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.

Surgery for Renal Hyperparathyroidism in the Era of Cinacalcet: A Single-Center Experience.

BACKGROUND AND AIMS: There are only few data on the influence of cinacalcet on the outcome of parathyroidectomy in patients with renal hyperparathyroidism. Indication and timing of surgery have changed since its introduction, especially with regard to kidney transplantation. Therefore, we retrospectively analyzed patients undergoing parathyroidectomy for renal hyperparathyroidism in our institution. MATERIAL AND METHODS: Between 2008 and 2015, 196 consecutive operations in 191 patients were analyzed. About 80 operations (41%) were performed in patients receiving cinacalcet compared with 116 operations (59%) in patients without cinacalcet. Clinical data, preoperative medication, pre- and postoperative laboratory values, type and details of surgery including complications, as well as cardiovascular complications and kidney transplantation with graft function were recorded. RESULTS: Demographical data were similar in patients with or without cinacalcet treatment. A total of 54% of patients received a kidney graft before or after parathyroidectomy. Pre- and postoperative parathormone levels were similar in both groups (preoperatively 755 vs 742 ng/L, postoperatively 50 vs 46 ng/L, p > 0.10), whereas patients with cinacalcet showed significantly lower calcium levels preoperatively (2.28 vs 2.41 mmol/L, p = 0.0002). There was no difference in recurrence or persistence of hyperparathyroidism, duration of surgery, hospital stay, or complication rate. Creatinine levels in patients with tertiary hyperparathyroidism were similar after 1-year follow-up. CONCLUSION: Cinacalcet did not influence outcome of patients with parathyroidectomy for renal hyperparathyroidism and can be safely offered to patients not responding to medical treatment.

[Possibilities and perspectives of hyperspectral imaging in visceral surgery]. / Möglichkeiten und Perspektiven der Hyperspektralbildgebung in der Viszeralchirurgie.

HyperSpectral Imaging (HSI) technology enables quantitative tissue analyses beyond the limitations of the human eye. Thus, it serves as a new diagnostic tool for optical properties of diverse tissues. In contrast to other intraoperative imaging methods, HSI is contactless, noninvasive, and the administration of a contrast medium is not necessary. The duration of measurements takes only a few seconds and the surgical procedure is only marginally disturbed. Preliminary HSI applications in visceral surgery are promising with the potential of optimized outcomes. Current concepts, possibilities and new perspectives regarding HSI technology together with its limitations are discussed in this article.

Surgical therapy of adrenal tumors: guidelines from the German Association of Endocrine Surgeons (CAEK).

BACKGROUND AND AIMS: Previous guidelines addressing surgery of adrenal tumors required actualization in adaption of developments in the area. The present guideline aims to provide practical and qualified recommendations on an evidence-based level reviewing the prevalent literature for the surgical therapy of adrenal tumors referring to patients of all age groups in operative medicine who require adrenal surgery. It primarily addresses general and visceral surgeons but offers information for all medical doctors related to conservative, ambulatory or inpatient care, rehabilitation, and general practice as well as pediatrics. It extends to interested patients to improve the knowledge and participation in the decision-making process regarding indications and methods of management of adrenal tumors. Furthermore, it provides effective medical options for the surgical treatment of adrenal lesions and balances positive and negative effects. Specific clinical questions addressed refer to indication, diagnostic procedures, effective therapeutic alternatives to surgery, type and extent of surgery, and postoperative management and follow-up regime. METHODS: A PubMed research using specific key words identified literature to be considered and was evaluated for evidence previous to a formal Delphi decision process that finalized consented recommendations in a multidisciplinary setting. RESULTS: Overall, 12 general and 52 specific recommendations regarding surgery for adrenal tumors were generated and complementary comments provided. CONCLUSION: Effective and balanced medical options for the surgical treatment of adrenal tumors are provided on evidence-base. Specific clinical questions regarding indication, diagnostic procedures, alternatives to and type as well as extent of surgery for adrenal tumors including postoperative management are addressed.

