Acute Pancreatitis and Type 2 Diabetes Mellitus: The Chicken-Egg Paradox-A Seven-Year Experience of a Large Tertiary Center.

(1) Background: Preexisting type 2 diabetes mellitus (T2DM) has been shown in some studies as a risk factor and a severity factor for acute pancreatitis (AP). In this study, we aimed to demonstrate the link between T2DM and AP using data from a large retrospective epidemiological registry in a tertiary center. (2) Methods: We conducted a retrospective, large-cohort study of 1855 cases of AP and recurrent AP drawn from the seven-year consecutive hospitalization electronic health records of the largest acute-care tertiary teaching center in Romania. (3) Results: We observed a significant association between T2DM and a more severe course of the disease, and between T2DM and admission to the intensive care unit (ICU) due to AP, in our cohort using a chi-square test. However, we did not see a meaningful difference in comparing LoS-ICU between T2DM-AP and OAP (other known cause of AP). AP patients with T2DM had a greater probability of a severe course of the disease and were more likely to be admitted to the ICU than to the OAP. (4) Conclusions: The association between T2DM and AP remains a topic very representative of the "chicken-egg paradox". We need further research on DM-related AP and their bidirectional association as our study is limited by its retrospective design.

Impact of adrenal surgeon volume on outcome: analysis of 4464 operations from the United Kingdom Registry of Endocrine and Thyroid Surgery (UKRETS).

BACKGROUND: There is a surgeon volume-outcome effect in adrenal surgery but the threshold for high-volume surgeon remains controversial. This study aimed to determine predictors of high-risk adrenal operations and to explore whether these should be restricted to high-volume surgeons. METHODS: Patients undergoing adrenal surgery and registered in the United Kingdom Registry of Endocrine and Thyroid Surgery between 2004 and 2021 were analysed. Outcomes included postoperative complications, duration of hospital stay, and mortality. Factors included in multivariable analysis were age, sex, diagnosis, surgical approach, laterality, and surgeon volume. Patients with missing data were excluded. RESULTS: A total of 4464 of 6174 patients (72.3%) were analysed. Postoperative complications occurred in 418 patients (9.4%) and 14 (0.3%) died. Median duration of hospital stay was 3 (i.q.r. 2-5) days. Co-variables significantly associated with an increase or decrease in postoperative complications (P < 0.050) were age (OR 1.02, 95% c.i. 1.01 to 1.03), adrenal cancer (OR 1.64, 1.14 to 2.36), minimally invasive approach (OR 0.317, 0.248 to 0.405), bilateral surgery (OR 1.66, 1.03 to 2.69), and surgeon volume (OR 0.98, 0.96 to 0.99). An increase or decrease in mortality was associated with patient age (OR 1.08, 1.03 to 1.13), minimally invasive approach (OR 0.08, 0.02 to 0.27), and bilateral surgery (OR 6.93, 1.40 to 34.34). The incidence of postoperative complications was significantly lower above a threshold of 12 operations per year (P = 0.034) and 20 per year (P < 0.001), but not six per year (P = 0.540). Median duration of hospital stay was 2 days for surgeons doing over 20 operations per year, compared with 3 days for those undertaking fewer than 20, fewer than 12 or fewer than 6 operations per year. CONCLUSION: Increasing surgical volume is associated with shorter hospital stay and fewer complications. This analysis supports the case for centralization of surgery for adrenal cancer and bilateral tumours to higher-volume surgeons performing a minimum of 12 operations per year.

The adrenal glands are found in the fatty tissue at the back of the abdomen above each kidney, and produce steroid and adrenaline hormones. Surgery on tumours of the adrenal gland is uncommon compared with surgery for other tumours such as those of the breast, bowel, kidney, and lung. Research has shown that the more adrenal operations a surgeon undertakes per year, the better the overall outcomes for patients undergoing that type of surgery. In this study, the outcomes from adrenal operations recorded over 18 years in the national adrenal surgical registry by members of the British Association of Endocrine and Thyroid Surgeons were analysed. The results confirmed previous findings showing that postoperative complications and length of hospital stay were reduced for patients operated by surgeons who did more adrenal operations per year. Operations done by keyhole surgery had better outcomes. Operations done either in older patients, or for the rare adrenal cancer tumours had worse outcomes, as did operations in which both adrenal glands were removed. The authors recommended that all surgeons performing adrenal surgery should monitor the outcomes of their operations, ideally in a national registry, and discuss these with patients before surgery; and undertake a minimum of 6 adrenal operations per year, but a minimum of 12 per year if doing surgery for adrenal cancer or surgery to remove both adrenal glands.

