Jörg Köninger

Acute cholecystitis: early versus delayed cholecystectomy, a multicenter randomized trial (ACDC study, NCT00447304).

Objective:Acute cholecystitis is a common disease, and laparoscopic surgery is the standard of care. Background:Optimal timing of surgery for acute cholecystitis remains controversial: either early surgery shortly after hospital admission or delayed elective surgery after a conservative treatment with antibiotics. Methods:The ACDC (“Acute Cholecystitis—early laparoscopic surgery versus antibiotic therapy and Delayed elective Cholecystectomy”) study is a randomized, prospective, open-label, parallel group trial. Patients were randomly assigned to receive immediate surgery within 24 hours of hospital admission (group ILC) or initial antibiotic treatment, followed by delayed laparoscopic cholecystectomy at days 7 to 45 (group DLC). For infection, all patients were treated with moxifloxacin for at least 48 hours. Primary endpoint was occurrence of predefined relevant morbidity within 75 days. Secondary endpoints were as follows: (1) 75-day morbidity using a scoring system; (2) conversion rate; (3) change of antibiotic therapy; (4) mortality; (5) costs; and (6) length of hospital stay. Results:Morbidity rate was significantly lower in group ILC (304 patients) than in group DLC (314 patients): 11.8% versus 34.4%. Conversion rate to open surgery and mortality did not differ significantly between groups. Mean length of hospital stay (5.4 days vs 10.0 days; P < 0.001) and total hospital costs (&OV0556;2919 vs &OV0556;4262; P < 0.001) were significantly lower in group ILC. Conclusions:In this large, randomized trial, laparoscopic cholecystectomy within 24 hours of hospital admission was shown to be superior to the conservative approach concerning morbidity and costs. Therefore, we believe that immediate laparoscopic cholecystectomy should become therapy of choice for acute cholecystitis in operable patients. (NCT00447304)

Chronic pain after hernia repair: a randomized trial comparing Shouldice, Lichtenstein and TAPP

IntroductionChronic pain after hernia repair is common, and it is unclear to what extent the different operation techniques influence its incidence. The aim of the present study was to compare the three major standardized techniques of hernia repair with regard to postoperative pain.Patients and methodsTwo hundred and eighty male patients with primary hernias were prospectively, randomly selected to undergo Shouldice, tension-free Lichtenstein or laparoscopic transabdominal pre-peritoneal (TAPP) hernioplasty repairs. Patients were examined after 52 months with emphasis on chronic pain and its limitations to their quality of life.ResultsChronic pain was present in 36% of patients after Shouldice repair, in 31% after Lichtenstein repair and in 15% after TAPP repair. Pain correlated with physical strain in 25% of patients after Shouldice, in 20% after Lichtenstein and in 11% after TAPP repair. Limitations to daily life, leisure activities and sports occurred in 14% of patients after Shouldice, 13% after Lichtenstein and 2.4% after TAPP repair.ConclusionChronic pain after hernia surgery is significantly more common with the open approach to the groin by Shouldice and Lichtenstein methods. The presence of the prosthetic mesh was not associated with significant postoperative complaints. The TAPP repair represents the most effective approach of the three techniques in the hands of an experienced surgeon.

Robot-assisted versus conventional laparoscopic fundoplication: short-term outcome of a pilot randomized controlled trial

BackgroundRobotic technology represents the latest development in minimally-invasive surgery. Nevertheless, robotic-assisted surgery seems to have specific disadvantages such as an increase in costs and prolongation of operative time. A general clinical implementation of the technique would only be justified if a relevant improvement in outcome could be demonstrated. This is also true for laparoscopic fundoplication. The present study was designed to compare robotic-assisted (RALF) and conventional laparoscopic fundoplication (CLF) with the focus on operative time, costs und perioperative outcome.MethodsForty patients with gastro-esophageal reflux disease were randomized to either RALF by use of the daVinci® Surgical System or CLF. Nissen fundoplication was the standard anti-reflux procedure. Peri-operative data such as length of operative procedure, intra-and postoperative complications, length of hospital stay, overall costs and symptomatic short-term outcome were compared.ResultsThe total operative time was shorter for RALF compared to CLF (88 vs. 102 min; p = 0.033) consisting of a longer set-up (23 vs. 20 min; p = 0.050) but a shorter effective operative time (65 vs. 82 min; p = 0.006). Intraoperative complications included one pneumothorax and two technical problems in the RALF group and two bleedings in the CLF group. There were no conversions to an open approach. Mean length of hospital stay (2.8 vs. 3.3 days; p = 0.086) and symptomatic outcome thirty days postoperatively (10% vs. 15% with ongoing PPI therapy; p = 1.0 and 25% vs. 20% with persisting mild dysphagia; p = 1.0) was similar in both groups. Costs were higher for RALF than for CLF (€ 3244 vs. € 2743, p = 0.003).ConclusionIn comparison with CLF, operative time can be shorter for RALF if performed by an experienced team. However, costs are higher and short-term outcome is similar. Thus, RALF can not be favoured over CLF regarding perioperative outcome.