Radiation exposure of adrenal vein sampling: a German Multicenter Study

Objective: Adrenal vein sampling (AVS) represents the current diagnostic standard for subtype differentiation in primary aldosteronism (PA). However, AVS has its drawbacks. It is invasive, expensive, requires an experienced interventional radiologist and comes with radiation exposure. However, exact radiation exposure of patients undergoing AVS has never been examined. Design and Methods: We retrospectively analyzed radiation exposure of 656 AVS performed between 1999 and 2017 at four university hospitals. The primary outcomes were dose area product (DAP) and fluoroscopy time (FT). Consecutively the effective dose (ED) was approximately calculated. Results: Median DAP was found to be 32.5 Gy*cm2 (0.3­3181) and FT 18 min (0.3­184). The calculated ED was 6.4 mSv (0.1­636). Remarkably, values between participating centers highly varied: Median DAP ranged from 16 to 147 Gy*cm2, FT from 16 to 27 min, and ED from 3.2 to 29 mSv. As main reason for this variation, differences regarding AVS protocols between centers could be identified, such as number of sampling locations, frames per second and the use of digital subtraction angiographies. Conclusions: This first systematic assessment of radiation exposure in AVS not only shows fairly high values for patients, but also states notable differences among the centers. Thus, we not only recommend taking into account the risk of radiation exposure, when referring patients to undergo AVS, but also to establish improved standard operating procedures to prevent unnecessary radiation exposure.

[Surgical strategies for non-metastatic adrenocortical carcinoma]. / Chirurgische Strategien beim nichtmetastasierten Nebennierenrindenkarzinom.

Adrenocortical carcinomas (ACC) are rare but highly aggressive tumors. It is very difficult to differentiate small locally limited ACCs from benign adenomas. A spontaneous density >10 Hounsfield units in non-enhanced CT scan and a slow washout after contrast injection are suspicious of malignancy but with a low specificity. Preoperatively, a hormonal work-up is mandatory for all adrenal tumors. Each patient should be discussed in an interdisciplinary board. For non-metastatic ACCs (ENSAT stages I-III) radical resection is the treatment of choice. R0-resection and avoiding violation of the tumor capsule are the most important prognostic factors for long-term survival. Although discrepant reports regarding the benefits of lymphadenectomy have been published, lymph node dissection at least in the periadrenal area and in the renal hilum (optional extension to paraaortal and paracaval nodes) should be performed in the case of lymph node involvement. The role of prophylactic lymphadenectomy needs to be analyzed in further studies. The gold standard remains the open approach but minimally invasive procedures are also an option, especially in stage I-II tumors, if the principles of oncological surgery are respected. In this case, long-term survival rates are comparable. As local recurrence rates are lower and time to local recurrence is longer in patients who are operated on at a dedicated center (>10 adrenalectomies/year), adrenalectomy for ACC should be performed by an experienced surgeon.

Glucose Metabolism in Primary Aldosteronism.

In recent years, an increasing number of studies have revealed deleterious effects of aldosterone via the mineralocorticoid receptor (MR). Especially in patients with primary aldosteronism (PA) a significant higher estimated risk of developing cardiovascular comorbidities and comortalities compared to essential hypertensives was reported. As diabetes mellitus and the metabolic syndrome are one of the major contributors to cardiovascular morbidity and mortality their connection to aldosterone excess became a focus of research in PA patients. Several studies assessed the effect of PA on glucose metabolism, the prevalence of diabetes mellitus, and the effect of PA treatment on both revealing different results. Therefore, we performed an extensive literature research. This review focuses on the current knowledge of the connection between aldosterone excess, glucose homeostasis, and diabetes mellitus in patients with PA. We have highlighted this topic from a pro and contra perspective followed by a summarizing concluding remark. Additionally, we have briefly reviewed the data on possible underlying mechanisms and indicated future considerations on the possible impact of cortisol co-secretion in PA.

[Clinical nutrition in surgery. Guidelines of the German Society for Nutritional Medicine]. / Klinische Ernährung in der Chirurgie. S3-Leitlinie der Deutschen Gesellschaft für Ernährungsmedizin e. V.

