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Background: Acute colonic pseudo-obstruction (ACPO) is characterized by severe colonic distension without mechanical obstruction. It has an uncertain pathogenesis and poses diagnostic challenges. This study aimed to explore risk factors and clinical outcomes of ACPO in polytrauma patients and contribute information to the limited literature on this condition., Methods: This retrospective study, conducted at a Level 1 trauma center, analyzed data from trauma patients with ACPO admitted between July 2009 and June 2018. A control cohort of major trauma patients was used. Data review encompassed patient demographics, abdominal imaging, injury characteristics, analgesic usage, interventions, complications, and mortality. Statistical analyses, including logistic regression and correlation coefficients, were employed to identify risk factors., Results: There were 57 cases of ACPO, with an incidence of 1.7 per 1,000 patients, rising to 4.86 in major trauma. Predominantly affecting those older than 50 years (75%) and males (75%), with motor vehicle accidents (50.8%) and falls from height (36.8%) being the commonest mechanisms. Noteworthy associated injuries included retroperitoneal bleeds (RPBs) (37%), spinal fractures (37%), and pelvic fractures (37%). Analysis revealed significant associations between ACPO and shock index >0.9, Injury Severity Score >18, opioid use, RPBs, and pelvic fractures. A cecal diameter of ≥12 cm had a significant association with cecal ischemia or perforation., Conclusion: This study underscores the significance of ACPO in polytrauma patients, demonstrating associations with risk factors and clinical outcomes. Clinicians should maintain a high index of suspicion, particularly in older patients with RPBs, pelvic fractures, and opioid use. Early supportive therapy, vigilant monitoring, and timely interventions are crucial for a favorable outcome. Further research and prospective trials are warranted to validate these findings and enhance understanding of ACPO in trauma patients., Level of Evidence: Prognostic and Epidemiological; Level IV., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Trauma to the pelvic ring and associated haemorrhage represent a management challenge for the multidisciplinary trauma team. In up to 10% of patients, bleeding can be the result of an arterial injury and mortality is reported as high as 89% in this cohort. We aimed to assess the mortality rate after pelvic trauma embolisation and whether earlier embolisation improved mortality., Methods: Retrospective study at single tertiary trauma and referral centre, between 1 January 2009 and 30 June 2022. All adult patients who received embolisation following pelvic trauma were included. Patients were excluded if angiography was performed but no embolisation performed., Results: During the 13.5-year time period, 175 patients underwent angiography and 28 were excluded, leaving 147 patients in the study. The all-cause mortality rate at 30-days was 11.6% (17 patients). The median time from injury to embolisation was 6.3 h (range 2.8-418.4). On regression analysis, time from injury to embolisation was not associated with mortality (OR 1.01, 95% CI 0.952-1.061). Increasing age (OR 1.20, 95% CI 1.084-1.333) and increasing injury severity score (OR 1.14, 95% CI 1.049-1.247) were positively associated with all-cause 30-day mortality, while non-selective embolisation (OR 0.11, 95% CI 0.013-0.893) was negatively associated., Conclusion: The all-cause mortality rate at 30-days in or cohort was very low. In addition, earlier time from injury to embolisation was not positively associated with all-cause 30-day mortality. Nevertheless, minimising this remains a fundamental principle of the management of bleeding in pelvic trauma., (© 2024 The Authors. Journal of Medical Imaging and Radiation Oncology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Radiologists.)

Background: Splenic artery embolisation (SAE) has become a vital strategy in the modern landscape of multidisciplinary trauma care, improving splenic salvage rates in patients with high-grade injury. However, due to a lack of prospective data there remains contention amongst stakeholders as to whether SAE should be performed at the time of presentation (prophylactic or pSAE), or whether patients should be observed, and SAE only used only if a patient re-bleeds. This systematic review aimed to assess published practice management guidelines which recommend pSAE, stratified according to their quality., Methods: The study was registered and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Medline, PubMed, Cochrane, Embase, and Google Scholar were searched by the study authors. Identified guidelines were graded according to the Appraisal of Guidelines Research and Evaluation II (AGREE-II) instrument., Results: Database and internet searches identified 1006 results. After applying exclusion criteria, 28 guidelines were included. The use of pSAE was recommended in 15 guidelines (54%). This included 6 out of 9 guidelines that were high quality (66.7%), 4 out of 9 guidelines that were moderate quality (44.4%), and 3 out of 10 (30%) guidelines that were low quality, p = 0.275., Conclusions: This systematic review showed that recommendation of pSAE is more common in guidelines which are of high quality. However, there is vast heterogeneity of recommended practice guidelines, likely based on individual trauma systems rather than the available evidence. This reflects biases with interpretation of data and lack of multidisciplinary system inputs, including from interventional radiologists., (© 2023. The Author(s).)

