHE III score is that its application and prognostic ability is independent from etiology of FHF. This accurate and reproducible evaluation system could be useful to identify patients with poor outcome.

Laparoscopic radiofrequency ablation of liver tumors: comparison of MR guidance versus conventional laparoscopic ultrasound for needle positioning in a phantom model.

Laparoscopic radiofrequency ablation (LapRFA) is an established procedure for liver tumors in patients who are unsuitable for resection. A novel technique of magnetic resonance (MR) guided needle positioning during LapRFA was developed and compared to conventional ultrasound (US) guidance in a phantom model. MR-guided procedures were conducted in a 1.0 tesla high field open MR using an MR compatible endoscope and camera. The ultrasound-guided procedure was performed with a clinically established laparoscopy setup and a 2D laparoscopic US probe. During both techniques an identical monopolar non-ferromagnetic RFA needle and a silicon-based phantom model were applied. Finally needle positioning was performed by two surgeons and one interventionalist. Time to needle placement and number of trials were recorded and statistically analyzed. MR-guided needle positioning under laparoscopic control was technically feasible. Average time to correct needle placement was 2' 6″ in the LapUS group and 1' 54″ in the MR group. The number of trials was 3.2 in the LapUS group and 2.6 in the MR group. Image quality was assessed by all participants. MR images showed a better tissue to tumor contrast and allowed an improved orientation due to multiplanar visualization. MR-guided laparoscopic RFA is a promising technique offering multiplanar needle positioning with high soft tissue contrast with immediate therapy control. In a phantom model it showed comparable results regarding needle positioning to the established technique of laparoscopic US guidance.

Additive growth inhibition after combined treatment of 2-methoxyestradiol and conventional chemotherapeutic agents in human pancreatic cancer cells.

OBJECTIVE: Most chemotherapeutic regimens for pancreatic cancer (PC) use combination therapy. 2-Methoxyestradiol (2-ME2) is a natural estrogen metabolite with proven tumor-inhibiting effect as a single agent. The aim of this study was to determine whether a combination of 2-ME2 with other established chemotherapeutic compounds increases its tumor-inhibiting effect on human PC cells. MATERIALS AND METHODS: The human PC cell lines AsPC-1 and MiaPaCa-2 were treated with 2-ME2 alone or in combination with different doses of gemcitabine, cisplatin, cetuximab, 5-fluorouracil and paclitaxel in vitro (range: 0.5-5 µM). FACS analysis and nuclear staining were used to reveal apoptotic cells and cell-cycle changes after treatment. Subsequent in vivo experiments were performed on a subcutaneous tumor model in nude mice using AsPC-1 cells. RESULTS: A tumor-reductive effect of 2-ME2 was found in both human PC cell lines. The combination of 2-ME2 with other agents resulted in additive growth inhibition of both cell lines through the induction of apoptosis and cell-cycle arrest. The growth inhibition was confirmed in vivo. After 32 days' treatment, gemcitabine alone showed no effect on tumor growth at a dose of 75 mg/kg body-weight. However, 2-ME2 at a daily dose of 2 mg per animal led to a growth inhibition of 63% with no evident toxicity. The combination of 2-ME2 and gemcitabine caused a growth-inhibition of 83%. Major toxicity was observed in the combination group, with six deaths out of eight animals in this group. CONCLUSION: 2-ME2 can be successfully combined with other chemotherapeutic agents. However, toxicity in the in vivo experiment is strong and requires further investigation.

Antiviral treatment of patients with recurrent hepatitis C after liver transplantation with pegylated interferon.

BACKGROUND: The recurrence of hepatitis C virus (HCV) after liver transplantation (OLT) leads to recurrent cirrhosis in up to 40% of patients. AIMS: To identify patients who profit the most from antiviral therapy and to delineate whether early treatment after OLT is effective to reach sustained virological response (SVR), we analyzed factors associated to SVR during pegylated interferon/ribavirin (PegIFN/RBV) therapy. METHODS: A retrospective analysis of efficiency and viral decline kinetics in 83 HCV-infected liver transplant recipients who received therapy with PegIFN/RBV was carried out. RESULTS: Forty-one of 83 (49.4%) patients became HCV RNA-negative. SVR was achieved in 26/83 (31.3%) patients. Viral decline of at least 2 log 10 (n = 47) at week 12 was significantly associated with an end-of-treatment (EOT) response. Eleven early viral response patients were not able to clear HCV RNA, whereas five patients without a 2 log decline achieved SVR. The highest predictive value for SVR was an undetectable viremia at week 24 (92%). CONCLUSIONS: The outcome of antiviral combination therapy for HCV reinfection after OLT can be best predicted by week-24 virologic response. The high SVR rates in patients with detectable HCV RNA at week 12 might suggest a prolonged treatment protocol in liver transplant recipients.

Symptomatic lymphoceles after kidney transplantation - multivariate analysis of risk factors and outcome after laparoscopic fenestration.