BACKGROUND: While enhanced recovery after surgery (ERAS) programs are the standard for perioperative management, special nutritional care has to be administered to malnourished patients and those at metabolic risk with special regard to patients with postoperative complications. METHODS: Existing guidelines of the German and European societies of nutritional medicine (DGEM and ESPEN) on enteral and parenteral nutrition in surgery were merged and in accordance with the principles of the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF, German Association of the Scientific Medical Societies) and Ärztliches Zentrum für Qualität in der Medizin (AeZQ, German Agency for Quality in Medicine) revised and extended. RESULTS AND DISCUSSION: The working group developed 41 consensus-based recommendations for perioperative nutrition. The recommendation strength is: 9x A (recommendation based on significant good quality literature containing at least one randomized controlled trial), 12x B (recommendation based on well-designed trial without randomization), 13x C (recommendation based on expert opinions and/or clinical experience of respected authorities) and 7x CCP (clinical consensus point). CONCLUSION: Even in patients without obvious malnutrition perioperative nutritional support is indicated when oral food intake is not feasible or inadequate for a longer period of time.

Effect of pre- and probiotics on liver regeneration after resection: a randomised, double-blind pilot study.

Liver regeneration is a prerequisite for extended liver surgery. Several studies have shown that the bacterial gut flora is able to modulate liver function. Previously we observed that synbiotics could partly reverse the impaired mitosis rate of hepatocytes in a rat model of synchronous liver resection and colon anastomosis. The effect of synbiotics on liver function after hepatic resection has not been analysed yet. A prospective randomised double-blind pilot trial was undertaken in 19 patients scheduled for right hepatectomy. All patients received enteral nutrition immediately post-operatively. Comparison was made between a group receiving a combination of four probiotics and four fibres and a placebo group receiving the fibres only starting the day before surgery and continuing for 10 days. Primary study endpoint was the liver function capacity measured by 13C-methacetin breath test and indocyanine green plasma disappearance rate. Portal vein flow, liver volumetry, laboratory parameters for liver function, length of hospital stay, post-operative complications and side effects of synbiotic therapy were recorded. Liver function capacity was comparable in both groups. Complications had a negative impact on liver function. Because complications were more severe in the verum group, a sub-analysis was performed. In case of an uncomplicated course, liver function capacity was better in the patients with synbiotics. No severe side effects occurred. Synbiotics might be able to increase liver function capacity in patients after liver resection, but patient numbers were too small and the clinical courses too heterogeneous to draw any definite conclusions.

Impact of image fusion and attenuation correction by SPECT-CT on the scintigraphic detection of parathyroid adenomas.

AIM: In addition to planar parathyroid scintigraphy, SPECT and image fusion with CT/MR improve adenoma detection in primary hyperparathyroidism (pHPT). This study evaluated the use of a hybrid SPECT-CT device concerning image fusion and attenuation correction (AC). PATIENTS, METHODS: The data of 26 patients with pHPT, preoperatively examined by (99m)Tc-sestamibi dual-phase scintigraphy plus SPECT-CT (low-dose CT), was retrospectively evaluated by two observers in a consensus reading. The images of planar scintigraphy, non-attenuation corrected SPECT (SPECT(NAC)), attenuation corrected SPECT (SPECT(AC)) and SPECT(AC)-CT were interpreted and compared to the results of surgery. The effect of AC on focus intensity was semiquantified by determination of the tumor-to-background (TB) ratio for SPECT(AC) and SPECT(NAC). Finally, the TB(AC)/TB(NAC)-ratio was calculated for each focus and correlated to the distance of a focus from the body surface. RESULTS: 20/26 (77%) patients were positive in planar scintigraphy. One focus was detected by SPECT only. AC of SPECT-data increased image contrast but had no impact on the detection rate. Additional SPECT(AC)-CT image fusion facilitated the localization of three mediastinal foci. In the semiquantitative analysis an increase in TB after AC was observed, although there was no strong correlation between depth of the focus (16-60 mm) and the TB(AC)/TB(NAC)-ratio (r = 0.213, p = 0.353). CONCLUSION: The detection rate of planar scintigraphy is only slightly improved by SPECT imaging. Due to the low spatial resolution of the CT component, the benefit of image fusion is limited to mediastinal foci. However, as TB and image contrast is measurably improved after AC there is a potential to improve the sensitivity of parathyroid SPECT.

Immunosuppression following intestinal transplantation.

