Management of primary and renal hyperparathyroidism: guidelines from the German Association of Endocrine Surgeons (CAEK).

BACKGROUND AND AIMS: The purpose of this review is to provide updated recommendations for the surgical management of primary (pHPT) and renal (rHPT) hyperparathyroidism, formulating a new guideline of the German Association of Endocrine Surgeons (CAEK). METHODS: Evidence-based recommendations for the diagnosis and therapy of pHPT and rHPT were assessed by a multidisciplinary panel using PubMed for a comprehensive literature search together with a structured consensus dialogue (S2k guideline of the Association of the German Scientific Medical Societies, AWMF). RESULTS: During the last 20 years, a variety of new preoperative localization procedures, such as sestamibi-SPECT, 4D-CT, and various PET/CT procedures, were established for pHPT. High-resolution imaging, together with intraoperative parathyroid hormone (IOPTH) measurement, enabled focused or minimally invasive surgery to become the most favored surgical technique. Patients with pHPT and nonlocalizing imaging have a higher risk of multiglandular disease. Surgical therapy provides very high cure rates, with a clear relation to the surgeon's experience in parathyroid procedures. Reoperative parathyroidectomy, children with pHPT or familial forms, and parathyroid carcinoma are addressed and require special surgical expertise. A multidisciplinary team of experienced nephrologists, transplant, and endocrine surgeons should assess the diagnosis and treatment of renal HPT. CONCLUSION: Surgery is the only curative treatment for pHPT and should be considered for all patients with pHPT. For rHPT, a more selective approach is required, and parathyroidectomy is indicated only when conservative treatment options fail. In parathyroid carcinoma, the adequacy of local resection influences local disease control.

[EUROCRINE®: adrenal surgery 2015-2019- surprising initial results]. / EUROCRINE®: Nebennierenoperationen 2015 bis 2019 ­ überraschende erste Ergebnisse.

BACKGROUND: Since 2015 operations performed in the field of endocrine surgery have been entered into the European registry EUROCRINE®. The aim of this analysis was a description of the current healthcare situation for adrenal surgery in a homogeneous healthcare environment corresponding to the German-speaking countries-or to the presence of the working group on surgical endocrinology (CAEK) of the German society for general and visceral surgery (DGAV)-and to assess the adherence to current international treatment guidelines. METHODS: An analysis of the preoperative diagnostics, the applied operative techniques and the underlying histological entities was carried out for all operations on adrenal glands in Germany, Switzerland and Austria, which were registered in EUROCRINE® from 2015 to 2019. RESULTS: In the total of 21 participating hospitals from the German-speaking EUROCRINE® countries, 658 operations on adrenal glands were performed. In 90% of cases unilateral adrenalectomy was performed, in 3% bilateral adrenalectomy and in 7% other resection procedures. In 41% the main histological diagnosis was an adrenocortical adenoma. In 15% malignant entities were detected on final histology, including 6% adrenocortical carcinoma (ACC) and 8% metastases to the adrenal glands. 23% of the operations were performed for pheochromocytoma. This entity was primarily resected using minimally invasive approaches (82%), whereas minimally invasive techniques were applied in 28% for ACC and in 66% for metastases to the adrenal glands. CONCLUSION: Surprisingly, following adrenocortical adenoma and pheochromocytoma, the third most common histological entity was metastasis of different extra-adrenal primary tumors to the adrenal gland. Of the operations for ACC 28% were scheduled for minimally invasive techniques, but conversion to open surgery was necessary in 20%. The analysis revealed discrepancies between treatment reality and international guideline recommendations that raise questions, which will be addressed by an updated version of the EUROCRINE® module for the documentation of adrenal surgery.

Toxic dermatolysis, tissue necrosis and impaired wound healing due to sunitinib treatment leading to forefoot amputation.

Innovative treatment strategies in urologic oncology confront the treating physician with a new spectrum of adverse events. With growing understanding of underlying pathomechanisms, we need to identify contraindications against the use of certain antiproliferative drugs. The management of toxicities involves a multidisciplinary approach and thus, the exchange of experience across medical specialties is mandatory. We report a case of fulminant toxic dermatolysis, tissue necrosis and impaired wound healing resulting in the amputation of one forefoot after 6 days of treatment with sunitinib.