Acute Pancreatitis-Drivers of Hospitalisation Cost-A Seven-Year Retrospective Study from a Large Tertiary Center.

(1) Introduction: Acute pancreatitis (AP) remains a global burden of cost for healthcare services. We found a high degree of heterogeneity in cost-related reports and a scarcity of data regarding the cost of AP episodes in European and Asian populations. We aimed to estimate the median daily cost of hospitalisation (DCH) of AP in our population. Our secondary aims included estimating the total cost of hospitalisation (TCH) and the total cost of AP in Romania, as well as assessing the correlation between median DCH and ward, age, sex, length of stay (LoS), intensive care unit (ICU), outcome, severity, morphology, and aetiology of AP. (2) Material and methods: This retrospective cohort study included 1473 cases recruited from the electronic health records of the University Emergency Hospital of Bucharest. Statistical tests used included Kolmogorov-Smirnov, Kruskal-Wallis with post-hoc Dunn-Bonferroni, and Pearson correlation two-tailed. (3) Results: We found a median DCH of AP of USD 203.8 and a median TCH of USD 1360.5. The total yearly cost of AP in Romania was estimated at around USD 19 million. The majority of males with AP (61.8%) were mostly discharged as healed/ameliorated (83.8%); a majority had local complications (55.4%), which were mostly alcohol-related (35.1%). Regarding the aetiology, biliary-related AP was a cost driver, with significant statistical differences observed in all studied groups (p < 0.01). Morphology assessment revealed that acute necrotic collections were associated with high cost and meaningful disparities among the groups (p < 0.01). Cost was also associated with severity, with significant deviations among all groups (p < 0.01). Outcome-at-discharge as deceased correlated with higher costs, with substantial differences within groups (p < 0.01). The need for an intensive care unit was also a large driver of cost (p < 0.01). Females were prone to more expensive costs (p < 0.01). Surgical cases necessitated more financial resources (p < 0.01). (4) Conclusions: To the best of our knowledge, this is the first study on the cost of AP in Romania. Our findings showed that the drivers of increased AP costs might be older age, ICU, intra-hospital mortality, severe AP, local complications such as acute necrotic collections, biliary aetiology, and female sex. We found large heterogeneity and scarcity regarding cost-related data in the literature.

Epidemiological trends in acute pancreatitis: A retrospective cohort in a tertiary center over a seven year period.

BACKGROUND: Acute pancreatitis (AP) remains a major cause of hospitalization and mortality with important health-related costs worldwide. Using an electronic database of a large tertiary center, we estimated the incidence, etiology, severity and costs of hospitalized AP cases in southern Romania. AIM: To estimate the incidence, cost and tobacco usage of hospitalized AP cases in southern Romania and to update and upgrade the knowledge we have on the etiology, severity (in regard to Revised Atlanta Classification), outcome, morphology and local complications of AP. METHODS: We performed an electronic health care records search on AP patients treated at Emergency University Hospital of Bucharest (Spitalul Universitar de Urgența București) between 2015 and 2022. The incidence, etiology, and severity were calculated; potential risk factors were evaluated, and the hospitalization costs of AP were documented and analyzed. The cohort of this study is part of the BUCharest - Acute Pancreatitis Index registry. RESULTS: A total of 947 consecutive episodes of AP where the patients were hospitalized in the gastroenterology department were analyzed, with 79.45% as 1st episode and the rest recurrent. The majority of the patients were males (68.9%). Alcoholic (45.7%), idiopathic (16.4%) and biliary (15.2%) were the main causes. The incidence was estimated at 29.2 episodes/100000 people. The median length of stay was 7 d. The median daily cost was 747.96 RON (165 EUR). There was a high prevalence of active tobacco smokers (68.5%). The prevalence of severe disease was 11.1%. The admission rate to the intensive care unit was 4.6%, with a mortality rate of 38.6%. The overall mortality was 5.5%. CONCLUSION: We estimated the incidence of AP at 29.2 episodes that required hospitalization per 100000 people. The majority of our cases were found in males (68.9%) and were related to alcohol abuse (45.7%). Out of the cases we were able to find data regarding tobacco usage, the majority were active smokers (68.5%). Most patients had a mild course (54.4%), with a mortality rate of 5.5%. Interstitial AP prevailed (45.3%). The median daily cost of hospitalization was 747.96 RON (165 EUR).