Modulation of osteoclast formation could be a therapeutic target for inhibiting pathological bone destruction. The receptor activator of nuclear factor (NF)-κB ligand (RANKL) is known to be an essential factor in osteoclast differentiation and activation inducers. However, whether Protaetia brevitarsis seulensis (P. brevitarsis) larvae-a traditional animal-derived medicine used in many Asian countries-can inhibit RANKL-induced osteoclast formation and prevent ovariectomy (OVX)-induced bone loss has not been evaluated. Here, we aimed to investigate the anti-osteoporotic effects of P. brevitarsis larvae ethanol extract (PBE) in RANKL-stimulated RAW264.7 cells and OVX mice. In vitro, PBE (0.1, 0.5, 1, and 2 mg/mL) decreased RANKL‑induced tartrate-resistant acid phosphatase (TRAP) activity and expression of osteoclastogenesis-associated genes and proteins. Furthermore, PBE (0.1, 0.5, 1, and 2 mg/mL) significantly inhibited the phosphorylation of p38 and NF-κB. Female C3H/HeN mice were divided into five groups (n = 5 per group), namely, sham-operated, OVX, OVX+PBEL (100 mg/kg, oral gavage), OVX+PBEH (200 mg/kg, oral gavage), and OVX+estradiol (0.03 μg/day, subcutaneous injection). High doses of PBE significantly increased femoral bone mineral density (BMD) and bone volume/tissue volume (BV/TV), whereas femoral bone surface/bone volume (BS/BV) and osteoclastogenesis-associated protein expression decreased compared to those in the OVX group. Moreover, PBE (200 mg/kg) significantly increased estradiol and procollagen type I N-terminal propeptide and decreased N-terminal telopeptide of type I collagen and C-terminal telopeptide of type I collagen compared to those in the OVX group. Our results suggest that PBE can be an effective therapeutic candidate for preventing or treating postmenopausal osteoporosis., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Morel-Lavallée lesions (MLL), also referred to as closed degloving injuries, result from traumatic shearing forces with separation of the subcutaneous fat from the underlying fascia. The aim of this study was to determine the incidence and treatment of MLLs at a level 1 trauma centre., Methods: Single-centre retrospective cross-sectional study of consecutive patients with an imaging diagnosis of a Morel-Lavallee lesion from 1/1/2010-31/12/2019. Demographic data, mechanism of injury, volume of lesion, management and outcome data were collated., Results: Sixty-six MLLs were identified in 63 patients (64% Male) with a median age of 49.5 years (19-94 years). Mechanism of injury were road traffic accidents in the majority (66%). Median injury severity score (ISS) was 17 (range 1-33). Patients on oral anti-coagulants had significantly larger lesions (181.9 cc v 445.5 cc, P = 0.044). The most common lesion location was the thigh (60.5%). Patients that underwent imaging within 72 h of injury had significantly larger lesions than those imaged more than 72 h after the inciting trauma (65 cc v 167 cc, P < 0.05). Management data were documented in 59% of lesions (39/66) in which 66.6% (n = 26) had invasive treatment. In the 31 patients where follow-up was available, 64.5% (n = 20) were persistent but decreasing in size. There was no significant difference in follow-up size for those who had invasive compared to conservative treatment (P = 0.3)., Conclusion: The diagnosis of MLL should be considered for soft-tissue swelling in the context of shearing trauma. A variety of management options have been employed, with good overall outcomes., (© 2022 Royal Australian and New Zealand College of Radiologists.)

Objective: Haemorrhagic shock is a life-threatening complication of trauma, but remains a preventable cause of death. Early recognition of retroperitoneal haemorrhage (RPH) is crucial in preventing deleterious outcomes including mortality. Injury to the 9-11th intercostal arteries (i.e. arteries of the lower thoracic region) are complicit in RPH. However, the associated injuries, implications and management of such bleeds remain poorly characterised., Methods: We performed a retrospective review of the medical records of patients diagnosed with RPH who presented to our level-1 trauma centre (2009-2019). We described the associated injuries, management and outcomes relating to RPH of the lower thoracic region (the 9-11th intercostal arteries) from this cohort to identify potential predictors and evaluate the impact of early identification and management of non-cavitary bleeds., Results: Haemorrhage of the lower intercostal arteries (LIA) into the retroperitoneal space is associated with an increased number of posterior lower rib fractures and pneumothorax/haemothorax. A higher proportion of patients in the LIA group required massive transfusion, angioembolisation or surgical ligation when compared to other causes of RPH., Conclusion: The present study highlights the importance of injury patterns, particularly posterior lower rib fractures, as predictors for early recognition and management of RPH in the prevention of deleterious patient outcomes. RPH secondary to bleeding of the LIA may require early and aggressive management of haemorrhage through massive transfusion, and angioembolisation or surgical ligation when compared to RPH because of other causes., (© 2022 Australasian College for Emergency Medicine.)