Acute rejection is still the main risk factor following intestinal transplantation. Potent immunosuppression decreases rejection frequency, but may increase immunosuppression-related complications. Isolated small intestinal transplantation was performed in 14 adult patients with short bowel syndromes. Immunosuppression included tacrolimus and rapamycin in combination with steroids for 6 months after ATG or daclizumab induction therapy. In addition to protocol biopsies, cellular immune status and soluble immune parameters were used to guide immunosuppression. CMV and EBV markers were determined on a routine basis. Ten of 14 patients (71%) survived for 1 to 38 months (median 26 months). Eight patients are at home, in good physical condition, completely on enteral nutrition. Among the 5 patients (36%) who developed acute rejection, 2 patients with early postoperative events underwent graft removal and 1 patient died due to multiple organ failure. Two patients developed severe acute rejection episodes at 10 and 24 months following transplantation. Both patients recovered following OKT3 rescue therapy and increased baseline immunosuppression with repeated methylprednisolone and infliximab treatment. Infections included peritonitis (n = 3), pneumonia (n = 3), central line infection (n = 5), urinary tract (n = 2), CMV (n = 2), and EBV (n = 4). Two patients developed anastomotic leaks at the esophageal and coloanal anastomosis. In conclusion, acute rejection episodes can be controlled by potent immunosuppression using tacrolimus in combination with rapamycin. Immunosuppression-associated complications, including infections, were in an acceptable range. However, even late after transplantation, reduction in immunosuppression may lead to severe rejection without major clinical symptoms.

[Influence of probiotics and fibre on the incidence of bacterial infections following major abdominal surgery - results of a prospective trial]. / Einfluss von Probiotika und Ballaststoffen auf die Inzidenz bakterieller Infektionen nach viszeralchirurgischen Eingriffen - Ergebnisse einer prospektiven Studie.

INTRODUCTION: Early enteral nutrition with fibre and probiotics has been effective in preventing bacterial translocation and is therefore expected to reduce the incidence of postoperative bacterial infections. PATIENTS AND METHODS: In a prospective randomized trial including 172 patients following major abdominal surgery or liver transplantation, the incidence of bacterial infections was compared in patients receiving either a) conventional parenteral or enteral nutrition, b) enteral nutrition with fibre and lactobacillus plantarum 299 or c) enteral nutrition with fibre and heat inactivated lactobacilli (placebo). Liver transplant recipients were also treated with selective bowel decontamination (SBD). Routine laboratory parameters, nutritional parameters and the cellular immune status were measured preoperatively and on postoperative days 1, 5 and 10. RESULTS: Patients were comparable regarding preoperative ASA-classification, Child-Pugh classification of cirrhosis, operative data and immunosuppression. The incidence of bacterial infections after liver, gastric oder pancreas resection was 31 % in the conventional group a) compared to 4 % in the lactobacillus-group b) and 13 % in the placebo-group c). In the analysis of 95 liver transplant recipients, 13 % group b)-patients developed infections compared to 48 % group a)-patients and 34 % group c)-patients. The difference between groups a) and b) was statistically significant in both cases. In addition, the duration of antibiotic therapy was significantly shorter in the lactobacillus-group. Cholangitis and pneumonia were the most frequent infections and enterococci the most frequently isolated bacteria. Fibre and lactobacilli were well tolerated in most cases. CONCLUSION: Fibre and probiotics could lower the incidence of bacterial infections following major abdominal surgery in comparison to conventional nutrition with or without SBD. With this new concept, costs can be reduced by shortening the duration of antibiotic therapy and sparing SBD.

Combination prophylaxis with Hepatitis B immunoglobulin and lamivudine after liver transplantation minimizes HBV recurrence rates unless evolution of pretransplant lamivudine resistance.

