Protective intraoperative ventilation with higher versus lower levels of positive end-expiratory pressure in obese patients (PROBESE): study protocol for a randomized controlled trial.

BACKGROUND: Postoperative pulmonary complications (PPCs) increase the morbidity and mortality of surgery in obese patients. High levels of positive end-expiratory pressure (PEEP) with lung recruitment maneuvers may improve intraoperative respiratory function, but they can also compromise hemodynamics, and the effects on PPCs are uncertain. We hypothesized that intraoperative mechanical ventilation using high PEEP with periodic recruitment maneuvers, as compared with low PEEP without recruitment maneuvers, prevents PPCs in obese patients. METHODS/DESIGN: The PRotective Ventilation with Higher versus Lower PEEP during General Anesthesia for Surgery in OBESE Patients (PROBESE) study is a multicenter, two-arm, international randomized controlled trial. In total, 2013 obese patients with body mass index ≥35 kg/m2 scheduled for at least 2 h of surgery under general anesthesia and at intermediate to high risk for PPCs will be included. Patients are ventilated intraoperatively with a low tidal volume of 7 ml/kg (predicted body weight) and randomly assigned to PEEP of 12 cmH2O with lung recruitment maneuvers (high PEEP) or PEEP of 4 cmH2O without recruitment maneuvers (low PEEP). The occurrence of PPCs will be recorded as collapsed composite of single adverse pulmonary events and represents the primary endpoint. DISCUSSION: To our knowledge, the PROBESE trial is the first multicenter, international randomized controlled trial to compare the effects of two different levels of intraoperative PEEP during protective low tidal volume ventilation on PPCs in obese patients. The results of the PROBESE trial will support anesthesiologists in their decision to choose a certain PEEP level during general anesthesia for surgery in obese patients in an attempt to prevent PPCs. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02148692. Registered on 23 May 2014; last updated 7 June 2016.

11C-methionine PET/CT after inconclusive 99mTc-MIBI-SPECT/CT for localisation of parathyroid adenomas in primary hyperparathyroidism.

AIM: To investigate the efficacy of PET/CT with 11C-methionine for localizing parathyroid adenomas in patients with suspected primary hyperparathyroidism and inconclusive results of cervical ultrasonography and 99mTc-MIBI-SPECT/CT. PATIENTS, METHOD: Retrospective analysis of imaging data of 18 patients and correlation with clinical outcome, in particular intraoperative findings and histopathology of excised tissue. RESULTS: 12 of 18 patients received surgery. In 10 patients single parathyroid adenomas were found (diameter: 5-20 mm), 2 patients presented parathyroid hyperplasia (5 excised hyperplastic glands (diameter: 2-12 mm). PET/CT correctly localized all adenomas and 1 of 5 hyperplastic glands. The sensitivity per patient was 91.7% (11 of 12), the sensitivity per lesion 73.3% (11 of 15). All lesions missed by PET/CT had a size smaller than 9 mm and a volume of less than 0.2 ml. In 6 patients no surgery was performed. Five of them had a negative or atypical PET/CT. Further follow-up indicated familial hypocalciuric hypercalcemia in 3 of them (thus, PET/CT true negative), in the remaining 2 patients no validation is available. One patient with 2 highly suggestive lesions rejected surgery so far. CONCLUSION: PET/CT with 11C-methionine is a very sensitive method for the detection of parathyroid adenomas, even if they are too small to be visualized by 99mTc-MIBI-SPECT/CT.

[Hypercalcemic crisis due to primary hyperparathyroidism]. / Hyperkalzämische Krise infolge eines primären Hyperparathyreoidismus.

HISTORY AND ADMISSION FINDINGS: A 54-year-old female patient presented with increasing somnolence since two days. Furthermore, the patient reported left-sided mid-abdominal pain and obstipation for one week. Immediately prior to admission, the patient had returned from a 14-day beach holiday on the Azores. Physical examination of the somnolent patient revealed a sun-tanned skin, signs of exsiccosis, and tachycardia with 116 beats per minute. INVESTIGATIONS: Laboratory studies showed marked hypercalcemia due to primary hyperparathyroidism and acute renal failure. Neck ultrasonography revealed a hypoechogenic, 5.8 x 3.5 x 3.1 cm-measuring mass behind the lower pole of the right thyroid lobe. DIAGNOSIS, TREATMENT AND COURSE: Serum calcium levels significantly decreased after immediate rehydration, bisphosphonate administration, and continuous hemodialysis that was also indicated because of acute renal failure with anuria. After knowledge of increased parathormone levels the patient underwent rapidly resection of the parathyroid adenoma which was histologically confirmed. CONCLUSIONS: Hypercalcemic crisis is often associated with acute renal failure due to calcium-induced polyuria.