Aging, and other disease-related muscle disorders are serious health problems. Dexamethasone (DEX), a synthetic glucocorticoid, can trigger skeletal muscle atrophy. This study examined the effects of mealworm ( Tenebrio molitor larva) ethanol extract (TME) on C2C12 myoblast differentiation and DEX-induced myotube atrophy. TME induced myotube formation compared to the differentiation medium (DM) group. TME also significantly increased the mRNA expression of muscle creatine kinase ( CKm ) and myogenic regulatory factors (MRFs), such as myogenin ( MyoG ), myogenic factor ( Myf )5, and MRF4 ( Myf6 ). TME dramatically increased the muscle-specific protein, MyoG, compared to the control, whereas the expression of myogenic differentiation 1 (MyoD) remained unchanged. It also activated the mammalian target of rapamycin (mTOR) signaling pathway. In the DEX-induced muscle atrophy C2C12 model, TME reduced the gene expression of atrogin-1 , muscle RING finger protein-1 ( MuRF-1 ), and myostatin , which are involved in protein degradation in skeletal muscles. Furthermore, TME elevated the phosphorylation of forkhead box O3 (FoxO3α) and protein kinase B (Akt). These findings suggest that TME can enhance myotube hypertrophy by regulating the mTOR signaling pathway, and can rescue DEX-induced muscle atrophy by alleviating atrophic muscle markers mediated by Akt activation. Thus, TME can be a potential therapeutic agent for treating muscle weakness and atrophy.

Background: Inferior vena cava (IVC) filters play a role in preventing venous thromboembolism after major trauma where deep venous thrombosis (DVT) risk is up to 80%. It has been suggested that IVC filters are thrombogenic and many patients are therefore placed on therapeutic anticoagulation during IVC filter dwell citing concern of in situ IVC thrombosis, even in the absence of existing DVT., Methods: Between 1 June 2018 and 31 December 2021, this retrospective study assessed the incidence of IVC thrombosis following prophylactic IVC filter insertion. Groups were defined according to the presence or absence of therapeutic anticoagulation during filter dwell. The primary outcome was the presence or absence of IVC thrombus at retrieval., Results: A total of 124 patients were included. Anticoagulation was prescribed in 29 and anticoagulation was not prescribed in 63. A further 32 patients developed a new thrombosis episode after the prophylactic IVC filter was placed, and 29 were prescribed anticoagulation part-way during filter dwell as a result of this diagnosis. No cases of IVC occlusion were observed in any patient group., Conclusions: Caval thrombosis was not observed after prophylactic filter placement, with or without the prescription of anticoagulation. While prospective trials are needed to increase the level of evidence, based on these results the use of therapeutic anticoagulation during IVC filter dwell should not be dictated by the presence of an IVC filter alone but rather by the presence of a related thrombosis event., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Spiradenocarcinoma is a rare skin adnexal neoplasm that may behave aggressively. It is often associated with a benign slow-growing spiradenoma that has undergone malignant transformation. Given the paucity of cases in the literature, there is a lack of consensus on treatment., Methods: The terms 'malignant spiradenoma' or 'spiradenocarcinoma' were systematically used to search the PubMed, MEDLINE and Google Scholar databases. A total of 182 cases of spiradenocarcinoma were identified as eligible for this comprehensive literature review., Results: Spiradenocarcinoma was commoner in older age and Caucasian race. In most cases, surgical excision for local disease is the mainstay of treatment. Lymph node dissection is usually reserved for those with suspected or confirmed lymph node metastases. High rates of local recurrence (20.8%), metastasis (37.4%) and mortality (19.1%) were identified, prompting some authors to suggest regular follow up including chest X-rays and liver function tests., Conclusions: Patients with spiradenocarcinoma may benefit from a magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography/computed tomography to establish the extent of disease. We recommend wide local excision as the treatment of choice to achieve surgical margins of ≥1 cm, with node resection to be determined on a case-to-case basis. Regular follow up is important given the high rate of local recurrence, metastasis and mortality. This should include an examination of the regional lymph nodes. Further research is required to refine an evidence-based approach to spiradenocarcinoma., (© 2021 Royal Australasian College of Surgeons.)

