Stefan W. Schmid

Protease-Antiprotease Interactions and the Rationale for Therapeutic Protease Inhibitors

A number of pancreatic enzymes have been suggested as the initiating factor for acute pancreatitis. In particular, the relationship between proteases and antiproteases has been examined extensively, based on the suspicion that an imbalance between them is the central factor in the pathogenesis of acute pancreatitis. Animal studies with antiproteolytic agents in models of acute pancreatitis have shown an improvement in outcome. However, more recently, prospective, randomized, multicentre trials treating human acute pancreatitis with antiproteolytic drugs (aprotinin, gabexate mesilate, and even fresh frozen plasma) have failed to show any benefit in the clinical setting. Thus, clinically, it seems likely that antiproteolytic therapy has no effect on the course of severe acute pancreatitis. Today, the mortality in severe acute pancreatitis is determined by septic complications due to infected pancreatic necroses in the late phase 2-3 weeks after the onset of the disease. Death in the early phase of the disease has become increasingly rare where an imbalance between proteases and antiproteases may be involved.

Human pancreas-specific protein. A diagnostic and prognostic marker in acute pancreatitis and pancreas transplantation.

SummaryConclusionHuman pancreas-specific protein (hPASP) is a very sensitive reflector of the extent of pancreatic necrosis on the cellular level, and is of both diagnostic and prognostic value in acute pancreatitis. Furthermore, it allows the estimation of the severity of graft pancreatitis soon after simultaneous renal and pancreatic transplantation.BackgroundDiagnosis of acute pancreatitis (AP) has been improved in the past 15 yr as new methods for the determination of specific pancreatic enzymes have been developed. However, these enzymes have no prognostic implications. In this prospective study, we evaluated the role of human pancreas-specific protein (hPASP) in comparison with pancreatic amylase and C-reactive protein (CRP) in acute pancreatitis and pancreas transplantation.Patients and MethodsThe study included 40 patients (22 female, 18 male; mean age 51 yr, range 22–88 yr) with AP and 7 patients (2 female, 5 male; mean age 37 yr, range 25–49 yr) with type I diabetes and renal insufficiency who underwent simultaneous kidney and pancreas transplantation. By means of contrast-enhanced computed tomography (CT) and/or intraoperative findings, patients were judged to have edematous-interstitial (AIP,n=20, mean age 55.2 yr, range 24–88 yr) or necrotizing pancreatitis (NP,n=20, mean age 46.3 yr, range 22–81 yr). Serum hPASP concentration was measured daily by a commercial radioimmunoassay technique. In 25 healthy subjects and in several control groups (35 patients with chronic pancreatitis, 20 patients with pancreatic carcinoma and 80 patients with different gastrointestinal diseases) a single blood specimen was taken at hospital admission for the determination of the normal range of hPASP and for specificity analysis.ResultsThe upper normal value for hPASP in healthy subjects was found to be 52 ng/mL. Serum hPASP was elevated in all patients suffering from AP, with a median of 343 ng/mL (lower-upper quartile: 192–478 ng/mL) at hospital admission. In the daily serum monitoring with respect to the onset of symptoms, significantly higher hPASP levels were found in NP compared with AIP after day 2 (p<0.001). In patients with NP, peak values of hPASP correlated significantly with the extent of pancreatic necroses measured by contrast-enhanced CT-scanning, whereas CRP did not. Six patients of the transplantation group had the same serum hPASP course as AIP, with almost normal values on the third postoperative day. One patient had elevated levels throughout the observation period. This patient suffered from necrotizing graft pancreatitis, confirmed by relaparotomy, and died because of subsequent septic complications.

Indocyanine Green Plasma Disappearance Rate During the Anhepatic Phase of Orthotopic Liver Transplantation

Non-invasive pulse spectrophotometry to measure indocyanine green (ICG) elimination correlates well with the conventional invasive ICG clearance test. Nevertheless, the precision of this method remains unclear for any application, including small-for-size liver remnants. We therefore measured ICG plasma disappearance rate (PDR) during the anhepatic phase of orthotopic liver transplantation using pulse spectrophotometry. Measurements were done in 24 patients. The median PDR after exclusion of two outliers and two patients with inconstant signal was 1.55%/min (95% confidence interval [CI] = 0.8–2.2). No correlation with patient age, gender, body mass, blood loss, administration of fresh frozen plasma, norepinephrine dose, postoperative albumin (serum), or difference in pre and post transplant body weight was detected. In conclusion, we found an ICG-PDR different from zero in the anhepatic phase, an overestimation that may arise in particular from a redistribution into the interstitial space. If ICG pulse spectrophotometry is used to measure functional hepatic reserve, the verified average difference from zero (1.55%/min) determined in our study needs to be taken into account.

