[Surgical treatment of esophageal diverticula : Endoscopic or open approach?] / Operative Therapie von Divertikeln der Speiseröhre : Endoskopisch oder offen?

Esophageal diverticula are comparatively rare. The majority are Zenker's diverticula but parabronchial and epiphrenic diverticula can also occur. Parabronchial diverticula are of low clinical relevance, whereas Zenker's and epiphrenic diverticula both belong to the group of pulsion diverticula and can become clinically apparent by dysphagia and regurgitation. Approximately 100 years after the first surgical treatment, peroral approaches (e.g. stapler dissection and flexible endoscopic diverticulotomy) have now achieved a certain level of importance. Both approaches are less invasive than the open approach but are evidently more prone to recurrences. Accordingly, traditional open diverticulectomy with cervical myotomy should be recommended to patients with a reasonable life expectancy and an acceptable operative risk. This holds particularly true for Brombart stages I-III of the disease, as complete myotomy cannot be achieved via the peroral access. The classical surgical treatment of epiphrenic diverticula is open or laparoscopic/thoracoscopic diverticulectomy with distal myotomy, mostly combined with an anterior partial fundoplication; however, the leakage rate is high and several alternative options are currently being evaluated.

[Long-term HR-Manometry of the Esophagus: first findings in clinical use]. / Langzeit-HR-Manometrie der Speiseröhre: Erste Beobachtungen aus dem klinischen Einsatz.

Diagnosis of oesophageal motility disorders has been well established for many years now, although circadian gastrointestinal motility is still purely understood. So far, high-resolution manometry (HRM) is only available for short-term measurement in clinical practice to evaluate simultaneous pressure conditions throughout the esophagus. Thus, only a very limited period of time can be investigated. There is evidence that disorders in esophageal motility can cause severe discomfort and symptoms even though they only tend to occur spontaneously. When performing short-term-measurements, these often cannot be detected. Therefore, one can assume that long-term analysis of the esophageal function will provide valuable new insights, which will contribute to more effective medicamenteous and operative treatment in esophageal motility disorders. At our gastrointestinal functional diagnostic laboratory, it has been possible to perform high-resolution manometry over the period of 24 hours since June 2014. We used a manometric probe consisting of 36 pressure sensors which are connected to a mobile recording device for ambulatory measurement. This article describes our experiences in clinical use when performing long-term high-resolution manometry and discusses usability and relevance of the results in the context of the underlying esophageal motility disorder.

Anti-platelet factor 4/heparin antibodies in patients with impaired graft function after liver transplantation.

BACKGROUND: Heparin, the standard perioperative anticoagulant for the prevention of graft vessel thrombosis in patients undergoing liver transplantation (LT), binds to the chemokine platelet factor 4 (PF4). Antibodies that are formed against the resulting PF4/heparin complexes can induce heparin-induced thrombocytopenia. LT is a clinical situation that allows the study of T-cell dependency of immune responses because T-cell function is largely suppressed pharmacologically in these patients to prevent graft rejection. OBJECTIVES: To investigate the immune response against PF4/heparin complexes in patients undergoing LT. PATIENTS AND METHODS: In this prospective cohort study, 38 consecutive patients undergoing LT were systematically screened for anti-PF4/heparin antibodies (enzyme immunoassay and heparin-induced platelet aggregation assay), platelet count, liver function, and engraftment. RESULTS: At baseline, 5 (13%) of 38 patients tested positive for anti-PF4/heparin IgG (non-platelet-activating) antibodies. By day 20, an additional 5 (15%) of 33 patients seroconverted for immunoglobulin G (two platelet-activating) antibodies. No patient developed clinical heparin-induced thrombocytopenia. Two of six patients with graft function failure had anti-PF4/heparin IgG antibodies at the time of graft function failure. Graft liver biopsy samples from these patients showed thrombotic occlusions of the microcirculation. CONCLUSIONS: Anti-PF4/heparin IgG antibodies are generated despite strong pharmacologic suppression of T cells, indicating that T cells likely have a limited role in the immune response to PF4/heparin complexes in humans.

[Diagnosis and surgical treatment of pancreatic cancer].

