Adrenal Crisis - Definition, Prevention and Treatment: Results from a Delphi Survey.

Based on recent data, a total number of about 29 000 patients with adrenal insufficiency can be calculated for Germany, and about 1500 fatalities due to adrenal crises have to be expected within the next decade. Management of adrenal crises is still unsatisfactory. The objectives of this study were to establish consensus for diagnostic criteria, prevention strategies, and treatment recommendations for adrenal crises. The study was conducted from January 2022 to April 2023, using Delphi technique. Four rounds of questionnaires were sent to 45 experts, selected by a coordinating group on behalf of the adrenal section of the German Society of Endocrinology. The survey was implemented online using the REDCap web application. Responses were captured anonymously. During the Delphi process the expert panel developed diagnostic criteria to identify patients likely to have an adrenal crisis. Education about adrenal insufficiency among patients as well as non-endocrine medical personnel were regarded as highly important. It was suggested that recommendations for the management of adrenal insufficiency have to be simplified and made widely available. This study provides pragmatic strategies to identify and treat patients prone to adrenal crisis, thereby highlighting the need for an improved management of patients with adrenal insufficiency.

False-positive results for pheochromocytoma associated with norepinephrine reuptake blockade.

Measurements of plasma metanephrines and methoxytyramine provide a sensitive test for diagnosis of pheochromocytoma/paraganglioma. False-positive results remain a problem, particularly in patients taking norepinephrine reuptake-blocking drugs. Therefore, in this retrospective observational study, we measured plasma metanephrines and methoxytyramine in 61 patients taking norepinephrine reuptake blockers (tricyclic antidepressants or serotonin-norepinephrine reuptake inhibitors) and 17 others taking selective serotonin reuptake inhibitors, all without pheochromocytoma/paraganglioma. We highlight a singular case with strongly elevated plasma normetanephrine and methoxytyramine concentrations associated with norepinephrine reuptake blockade. Data were compared to results from 252 and 1804 respective patients with and without tumors. Plasma normetanephrine was 40% higher (P < 0.0001) in patients on norepinephrine reuptake blockers and methoxytyramine was 127% higher (P = 0.0062) in patients taking tricyclic antidepressants compared to patients not taking uptake blockers and without tumors. The corresponding false-positive rates rose (P < 0.0001) from 4.8% to 23.0% for normetanephrine and from 0.9% to 28.6% for methoxytyramine. Selective serotonin reuptake inhibitors did not increase plasma concentrations of metabolites. In the highlighted case, plasma normetanephrine and methoxytyramine were elevated more than six times above upper reference limits. A pheochromocytoma/paraganglioma, however, was excluded by functional imaging. All biochemical test results normalized after discontinuation of norepinephrine reuptake blockers. These findings clarify that norepinephrine reuptake blockers usually result in mild elevations of normetanephrine and methoxytyramine that, nevertheless, significantly increase the number of false-positive results. There can, however, be exceptions where increases in normetanephrine and methoxytyramine reach pathological levels. Such exceptions may reflect failure of centrally mediated sympathoinhibition that normally occurs with the norepinephrine reuptake blockade.

Spectral Similarity Measures for In Vivo Human Tissue Discrimination Based on Hyperspectral Imaging.

PROBLEM: Similarity measures are widely used as an approved method for spectral discrimination or identification with their applications in different areas of scientific research. Even though a range of works have been presented, only a few showed slightly promising results for human tissue, and these were mostly focused on pathological and non-pathological tissue classification. METHODS: In this work, several spectral similarity measures on hyperspectral (HS) images of in vivo human tissue were evaluated for tissue discrimination purposes. Moreover, we introduced two new hybrid spectral measures, called SID-JM-TAN(SAM) and SID-JM-TAN(SCA). We analyzed spectral signatures obtained from 13 different human tissue types and two different materials (gauze, instruments), collected from HS images of 100 patients during surgeries. RESULTS: The quantitative results showed the reliable performance of the different similarity measures and the proposed hybrid measures for tissue discrimination purposes. The latter produced higher discrimination values, up to 6.7 times more than the classical spectral similarity measures. Moreover, an application of the similarity measures was presented to support the annotations of the HS images. We showed that the automatic checking of tissue-annotated thyroid and colon tissues was successful in 73% and 60% of the total spectra, respectively. The hybrid measures showed the highest performance. Furthermore, the automatic labeling of wrongly annotated tissues was similar for all measures, with an accuracy of up to 90%. CONCLUSION: In future work, the proposed spectral similarity measures will be integrated with tools to support physicians in annotations and tissue labeling of HS images.