Morbidity rate of reoperation in thyroid surgery: a different point of view

BACKGROUND Goitre recurrence is a common problem following subtotal thyroid gland resection for multinodular goitre disease. The aim of the present study was to evaluate morbidity rate in relation to the side of initial and redo-surgery for recurrent disease. METHODS A total of 1699 patients underwent consecutive thyroid gland surgery between 1997 and 2010 at our institution. One hundred and eighteen patients (6.9%) underwent redo-surgery for recurrent disease after subtotal resection. One hundred and nine patients with complete follow-up were included in the present study. RESULTS Recurrent disease was found in 79 patients (72.5%) in the ipsilateral lobe and in 30 patients (27.5%) in the contralateral lobe. The incidence of permanent recurrent laryngeal nerve palsy was significantly higher in patients undergoing redo-surgery on the ipsilateral lobe compared to patients undergoing initial operation (3.8% vs. 1.1%; p = 0.03), whereas no difference was found in patients with contralateral redo-surgery compared to patients undergoing initial operation (p = 1.0). Independent risk factors for contralateral recurrent disease were age at primary operation <37 years (OR 4.86; 95% CI 1.58-15.01) and time to recurrence <20 years (OR 6.53; 95% CI 2.23-19.01). CONCLUSION Morbidity rate for recurrent disease after subtotal resection was significantly higher for ipsilateral redo-surgery compared to initial surgery, whereas redo-surgery can be performed safely on the contralateral lobe. Young age at primary operation and short time to recurrence are independent risk factors for contralateral recurrent disease.

Bladder tamponade due to vesical varices during orthotopic liver transplantation

Vesical varices due to portal hypertension and liver cirrhosis are extremely rare. Only four cases of such a phenomenon have been published [1–4]. We report a patient with primary biliary cirrhosis, who developed vesical varices accompanied by two episodes of hematuria. During orthotopic liver transplantation (OLT) the patient experienced massive urinary tract bleeding resulting in bladder tamponade requiring intraoperative hemostasis through a cystostomy. The 58-year-old female patient was hospitalized with hematuria and urinary retention in a district hospital 5 month before OLT. Her personal history revealed an appendectomy in 1961 and a hysterectomy with adnexectomy due to ovarian cysts in 1988. Since 6 years, she was suffering from mild hyperbilirubinemia of unknown origin resulting in recurrent attacks of jaundice. Physical examination was only positive for hepatosplenomegaly. Her hemoglobin level was 6.8 mmol/l (normal 7.5–10.6), hematocrit 37% (normal 36–49), white blood count 3.9 · 10/l (normal 4–9), platelet count 140 · 10/l (normal 180–300) and thromboplastin time 23% (normal 80– 110). Liver and cholestatic values included total bilirubin 152 lmol/l (normal <17), glutamic oxaloacetic transaminase 156 U/l (normal 11–50), glutamic pyruvic transaminase 107 U/l (normal 9–60), and alkaline phosphate 649 U/l (normal < 117). Cystoscopic examination of the urinary bladder revealed massive varices up to 1.5 cm in diameter on the left lateral wall without active bleeding, but with fibrin on one varix, indicative for an inactive bleed. One week after admission, the bladder catheter was removed; the prothrombin time had normalized under vitamin K substitution. Further examinations by duplex sonography and upper endoscopy revealed portal hypertension with hepatosplenomegaly, esophageal varices and ascites. Neither clinical examination nor duplex sonography of the abdomen showed evidence for an iliac vein thrombosis. Special hepatological examinations revealed an enormous elevation of antimitochondrial antibodies with a value of 1290 (normal <21), and the liver biopsy confirmed a primary biliary cirrhosis stage IV. Based on clinical and laboratory findings the patient was put on the waiting list for liver transplantation. Only 1 week after evaluation for OLT, the patient had to be readmitted with hematuria, successfully treated by placement of a urinary catheter which was removed 2 weeks later. Five months later, the OLT was performed with a model for end-stage liver disease (MELD) score of 24 points, and a Child Pugh score of 12 points (class C). At this time period, we used the classic transplantation technique with replacement of the caval vein and a femoro-porto-axillary venovenous bypass. During the venovenous bypass time (flow 1.4–3.2 l/min) a massive hematuria via transurethral Nelaton catheter (size: 14 French) was observed. Subsequently the patient became anuric due to a vesical tamponade manifesting as a huge palpable vesical ‘tumor’. After the implantation of the liver graft, an additional lower midline incision for an extraperitoneal access was performed and 800 ml of partially clotted blood was removed from the bladder. As already seen 5 months earlier multiple 1.5 cm large and actively bleeding vesical varices on the left lateral wall of the bladder were detected, transfixed and ligated. With the exception of the intraoperative massive hematuria and bladder tamponade, no increased bleeding tendency was observed. Intraoperative values for prothrombin time were between 58% and 72% and for platelet count between 100 and 202 · 10/l. During the procedure, nine units of erythrocyte concentrates and 38 units of fresh-frozen plasma were given. The postoperative urologic course was uneventful with removal of the urinary catheter 2 weeks after OLT. Follow-up 48 months after transplantation with decompression of the portal hypertension was uneventful hepatologically as well as urologically with absent signs of urinary bladder varices. Ectopic varices due to intrahepatic portal hypertension are predominantly located in the digestive tract. The prevalence is between 10% and 40% dependent on the cause of hypertension and the sensitivity of the diagnostic test [5]. Vesical varices are rare and seem to develop mainly after intestinal conduits, schistomosiasis and