Despite sustained efforts, intensive research has not been proven successful to reveal risk factors, which relevantly influence early diagnostics or effective treatment of pancreatic carcinoma. Principally, it must be noted, that currently no ideal tumor marker exists for the (early) detection of pancreatic carcinoma. The most important imaging modalities are high-resolution computed tomography, abdominal ultrasound, and endosonography. Surgical procedures in therapy have become more and more standardised and lead to a decrease in morbidity and mortality on the one hand and to an increase in resectability on the other hand. Pylorus-preserving partial pancreaticoduodenectomy is the treatment of choice for a tumor of the pancreatic head, whereas resection of the left pancreas (including splenectomy) is the standard therapy for carcinomas of the pancreatic tail. In all cases, a local systematic lymphadenectomy is mandatory; hence the prognostic gain of an extended lymphadenectomy remains indeterminate. An infiltration of mesenteric and portal veins does not prevent respectability, as long as by venous resection an R0 status can be achieved. However arterial involvement in general excludes resection. Patients with marginally resectable or locally non-resectable tumors should be recruited into neoadjuvant radiochemotherapy trials since one third of these patients could be considered for potentially curative resection. However the majority of pancreatic cancer patients show locally unresectable or metastasized disease and therefore palliative treatment concepts are needed. Both, endoscopic or percutaneous stenting procedures and operative bypass surgery, are safe and reach high success rates.

[Unresectable pancreatic cancer--palliative interventional and surgical treatment]. / Das inoperable Pankreaskarzinom--palliative interventionelle und chirurgische Therapie.

In most cases pancreatic cancer appears in a non-curatively resectable stage at time the diagnosis is made. Thus, palliative treatment concepts come to the fore in these patients. Patients without metastases, but presenting with marginally resectable or locally non-resectable tumours should not be treated in a palliative therapeutic scheme. These patients should be enrolled in neoadjuvant radiochemotherapy trials. After finishing treatment and restaging, a potentially curative resection can be achieved in approximately one-third of these patients. Within the scope of the best possible palliative care, excision of metastases together with resection of the primary cancer represents a therapeutic option to be contemplated in selected cases. For distinct locally unresectable or metastasised advanced pancreatic cancer, treatment of bile duct or duodenal obstruction is an essential part of the comprehensive palliative therapy. However, both endoscopic / percutaneous stenting procedures and surgical bypass makeshifts constitute safe and highly effective therapeutic alternatives in this context. In the case of operative drainage of the biliary tract the prophylactic creation of a gastro-intestinal bypass (double bypass) is recommended. The decision on a surgical versus an endoscopic procedure for palliation depends considerably on the tumour stage and the estimated prognosis and has to be determined interdisciplinary and individually in each case.

Liver transplantation in the rat: single-center experience with technique, long-term survival, and functional and histologic findings.

OBJECTIVE: Orthotopic liver transplantation (OLT) in rats is frequently used as an experimental model. Numerous surgical techniques have been developed that enable the investigator to conduct clinically relevant studies. The objective of this study was to develop a rat model of acute and chronic rejection, to explicitly study technical modifications of vascular anastomoses with precision, and to examine histopathologic and functional changes in the graft. MATERIALS AND METHODS: With DA-(RT1av1) rats as donors and Lewis-(RT1) rats as recipients, arterialized OLT was performed using a combined suture, cuff, and splint method. Recipients were divided into 5 groups: syngeneic control rats (group 1), allogeneic control rats (group 2), allogeneic OLT rats with low-dose tacrolimus (FK506) immunosuppression (group 3), allogeneic OLT rats with high-dose tacrolimus immunosuppression (group 4), and allogeneic OLT rats with high-dose tacrolimus immunosuppression and retrograde reperfusion via the infrahepatic caval vein (group 5). After OLT, serum parameters were determined and hepatic biopsy specimens were sampled. We examined the effects of acute rejection with or without immunosuppression therapy at histopathologic evaluation. RESULTS: Liver grafts in syngeneic and allogeneic rats (groups 1, 2, 4, and 5) demonstrated normal serum parameters and histopathologic findings at 10 days after OLT, and 93% survival at 3 months. The simplified technique using 1 suture and 2 cuff anastomoses provided the best short- and long-term survival after OLT in all groups. Retrograde perfusion via the infrahepatic caval vein resulted in lower postoperative liver enzyme values. CONCLUSION: The present model is feasible, enabling comprehensive preclinical experimental research on liver transplantation. Furthermore, we provide helpful instructions for learning this surgical technique.

Microsurgical technique of simultaneous pancreas/kidney transplantation in the rat: clinical experience and review of the literature.