The challenge to differentiate between sarcoma or adrenal carcinoma-an observational study.

BACKGROUND: Adrenal sarcomas are rare malignant tumors with structural and clinical similarities to sarcomatoid adrenocortical carcinoma. Preoperative diagnosis of tumors of the adrenal gland can be challenging and often misleading thus detaining patients from appropriate oncological strategies. OBJECTIVE: This analysis of a case series evaluated the predictive capability of the primary clinical diagnosis in case of malignancies of the adrenal gland. METHODS: Thirty two patients were treated from 2009 to 2015 at our clinic and analyzed retrospectively. All patients had computed tomography and/or magnet resonance imaging and a primary histopathological examination at our institution after surgery. Ten questionable cases were surveyed by a reference pathologist. RESULTS: Twelve out of 32 diagnoses had to be revised (37.5%). Only 15 out of 24 tumors primarily classified as adrenocortical carcinoma were finally described as primary adrenal cancer. We found two leiomyosarcomas, one liposarcoma, one sarcomatoid adrenocortical carcinoma, and one epitheloid angiosarcoma among 12 misleading diagnoses. Other tumors turned out to be metastases of lung, hepatocellular, and neuroendocrine tumors. Larger tumors were significantly more often correctly diagnosed compared to smaller tumors. Four patients of the group of revised diagnoses died whereas all patients with confirmed diagnoses survived during the follow-up. CONCLUSION: Preoperative assessment of tumors of the adrenal gland is still challenging. In case of wrong primary diagnosis, the prognosis could be impaired due to inadequate surgical procedures or insufficient preoperative oncological treatment.

Adhesion GPCR GPR56 Expression Profiling in Human Tissues.

Despite the immense functional relevance of GPR56 (gene ADGRG1) in highly diverse (patho)physiological processes such as tumorigenesis, immune regulation, and brain development, little is known about its exact tissue localization. Here, we validated antibodies for GPR56-specific binding using cells with tagged GPR56 or eliminated ADGRG1 in immunotechniques. Using the most suitable antibody, we then established the human GPR56 tissue expression profile. Overall, ADGRG1 RNA-sequencing data of human tissues and GPR56 protein expression correlate very well. In the adult brain especially, microglia are GPR56-positive. Outside the central nervous system, GPR56 is frequently expressed in cuboidal or highly prismatic secreting epithelia. High ADGRG1 mRNA, present in the thyroid, kidney, and placenta is related to elevated GPR56 in thyrocytes, kidney tubules, and the syncytiotrophoblast, respectively. GPR56 often appears in association with secreted proteins such as pepsinogen A in gastric chief cells and insulin in islet ß-cells. In summary, GPR56 shows a broad, not cell-type restricted expression in humans.

[Gastroenteropancreatic neuroendocrine tumors]. / Gastroenteropankreatische neuroendokrine Tumoren.

Neuroendocrine tumors (NET), or more generally neuroendocrine neoplasms (NEN), represent a very heterogeneous group of rare tumors with varying location which are only defined by their endocrine biology and secretion of synaptophysin and chromogranin A. They originate from mesoderm-derived stem cells. In the last few years, the incidence and prevalence of NEN have been steadily increasing. Classification is based on the affected organ, the proliferation rate and presence or absence of hormone production with typical symptoms. Diagnosis and treatment of these tumors is therefore very specific and requires an interdisciplinary approach. Treatment options include endoscopic or surgical resection, drug therapy for control of symptoms and proliferation, locoregional therapy and radionuclide therapy. Guidelines with algorithms for diagnostic workup and treatment are constantly updated.