[Hypercalcaemic crisis and acute renal failure due to primary hyperparathyroidism]. / Hyperkalzämische Krise und akutes Nierenversagen infolge eines primären Hyperparathyreoidismus.

Hypercalcaemic crisis is a rare endocrine emergency. Often, an acute renal failure develops due to hypercalcaemia-induced polyuria. The molecular causes comprise stimulation of the calcium-sensing receptor in the ascending Henle loop and a reduced aquaporin expression in the collecting ducts. We report on a 54-year-old woman who was admitted for hypercalcaemic crisis and acute renal failure. Immediate rehydratation, bisphosphonate administration, and slow-extended daily dialysis (SLEDD) were initiated leading to a marked reduction of serum calcium. Endocrine work-up revealed primary hyperparathyroidism due to a parathyroid adenoma, which was treated by emergency surgery. Haemodialysis was continued in the first post-operative weeks for prolonged acute renal failure.

[Clinical pathways in endocrinology and diabetology]. / Behandlungspfade in der Endokrinologie und Diabetologie.

Endocrinology and diabetology are disciplines with an interdisciplinary approach. Patients with diabetes or endocrine disorders are diagnosed and treated by multiple disciplines both in an outpatient or in-hospital setting. Additional diabetes-specific professions also participate in the care of diabetic patients. The development of clinical pathways and case-management in institutionalized "Diabetes Centers" and "Endocrinology Centers" as platforms of cooperation is one way to improve patient care and to pool resources. In such centers an interdisciplinary decision support within the diagnostic and therapeutic process is important. E. g., interdisciplinary case conferences expediate and intensify the necessary flow of information. This guarantees the implementation of a rational and concerted treatment according to guidelines and finally optimize the clinical pathways in a continuous process improvement.

Steroid profile in an adrenocortical carcinoma producing aldosterone.

We report a rare case of primary aldosteronism due to an adrenocortical carcinoma. A 61-year-old woman with a history of hypertension and hypokalemia was referred for evaluation of a 4.2 cm measuring adrenal mass without secondary signs of malignancy. Endocrinological testing was consistent with primary aldosteronism. The patient underwent surgical resection of the adrenal mass; histology revealed an adrenocortical carcinoma. Postoperatively blood pressure, serum potassium, and aldosterone returned to normal. Four months after adrenalectomy, the patient presented again with hypokalemic hypertension and was found to have metastatic disease. Endocrinological investigation revealed primary aldosteronism and subclinical autonomous glucocorticoid hypersecretion. Careful hormonal investigation should be obtained in patients with adrenal masses causing excessive aldosterone secretion. In uncertain cases of primary aldosteronism, we would suggest to measure 18-hydroxycortisol levels, as excessive amounts may indicate adrenocortical carcinoma.

[Design and use of patient pathways in general surgery]. / Entwicklung und Einsatz von Patientenpfaden in der Allgemeinchirurgie.

BACKGROUND: Clinical pathways are a new initiative intended to reduce costs while maintaining or even improving the quality of care. Based on treatment guidelines, patient pathways display an optimal sequence of staff actions in the preoperative, operative, and postoperative in- and outpatient treatment. METHODS: In this study, patient pathways were developed for selected elective general surgical disease entities following a new modular approach. All elements of care and their direct costs to the hospital were identified. Multidisciplinary teams of physicians, nurses, and administrative staff constructed and implemented the patient pathways. RESULTS: In the 1-year pilot phase, we developed and implemented 7 pathways with 16 subpathways: open herniorrhaphy, laparoscopic cholecystectomy and fundoplication, thyroidectomy, surgical treatment of diverticulitis and colon carcinoma and kidney transplantation. CONCLUSIONS: Patient pathways combine the management of care, hospital processes, and costs in a new integrated concept. Patient pathways streamline and standardize care, facilitate communication, and contribute to cost control efforts.

Inhibition of Ret oncogene activity by the protein tyrosine phosphatase SHP1.