BACKGROUND: For experimental basic research, standardized transplantation models reflecting technical and immunologic aspects are necessary. This article describes an experimental model of combined pancreas/kidney transplantation (PKTx) in detail. MATERIALS AND METHODS: Donor rats underwent en bloc pancreatectomy and nephrectomy. Revascularization was performed using the aorta with the superior mesenteric artery and the inferior vena cava with the portal vein. Exocrine drainage of the pancreas took place over a segment of the duodenum which was transplanted side-to-side to the jejunum. The kidney vessels were transplanted end-to-side. The ureter was anastomosed by patch technique. Postoperatively, serum parameters were monitored daily. Biopsies for histopathology were taken on days 5, 8 and 12. RESULTS: All 12 recipients survived the combined PKTx without serious surgical complications. One thrombosis of the portal vein led to organ failure. Blood glucose levels were normal by the 3rd postoperative day. The transplanted duodenal segment showed slight villous atrophy, and the kidneys were well perfused without vascular complications. The anastomosis between ureter and bladder was leakproof. CONCLUSIONS: Excellent graft function and survival rates can be achieved due to simplified operation technique and short operation time. It may thus have high clinical relevance to immunologic issues within the scope of basic research.

Systematic review and meta-analysis of prophylactic gastroenterostomy for unresectable advanced pancreatic cancer.

BACKGROUND: The value of prophylactic gastroenterostomy (usually combined with a biliary bypass) in patients with unresectable cancer of the pancreatic head is controversial. METHODS: A systematic review of retrospective and prospective studies, and a meta-analysis of prospective studies, on the use of prophylactic gastroenterostomy for unresectable pancreatic cancer were performed. RESULTS: Analysis of retrospective studies did not reveal any advantage or disadvantage of prophylactic gastroenterostomy. Three prospective studies comparing prophylactic gastroenterostomy plus biliodigestive anastomosis with no bypass or a biliodigestive anastomosis alone were identified (altogether 218 patients). For patients who had prophylactic gastroenterostomy, the chance of gastric outlet obstruction during follow-up was significantly lower (odds ratio (OR) 0.06 (95 per cent confidence interval (c.i.) 0.02 to 0.21); P < 0.001). The rates of postoperative delayed gastric emptying were similar in both groups (OR 1.93 (95 per cent c.i. 0.57 to 6.53); P = 0.290), as were morbidity and mortality. The estimated duration of hospital stay after prophylactic gastroenterostomy was 3 days longer than for patients without bypass (weighted mean difference 3.1 (95 per cent c.i. 0.7 to 5.5); P = 0.010). CONCLUSION: Prophylactic gastroenterostomy should be performed during surgical exploration of patients with unresectable pancreatic head tumours because it reduces the incidence of long-term gastroduodenal obstruction without impairing short-term outcome.

Nitric oxide inhibition and consecutive Aspisol application show a prolonged survival of orthotopic transplanted livers in a rat model.

BACKGROUND: It is generally accepted that nitric oxide (NO) plays a crucial role in acute rejection caused by inflammatory responses. Therefore, the purpose of this study was to investigate the effect on survival following arterialized orthotopic rat liver transplantations (o-RLTx) of NO inhibition and consequent blockade of platelet aggregation by application of Aspisol. MATERIALS AND METHODS: Inbred LEWIS-(RT(1)) rats underwent arterialized o-RLTx under ether anesthesia with DA-(RT1av1) rats as organ donors. After liver transplantation, serum parameters were determined and hepatic biopsy specimens were sampled on postoperative days 5, 8, 10, 30, and 90. Sixty-one rats were divided into 5 groups: syngenic controls (group I, n = 12); allogenic controls (group II, n = 11); allogenic with FK506 immunosuppression (group III, n = 12); allogenic with AGH-treatment (group IV, n = 13); and allogenic with AGH/low- dose Aspisol treatment for 5 days after liver transplantation (group V, n = 13) (Bayer, Leverkusen, Germany). RESULTS: Rats of group V with AGH/low-dose Aspisol treatment showed significantly longer graft survival (18.2 days +/- 1.8 days) compared with group II rats with untreated grafts (11.3 days +/- 1.7 days) the allogenic group IV with AGH treatment (11.2 days +/- 1.8 days; P < .05). Histological examination revealed moderate graft rejection among the AGH-treated group IV; however, marked platelet aggregation in sinusoids was present, which was not observed in the AGH/low-dose Aspisol-treated animals (group V). CONCLUSION: Our data suggested that simultaneous treatment with AGH/low-dose Aspisol leads to a significant increase in survival and inhibition of platelet aggregation in the graft after orthotopic liver transplantation.

The effect of selective inhibition of inducible nitric oxide synthase on cytochrome P450 after liver transplantation in a rat model.