Assessment of inter-centre agreement across multidisciplinary team meetings for patients with retroperitoneal sarcoma.

BACKGROUND: Decision-making in the management of patients with retroperitoneal sarcoma is complex and requires input from a number of different specialists. The aim of this study was to evaluate the levels of agreement in terms of resectability, treatment allocation, and organs proposed to be resected across different retroperitoneal sarcoma multidisciplinary team meetings. METHODS: The CT scans and clinical information of 21 anonymized retroperitoneal sarcoma patients were sent to all of the retroperitoneal sarcoma multidisciplinary team meetings in Great Britain, which were asked to give an opinion about resectability, treatment allocation, and organs proposed to be resected. The main outcome was inter-centre reliability, which was quantified using overall agreement, as well as the chance-corrected Krippendorff's alpha statistic. Based on the latter, the level of agreement was classified as: 'slight' (0.00-0.20), 'fair' (0.21-0.40), 'moderate' (0.41-0.60), 'substantial' (0.61-0.80), or 'near-perfect' (>0.80). RESULTS: Twenty-one patients were reviewed at 12 retroperitoneal sarcoma multidisciplinary team meetings, giving a total of 252 assessments for analysis. Consistency between centres was only 'slight' to 'fair', with rates of overall agreement and Krippendorff's alpha statistics of 85.4 per cent (211 of 247) and 0.37 (95 per cent c.i. 0.11 to 0.57) for resectability; 80.4 per cent (201 of 250) and 0.39 (95 per cent c.i. 0.33 to 0.45) for treatment allocation; and 53.0 per cent (131 of 247) and 0.20 (95 per cent c.i. 0.17 to 0.23) for the organs proposed to be resected. Depending on the centre that they had attended, 12 of 21 patients could either have been deemed resectable or unresectable, and 10 of 21 could have received either potentially curative or palliative treatment. CONCLUSIONS: Inter-centre agreement between retroperitoneal sarcoma multidisciplinary team meetings was low. Multidisciplinary team meetings may not provide the same standard of care for patients with retroperitoneal sarcoma across Great Britain.

Voice and swallowing symptoms after thyroid surgery assessed using the ThyVoice online platform.

Objective: The aim of this multicentre study was to investigate the progression of patient-reported outcomes after thyroid surgery, with emphasis on voice and swallowing difficulties. Methods: An online platform was used to collect replies to standardised questionnaires (voice handicap index, VHI; voice-related quality of life, VrQoL; EAT-10) preoperatively and at 2-6 weeks and 3-6-12 months after surgery. Results: A total of 236 patients were recruited from five centres that contributed with median of 11 cases (range 2-186 cases). Average symptoms scores showed voice changes lasting up to 3 months: VHI increased from 41 ± 15 (preop) to 48 ± 21 (6 weeks) and returned to 41 ± 15 at 6 months. Similarly, VrQoL increased from 12 ± 4 to 15 ± 6 and returned to 12 ± 4 (6 months). Severe voice changes (VHI > 60) were reported in 12% of patients preop, 22% at 2 weeks, 18% at 6 weeks, 13% at 3 months and 7% at 12 months. Only five patients with normal preoperative voice had persistent severe voice changes after 6-12 months. Those with severe voice changes at 2 weeks (median VHI 70.5, IQR 65-81) had significant improvement by 6 months (median VHI 54, IQR 39-65) (P < 0.001). Swallowing assessment showed a median preop score of 0 (IQR 0-3) increasing to a median of 2 (IQR 0-8) at 2 weeks and normal values afterwards. Conclusion: The ThyVoice online platform allows the assessment of patient-reported outcome measures in thyroid surgery. Voice morbidity appears to be more frequent than commonly reported, and this risk should the quoted during informed consent. Swallowing difficulties are mild but significant in the first 2 weeks.