Real-World Efficacy and Safety of Multi-Tyrosine Kinase Inhibitors in Radioiodine Refractory Thyroid Cancer.

Background: The management of patients with locally advanced or metastatic differentiated thyroid cancer (DTC) that is refractory to radioiodine (RAI) remains a therapeutic challenge. The multi-tyrosine kinase inhibitors (TKIs) sorafenib and lenvatinib have been approved based on phase 3 clinical trials. Patients and Methods: We aimed at describing the efficacy and safety of TKI treatment of RAI-refractory DTC in a real-world setting at six German referral centers. One hundred and one patients with locally advanced or metastatic RAI-refractory DTC treated with sorafenib, lenvatinib, and/or pazopanib were included. Progression-free survival (PFS) and overall survival (OS) probabilities were estimated by using the Kaplan-Meier method. Results: Ninety-seven of 101 patients had progressive disease before TKI initiation. The median PFS for first-line treatment with sorafenib (n = 33), lenvatinib (n = 53), and pazopanib (n = 15) was 9 (95% confidence interval 5.2-12.8), 12 (4.4-19.6), and 12 months (4.4-19.6), respectively. The median OS for first-line treatment was 37 (10-64) for sorafenib, 47 (15.5-78.5) for lenvatinib, and 34 months (20.2-47.8) for pazopanib. Serious complications (e.g., hemorrhage, acute coronary syndrome, and thrombosis/venous thromboembolism) occurred in 16 out of 75 (21%) patients taking lenvatinib, in 3 out of 42 (7%) patients taking sorafenib, and in 3 out of 24 (13%) patients taking pazopanib. Conclusions: Sorafenib, lenvatinib, and pazopanib are effective treatment options in the majority of patients with RAI-refractory DTC. The PFS and six-month survival rate in patients treated with lenvatinib und pazopanib appear to compare favorably with sorafenib in the first-line treatment setting. However, a more advanced disease stage at treatment initiation in sorafenib- and pazopanib-treated patients in the era before TKI-approval and the retrospective nature of this study precludes a direct comparison of TKIs.

Prospective evaluation of aldosterone LC-MS/MS-specific cutoffs for the saline infusion test.

OBJECTIVE: Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) has become state of the art for the quantitative analysis of steroid hormones. Although method comparisons show that aldosterone measurement using LC-MS/MS yields considerably lower levels than immunoassays (IAs), method-specific cutoff values for primary aldosteronism (PA) are largely missing. Objective of this study was to analyze the diagnostic accuracy of proposed LC-MS/MS-specific cutoff values for the saline infusion test (SIT). DESIGN AND METHODS: From 2016 to 2019, 104 consecutive patients suspected of PA underwent the SIT and captopril challenge test in the tertiary medical center at the University Hospital of Leipzig, Germany. Patients with positive case confirmation underwent adrenal imaging and adrenal venous sampling for subtype classification. RESULTS: Overall, proposed assay-specific PACLC-MS/MS cutoff values for the SIT achieved higher diagnostic accuracy than established PACIA values with a sensitivity and specificity of 87.5% (95% CI: 71.0-96.5) and 97% (95% CI: 89.6-99.6) for a cutoff of 120 pmol/L and 93.8% (95% CI: 79.2-99.2) and 92.5% (95% CI: 83.4-97.5) for a cutoff of 94 pmol/L. The most accurate post-SIT PACLC-MS/MS cutoff value in this study was 83 pmol/L, yielding a sensitivity and specificity of 96.9% (95% CI: 83.8-99.9) and 92.5% (95% CI: 83.4-97.5), respectively. CONCLUSIONS: The present data confirm the need for the implication of lower method-specific aldosterone cutoff values for the diagnosis of PA with LC-MS/MS based aldosterone measurement.

Influence of Parathyroidectomy on Kidney Graft Function in Secondary and Tertiary Hyperparathyroidism.