Germline mutations in the Ret protooncogene give rise to the inherited endocrine cancer syndromes MEN types 2A and 2B and familiar medullary thyroid carcinoma. Although it is well accepted that the constitutive active tyrosine kinase of Ret oncogenes ultimately leads to malignant transformation, it is not clear whether a decrease in the autophosphorylation of oncogenic Ret forms can affect the mitogenic and transforming activities of Ret. Potential modulators of the tyrosine kinase activity of Ret could be tyrosine phosphatases that are expressed in human thyroid tissue. Therefore, we investigated the impact of the tyrosine phosphatases SHP1 and SHP2 on the intrinsic tyrosine kinase activity and oncogenic potency of Ret with a 9-bp duplication in the cysteine-rich domain (codons 634-636), which was described in a patient with MEN type 2A recently. SHP1 and SHP2 were stably overexpressed in NIH3T3 fibroblasts together with Ret-9bp. Coexpression of SHP1 with Ret-9bp reduced the autophosphorylation of Ret-9bp by 19 +/- 7% (P = 0.01, n = 4), whereas no effect was seen with SHP2. Furthermore, Ret-9bp could be coimmunoprecipitated with SHP1 but not with SHP2 antibodies. Suppression of the Ret-9bp tyrosine kinase activity by SHP1 caused a decrease in activation of Erk2 (extracellular signal-regulated kinase) and abolished PKB/Akt (protein kinase B) phosphorylation. In addition, diminished Ret-9bp autophosphorylation led to reduced phosphorylation of the transcription factor jun-D. Finally, the inhibitory effect on Ret-9bp signaling resulted in a 40-60% reduction of [(3)H]thymidine incorporation and in reduced ability of NIH3T3 cells to form colonies in soft agar. In conclusion, the data suggest that SHP1 caused a moderate reduction of Ret autophosphorylation, which led to a strong suppression of the Ret oncogene activity.

[Intra-arterial calcium stimulation for preoperative localization of insuloma]. / Intraarterieller Kalzium-Stimulationstest zur präoperativen Lokalisationsdiagnostik des Insulinoms.

PURPOSE: Objective is to evaluate the efficacy of the intraarterial calcium test in the preoperative localisation of insulinomas. MATERIAL AND METHOD: To stimulate the pathological release of insulin, calcium gluconate (0.015 meq Ca++/kg) was selectively injected into the arteries supplying the pancreas. Prior to calcium injection and 30, 60, 90 and 120 seconds later, 5 ml samples of blood were obtained from the right or from both right and left hepatic veins. Insulin levels were then determined by mean of immunoassays. A twofold increase in insulin level in the venous sample after 30 or 60 seconds localised the insulinoma to the region of the pancreas supplied by the selectively injected artery. Results of the calcium test were prospectively analysed in 6 patients and compared with operative findings. RESULTS: All 6 patients had a surgically proved solitary and benign insulinoma. Calcium stimulation with venous sampling provided true-positive localisation of insulinomas in all patients without suspicion of liver metastasis. All 6 patients currently have normal insulin levels after a mean period of 16 months (range 4-24 months) with no evidence of hypoglycaemia on fasting. CONCLUSION: Intraarterial stimulation with calcium and hepatic vein samplings for insulin gradients is a very sensitive minimally invasive functional method and may replace transhepatic portal venous samplings for the preoperative detection of insulinomas.

Cholecystokinin is partly responsible for reduced food intake and body weight loss after total gastrectomy in rats.

PURPOSE: To determine the cause of body weight loss after total gastrectomy. METHODS: We evaluated the acute effect of exogenous cholecystokinin (CCK) on food intake and the chronic effect of CCK receptor blockade on food intake and body weight after total gastrectomy in rats. RESULTS: Exogenous CCK significantly reduced food intake in gastrectomized rats; this was blocked by administration of a CCK-A but not a CCK-B receptor antagonist. Chronic treatment with a CCK-A or CCK-B receptor antagonist after total gastrectomy in rats significantly increased postoperative food intake and body weight. CONCLUSION: Our data indicate that endogenous CCK is partly responsible for reduced food intake and body weight loss after total gastrectomy in rats.

Recovery of hypoglycaemia-associated compromised cerebral function after a short interval of euglycaemia in insulin-dependent diabetic patients.

To test the hypothesis that compromised cerebral function, induced by recurrent hypoglycaemic episodes, may recover after a short interval of euglycaemia, we examined electrophysiological activity and symptom awareness during two sequential euglycaemic-hypoglycaemic clamp studies in 11 insulin-dependent diabetic patients without any signs of peripheral or autonomic neuropathy. Neurophysiological testing and evaluation of hypoglycaemic symptoms were performed at stable glycaemic plateaus of 5.6, 3.3, 2.2, and 1.7 mmol/l. The first clamp study was preceded by 3 short-term hypoglycaemic episodes, whereas the second clamp study followed a 2 day interval of strict euglycaemia. The latter caused a recovery of electrophysiological activity, which was demonstrated by recovery of delays of the middle latency auditory evoked potentials (latency shift of the P(a) component, MANOVA, P < 0.01). Reversal of hypoglycaemic symptom unawareness involved the overall symptom perception (MANOVA, P < 0.04), as well as the autonomic symptoms of heart pounding (P < 0.05) and sweating (P < 0.05). We conclude that the previously reported impaired cerebral function, occurring as a consequence of repetitive hypoglycaemic episodes, may recover after a single euglycaemic interval.