BACKGROUND: Survival rates of hepatitis B patients after liver transplantation improved significantly by introduction of passive immunoprophylaxis. Due to viral escape mutations recurrence still occurs, but recently a combination prophylaxis with hepatitis B immunoglobuline plus lamivudine is evaluated in transplant centers in terms of a further reduction of recurrence rates. PATIENTS AND METHODS: Between 1996 and 2000 a postoperative combination prophylaxis with HBIg and lamivudine was initiated in 44 HBsAg positive liver transplant recipients. In total 14 patients were HBV-DNA negative and 30 were HBV-DNA positive at the time of evaluation. In 22 HBV-DNA positive patients a pre-operative lamivudine treatment (150 mg/die) was started. Five of them developed pre-transplant lamivudine resistance with high viral replication (mean HBV-DNA prior to transplantation 728 +/- 219 pg/ml). In all patients passive immunoprophylaxis was started in the anhepatic phase with application of 10.000 units hepatitis B immunoglobuline. It was continued after seroconversion to HBsAg negativity with an aimed titer of more than 100 U/l and only stopped in case of HBV recurrence. Lamivudine was also continued indefinitely after liver transplantation. RESULTS: Overall recurrence rate in the 44 patients, including retransplantations and patients with pretransplant lamivudine resistance, was 11.5 % under combination prophylaxis. Recurrence was seen only in one of 39 patients (2.6 %) without preoperative lamivudine resistance, in contrast 4 out of 5 patients (80 %) with pre-existing lamivudine resistance suffered from early hepatitis B recurrence. The single patient without preoperative lamivudine resistance, who developed recurrence was pre-transplant HBV-DNA negative without lamivudine treatment, but a postoperative seroconversion to negative HBsAg could not be achieved. The overall 3 year patient survival rate was 91 % in the study population. One patient, who was retransplanted with preoperative lamivudine resistance, died 4.5 months after retransplantation due to hepatitis B recurrence and sepsis, three other patients died for reasons not related to hepatitis B recurrence. Combination prophylaxis was well tolerated in all patients and no severe side effects were observed. CONCLUSION: Combination prophylaxis with hepatitis B immunoglobulin and lamivudine is safe and highly effective in prevention of HBV recurrence after liver transplantation, even in case of positive viral replication. In accordance with the results of other centers it should therefore be the standard regimen. However it fails in the majority of patients with preoperative evolution of YMDD mutations, in which the optimal management has to be determined yet. To minimize preoperative resistance formation universal preoperative antiviral treatment of HBV-DNA positive patients should be replaced by individualized indication for preoperative treatment.

Intraoperative measurement of intact parathyroid hormone in renal hyperparathyroidism by an inexpensive routine assay.

Although the kinetics of intraoperative intact parathyroid hormone (iPTH) are well characterised in primary hyperparathyroidism, no data are available for patients with renal hyperparathyroidism and renal insufficiency, partially because of the high costs of intraoperative quick iPTH measurement. Therefore we evaluated an inexpensive laboratory test with a duration of 18 min for intraoperative use and measured iPTH intraoperatively in 34 patients with renal hyperparathyroidism. Samples were taken before and 5 min and 15 min after parathyroid resection. Blood samples were put on ice immediately and sent to the hospital central laboratory via a pneumatic tube system. The first 76 probes were measured in parallel using three assays: the Nichols Quick PTH, the Roche Elecsys and the Biermann Immulite assay. The subsequent samples were only measured using the Elecsys assay. Determination of iPTH from 76 samples showed a correlation coefficient of 0.997 between the Immulite and Elecsys assay and a correlation coefficient of 0.987 for the Nichols Quick PTH and the Elecsys test. In renal hyperparathyroidism the mean iPTH was 26+/-2% of the starting value 5 min after subtotal parathyroidectomy and 18+/-2% after 15 min. Renal function influenced absolute iPTH values in patients with renal hyperparathyroidism but not relative changes. In patients with terminal renal insufficiency iPTH decreased from 615+/-57 pg/m before preparation to 109+/-13 pg/ml 15 min after subtotal resection. In contrast in patients after kidney transplantation iPTH decreased from a lower starting value of 341+/-94 pg/ml to 58+/-9 pg/ml after 15 min. The iPTH kinetics showed a biphasic clearance of iPTH with an initial dominant half-life of 3.2 min and a terminal half-life of 29.2 min. Half-life did not correlate with renal function. All operations were successful as indicated by an adequate drop in PTH (from 709+/-92 pg/ml preoperatively to 22+/-6 pg/ml at discharge) and calcium (from 2.57+/-0.04 mmol/l to 2.32+/-0.04 mmol/l). In conclusion, intraoperative measurement of iPTH is also reliable in patients with renal hyperparathyroidism. Elimination kinetics are similar to that in patients with primary disease. However, the half-life was not influenced by renal function. The availability of a quick, inexpensive, routine iPTH test might expand its use to renal hyperparathyroidism, specifically for surgical decisions in problem cases.