BACKGROUND: Timing of parathyroidectomy (PTX) remains controversial in candidates for kidney transplant with concomitant renal hyperparathyroidism (HPT). The aim of this retrospective study was to identify the influence of early vs late posttransplant PTX compared to pretransplant PTX on renal graft function and morbidity. METHODS: This single-center cohort study includes 57 patients with renal HPT and kidney transplantation treated between 2007 and 2017. Ninety-six patients had surgery for renal HPT between 2007 and 2017 as a consecutive sample. Group 1 (n = 30; tertiary HPT), group 2 (n = 66; secondary HPT). Of group 1, 4 patients were excluded for PTX before and after kidney transplantation. In group 2, 20 patients were excluded since they had not undergone kidney transplantation during follow-up. Twelve patients were excluded because of short follow-up (kidney transplantation in 2018), and 3 patients were excluded because of transplant failure within 90 days. Twenty-six patients underwent posttransplant PTX (10 patients within 12 months after transplant), and 31 patients had undergone PTX prior to kidney transplantation. Graft function, serum calcium concentrations, parathyroid hormone (PTH) levels, postoperative morbidity, and 90-day mortality were recorded. RESULTS: Median age was 53.1 years in group 1 and 49.1 years in group 2. Most patients were male (53.8% in group 1; 54.8% in group 2). Median preoperative PTH levels were significantly different with 331.6 pg/mL in group 1 and 667.5 pg/mL in group 2 (P = .003). Creatinine levels changed little from 1.4 mg/dL (range, 0.8-2.5) to 1.7 mg/dL (range, 0.7-7.3) in group 1, and no difference was seen between early or late PTX after transplantation. In group 2, creatinine levels were 8.5 mg/dL (range, 4.6-11.7) before PTX and 8.7 mg/dL (range, 5.1-11.9) after PTX. We saw no correlation between postoperative PTH and kidney function. Thirty-five patients with postoperative PTH < 15 pg/mL displayed a mean postoperative creatinine of 5.5 mg/dL (range, 4.3-6.8), similar to other patients. Both the 30-day and 90-day mortality rates were zero. CONCLUSIONS: PTX had no negative effect on graft function, whether performed before or after (early or late) kidney transplantation. Surgical cure of renal HPT should be performed as soon as possible to prevent secondary complications and can also be safely carried out early after transplantation.

Classification of hyperspectral endocrine tissue images using support vector machines.

BACKGROUND: Thyroidectomy is one of the most commonly performed surgical procedures. The region of the neck has a very complex structural organization. It would be beneficial to introduce a tool that can assist the surgeon in tissue discrimination during the procedure. One such solution is the noninvasive and contactless technique, called hyperspectral imaging (HSI). METHODS: To interpret the HSI data, we implemented a supervised classification method to automatically discriminate the parathyroid, the thyroid, and the recurrent laryngeal nerve from surrounding tissue(muscle, skin) and materials (instruments, gauze). A leave-one-patient-out cross-validation was performed. RESULTS: The best performance was obtained using support vector machine (SVM) with a classification and visualization in less than 1.4 seconds. A mean patient accuracy of 68% ± 23% was obtained for all tissues and material types. CONCLUSIONS: The proposed method showed promising results and have to be confirmed on a larger cohort of patient data.

Adrenal Metastasis of Hepatocellular Carcinoma in Patients following Liver Resection or Liver Transplantation: Experience from a Tertiary Referral Center.