Background: Bile leak following blunt liver trauma is uncommon. Management is difficult due to complex vasculo-biliary and liver parenchymal injury and lack of consensus on optimal care compared with bile leak following elective hepatectomy especially in regards to endoscopic retrograde pancreaticocholangiography (ERCP) timing and patient selection., Methods: This is a retrospective cohort study from a level 1-trauma centre of patients with bile leak following blunt liver injury between July 2010 and December 2019 identified from the trauma registry. Clinical data retrieved include patient demographics, injury severity score, liver injury grading and its associated complications and treatment. This was supplemented by surgical audit database and patients' electronic medical record., Results: There were 31 bile leaks amongst 639 patients with blunt liver trauma (4.9%). Bile leak was associated with higher liver injury grade (odds ratio (OR) 36, P = 0.001), hepatic embolization (OR 16, P = 0.003) and need for trauma laparotomy (OR 14, P = 0.024). ERCP was performed in 58.1% (n = 18). This was complicated in 27.7% (n = 5) by mild pancreatitis (n = 1) and intra-abdominal sepsis (n = 4) requiring surgical drainage of abscess (n = 2) and liver resection (n = 1). Bile leak settled conservatively (including percutaneous drainage) without ERCP in the remaining patients (41.9%). Overall mortality was not increased in those with bile leak (P = 0.998)., Conclusion: Bile leaks resolved conservatively in 41.9% of patients. Complications following ERCP were seen in 27.7%, frequently requiring intervention. Failure of conservative management was more likely in patients with hepatic embolization, in whom early ERCP remains appropriate. ERCP should otherwise be reserved for those who fail conservative management to minimize infective complications., (© 2021 Royal Australasian College of Surgeons.)

Background: Several cancers show increased levels of lactate dehydrogenase A (LDHA), which are associated with cancer progression. However, it remains unclear whether LDHA levels are associated with papillary thyroid cancer (PTC) aggressiveness or with the presence of the PTC prognostic marker, the BRAFV600E mutation. This study aimed to evaluate the potential of LDHA as a PTC prognostic marker., Methods: LDHA expression was examined in 83 PTC tissue specimens by immunohistochemistry. Human thyroid cell lines were genetically manipulated to overexpress BRAFV600E or were treated with a BRAF-specific short hairpin RNA (shBRAF), whose effects on LDHA expression were evaluated by Western blotting. Data from 465 PTC patients were obtained from The Cancer Genome Atlas (TCGA) database and analyzed to validate the in vitro results., Results: LDHA was aberrantly overexpressed in PTC. Intense immunostaining for LDHA was observed in PTC specimens carrying mutated BRAF, whereas the intensity was less in wild-type BRAF samples. Overexpression of BRAFV600E resulted in LDHA upregulation, whereas treatment with shBRAF downregulated LDHA in human thyroid cell lines. Furthermore, LDHA mRNA expression was significantly elevated and associated with BRAFV600E expression in thyroid cancer tissues from TCGA database. Additionally, LDHA overexpression was found to be correlated with aggressive clinical features of PTC, such as lymph node metastases and advanced tumor stages., Conclusion: LDHA overexpression is associated with the BRAFV600E mutation and an aggressive PTC behavior. Therefore, LDHA may serve as a biomarker and therapeutic target in PTC.

Hemodynamic stability is one of the most critical aspects of adrenal surgery for pheochromocytoma. Few articles have evaluated the hemodynamic status of patients undergoing posterior retroperitoneal adrenalectomy (PRA) for pheochromocytoma. The aim of this study is to compare the intraoperative hemodynamic parameters between lateral transperitoneal adrenalectomy (TPA) and PRA in this groups of patients.This report describes a retrospective study of 53 pheochromocytoma patients who underwent endoscopic adrenalectomy via transperitoneal (22 patients) or posterior retroperitoneal (31 patients) approaches from January 2008 to March 2015. Data from these patients were compared to investigate the differences in hemodynamic parameters between the 2 approaches.Clinical parameters at presentation were similar between the 2 groups, except for tumor size, which was larger in the TPA group. The PRA group is associated with reduced operative time, blood loss, and length of hospital stay compared to TPA even after adjusting for the tumor size. There was greater BP fluctuations and higher maximum systolic and diastolic blood pressure (BP) within the TPA group compared to PRA during univariate analysis. This was however not significant after adjusting for tumor size. There was no difference in the intraoperative inotropic support requirement between the 2 groups.PRA is associated with stable intraoperative hemodynamic status, as well as favorable perioperative outcomes compared to TPA in patients with small pheochromocytomas.

Background: Left hepatic trisectionectomy (LHT) is a complex hepatic resection; its' role and outcomes in hepatobiliary malignancies remains unclear., Materials and Methods: All patients undergoing LHT at the tertiary HPB referral unit at RSCH, Guildford, UK from September 1996 to October 2015 were included. Data were collected from a prospectively maintained database., Results: Twenty-eight patients underwent LHT. The M:F ratio was 1.8:1. Median age was 60 years (range 43-76 years). Diagnoses included colorectal liver metastases (CRLM; n = 20); cholangiocarcinoma (CCA; n = 4); and other (neuroendocrine tumour metastases (NET; n = 3) and breast metastases (n = 1)). Median duration of surgery was 270 min (range 210-585 min). Median blood loss was 750 ml (300-2400 ml) with a perioperative transfusion rate of 21% (n = 6/28). The rate of all post-operative complications was 21% for all patients, and given the extensive resection performed four patients (14%) developed varying degrees of hepatic insufficiency. One patient with cholangiocarcinoma developed severe hepatic insufficiency, which was fatal within 90 days of surgery. 1 and 3-year survivals were 92% and 68% respectively., Conclusion: This study supports LHT in patients with significant tumour burden. Despite extensive resection, our favourable morbidity and mortality rates show this is a safe and beneficial procedure for patients with all hepatobiliary malignancies. Given the nature of resection the incidence of post-operative hepatic insufficiency is higher than less extensive hepatic resections., Competing Interests: There are no conflicts of interest to declare., (Crown Copyright © 2019 Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd.)