Autophagy Plays Multiple Roles in the Soft-Tissue Healing and Osseointegration in Dental Implant Surgery-A Narrative Review.

Dental endo-osseous implants have become a widely used treatment for replacing missing teeth. Dental implants are placed into a surgically created osteotomy in alveolar bone, the healing of the soft tissue lesion and the osseointegration of the implant being key elements to long-term success. Autophagy is considered the major intracellular degradation system, playing important roles in various cellular processes involved in dental implant integration. The aim of this review is an exploration of autophagy roles in the main cell types involved in the healing and remodeling of soft tissue lesions and implant osseointegration, post-implant surgery. We have focused on the autophagy pathway in macrophages, endothelial cells; osteoclasts, osteoblasts; fibroblasts, myofibroblasts and keratinocytes. In macrophages, autophagy modulates innate and adaptive immune responses playing a key role in osteo-immunity. Autophagy induction in endothelial cells promotes apoptosis resistance, cell survival, and protection against oxidative stress damage. The autophagic machinery is also involved in transporting stromal vesicles containing mineralization-related factors to the extracellular matrix and regulating osteoblasts' functions. Alveolar bone remodeling is achieved by immune cells differentiation into osteoclasts; autophagy plays an important and active role in this process. Autophagy downregulation in fibroblasts induces apoptosis, leading to better wound healing by improving excessive deposition of extracellular matrix and inhibiting fibrosis progression. Autophagy seems to be a dual actor on the scene of dental implant surgery, imposing further research in order to completely reveal its positive features which may be essential for clinical efficacy.

Long-term Cure of Primary Hyperparathyroidism After Scan-Directed Parathyroidectomy: Outcomes From A UK Endocrine Surgery Unit.

BACKGROUND: Two-decades ago, the advent of sestamibi scintigraphy led to an enthusiastic acceptance of minimally invasive parathyroidectomy (MIP) in most surgical centres. More recently, concerns have been raised about the efficacy of limited neck exploration and some surgeons proposed bilateral neck exploration to be (once again) the gold standard operation for primary hyperparathyroidism in 2020s. METHODS: A departmental database was used to identify patients who had MIP after concordant dual localisation with sestamibi scintigraphy and ultrasound scans. Long-term follow-up data were obtained from electronic patient records to ascertain any further treatment for recurrent disease and confirm most recent biochemical status. Patients with negative localisation scans and those with familial disease were excluded from analysis. RESULTS: Between June 2001 and August 2014 a total of 404 patients (108 M:296F, median age 63 years, range 17-90 years) underwent MIP and had normalisation of calcium in first 6 weeks after the operation. Information on electronic patient records were missing in 14 patients; therefore, data on 390 patients were analysed. During median follow-up of 78 months (IQR: 21.25-111.75 months), 375 patients had normocalcaemia (2.36 mmol/L, IQR: 2.29-2.44 mmol/L) at a median 75 months, (IQR: 20-118 months) after their operation. Overall, 15 (3.85%) patients had biochemical evidence of recurrent disease (2.70 mmol/L IQR: 2.63-2.75 mmol/L) at 92 months (Range: 6-196) after initial operation. Of these, 5 (1.28%) patients underwent a second parathyroid procedure. CONCLUSION: Recurrence after scan-directed unilateral neck exploration occurred in 4% of patients after a long disease-free interval. Only one patient had recurrent disease within 1-year of primary surgery. The data suggest that bilateral neck exploration at the time of initial operation, in this selected cohort, is unlikely to have uncovered multi-gland disease and prevent disease recurrence. Focused parathyroidectomy in patients with convincing localisation studies should continue.

