Partial pancreatoduodenectomy versus duodenum-preserving pancreatic head resection in chronic pancreatitis: the multicentre, randomised, controlled, double-blind ChroPac trial.

BACKGROUND: There is substantial uncertainty regarding the optimal surgical treatment for chronic pancreatitis. Short-term outcomes have been found to be better after duodenum-preserving pancreatic head resection (DPPHR) than after partial pancreatoduodenectomy. Therefore, we designed the multicentre ChroPac trial to investigate the long-term outcomes of patients with chronic pancreatitis within 24 months after surgery. METHODS: This randomised, controlled, double-blind, parallel-group, superiority trial was done in 18 hospitals across Europe. Patients with chronic pancreatitis who were planned for elective surgical treatment were randomly assigned to DPPHR or partial pancreatoduodenectomy with a central web-based randomisation tool. The primary endpoint was mean quality of life within 24 months after surgery, measured with the physical functioning scale of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. Primary analysis included all patients who underwent one of the assigned procedures; safety analysis included all patients who underwent surgical intervention (categorised into groups as treated). Patients and outcome assessors were masked to group assignment. The trial was registered, ISRCTN38973832. Recruitment was completed on Sept 3, 2013. FINDINGS: Between Sept 10, 2009, and Sept 3, 2013, 250 patients were randomly assigned to DPPHR (n=125) or partial pancreatoduodenectomy (n=125), of whom 226 patients (115 in the DPPHR group and 111 in the partial pancreatoduodenectomy group) were analysed. No difference in quality of life was seen between the groups within 24 months after surgery (75·3 [SD 16·4] for partial pancreatoduodenectomy vs 73·0 [16·4] for DPPHR; mean difference -2·3, 95% CI -6·6 to 2·0; p=0·284). The incidence and severity of serious adverse events did not differ between the groups. 70 (64%) of 109 patients in the DPPHR group and 61 (52%) of 117 patients in the partial pancreatoduodenectomy group had at least one serious adverse event, with the most common being reoperations (for reasons other than chronic pancreatitis), gastrointestinal problems, and other surgical morbidity. INTERPRETATION: No differences in quality of life after surgery for chronic pancreatitis were seen between the interventions. Results from single-centre trials showing superiority for DPPHR were not confirmed in the multicentre setting. FUNDING: German Research Foundation (DFG).

Impact of daclizumab, low-dose cyclosporine, mycophenolate mofetil and steroids on renal function after kidney transplantation.

BACKGROUND: Early and long-term use of cyclosporine A (CsA) leads to increased risks of renal toxicity. We hypothesized that administration of daclizumab in combination with mycophenolate mofetil (MMF) allows a relevant reduction in the dose of CsA. METHODS: We carried out a 3-year, prospective, randomized, controlled clinical multi-centre trial in 156 patients. The patients were randomized to standard treatment (CsA, MMF, steroids) or to high-dose daclizumab (first dose: 2 mg/kg), in combination with low-dose CsA, MMF and steroids. We maintained the mean CsA levels of daclizumab patients at 57% of standard patients (132 versus 216 ng/ml) on Day 7 post-transplant, and 84% by 6 months. RESULTS: Primary outcome, creatinine clearance (with imputation of informative dropouts) at 12 months, was significantly better in daclizumab-treated (34 +/- 17) than standard patients (29 +/- 17; P = 0.028, two sided). Only 5 cases of BPAR were recorded in the daclizumab compared to 22 in the standard group (P = 0.0016). Daclizumab patients had 91% event-free survival after 1 year compared to 66% in standard patients (P = 0.00017). CONCLUSION: We demonstrate here that high-dose daclizumab in combination with lower CsA levels in adult renal transplant recipients is as or more effective than standard regimen (CsA, MMF, steroids) and may result in better outcomes at 12 months post-transplant with no increase in adverse reactions.

Physiologic microcirculation of the heterotopically transplanted rat liver with portal vein arterialization depending on optimal stent diameter.

BACKGROUND: Clinical experience with portal vein arterialization (PVA) in liver transplantation is controversial. One reason for this is the lack of standardized flow regulation. The present experiments aimed to establish flow regulation in the arterialized portal vein for heterotopic auxiliary liver transplantation (HALT), to obtain physiological portal blood flow, and to compare this technique with orthotopic liver transplantation. MATERIAL/METHODS: Lewis rats were divided into 7 groups (n = 8 transplantations/group). Group: A I-IV: In HALT, the portal vein was anastomosed to the right renal artery using stents with different diameters (0.2, 0.3, 0.4, 0.5 mm). Afterwards, HALT with PVA using the stent diameter that had achieved the most physiological portal blood flow (group B II) was compared with orthotopic liver transplantation with porto-portal anastomosis (group B III) and to the sham group (B I). RESULTS: After reperfusion, only the 0.3 mm stent resulted in an average blood flow in the arterialized portal vein in HALT which was within the normal range (1.7+/-0.4 ml/min/g liver weight). The parameters of microcirculation and early graft function were significantly better in group B II than in group B III (functional sinusoidal density: 335+/-48 vs. 224+/-31/cm, diameter of sinusoids: 6.4+/-0.6 vs. 5.2+/-0.6 microm, diameter of postsinusoidal venules: 31.1+/-3.3 vs. 25.5+/-2.0 microm, bile-production: 27+/-8 vs. 19+/-5 microl/h/g liver weight). CONCLUSIONS: Using an optimal stent diameter in HALT with portal vein arterialization, an adequate flow-regulation can be achieved. Avoiding portal hyper- and hypoperfusion, good results for microcirculation and early graft function can be obtained.

Lymph node staging of esophageal squamous cell carcinoma in patients with and without neoadjuvant radiochemotherapy: histomorphologic analysis.

In patients with squamous cell carcinoma of the esophagus, the preoperative clinical staging of the N category is primarily based on the lymph node size. Lymph nodes > 10 mm are considered to be tumor-infiltrated. This histopathologic study investigated the correlation of lymph node size and metastatic infiltration in esophageal carcinoma of patients with and without neoadjuvant radiochemotherapy. The specimens of 40 patients with squamous cell carcinoma of the esophagus were included in a prospective morphometric study. Half of these patients (n = 20) received preoperative radiochemotherapy. The number of resected lymph nodes were counted, and the largest diameter of each node was measured. Metastatic involvement of each node was analyzed by histologic examination. The frequency of lymph node metastases was calculated and correlated to the lymph node size. A total of 1196 lymph nodes with an average of 29.9 nodes per patient were resected and analyzed; 129 lymph nodes (10.8%) showed metastatic infiltration. The average size of 1067 tumor-free lymph nodes was 5.1 +/- 3.8 mm in maximum diameter, whereas the average size of 129 metastatic lymph nodes was 6.7 +/- 4.2 mm (p = 0.00006). Of all resected lymph nodes, 761 (63.6%) were < or = 5 mm in maximum diameter. Only 9.3% (n = 111) of all resected lymph nodes were > 10 mm in maximum diameter. There was no significant correlation between lymph node size and the frequency of nodal metastases. No difference in size could be demonstrated between patients with and without neoadjuvant radiochemotherapy. Diagnostic imaging techniques using size as the criterion of nodal infiltration cannot exactly assess the nodal status of patients with esophageal carcinoma. This is also true for patients after neoadjuvant radiochemotherapy. Therefore, evaluation of the nodal status in patients with squamous cell carcinoma of the esophagus is entirely based on pathohistologic analysis after a well defined lymphadenectomy.