Background: Recent guidelines advocate unilateral thyroidectomy for low-risk 1-cm to 4-cm differentiated thyroid cancer (DTC). This study was designed to examine the association between the extent of thyroidectomy and oncologic outcomes in patients with 1-cm to 4-cm DTC., Materials and Methods: From April 1978 to December 2011, 16 057 patients with DTC underwent thyroidectomy at Yonsei University Hospital. Among them, 5266 (32.8%) patients were classified as having 1-cm to 4-cm DTC and were enrolled in this study. Clinicopathologic features and prognostic results (disease-free survival [DFS] and disease-specific survival [DSS] rates) were analyzed by retrospective medical record review. The mean follow-up duration was 57.3 ± 58.1 months., Results: Of tumor subtypes in the study group, papillary thyroid carcinoma was the most common (97.5%) and follicular thyroid carcinoma occurred at a rate of 2.5%. In this study, the mean tumor size was 1.84 ± 0.74 cm. Patients had extrathyroidal extension (69.3%), multiplicity (35.1%), bilaterality (26.4%), central lymph node metastasis (53.0%), and lateral neck node metastases (19.9%). Of the 5266 patients, 4292 (81.5%) underwent total thyroidectomy and 974 (18.5%) had lobectomies. Recurrence rates in the total thyroidectomy and lobectomy groups were 5.7% and 9.4%, respectively. The lobectomy group had lower DFS (P = .007) and higher DSS (P = .034) than the total thyroidectomy group. A multivariate analysis for DFS revealed that tumor size, N classification, and extent of thyroidectomy were independent risk factors. On multivariate analysis, independent risk factors for DSS were age, sex, tumor size, and M classifications., Conclusion: Although extent of thyroidectomy does not affect DSS, total thyroidectomy is beneficial for reducing recurrence in patients with 1-cm to 4-cm DTC. However, if such tumors have such low-risk features as being unifocal, intrathyroidal, and lymph node metastasis-negative, extent of thyroidectomy does not affect oncologic outcome and lobectomy may be sufficient., (© 2018 Wiley Periodicals, Inc.)

Recently, dynamic risk stratification has been found to be more valuable than static anatomic staging system in nonmedullary thyroid cancer and this strategy has also been accepted in medullary thyroid cancer (MTC). The present study was designed to compare the clinical usefulness of response to initial therapy stratification with a traditional anatomic staging system.From August 1982 to December 2012, a total of 144 MTC patients underwent thyroidectomy in Yonsei University Hospital. Among them, 117 (82.2%) patients with complete clinical data and sustained follow-up were enrolled in this study. Clinicopathological features and surgical outcomes were analyzed by retrospective medical chart review. Mean follow-up duration was 85.78 ± 62.51 months.In this study, mean tumor size was 1.94 ± 1.40 cm and 22 (18.9%) patients had hereditary MTC; 95 (81.1%) patients had sporadic MTC. Stage I patients had highest probability of excellent response to initial therapy (92.1%). Stage IV patients had highest probability of biochemical and structural incomplete response to initial therapy (57.5% and 30.3%) and lowest probability of excellent response to initial therapy (12.1%). Both response to initial therapy stratification and TNM staging system offered useful prognostic information in this study. The TNM staging system provided risk stratification pertaining to disease-free survival (DFS), disease-specific survival (DSS), and the probability of having no evidence of disease at final outcome, but did not provide risk stratification pertaining to the probability of having biochemical persistent/recurrence disease at final outcome. However, response to initial therapy stratification provided risk stratification pertaining to not only DFS, DSS, and the probability of having no evidence of disease at final outcome but also the probability of having biochemical persistent/recurrence disease at final outcome.In this study, we demonstrated that dynamic risk stratification with adjusted response to initial therapy system can offer more useful prognostic information than anatomic staging system in MTC., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Robotic modified radical neck dissection (MRND) using a gasless transaxillary approach has been reported to be a safe and meticulous technique in patients with papillary thyroid carcinoma (PTC) and lateral neck node metastasis (N1b). Few studies, however, have attempted to assess the long-term oncologic outcomes of robotic MRND in these patients. This study aimed to compare perioperative and 5-year oncologic outcomes of robotic MRND with conventional open procedures in patients with N1b PTC., Methods: Between September 2007 and February 2010, 193 patients with N1b PTC underwent total thyroidectomy and MRND by a single surgeon. Of these, 42 (21.8 %) underwent robotic procedures and 151 (78.2 %) underwent conventional open procedures. All patients received 3.7- to 5.5-GBq radioactive iodine (RAI) ablation, post-therapy whole-body scans (TxWBSs), and diagnostic WBS (DxWBSs) during follow-up. An exact 1:3 matching for age and stage was performed to minimize selection bias, and perioperative and 5-year oncologic outcomes were compared in the matched groups., Results: The mean follow-up period was 66.0 months (range 60-90 months). Number of retrieved cervical lymph nodes (LNs) (p = .102) and postoperative ablation success rates (p = .864) were similar between the two groups. TSH-suppressed serum Tg concentrations after 5 years (0.7 ± 1.5 vs. 2.4 ± 14.1 ng/ml; p = .471) and recurrence rates in the robotic and open groups (1/41 [2.4 %] vs. 3/102 [2.9 %]; p = .864) were similar for the 5-year follow-up period. Four patients experienced recurrence: Three exhibited regional lymph node metastasis, and one showed bilateral lung metastases., Conclusion: The perioperative and 5-year oncologic outcomes were similar after robotic and conventional open MRND. Large, prospective randomized controlled trials with long-term follow-up data are needed to validate these results.