Sarcopenia is Associated with Reduced Survival following Surgery for Adrenocortical Carcinoma.

AIM: Adrenocortical cancer (ACC) is an aggressive malignancy and robust prognostic factors remain unclear. The presence of sarcopenia has been shown to negatively impact survival for other malignancies, but has not been extensively analyzed in ACC. METHODS: Patients who underwent resection of their ACC between 2010 and 2020 were identified; therapeutic, operative, and outcome data were analyzed. Sarcopenia was assessed by calculation of the skeletal muscle index (SMI) and was defined as an SMI <52.4cm2/m2 for males and <38.5cm2/m2 for females. RESULTS: Data on 35 patients (18 F: 17 M; median age 54 [range: 18-86]) who had primary surgical treatment were analyzed. Median tumor size was 10 cm [range:3-15]. In eleven patients (31%), the tumor was hormonally active (cortisol = 8;23%). Seventeen patients (49%) were classified as having sarcopenia on their pre-operative CT scan. The Intraclass Correlation Coefficient (ICC) for intra- and inter-observer variability showed very good agreement (0.99 and 0.98). There was no difference in incidence of sarcopenia stratifying for sex, BMI, or tumor-size, but incidence was higher with increasing age (p < .05). Overall median survival was 36 months, with 1- and 3-year survival rates of 77% and 52%. The presence of sarcopenia was strongly associated with a shorter overall survival (HR = 3.21; [95%CI: 1.06-9.69];p = .03) on unadjusted analyses. Moreover, age, higher T-stage, and presence of capsular invasion were also associated with poorer survival on univariable analyses. CONCLUSION: The presence of sarcopenia in patients undergoing surgery for ACC could be a predictor of reduced overall survival, although replications of these analyses should be performed in similar, larger cohorts. Specifically, the influence of a patient's hormonal status on the manifestation of sarcopenia should be further defined.

Multiple endocrine neoplasia type 1 in children and adolescents: Clinical features and treatment outcomes.

BACKGROUND: Clinical manifestations and treatment outcomes in children and adolescents with multiple endocrine neoplasia type 1 are not well characterized. METHODS: We conducted a retrospective cohort study of 80 patients with multiple endocrine neoplasia type 1 who commenced tumor surveillance at ≤18 years of age. RESULTS: Fifty-six patients (70%) developed an endocrine tumor by age ≤18 years (median age = 14 years, range = 6-18 years). Primary hyperparathyroidism occurred in >80% of patients, with >70% undergoing parathyroidectomy, in which less-than-subtotal (<3-gland) resection resulted in decreased disease-free outcomes versus subtotal (3-3.5-gland) or total (4-gland) parathyroidectomy (median 27 months versus not reached; P = .005). Pancreaticoduodenal neuroendocrine tumors developed in ∼35% of patients, of whom >70% had nonfunctioning tumors, >35% had insulinomas, and <5% had gastrinomas, with ∼15% having metastases and >55% undergoing surgery. Pituitary tumors developed in >30% of patients, and ∼35% were macroprolactinomas. Tumor occurrence in male patients and female patients was not significantly different. Genetic analyses revealed 38 germline MEN1 mutations, of which 3 were novel. CONCLUSION: Seventy percent of children aged ≤18 years with multiple endocrine neoplasia type 1 develop endocrine tumors, which include parathyroid tumors for which less-than-subtotal parathyroidectomy should be avoided; pancreaticoduodenal neuroendocrine tumors that may metastasize; and pituitary macroprolactinomas.

Management of endocrine surgical disorders during COVID-19 pandemic: expert opinion for non-surgical options.