Duodenum-preserving pancreatic head resection—A randomized controlled trial comparing the original Beger procedure with the Berne modification (ISRCTN No. 50638764)

OBJECTIVE A prospective, randomized study was performed to evaluate two variations of the duodenum-preserving pancreatic head resection (DPPHR), either with (Beger procedure) or without (Berne modification) the division of the pancreas anterior to the portal vein, in patients with chronic pancreatitis. METHODS Randomized, controlled, patient-blinded trial of patients with inflammatory pancreatic head tumors. The primary endpoint was the duration of surgery. Other a priori-ordered endpoints were length of ICU stay, postoperative complication, length of hospital stay, and quality of life after 24 months. RESULTS Sixty-five patients were randomized to the Berne or Beger procedures. The Berne modification could be performed faster (46 minutes difference, P < .05). The median length of stay on the ICU was one day in both groups (P = .97) but the median hospital stay was shorter in the Berne group (11 (8-39) versus 15 (8-47); P = .015). The quality of life two years after surgery did not differ significantly between the two groups (EORTC-QLQ-C30, Beger 65.6% vs. Berne 71.3%, P = .371). Three patients who had received the Berne procedure were reoperated on during the follow-up period due to ongoing pancreatitis and bile duct obstruction (P = .22). CONCLUSION The Berne technique is technically simpler compared with the original Beger procedure, reflected in its significantly shorter operation times and hospital stays. The quality of life is similar after both procedures. The Berne modification of DPPHR adds to our panel of surgical procedures that can be applied with effective early and late outcomes.

Long‐term results of a randomized clinical trial of Shouldice, Lichtenstein and transabdominal preperitoneal hernia repairs

There is an ongoing debate about the preferred technique for inguinal hernia repair. In this randomized study the long‐term results of Shouldice, Lichtenstein and transabdominal preperitoneal (TAPP) hernia repair were compared.

Overexpressed Decorin in Pancreatic Cancer Potential Tumor Growth Inhibition and Attenuation of Chemotherapeutic Action

Purpose: The aim of this study was to investigate the expression and significance of decorin in pancreatic cancer. Experimental Design: Decorin expression in normal pancreas and excised tumors was examined by real-time quantitative PCR, Western blot analysis, and immunohistochemistry. Reverse transcription-PCR was used to analyze cultures of pancreatic cancer and stellate cells. Growth-inhibitory effects of decorin in vitro were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test, Western blot, and fluorescence-activated cell-sorting analysis. Results: Pancreatic cancer was characterized by striking overexpression of decorin mRNA in tumor tissues (9-fold by real-time quantitative PCR; 44 patients versus 18 healthy donors; P < 0.01). Strong decorin immunostaining was observed in the extracellular matrix of pancreatic cancer tissue, whereas tumor cells were devoid of decorin. Double staining for anti-smooth muscle actin and decorin and reverse transcription-PCR analysis of primary cultures revealed pancreatic stellate cells as the putative source of decorin. Human recombinant decorin was able to suppress growth of pancreatic cancer cells in vitro through p21mediated G1-S block of the cell cycle. However, in contrast to the previously described chemotherapy-potentiating capacity of decorin, this proteoglycan attenuated the cytostatic action of carboplatin and gemcitabine toward pancreatic cancer cells. Conclusions: Decorin might exert an antiproliferative effect toward pancreatic cancer cells, thus playing a role in a host stromal reaction aimed at sequestering and inhibiting growing malignant cells. However, in clinical settings, the importance of collagen-associated decorin as a moderate antitumor modality would be undermined by its ability to attenuate the efficiency of chemotherapeutics. Considering the general failure of adjuvant therapies in pancreatic cancer, the role of decorin in this process warrants further investigation.

Perioperative and follow-up results after central pancreatic head resection (Berne technique) in a consecutive series of patients with chronic pancreatitis.

BACKGROUND Many patients require surgery for chronic pancreatitis (CP). By combining the essences of the Beger and the Frey procedures, a hybrid procedure was developed: central pancreatic-head resection (CPHR) (Berne technique). METHODS A prospective evaluation of 100 consecutive patients who underwent CPHR for CP between January 2002 and December 2006 was performed. Long-term follow-up, including quality-of-life (QOL) assessment, was carried out. RESULTS The hospital mortality rate was 1%; the surgical morbidity rate was 16%; and the relaparotomy rate was 6%. Mean surgery time was 295 +/- 7 minutes; mean intraoperative blood loss was 763 +/- 75 mL; and the mean postsurgical hospital stay was 11.4 +/- .8 days. After a median follow-up of 41 months, pain was improved in 55% of patients; weight increase occurred in 67% of patients; and insulin-dependent diabetes mellitus developed in 22% of the patients. Comparison of QOL parameters with a German adult control population showed no statistically significant differences. CONCLUSIONS CPHR is a safe surgical option to resolve CP-associated problems. Long-term follow-up QOL after CPHR shows results comparable with date published data after the Beger and the Frey procedures.