Purpose: The aim of this study was to determine whether focused or complete parathyroidectomy was more appropriate and to compare follow-up data in primary hyperparathyroidism (PHPT)., Methods: We retrospectively analyzed 225 operations for PHPT at Yonsei University Health System between 2000 and 2012. After excluding 93 patients, the remaining 132 were divided into 2 groups: those who underwent focused parathyroidectomy (FP) and those who underwent conventional parathyroidectomy (CP). We compared clinicopathological features; preoperative calcium, parathyroid hormone (PTH), phosphorus, vitamin D, 24-hour urine calcium, and alkaline phosphatase levels; postoperative calcium and PTH levels; pathologic diagnosis; multiplicity; and results of a localization study between the 2 groups., Results: There was no significant difference in the rates of development of postoperative persistent hyperparathyroidism (1/122 FP patients and 1/10 CP patients) between the 2 groups due to a technical reason (FP 0.8% vs. CP 10.0%, P = 0.146). Multiglandular disease (MGD) was uncommon in all cases (6 of 132, 4.5%). All MGD cases were diagnosed using a preoperative localization study. Sestamibi scan and ultrasonography sensitivity were 94.2% and 90.2%, respectively., Conclusion: We suggest that FP is appropriate in PHPT, except in cases of MGD if detected before the operation using preoperative imaging. Knowledge of hereditary PHPT and improved preoperative localization studies, such as high-resolution ultrasonography, contributed to the decision to perform FP rather than CP in all cases of unilateral results of the localizing study., Competing Interests: No potential conflict of interest relevant to this article was reported.

Purpose: The role of the robot in thyroid surgery remains uncertain, and it is unclear whether robotic total thyroidectomy (R-TT) can be justified as a standard treatment for patients with thyroid cancer. This study compared the long-term operative results and oncologic outcomes of R-TT and conventional open TT (O-TT) after propensity score matching of the cohorts., Methods: This study retrospectively evaluated patients with papillary thyroid cancer (PTC) who underwent TT with central compartment node dissection (CCND) by a single surgeon in tertiary medical center. Of the 833 patients, 94 (11.3 %) were lost to follow-up. 245 (33.2 %) underwent R-TT, and 494 (66.8 %) underwent O-TT. The mean follow-up duration was 74 (range 61-91) months. Propensity score matching in age, gender, tumor size, extrathyroidal invasion, multiplicity, bilaterality, and TNM stage identified 206 pairs of patients. The long-term oncologic outcomes were assessed in the R-TT and O-TT groups before and after adjustment for baseline covariates., Results: After adjustment for baseline covariates, serum thyroglobulin (Tg) (p = 0.746) and anti-thyroglobulin antibody (TgAb) (p = 0.394) concentrations were similar in the two groups 5 years after surgery. Nine patients experienced locoregional recurrence, six in the O-TT and three in the R-TT group, with all recurrences in regional LNs. Disease-free survival (DFS) was similar in the R-TT and O-TT groups before matching (p = 0.890) and after adjustment for baseline covariates (p = 0.882)., Conclusion: This represents the first report of 5-year surgical outcomes in patients who underwent R-TT for thyroid cancer. Long-term oncologic quality was similar after R-TT and O-TT.