INTRODUCTION: Adrenal metastasis of hepatocellular carcinoma (HCC) is a rare entity and can be treated by resection, local ablative therapy, or systemic therapy. Unfortunately, data about treatment outcome, especially in liver transplant recipients, are rare. PATIENTS AND METHODS: From 2005 to 2015, 990 liver resections and 303 liver transplantations because of HCC were performed at our clinic. We retrospectively analyzed treatment outcome of the patients with metachronous adrenal metastasis of HCC, who received either resection, local ablation, or surveillance only. RESULTS: 10 patients were identified (0.8%). 7 patients received liver transplantation for primary HCC therapy, 3 liver resection, and 1 a local ablative therapy. 8 patients underwent adrenalectomy (one via retroperitoneoscopy), one was treated with local ablation, and one had surveillance only. Seven out of eight patients had no surgical complications and one experienced a pancreatic fistula, treated conservatively. 37.5% of the resected patients had recurrence 1 year after adrenalectomy and 75% after 2 years. The mean survival time after primary diagnosis of HCC was 96.6±22.4 months. After adrenalectomy, the mean survival time was 112.4±25.2 months. The mean time until tumor recurrence was 13.2±3.8 in the total cohort and 15.8±3.8 months in patients after adrenalectomy. The estimated overall survival after adrenalectomy was 77.2±17.4 months. CONCLUSION: Metachronous adrenal metastasis occured in less than 1% of HCC patients. Adrenalectomy is a safe procedure and leads to acceptable survival rates even after liver transplantion. Therefore, it should be performed whenever the primary tumor is well controlled and the patient is in adequate physical condition.

Targeting CXCR4 (CXC Chemokine Receptor Type 4) for Molecular Imaging of Aldosterone-Producing Adenoma.

Primary aldosteronism is the most frequent cause of secondary hypertension and is associated with increased morbidity and mortality compared with hypertensive controls. The central diagnostic challenge is the differentiation between bilateral and unilateral disease, which determines treatment options. Bilateral adrenal venous sampling, currently recommended for differential diagnosis, is an invasive procedure with several drawbacks, making it desirable to develop novel noninvasive diagnostic tools. When investigating the expression pattern of chemokine receptors by quantitative real-time polymerase chain reaction and immunohistochemistry, we observed high expression of CXCR4 (CXC chemokine receptor type 4) in aldosterone-producing tissue in normal adrenals, adjacent adrenal cortex from adrenocortical adenomas, and in aldosterone-producing adenomas (APA), correlating strongly with the expression of CYP11B2 (aldosterone synthase). In contrast, CXCR4 was not detected in the majority of nonfunctioning adenomas that are frequently found coincidently. The specific CXCR4 ligand 68Ga-pentixafor has recently been established as radiotracer for molecular imaging of CXCR4 expression and showed strong and specific binding to cryosections of APAs in our study. We further investigated 9 patients with primary aldosteronism because of APA by 68Ga-pentixafor-positron emission tomography. The tracer uptake was significantly higher on the side of increased adrenocortical aldosterone secretion in patients with APAs compared with patients investigated by 68Ga-pentixafor-positron emission tomography for other causes. Molecular imaging of aldosterone-producing tissue by a CXCR4-specific ligand may, therefore, be a highly promising tool for noninvasive characterization of patients with APAs.

Cortisol-related metabolic alterations assessed by mass spectrometry assay in patients with Cushing's syndrome.

OBJECTIVE: Endogenous hypercortisolism is a chronic condition associated with severe metabolic disturbances and cardiovascular sequela. The aim of this study was to characterize metabolic alterations in patients with different degrees of hypercortisolism by mass-spectrometry-based targeted plasma metabolomic profiling and correlate the metabolomic profile with clinical and hormonal data. DESIGN: Cross-sectional study. METHODS: Subjects (n = 149) were classified according to clinical and hormonal characteristics: Cushing's syndrome (n = 46), adrenocortical adenomas with autonomous cortisol secretion (n = 31) or without hypercortisolism (n = 27). Subjects with suspicion of hypercortisolism, but normal hormonal/imaging testing, served as controls (n = 42). Clinical and hormonal data were retrieved for all patients and targeted metabolomic profiling was performed. RESULTS: Patients with hypercortisolism showed lower levels of short-/medium-chain acylcarnitines and branched-chain and aromatic amino acids, but higher polyamines levels, in comparison to controls. These alterations were confirmed after excluding diabetic patients. Regression models showed significant correlation between cortisol after dexamethasone suppression test (DST) and 31 metabolites, independently of confounding/contributing factors. Among those, histidine and spermidine were also significantly associated with catabolic signs and symptoms of hypercortisolism. According to an discriminant analysis, the panel of metabolites was able to correctly classify subjects into the main diagnostic categories and to distinguish between subjects with/without altered post-DST cortisol and with/without diabetes in >80% of the cases. CONCLUSIONS: Metabolomic profiling revealed alterations of intermediate metabolism independently associated with the severity of hypercortisolism, consistent with disturbed protein synthesis/catabolism and incomplete ß-oxidation, providing evidence for the occurrence of metabolic inflexibility in hypercortisolism.