BACKGROUND: Activity levels of cytochrome P450 (CYP) provide markers for liver function and graft rejection episodes after orthotopic liver transplantation (OLT). Some in vitro studies have shown decreased CYP activation of inducible nitric oxide synthase (iNOS) in rejecting liver grafts. The aim of this study was to evaluate CYP isoenzyme activity changes in vivo and to examine histopathologic aspects during inhibition of iNOS after treatment with aminoguanidine (AG) using OLT in the rat. MATERIALS AND METHODS: Thirty DA-(RT1av1) rats that served as donors and LEWIS-(RT(1)) rats as recipients were divided into three groups: group I (controls, syngeneic rats; n = 6), group II (allogeneic rats without immunosupression; n = 11), and group III (allogeneic rats with AG treatment; n = 13). On postoperative days 5, 8, and 10 we performed laboratory investigations and liver biopsies for histopathologic investigations. RESULTS: On postoperative day 5, activities of CYP-1A1 and -3A4 were significantly lower (P = .022) in group III and the activity of CYP-1A2 higher (P < .05) compared with group II. At postoperative days 8 and 10, the activities of all CYP isoenzymes were significant higher in AG-treated rats (group III) in contrast with group II after allogeneic OLT without immunosuppression. Histopathologic findings revealed less distinct rejection signs in group III specimens after AG treatment compared with group II. CONCLUSION: Summarizing our results, we concluded that AG treatment led to increased CYP activity and less distinction of graft rejection after OLT in rats.

High-risk constellation in living renal transplantation.

There is only limited information about recipient risk factors for graft survival in living- donor kidney transplantation. This study aimed to investigate prognostic factors and their impact on living-related and unrelated renal transplant recipients. From October 2000 until October 2004, 81 adult living-related renal transplantations were performed at our institution. Using multivariate analysis, the association of the following variables with kidney graft outcome was studied: ages of donors and recipients, gender and body mass index, cold and warm ischemia, HLA mismatches, identity and compatibility of blood group, duration of dialysis, cytomegalovirus (CMV) status, recipient original disease, surgical and general complications, and status of retransplantation. Multivariate analysis revealed significant reduction of graft function and graft survival in recipients with retransplantation, more than 4 mismatches, and a high body mass index. Thus, living-donor kidney transplantation can be regarded as a safe and standardized operation relating to surgical technique, but further consideration of the recipient body mass index and the number of mismatches are recommended during the preparation for transplantation.

Efficacy of conventional immunosuppressive therapy in related and unrelated living renal transplantation.

BACKGROUND: The application of antibody induction therapy in adult living-related kidney transplantation remains under discussion. The purpose of this study was to compare the outcome of living-related (LRT) and unrelated renal transplant recipients (LURT) using standardized immunosuppressive protocols. From October 2000 to October 2004, 72 adult LRT (TX) were performed at our institution. Thirty-nine LRT (group A) and 33 LURT (group B) recipients received a standardized immunosuppressive therapy consisting of tacrolimus (Tac), steroids and mycophenolate mofetil (MMF) without antibody induction therapy. This prolective analysis included immediate graft function, rejection rate and loss of the transplanted organ. The incidence of post-operative good graft function (>90%) was similar for both groups, as well as the rejection rate showed 57.8% for patients of group A and 58.8% for patients of group B (p < 0.5). However, the number of rejections (>1 rejection) was significantly higher in group B (11.8%) compared to patients in group A (4.4%). No difference concerning loss of transplanted kidney was observed for both groups. Conventional Tac, MMF and steroid-based immunosuppression therapy is equivalent in efficacy of therapy in living-related and unrelated renal transplants. In our opinion, induction therapy in patients without immunologic risk factors has no favourable effect.

Inhibition of natural killer cells results in acceptance of cardiac allografts in CD28-/- mice.

Successful transplantation of allogeneic organs is an important objective in modern medicine. However, sophisticated immune defense mechanisms, primarily evolved to combat infections, often work against medical transplantation. To investigate the roles of natural and adaptive immune responses in transplant rejection, we functionally inactivated key effector systems of the innate (NK cells) and the adaptive immune system (CD28-mediated costimulation of T cells) in mice. Neither of these interventions alone led to acceptance of allogeneic vascularized cardiac grafts. In contrast, inhibition of NK-receptor-bearing cells combined with CD28-costimulation blockade established long-term graft acceptance. These results indicate a concerted interplay between innate and adaptive immune surveillance for graft rejection. Thus we suggest that inactivation of NK-receptor-bearing cells could be a new strategy for successful survival of solid-organ transplants.