Regional lymph node (LN) metastasis has a significant impact for prediction of recurrence in patients with papillary thyroid cancers (PTC); however, the prognostic value of the lymph node ratio (LNR), which is defined as the ratio of the number of metastatic LNs to the total number of investigated LNs, is controversial. In this study, we determined the optimal cut-off values of LNRs for the prediction of recurrence in PTC patients.This large cohort study retrospectively evaluated 2294 patients who had undergone total thyroidectomy for PTC at a single institution from October 1985 to June 2009. The prediction probability of central LNR (cLNR, level VI) and total LNR (tLNR, levels II-VI) were estimated by binominal logistic regression analysis. Hazard ratios of the cut-off LNR values for cancer recurrence were calculated for relevant covariates using multivariate Cox regression analyses. Kaplan-Meier analyses were also utilized to assess the effects of estimated LNR cut-off values on recurrence-free survival (RFS).Of the 2294 patients, 138 (6.0%) presented cancer recurrence during the follow-up period (median duration = 107.1 months). The prediction probability indicated that LNRs of 0.4 and 0.5 for central LN and total LN, respectively, are optimal cut-off values for precise prediction with minimization of outliers. Multivariate Cox regression analyses revealed that cLNR ≥0.4 was independently predictive of recurrence in patients with N0 and N1a PTCs (hazard ratio [HR]: 7.016, 95% confidence interval [CI]: 3.72-12.986, P < 0.001) and that tLNR ≥0.5 indicated a significantly increased risk of recurrence in patients with N1b PTCs (HR: 2.372, 95% CI: 1.458-3.860, P < 0.001). In addition, Kaplan-Meier analyses clearly demonstrated that these LNR cut-off values are precisely operational in RFS estimation.The cut-off LNR values of 0.4 and 0.5 for cLNR and tLNR, respectively, were identified. Risk stratification combined with these LNR cut-off values may prove useful to determine treatment and follow-up strategies for PTC patients.

Background: Although some studies have reported that preoperative vitamin D deficiency (VDD) is a risk factor for hypocalcemia after total thyroidectomy (TT) in patients with nontoxic multinodular goiter or Graves' disease, the association between VDD and postoperative hypocalcemia in thyroid cancer patients undergoing TT plus central compartment neck dissection (CCND) remains unclear. This study evaluated whether preoperative VDD was associated with postoperative symptomatic hypocalcemia., Materials and Methods: Data were collected prospectively between September 2012 and May 2013. A total of 267 consecutive thyroid cancer patients who underwent TT with CCND were analyzed. Patients were divided into two groups--VDD or non-VDD--by preoperative vitamin D level of <10 or ≥10 ng/mL. Symptomatic hypocalcemia was defined as serum calcium <8.2 mg/dL and symptoms or signs of hypocalcemia. The rates of postoperative symptomatic hypocalcemia and clinicopathological features were compared between the two patient groups., Results: The rate of postoperative symptomatic hypocalcemia was higher in the VDD group than in the non-VDD group (43.8% vs. 30.4%, p=0.043). By logistic regression analysis, predictive factors for postoperative symptomatic hypocalcemia included a preoperative vitamin D level of <10 ng/mL (p=0.007; odds ratio=3.00). In patients who had postoperative intact parathyroid hormone (iPTH) levels <15 pg/mL, symptomatic hypocalcemia was more common in the VDD group than in the non-VDD group (77.5% vs. 53.2%, p=0.008). The findings show that a preoperative vitamin D threshold level of >20 ng/mL reduced the risk of symptomatic hypocalcemia by 72% when compared with patients with VDD (p=0.003)., Conclusion: VDD is significantly associated with postoperative symptomatic hypocalcemia in thyroid cancer patients undergoing TT plus CCND. VDD was predictive for symptomatic hypocalcemia when patients had postoperative serum iPTH levels <15 pg/mL. Thus, preoperative supplementation with oral vitamin D should be considered to minimize postoperative symptomatic hypocalcemia.

Despite the favorable therapeutic outcomes reported in differentiated thyroid cancer (DTC), a significant proportion of DTC patients present with refractory behavior to conventional therapy. The sirtuin (Sirt) family has recently been implicated in the maintenance of cellular homeostasis under genotoxic stress. Here, we investigated the induction of Sirt1 expression by etoposide-induced genotoxic stress to gain insights into thyroid carcinogenesis and identify novel therapeutic targets. Immunohistochemical staining analyses of Sirt1 and Sirt3 were performed using human thyroid cancer tissues and matched normal tissues, and bioinformatic analyses were done using public repositories, including the Human Protein Atlas, BioGPS, NCBI Gene Expression Omnibus (GEO) profiles, and GeneNetwork. TPC1, FTC133 and FRO cells were used for molecular biological experiments including apoptosis assays, MTT, immunofluorescence staining and qRT-PCR assays. The IHC data and public repositories data consistently showed variable Sirt1 and Sirt3 expression patterns in normal thyroid follicular cells and papillary thyroid cancer cells. The induction of Sirt1 and Sirt3 was cell type-specific and the expression levels of these genes correlated with apoptotic cell death and cell viability after etoposide-induced genotoxic stress. Sirt1‑Foxp3 signaling-mediated regulation of Bax and p21 mRNA expression was a signature molecular event in TPC1 cells, which showed remarkable resistance to etoposide-induced genotoxic stress. The induction of Sirt1 and Sirt3 may be a determinant of thyroid cancer cell survival under genotoxic stress conditions. Further examination of the Sirt1-Foxp3 signal may improve our understanding of thyroid carcinogenesis and help identify new druggable targets.