Presentation of 6 cases with parathyroid cysts and discussion of the literature.

INTRODUCTION: Cystic lesions of the parathyroid glands are uncommon, and rare are those that cause primary hyperparathyroidism. Preoperative diagnosis can be challenging and some of these tumors might be misinterpreted as parathyroid carcinoma. With an expertise of more than 1700 patients operated on primary hyperparathyroidism, we present six cases with cystic degeneration of a parathyroid gland causing primary hyperparathyroidism in five patients. CASE REPORTS: A woman at the age of 67 presented with hypercalcaemic crisis due to persistent primary hyperparathyroidism after an operation four years ago. As cervical exploration was unsuccessful, sternotomy was performed and a cystic adenoma of a parathyroid gland could be resected from the anterior mediastinum. The second patient - a 63-year-old female with severe hypercalcaemic crisis, operated on under suspicion of a parathyroid carcinoma - had a functional cyst of the parathyroid gland with a parathyroid hormone level of 700,000 pg/ml in the aspirated fluid. Third, operation on a 70-year-old woman with a benign euthyreot goiter and the laboratory findings of primary hyperparathyroidism revealed a cystic adenoma adjacent to the thyroid gland, whose aspirate had a parathyroid hormone level of 1,500,000 pg/ml. In the fourth case of a 67-year-old female with an adenoma of the right inferior parathyroid gland localized by ultrasonography, the cystic parathyroid adenoma was operated on by video-assistance. A cystic structure in the upper mediastinum was diagnosed in the fifth patient, a 66-year-old woman. It was suspected to be a thyroid cyst at the left-lower pole of the thyroid gland. After hemithyroidectomy pathological evaluation revealed a large parathyroid cyst. The last case of a 56-year-old male illustrates the extensive preoperative work-up of a patient with primary hyperparathyroidism who was preoperatively diagnosed as having a thyroid cyst. Final histopathological examination exposed multiple gland disease with a parathyroid adenoma as well as a cystic parathyroid gland. DISCUSSION: Cystic adenomas of the parathyroid glands are often misdiagnosed as thyroid cysts or - in the case of extremely elevated parathyroid hormone levels - even as parathyroid carcinoma. The routine preoperative diagnostic tools, such as ultrasonography or (99m)Tc-sestamibi-scintigraphy, cannot clearly distinguish between these entities and might be jeopardized by mediastinal localization, which is not uncommon in parathyroid adenomas with cystic degeneration.

[Pathophysiology of wound healing and current treatment strategies in a urological context]. / Pathophysiologie der Wundheilung und modernes Wundmanagement im urologischen Kontext.

Acute wound healing is a dynamic, interactive process culminating in the closure of a tissue defect. Chronic wounds result when the healing cascade is impaired. Proteases destroy important growth factors and matrix proteins, inflammation is prolonged, and the normal healing process does not take place within the expected time span. Owing to demographic changes the investigation of age-related pathologies, including treatment-resistant wounds, has become increasingly important. The TIME concept (tissue, infection, moisture imbalance, edge of wound) assesses essential elements in the healing process that can be addressed in the treatment of chronic wounds. Moist wound treatment is standard therapy. Definitive research trials on the level of success that can be achieved with different dressings are still needed. New types of treatment should be selected with due consideration for clinical variables, the patient's quality of life and independence, and cost effectiveness.

Virological treatment failure of protease inhibitor therapy in an unselected cohort of HIV-infected patients.