Novel somatic mutations in the catalytic subunit of the protein kinase A as a cause of adrenal Cushing's syndrome: a European multicentric study.

CONTEXT: Somatic mutations in PRKACA gene, encoding the catalytic subunit of protein kinase A (PKA), have been recently found in a high proportion of sporadic adenomas associated with Cushing's syndrome. The aim was to analyze the PRKACA mutation in a large cohort of patients with adrenocortical masses. METHODS: Samples from nine European centers were included (Germany, n = 4; Italy, n = 4; France, n = 1). Samples were drawn from 149 patients with nonsecreting adenomas (n = 32 + 2 peritumoral), subclinical hypercortisolism (n = 36), Cushing's syndrome (n = 64 + 2 peritumoral), androgen-producing tumors (n = 4), adrenocortical carcinomas (n = 5 + 2 peritumoral), and primary bilateral macronodular adrenal hyperplasias (n = 8). Blood samples were available from patients with nonsecreting adenomas (n = 15), subclinical hypercortisolism (n = 10), and Cushing's syndrome (n = 35). Clinical and hormonal data were collected. DNA amplification by PCR of exons 6 and 7 of the PRKACA gene and direct sequencing were performed. RESULTS: PRKACA heterozygous mutations were found in 22/64 samples of Cushing's syndrome patients (34%). No mutations were found in peritumoral tissue and blood samples or in other tumors examined. The c.617A>C (p.Leu206Arg) occurred in 18/22 patients. Furthermore, two novel mutations were identified: c.600_601insGTG/p.Cys200_Gly201insVal in three patients and c.639C>G+c.638_640insATTATCCTGAGG/p.Ser213Arg+p.Leu212_Lys214insIle-Ile-Leu-Arg) in one. All the mutations involved a region implicated in interaction between PKA regulatory and catalytic subunits. Patients with somatic PRKACA mutations showed higher levels of cortisol after dexamethasone test and a smaller adenoma size, compared with nonmutated subjects. CONCLUSIONS: These data confirm and extend previous observations that somatic PRKACA mutations are specific for adrenocortical adenomas causing Cushing's syndrome.

The surgical treatment of bilateral benign nodular goiter: balancing invasiveness with complications.

BACKGROUND: About 100,000 thyroid operations are performed in Germany each year. There is a current trend toward more radical surgery for bilateral euthyroid nodular goiter. In recent years, thyroid specialists and specialty guidelines have recommended total thyroidectomy, because it ensures that nodules will not recur and already provides an adequately radical excision in case an incidental carcinoma is found postoperatively on histological study of the specimen. An alternative method is unilateral hemithyroidectomy with contralateral subtotal resection (the Dunhill procedure). METHOD: Selective literature review. RESULTS: Three randomized controlled trials (RCTs) have compared the longterm outcomes of different surgical methods. In addition, retrospective studies have been published, but their findings must be interpreted with caution because of limitations of method. When all of the data are considered, it appears that radical procedures are often not justified. According to the RCTs, nodules arose during long-term follow-up in 4.7-14% of patients who had undergone subtotal resection; yet, in the two more recent and methodologically more valid RCTs, surgery for recurrent goiter was needed in only 0-0.5% of patients treated with a Dunhill procedure and given adequate hormone supplementation. Most incidental carcinomas are papillary microcarcinomas; this entity is usually adequately treated with hemithyroidectomy. The reported complication rates of total thyroidectomy for permanent hypoparathyroidism in particular range from 0.5% (in specialized centers) to 10% (in a cross-sectional study) and thus seem higher than the corresponding rate for a Dunhill procedure (1-2%). CONCLUSION: Total thyroidectomy has significant risks and should only be performed if the indication has been critically assessed. Alternative methods such as the Dunhill procedure are often radical enough with a much lower rate of postoperative hypoparathyroidism; they remain an important option in thyroid surgery. Further RCTs with sufficient long-term follow-up are needed so that the different surgical methods can be reliably compared in detail.