Lymphocele formation is a common complication after kidney transplantation, and laparoscopic surgery has become a widely accepted treatment option. The aim of this retrospective study was to analyze the risk factors of lymphocele development and to assess the treatment outcome after laparoscopic fenestration. We analyzed 426 renal allograft recipients operated between 2002 and 2006 receiving triple immunosuppression with calcineurin inhibitors. The incidence of lymphocele was 9.9%, while 24 (5.6%) patients with symptomatic lymphoceles required laparoscopic surgery. Serum creatinine at diagnosis was significantly higher in patients with lymphoceles treated surgically (3.2 +/- 0.7 vs. 1.7 +/- 0.6 mg/dL; p < 0.001). After successful laparoscopic intervention, creatinine concentrations recovered until discharge and were comparable to other patients (1.6 +/- 0.5 vs. 1.5 +/- 0.5 mg/dL; p = NS). While we observed a significant association of lymphocele formation with diabetes, tacrolimus therapy, and acute rejection in univariate testing, only diabetes remained a significant factor after multivariate analysis. Laparoscopic fenestration proved to be a safe and efficient method without any associated mortality and a low recurrence rate of 8.3% (n = 2). We conclude that diabetes is an independent risk factor for lymphocele development, and laparoscopic fenestration should be the treatment of choice for larger and symptomatic lymphoceles, as it is safe and offers a low recurrence rate.

Mayo risk score for primary biliary cirrhosis: a useful tool for the prediction of course after liver transplantation?

BACKGROUND: Survival after orthotopic liver transplantation (OLT) for primary biliary cirrhosis (PBC) is excellent. In order to define the optimal time point for OLT, the Mayo risk score (MRS) was developed and a score of 7.8 was identified for transplantation. However, in reality most recipients are in a bad condition with a MRS above 7.8. So far it is still unknown if a higher score is associated with more complications after OLT perioperatively and in a long-term follow-up. Therefore, this study was designed to investigate the association of the MRS score with postoperative survival and complications. MATERIAL/METHODS: Between 1989 and 2006, 115 patients were transplanted for histologically proven PBC at the Charité Campus Virchow Clinic. In 98 of these patients, MRS data was available and retrospectively analyzed. Median age of 87 women and 11 men was 54 years (25 to 66 years). RESULTS: The median follow-up after liver transplantation was 109 months (0.5-205 months). Actuarial patient survival after 5, 10 and 15 years was 90%, 88%, and 83%. Calculated survival by MRS without transplantation after 1, 5 and 7 years was 20%, 2% and 1% for these patients. Twelve patients (12%) died and histological recurrence of PBC was detected in 14 patients (14%). Seven patients underwent retransplantation (7%) and 58 patients developed an acute rejection episode (59%). Mean MRS was in all patients 9.54+/-1.35 and did not differ between patients with lethal course, retransplantations, PBC recurrence, rejection episodes and duration of hospital stay. Classification of all patients into a low (<8.5), middle (8.5-10) and high MRS score (>10) did not show a significant difference in long-term survival. Univariate analysis for identifying the level of MRS as risk for death, PBC-recurrence, retransplantation, acute rejection episodes and hospital stay only showed a significant increased risk for acute rejection episodes (1 episode = 0.04; 2 episodes = 0.01) for patients with a MRS above 8.5. CONCLUSIONS: The Mayo risk score is an approved mathematical model predicting survival in non-transplanted patients suffering from PBC. However, the score did not predict the course of our liver transplanted patients in a long-term follow-up. We could not demonstrate a reduced patient survival at a median MRS of 9.4 and about 10.0. Therefore, it is, from our point of view, questionable if the optimal time point for OLT is still 7.8.

Laparoscopic-assisted placement of peritoneal dialysis catheters: implantation technique and results.

BACKGROUND: Peritoneal dialysis is a generally accepted method for the treatment of patients with end-stage renal failure. The laparoscopic placement of peritoneal dialysis catheters is a well-established technique and offers some advantages, such as a safer placement of the catheter, less post-operative complications, and a longer functional survival, compared to the conventional open technique. The aim of this study was to describe our implantation technique and to determine the results of our approach. PATIENTS AND METHODS: Between January 2000 and February 2006, 47 patients with end-stage chronic renal failure underwent a laparoscopic peritoneal dialysis catheter insertion procedure. Perioperative and follow-up data were collected prospectively. RESULTS: The mean operating time was 35 minutes (range, 16-100). There was no perioperative morbidity. Nine (19.1%) patients experienced 10 mechanical complications: fluid leakage in 6 (12.8%) patients, acute hydrothorax in 1 (2.1%), catheter tip migration in 2 (4.3%), and catheter obstruction in 1 (2.1%) patient. Episodes of peritonitis were observed in 5 (10.6%) patients. One (2.1%) patient developed a catheter infection. In 3 (6.4%) patients, a port site hernia occurred that required surgical repair, 5 (10.6%) patients underwent laparoscopic revisions owing to mechanical complications, 9 (19.1%) patients underwent renal transplantation, and 6 (12.8%) patients died during the later follow-up. After a mean follow-up time of 17 months (range, 2-76), 30 (63.8%) catheters are still in use for dialysis. CONCLUSIONS: The functional outcome of the dialysis catheters was satisfactory in the majority of patients in this study. The described technique for catheter implantation is simple and safe, and in our opinion, the laparoscopic technique should be considered as the method of choice in patients with end-stage chronic renal failure.