Is there an advantage in performing a pancreas-preserving total duodenectomy in duodenal adenomatosis?

BACKGROUND Duodenal adenomatosis is a premalignant condition often not treatable by local resection or endoscopy. An option for treatment is a pylorus-preserving (pp)-Whipple resection. Since the introduction of pancreas-preserving total duodenectomy (PPTD), the question has arisen whether a pp-Whipple resection is still needed to treat duodenal adenomatosis. PATIENTS AND METHODS In a 5-year period 23 PPTDs were performed for duodenal adenomatosis. In a matched-pairs analysis the outcome following PPTD (16 patients with a follow-up longer than 12 months) was compared with pp-Whipple. RESULTS Hospital mortality in all 23 patients was 4.3% and total morbidity 30% after PPTD. Operation time, intensive care and hospital stay, morbidity, and mortality were comparable between the matched paired groups (16 patients). Patients with PPTD had significantly lower intraoperative blood loss. No PPTD patient required pancreatic enzyme substitution, compared with 12 patients after pp-Whipple. Quality-of-life analysis in PPTD patients revealed no difference compared to a normal control population and the pp-Whipple group. CONCLUSIONS PPTD is a safe surgical procedure for duodenal adenomatosis that avoids pancreatic head resection, provides high quality of life, and shows advantages over the pp-Whipple procedure.

Robotic-assisted transhiatal esophagectomy

BackgroundDespite its reduced aggressiveness and excellent results obtained in certain diseases, minimally invasive surgery did not manage to significantly lower the risks of esophageal resections. Further advances in technology led to the creation of robotic systems with their unique maneuverability of the instruments and exceptional view on the operative field, thus setting the prerequisites for performance in complex surgical procedures and offering new possibilities to a disease notorious for its dismal prognosis.Materials and methodsThe robotic-assisted transhiatal esophagectomy technique was used in a patient with squamous cell carcinoma of the lower esophagus that had high medical risk for surgical therapy.ResultsEsophageal resection and reconstruction were possible through a robotic-assisted minimally invasive transhiatal approach. There were no intraoperative incidents, blood loss was minimal, and lymph node dissection and removal was possible during the procedure. Early ambulation and conservative treatment of the mild complications that occurred offered a favorable postoperative outcome.ConclusionThe robotic-assisted transhiatal esophagectomy technique is feasible and safe. Complex procedures become less technically demanding with the help of the robotic system and, thus, the minimally invasive approach can be offered for the benefit of selected patients. Further studies are required to confirm these observations and to establish the role of this procedure in the future.

The ECM proteoglycan decorin links desmoplasia and inflammation in chronic pancreatitis

Background: Recurrent inflammation in chronic pancreatitis (CP) is not well understood. Aims: To investigate whether decorin, an extracellular matrix (ECM) proteoglycan with macrophage modulating activity, is a pathogenic factor allowing diseased pancreatic stroma to sustain inflammation by affecting the cytokine profile of accumulating inflammatory cells. Methods: Decorin was examined in 18 donors and 32 patients with CP by quantitative reverse transcription polymerase chain reaction (QRT-PCR), western blotting, and immunohistochemistry of pancreatic specimens. QRT-PCR was used to assess cytokine expression in donor peripheral blood mononuclear cells (PBMC), exposed or not to decorin in vitro, and to compare it with the cytokine profile of circulating and resident mononuclear cells (MNC) of patients with CP. Results: In CP, desmoplasia is associated with overexpression of decorin in the growing ECM and enlarged pancreatic nerves. In culture, exposure of MNC to decorin stimulated expression of the MNC recruiting chemokine MCP-1. In biopsies, MNC infiltrates in decorin rich CP tissue showed a 300-fold upregulation of MCP-1 compared with decorin free peripheral blood, whereas no difference was found in basal MCP-1 expression in PBMC of patients versus donors. This effect was specific for MCP1—other inflammatory cytokines, such as interleukin 1β and tumour necrosis factor α, were not affected. Conclusion: Decorin is a molecular marker of desmoplasia in CP, and excessive decorin may allow fibrotic masses to nourish and protract inflammation by deregulating the process of MNC accumulation and activation. These data provide a molecular basis for surgical resection of diseased tissue as a treatment option in CP.