Bridging hyperacute liver failure by ABO-incompatible auxiliary partial orthotopic liver transplantation

Uncontrollable intracranial pressure elevation in hyperacute liver failure often proves fatal if no suitable liver for transplantation is found in due time. Both ABO‐compatible and auxiliary partial orthotopic liver transplantation have been described to control such scenario. However, each method is associated with downsides in terms of immunobiology, organ availability and effects on the overall waiting list.

Intrathyroid Adenomas in Primary Hyperparathyroidism: Are They Frequent Enough to Guide Surgical Strategy?

Background. Ectopic parathyroid adenoma, including intrathyroid adenoma, is a common cause of failed parathyroid operations. The aim of this study was to evaluate the operative strategy/outcome in patients with primary hyperparathyroidism (pHPT), with special regard to intrathyroid adenomas. Method. The authors performed an analysis of all patients receiving operative treatment for pHPT from 2003 through 2005. The operative strategy consisted of systematic perithyroid exploration followed by extended cervical exploration in cases where the adenoma was not found initially. In cases of persistent, high intraoperative parathyroid hormone levels, hemithyroidectomy was performed on the side with higher suspicion of intrathyroid adenoma or with more extended thyroid changes. Results. During the study, 115 patients received surgical treatment for sporadic pHPT. A single parathyroid adenoma (normal parathyroid position) was found in 95 patients (82.6%), ectopic single adenoma was found in 7 patients (6.1%), and double adenomas were found in 10 (8.7%) patients. Operative failure occurred in 3 cases (2.6%). In all, 4 of 7 ectopic single adenomas were intrathyroidal and were removed by hemithyroidectomy according to the authors’ standard protocol. Conclusion. The strategy of (a) cervical exploration, (b) extended cervical exploration, and (c) hemithyroidectomy was highly successful for removing undetectable intrathyroid parathyroid adenomas during primary intervention, thereby reducing the risks associated with reintervention.

Determinants of inpatient rehabilitation length of stay and discharge modality after hip and knee replacement surgery in Switzerland - a retrospective observational study

QUESTIONS UNDER STUDY / PRINCIPLES The aims of this study were to identify the determinants influencing the inpatient rehabilitation length of stay (LoS) and discharge modality (DisMod) after hip or knee replacement surgery. METHODS Data were retrieved for 306 patients (185 females, 121 males) who were admitted to a Swiss orthopaedic rehabilitation facility between 2007 and 2008 after hip or knee replacement surgery. LoS and DisMod were extracted from the medical files along with an additional seven binary and six continuous variables (including scores of timed-get-up-and-go [TUG], walking distance [WDT] and stair climbing tests [FIM_St]). Nonparametric procedures were used to detect differences between the gender groups. For the analysis of the LoS determinants, a linear regression model was used. The nonmotor performance test determinants of DisMod were analysed using a logistic regression model, whereas the motor performance test determinants were examined using binary classification. For both regression models, a backward procedure was used. RESULTS Unlike DisMod, LoS calculations were conducted after stratification for gender. The simplified regression models explained 22% (females) and 31% (males) of the LoS variance and 20% (both genders) of the DisMod variance. TUG, WDT and FIM_St were all important predictors for LoS, whereas DisMod could be best predicted by WDT. CONCLUSIONS Patients with good motor ability at admission were discharged earlier and more frequently to home. These findings might be of importance for preoperative physiotherapeutic care and might help to improve care planning as well as more accurately predict the access to inpatients beds and the allocation of resources.