PURPOSE: The COVID-19 pandemic brought unprecedented conditions for overall health care systems by restricting resources for non-COVID-19 patients. As the burden of the disease escalates, routine elective surgeries are being cancelled. The aim of this paper was to provide a guideline for management of endocrine surgical disorders during a pandemic. METHODS: We used Delphi method with a nine-scale Likert scale on two rounds of voting involving 64 experienced eminent surgeons and endocrinologists who had the necessary experience to provide insight on endocrine disorder management. All voting was done by email using a standard questionnaire. RESULTS: Overall, 37 recommendations were voted on. In two rounds, all recommendations reached an agreement and were either endorsed or rejected. Endorsed statements include dietary change in primary hyperparathyroidism, Cinacalcet treatment in secondary hyperparathyroidism, alpha-blocker administration for pheochromocytoma, methimazole ± ß-blocker combination for Graves' disease, and follow-up for fine-needle aspiration results of thyroid nodules indicated as Bethesda 3-4 cytological results and papillary microcarcinoma. CONCLUSION: This survey summarizes expert opinion for the management of endocrine surgical conditions during unprecedented times when access to surgical treatment is severely disrupted. The statements are not applicable in circumstances in which surgical treatment is possible.

The Unforeseen Diagnosis: Hyperparathyroidism-Jaw Tumour Syndrome Case Report and Review of the Literature.

Hypercalcaemia and its systemic sequelae are a relatively common finding amongst patients in the field of endocrinology. Primary hyperparathyroidism, a frequent cause of hypercalcaemia, is often seen among middle-aged female patients, typically resulting from an underlying single-gland adenoma. Although patients may present with symptoms (nephrolithiasis, musculoskeletal discomfort, dehydration, or mood disturbance, to name a few), hypercalcaemia is rather frequently identified incidentally. In younger patients, a familial form of primary hyperparathyroidism must be considered, with a positive diagnosis mandating familial screening. Hyperparathyroidism-jaw tumour syndrome is one such autosomal dominant familial disorder, characterised by a mutation in the cell division cycle 73 (CDC73; also known as HRPT-2) tumour suppressor gene. This disorder is characterised by multiple pleiotropic phenomena, including recurrent primary hyperparathyroidism (and the effects of hypercalcaemia), neoplasms (such as uterine, renal, mandibular, and maxillary), and infertility. A patient not conforming to the classic candidacy for primary hyperparathyroidism requires consideration for a familial cause. Case Description. We present a rare diagnostic entity-hyperparathyroidism-jaw tumour (HPT-JT) syndrome-in a 36-year-old female with recurrent primary hyperparathyroidism, frequent nephrolithiasis, and infertility for 18 years prior to the diagnosis. We aim to promote awareness amongst medical professionals of this rare, but nonetheless essential differential diagnosis through a case report and review of the literature. Conclusion. Medical professionals must avoid diagnostic overshadowing and display a low threshold for genetic testing in younger patients with primary hyperparathyroidism. The importance of proper identification extends beyond the patient to their relatives and offspring.

MANAGEMENT OF ENDOCRINE DISEASE: Postsurgical hypoparathyroidism: current treatments and future prospects for parathyroid allotransplantation.

BACKGROUND: Permanent postsurgical hypoparathyroidism (POSH) is a major complication of anterior neck surgery in general and of thyroid surgery in particular. Depending on diagnostic criteria, up to 10% of patients undergoing bilateral thyroid surgery develop POSH. This leads to a multitude of symptoms that decrease the quality of life and burden the healthcare provision through complex needs for medication and treatment of specific complications, such as seizures and laryngospasm. METHODS: Narrative review of current medical treatments for POSH and of the experience accumulated with parathyroid allotransplantation. RESULTS: In most patients, POSH is controlled with regular use of calcium supplements and active vitamin D analogues but a significant proportion of patients continue to experience severe symptoms requiring repeated emergency admissions. Replacement therapy with synthetic PTH compounds (PTH1-34, Natpara® and PTH1-84, teriparatide, Forsteo®) has been assessed in multicentre trials, but the use of this medication is restricted by costs and concerns related to the risk of development of osteosarcoma. Based on recent case reports of successful allotransplantation of parathyroid tissue between siblings, there is renewed interest in this technique. Data on selection of donors, parathyroid cell preparation before allotransplantation, site and timing of transplantation, need for immunosuppression and long-term outcomes are reviewed. CONCLUSION: A prospective trial to assess the efficacy of parathyroid allotransplantation in patients with severely symptomatic protracted post-surgical hypoparathyroidism is warranted.