Iron uptake by human upper small intestine microvillous membrane vesicles. Indication for a facilitated transport mechanism mediated by a membrane iron-binding protein.

To investigate the hypothesis that iron absorption in man involves a carrier-mediated cellular uptake mechanism, influx velocity (Vo) of 59Fe3+ by isolated human microvillous membrane (MVM) vesicles of the upper small intestine was examined. Vo revealed saturation kinetics (Km = 315 nM; Vmax = 361 pmol Fe3+ x min-1 x mg protein-1) was temperature dependent and inhibited by pronase pretreatment of MVM. In the presence of an inwardly directed Na(+)-gradient a typical overshoot phenomenon with maximal uptake at 30-40 s was observed. The suggestion of an active, carrier-mediated uptake mechanism for iron was pursued by isolation of a 160-kD iron-binding protein from solubilized human MVM proteins. This glycoprotein was assembled as a trimer composed of 54-kD monomers. A monospecific antibody against the 54-kD subunit inhibited vesicular influx of Fe3+ into MVM by greater than 50%. Immunofluorescence and immunoblot analysis confirmed the localization of the protein in brush border plasma membranes. It was detectable in human intestinal mucosa and liver, but not in esophagus. These data indicate that the translocation of Fe3+ across human MVM represents a facilitated transport mechanism which is, at least in part, mediated by a membrane iron-binding protein.

Surgical intervention following fragmentation of gallstones by extracorporeal shock waves.

Five cases of surgical intervention following extracorporeal shock wave lithotripsy (ESWL) of gallbladder and bile duct stones are reported. This represents an incidence of surgical intervention in 1% of patients with gallbladder stones and in 9% of patients with common bile duct stones who underwent ESWL during a two-and-a-half-year investigation period. There was no mortality. In 2 patients with gallbladder stones and persistent colic after ESWL, elective cholecystectomy was performed. There was no evidence of macroscopic or microscopic damage or bleeding within the wall of the gallbladder. Furthermore, no damage to the liver, common bile duct, duodenum, or stomach was noted. ESWL was applied in 34 patients with common bile duct stones in whom endoscopic sphincterotomy and stone extraction had proved ineffective. Three (9%) of these patients required surgery. In 1 patient, a Dormia basket got stuck and the basket, together with the stone, were removed by choledochotomy. In a second patient, rupture of a juxtapapillary diverticulum occurred 10 days after ESWL and 2 days after endoscopic extraction of stone fragments. At laparotomy, the retroperitoneum was drained. In a third patient with gallbladder and common bile duct stones, acute cholecystitis developed after lithotripsy of common bile duct stones. Cholecystectomy was performed and a t-tube was inserted in the bile duct. In all patients, the postoperative course was uneventful. In our experience, ESWL is a safe procedure with no mortality and an infrequent need for surgical intervention.

Changes of immunoglobulin concentrations in the bile after proximal gastric vagotomy in rats.

We have investigated the influence of proximal gastric vagotomy in rats (PGV) on the immunoglobulin concentration in the serum, bile, and intestinal fluid. Clear differences for serum IgA were noted: after PGV, rats had 1.5 mg/ml IgA in contrast to only 0.25 mg/ml in sham-operated controls. The other serum immunoglobulins remained unchanged. Bile immunoglobulins were elevated in PGV rats with regard to IgA, IgG1, IgG2a, and IgG2b. In addition, PGV rats had higher IgA, IgG1, IgG2a, and IgG2b concentrations in the intestinal fluid than controls. An explanation for these high Ig concentrations in the secretions might be the challenge by intestinal (microbial) antigens and, perhaps, mucosal inflammation with changes in the permeability. Indications for the former were the increase in the number of bacteria after PGV.

[Intraoperative electron irradiation of malignant pancreatic tumors--initial experiences at Grosshadern]. / Intraoperative Elektronenbestrahlung (IORT) maligner Pankreastumoren--erste Grosshaderner Erfahrungen.

15 patients with locally unresectable pancreatic carcinomas were treated by IORT and bypass surgery. 13 patients without distant metastases were additionally treated by external beam irradiation. Although only one patient had a local failure, the median survival was only eight months. Severe complications were seen in eight patients, gastrointestinal bleeding occurred in six patients and was the cause of death in three patients. The stop of weight loss and the impressive pain relief within ten days after IORT demonstrate the significance of this treatment modality with respect to palliative effects.