OBJECTIVE: To determine the rate of virological treatment failure with protease inhibitor therapy in unselected patients and to assess underlying risk factors. DESIGN AND SETTING: Retrospective study in two German tertiary care treatment centres. PATIENTS: A total of 198 HIV-infected patients treated with protease inhibitors in 1996. MAIN OUTCOME MEASURES: Levels of HIV RNA 1-6 months after start of treatment; definition of treatment failure of < 1 log10 reduction in plasma HIV RNA within 6 months after starting protease inhibitor therapy; multivariate analysis of risk factors for treatment failures. RESULTS: A total of 226 treatment episodes with protease inhibitors were evaluable (saquinavir, 83; ritonavir, 47; indinavir, 96). The rate of virological treatment failure was 44% (saquinavir, 64%; ritonavir, 38%; indinavir, 30%). In a multivariate analysis, the following independent risk factors for virological failure were found: CD4 cell count, pretreatment with antiretroviral drugs (number), and protease inhibitor (compound). The relative risk reduction for each CD4 cell count increase was 0.997 (P = 0.012), 2.64 for pretreatment with one or two drugs versus no drug (P = 0.05), 2.97 for pretreatment with more than two drugs versus no drug (P = 0.05), and 4.62 for treatment with saquinavir versus indinavir (P = 0.001). CONCLUSION: An unexpectedly high rate of virological treatment failure of protease inhibitor therapy was found in an unselected cohort of HIV-infected patients. Response to antiretroviral combination therapy in normal clinical practice may considerably differ from results of randomized clinical trials. Further studies are warranted to find optimal treatment strategies for both initial and salvage therapy.

Effects of steroids and retinoids on wound healing.

HYPOTHESIS: Anti-inflammatory corticosteroids significantly impair wound healing. Retinoids partially, but significantly, reverse this effect. Little is known about the mechanism of steroid retardation or retinoid reversal. We hypothesized that corticosteroids lower transforming growth factor-beta (TGF-beta) and insulin-like growth factor-I (IGF-I) levels and tissue deposition in wounds and that retinoids stimulate corticosteroid-impaired TGF-beta and IGF-I release and collagen production. DESIGN: Randomized controlled trial. SETTING: Wound healing research laboratory. PARTICIPANTS: Animal study. INTERVENTIONS: Four wire mesh wound cylinders were implanted subcutaneously into the backs of 72 male Sprague-Dawley rats. Wound healing was impaired by a single subcutaneous injection of 6 mg of methylprednisolone acetate (Depo-Medrol). Two preparations of retinoids were used in separate experiments: all-trans-retinoic acid and 9-cis-retinoic acid that were fed orally. MAIN OUTCOME MEASURES: Hydroxyproline content was measured in the healing tissue and TGF-beta and IGF-I levels were analyzed in the wound fluid. RESULTS: Methylprednisolone treatment significantly decreased TGF-beta and IGF-I levels in the wound fluid and hydroxyproline content in the tissue (P<.05). Oral all-trans- and 9-cis-retinoic acid partially reversed the TGF-beta and IGF-I decrease and significantly increased hydroxyproline content toward normal levels (P<.05). Oral all-trans-retinoic acid enhanced collagen deposition, TGF-beta and IGF-I levels over normal chow fed control animals (P<.05). CONCLUSIONS: Steroids and retinoids have antagonistic effects on growth factors and collagen deposition in wound healing. These effects can be relevant for treatment options in a clinical setting.

Wound hypoxia and acidosis limit neutrophil bacterial killing mechanisms.

BACKGROUND: "Respiratory burst" activity, ie, O2- production, is dependent on PO2, temperature, pH, and glucose concentrations within the physiologic range. OBJECTIVES: To determine whether environmental conditions characteristic of wounds may limit human neutrophil respiratory burst metabolism and to clarify the degree to which bactericidal oxidant production depends on local PO2. METHODS: Human blood and wound neutrophils were stimulated with phorbol myristate acetate. Oxygen consumption and superoxide production were measured over a range of 30 to 300 mm Hg PO2, 0 to 40 mmol/L glucose, pH 6.0 to 8.0, and 30 degrees C to 37 degrees C. The apparent Michaelis Menten constant for oxidant production with respect to PO2 was calculated. RESULTS: Oxygen consumption and O2- production were dependent on PO2 throughout the range tested. Half-maximal oxidant production occurred in the range of 45 to 80 mm Hg PO2 and maximal at PO2 higher than 300 mm Hg. These data agree with the highest previous estimates. Oxidant generation was also dependent on pH, temperature, and glucose concentration, but to a lesser extent. CONCLUSIONS: Leukocyte bacterial killing capacity as measured by oxygen consumption and superoxide production are substantially impaired at the low oxygen tensions often found in wounds. Changes in pH, temperature, and glucose concentration have lesser but nonetheless significant consequences. The data provide a plausible mechanism for the vulnerability of some wounds to infection and for the previous finding that increasing oxygen tension at wound sites enhances bactericidal function. Thus, the data serve as a basis for future studies on prevention of wound infection.