Postoperative bile leakage inhibits liver regeneration after 70% hepatectomy in rats.

BACKGROUND: Postoperative bile leakage is a typical complication in liver surgery. The influence of small bile leakage and concomitant bile peritonitis on the regenerative capacity of the liver remnant has not yet been investigated thoroughly. MATERIAL AND METHODS: Fifty-four rats were randomized in the following groups: Sham operation (Sh), 70% liver resection (LR), and 70% LR with simultaneous induction of a small bile leakage. Animals were euthanized 6, 24, 48, and 96 hr after surgery. Liver regeneration was measured by relative liver weight, mitotic index, Ki-67 immunohistochemistry, and BrdU labeling index. Liver function was evaluated by thromboplastin time, serum bilirubin, and albumin levels as well as indocyanine green plasma disappearance rate (ICG-PDR). The inflammatory response was characterized by assessment of the hepatic transcription of TNF-α, IL-6, and TGF-ß and the serum concentration of IL-1ß. In addition, myeloperoxidase (MPO) activity in liver tissue was measured. Transaminases and histological sections of the liver were used as markers for hepatocellular damage, and the bacterial concentration in different organs was quantified. RESULTS: With a small bile leakage, mitotic index was reduced by 89% ( p < .05) and the number of Ki-67 positive hepatocytes was reduced by 92% ( p < .05) 24 hr after LR. Likewise, the ICG-PDR dropped by 57% ( p < .05). No differences in liver histology were observed between the groups. With bile leakage, the postoperative transcription of cytokines was markedly higher. A bacterial superinfection could be excluded. CONCLUSION: Small intraabdominal bile leakage can suppress liver function and impair the regenerative capacity of the liver.

Bilateral subtotal thyroidectomy versus hemithyroidectomy plus subtotal resection (Dunhill procedure) for benign goiter: long-term results of a prospective, randomized study.

BACKGROUND: Two recent meta-analyses of mostly retrospective studies have shown high recurrence rates following subtotal resection of bilateral multinodular goiter. Therefore, many endocrine centers have changed their operative procedures in favor of thyroidectomy. Consequently, the rate of complications, especially hypoparathyroidism, has increased. Hemithyroidectomy plus subtotal resection (Dunhill operation) overcomes some disadvantages of bilateral subtotal resection (BST). We performed a prospective, randomized trial to compare the Dunhill operation (DO) and BST for benign goiters. METHODS: Between October 1994 and March 1997, a total of 200 consecutive patients were randomized into two study groups. Primary outcome measure was the incidence of recurrent goiter. Secondary outcome measures were incidence of recurrent nerve palsy and hypoparathyroidism. In all patients, ultrasonography of the thyroid and measurement of serum calcium and parathyroid hormone were performed. Recurrent nerve function was analyzed by indirect laryngoscopy. Long term data (>10 years after surgery) were available in 70 DO patients and 65 BST patients. Mean follow-up was 11.3 ± 4.2 years (10-12 years). RESULTS: No differences were seen in the operating times, transient and permanent hypoparathyroidism, or recurrent nerve palsy. In the long-term, mean thyroid volumes were significantly lower in the DO group (3.5 ± 3.5 vs. 6.4 ± 6.5 ml, p = 0.01). One reoperation was required in the BST group because of recurrence versus none in the DO group. 68 of 70 (97 %) patients in group DO and 59 of 65 (91 %) in group BST had ongoing thyroid hormone therapy with no significant differences in mean dosages of L-thyroxine. CONCLUSIONS: The Dunhill operation and BST are safe procedures. In case of small remnants, clinically significant recurrence is a rare event especially after the Dunhill operation.