Preoperative high-dose steroid administration attenuates the surgical stress response following liver resection: results of a prospective randomized study.

BACKGROUND/PURPOSE: Major abdominal surgery such as liver resection is associated with an excessive hyperinflammatory response and transient immunosuppression. We investigated the immunomodulating effect of preoperative pulse administration of high-dose methylprednisolone in patients undergoing hepatic resection without pedicle clamping. METHODS: Twenty patients who underwent hepatic resection were randomized into two groups: a steroid group (n = 10), in which patients were given 30 mg/kg per body weight (BW) methylprednisolone intravenously, and a control group (n = 10), in which patients received a placebo (sodium chloride) infusion. The main outcome parameter to assess systemic stress was the serum plasma level of interleukin-6 (IL-6). To evaluate cell-mediated immune function, human leukocyte antigen-DR (HLA-DR) expression on peripheral blood monocytes and lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) release by peripheral monocytes was measured. Other investigated serum parameters included C-reactive protein (CRP), total bilirubin, alanine aminotransferase (ALT), prothrombin time (PT)-INR, and cytokines such as IL-8 and IL-10 and TNF-alpha. Postoperative convalescence, complication rate, and length of hospital stay were compared between the groups. RESULTS: Postoperative plasma concentrations of IL-6 (days 1 and 2), IL-8 (days 2 and 3), and CRP (days 1-4) were significantly lower in the steroid than in the control group. The total bilirubin concentration was significantly lower on day 6 in the steroid than in the control group. Four hours after surgery, LPS-induced TNF-alpha secretion was significantly reduced in the steroid group, but it increased rapidly during the following days. HLA-DR, ALT, and PT-INR levels were not different between the two groups. The postoperative hospital stay in the steroid group was significantly lower compared to that in the control group (mean, 10.5 days versus 14.8 days; P < 0.05). No differences were found in the convalescence score or postoperative complication rate. CONCLUSIONS: Intravenous methylprednisolone administration before hepatic resection significantly reduced systemic inflammatory cytokine release. No adverse effect on immunity was noted due to the methylprednisolone. We found no significant difference in the convalescence score, but a significantly shorter hospital stay in the steroid group. Further studies with more patients are needed to elucidate the clinical impact of preoperative steroid bolus therapy in liver surgery.

Management and outcome of patients with combined bile duct and hepatic arterial injuries after laparoscopic cholecystectomy.

BACKGROUND: Recent collective reviews have described the management and outcome of bile duct injuries during laparoscopic cholecystectomy. However, few have reported on the clinical significance of concomitant right hepatic arterial injuries. This study was conducted to examine the correlation of combined bile duct and vascular injuries and to evaluate the impact of these injuries on patient morbidity. METHODS: From January 1990 to February 2002, a total of 54 patients with bile duct injuries during laparoscopic cholecystectomy were surgically treated in our institution. In 46 patients a Roux-en-Y hepaticojejunostomy was performed. Eleven patients had a concomitant vascular injury. Arterial reconstruction was performed in addition to Roux-en-Y hepaticojejunostomy in 2 patients. Eight patients underwent other surgical procedures and were not included in the statistical analysis. To evaluate the impact of vascular injuries, univariate and multivariate analysis was performed. RESULTS: The rate of postoperative biliary complications was 21.7% for all patients. Univariate and multivariate analysis identified 2 risk factors for the development of biliary complications after reconstructive surgery: (1) combined bile duct and hepatic arterial injuries (6 of 11 patients [54.5%] vs 4 of 35 patients [11.4%]; P=.006) and (2) surgical repair in active peritonitis (8 of 13 patients [61.5%] vs 2 of 33 [6.1%]; P <.001). In the other, late referred patients with concomitant right hepatic arterial injury, the distal part of the artery was not exposable. After a median follow-up time of 44.6 months (range, 2 to 143.5 months) a successful outcome was achieved in 42 of 46 patients (91.3%), which included the patients who required additional endoscopic or surgical treatment after primary reconstruction. CONCLUSIONS: The outcome of bile duct reconstruction is worse in patients with concomitant arterial injuries. We therefore recommend the assessment of patients with major bile duct injuries for additional vascular injuries. Further studies are needed to evaluate the importance of hepatic arterial revascularization in early recognized injuries to the long-term outcome of bile duct reconstructions.