Brief clinical report: glutamine-enriched total parenteral nutrition in a patient with radiation-induced renal and intestinal fibrosis.

This brief clinical report illustrates the case of a 50-y-old male patient with severe radiation-induced renal and intestinal fibrosis who received glutamine-enriched total parenteral nutrition (TPN). The patient had end-stage renal disease and, therefore, underwent a kidney transplant. In the postoperative course the patient developed signs of bowel obstruction and cachexia. He received two courses of glutamine-enriched TPN before he underwent surgery for small bowel stenosis. Postoperatively, the patient received a third course of glutamine-enriched TPN. During the patient's hospital course the following indexes were monitored: patient's weight, serum concentrations of protein, albumin, and trialglycerol. Intestinal permeability was assessed with the lactulose-mannitol sugar test (L-M test). We measured changes in the patient's weight and the L-M test. We hypothesize that glutamine-enriched TPN may have been beneficial in the hospital course of this critically ill patient and may have influenced the patient's intestinal function and permeability.

[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.

[Soft tissue chondromatosis of the foot: diagnosis and therapy]. / Chondromatose der Weichteile am Fuss. Diagnose und Therapie.

Chondromas of the soft tissue are uncommon, benign tumors. They are most frequently found adjacent to periarticular tissues or tenosynovium with a predilection for the hands and feet. We report a case of a patient with a large, increasing tumor of the left foot. Because of subjective complaints and mechanical irritation the patient was scheduled for surgery. The preoperative radiological work-up showed popcorn like clusters of calcifications around the dorsum of the foot. The tumor mass was reduced using several incisions. Histology showed soft tissue chondromatosis of the foot without malignancy. Following the operative procedure, the patient was free of pain and able to wear normal shoes. This case illustrates the clinical and radiological characteristics as well as the surgical treatment of progressive soft tissue chondromatosis.

Examination of expanded polytetrafluoroethylene wound healing models.

The object of this animal study was to examine and further develop the expanded polytetrafluoroethylene wound healing model. The goal was to increase its potential for assessing wound healing by increasing yield, reducing variability, establishing the elements of a standard technique, and further testing its ability to detect variations of healing which have clinical significance. Expanded polytetrafluoroethylene implants of various dimensions and fabrications and several implantation and sterilization techniques were compared in rats. Hydroxyproline, DNA, and protein deposition into the expanded polytetrafluoroethylene implants as parameters for wound healing were assessed. Additionally, a 4 cm skin incision for tensile strength assessment was created. Wound healing was assessed under normal and corticosteroid-impaired healing conditions. The highest yield of collagen was found in the stiffer fabrication of expanded polytetrafluoroethylene with the larger pore size and after the more traumatic implantation technique of incisional placement. Variability was unaffected by fabrication, implantation technique, indexing by various geometric dimensions of the implant, sterilization, or sampling techniques. Variability was the same in the individual animals as in groups of animals. The expanded polytetrafluoroethylene method also detects the influence of antiinflammatory corticosteroids and reflects the tensile strength of incisional wounds made in other sites in the same animal.

Production and structure elucidation of glycoglycerolipids from a marine sponge-associated microbacterium species.

The bacterium Microbacterium sp., isolated from the sponge Halichondria panicea, produced four unusual cell-associated glycoglycerolipids and one diphosphatidylglycerol when grown on marine broth and on artificial seawater media. The lipids were isolated by chromatography on silica columns and their structures elucidated using a combination of multidimensional NMR and MS techniques. The main compound was 1-O-acyl-3-[alpha-glucopyranosyl-(1-3)-(6-O-acyl-alpha-mannopyranosyl )]glycerol (GGL.2) with 14-methyl-hexadecanoic acid and 12-methyl-tetradecanoic acid positioned at C-6 of the mannose unit and at the glycerol moiety. Glycolipid production was correlated with growth and reached a maximum value of 200 mg/L when grown on artificial seawater medium with 20 g/L glucose. The main compound decreased the surface tension of water down to 33 mN/m and the interfacial tension of the water/n-hexadecane system down to 5 mN/m. In addition to this good surface-active behavior, the main glycoglycerolipid showed antitumor activities.