Background: Robotic thyroidectomy (RT), a new gasless, transaxillary approach developed by the Yonsei University group in Seoul, Korea, eliminates the need for a cervical incision. Since RT is technically complex and has a steep learning curve, the surgical complication rate may initially be higher than with conventional surgery. This study evaluated the complication rates of transaxillary RT and assessed ways to prevent surgical complications., Methods: Between October 2007 and March 2013, 3,000 patients underwent RT for thyroid cancer in the Department of Surgery, Yonsei University College of Medicine at Severance Hospital, Seoul. The medical records of these patients were reviewed retrospectively, and surgical complications were assessed on the basis of clinical findings., Results: The most common surgical complication was symptomatic hypocalcemia, of which 37.43 % cases were transient and 1.10 % permanent. Other surgical complications included recurrent laryngeal nerve injury (1.23 % transient, 0.27 % permanent), seroma (1.73 %), hematoma (0.37 %), chyle leakage (0.37 %), trachea injury (0.2 %), Horner's syndrome (0.03 %), carotid artery injury (0.03 %), and brachiocephalic vein injury (0.03 %). The technique-related complications, which were never seen in conventional open thyroidectomy, were axillary skin flap perforation (0.1 %), and traction injury of the arm on the side the lesion was located (0.13 %)., Conclusions: Surgeons who have mastered standardized robotic surgical procedures and who understand potential complications and how to prevent them can perform RT safely.

Background: The histological characteristics of follicular thyroid carcinomas (FTCs) are important predictors of prognosis, and lesions can be classified as either minimally invasive follicular carcinoma (MIFC) or widely invasive follicular carcinoma (WIFC) based on histopathological characteristics. There has been controversy surrounding the histological classification of FTC, which can present challenges to clinicians attempting to deliver accurate prognostic information to their patients. The aim of the present study was to examine cases of metastatic FTC for characteristics that may predict aggressive tumour behaviour., Methods: The Monash University Endocrine Surgery Unit database was searched for patients with FTC. The histopathology reports were collated for these patients to confirm the diagnosis of FTC, classify patients into MIFC versus WIFC, and examine for key characteristics such as the capsular and/or vascular invasion. The thyroid specimens from patients with metastatic FTC were examined by reviewing pathologists. It was hypothesized that patients with metastatic disease would likely have WIFC as their primary lesion., Results: There were 64 patients with FTC identified during the period of 1997-2009. Of these, 10 patients were found to have metastatic disease. On review of the histopathology, three patients were found to have WIFC,four patients had MIFC and three patients did not have definite features of FTC found in the thyroid gland., Conclusion: Currently accepted histological classification of FTC is inadequate and fails to accurately predict patients with distant metastatic disease and a more aggressive clinical course. It is thus the policy of our unit to recommend total thyroidectomy and radioactive iodine ablation for all patients with FTC., (© 2012 The Authors. ANZ Journal of Surgery © 2012 Royal Australasian College of Surgeons.)

Purpose: During a sentinel lymph node biopsy (SLNB) for breast cancer, the appropriate number of sentinel lymph nodes (SLNs) to be removed for accurate axillary staging is still controversial. We hypothesized that there might be an optimal threshold number of SLNs. We investigated how many SLNs should be removed to achieve an acceptable accuracy and ensure minimal morbidity., Methods: We reviewed data of 328 patients with invasive breast cancer who underwent SLNB followed by complete level I and II axillary dissection between January 2004 and December 2005. The false negative rate (FNR) and accuracy of SLNB according to the number of removed SLNs were evaluated., Results: The mean number of SLNs removed was 3.0 (range, 1-14), and that of total retrieved axillary lymph nodes was 17.5 (range, 10-40). In total, 111 (33.8%) patients had positive nodes on the permanent pathological report. Among them, 12 patients had negative SLNs; thus, the overall FNR of SLNB was 10.8% (12/111) and the accuracy was 96.3% (316/328). The FNR was 26.6% for a single SLN, 8.0% for two, and 11.1% for three. In cases where four or more SLNs were removed, the FNR decreased to 0% and accuracy reached 100%., Conclusion: Our data suggest that a SLNB should not only remove one or two of the hottest node(s) when other hot nodes exist. We also suggest that four might be an optimal threshold number of SLNs to be removed and that removal of more than four SLNs does not improve axillary staging accuracy.

Autoimmune diseases are incurable. We have hypothesized that these diseases can be cured by the transplantation of bone marrow (BM) stem cells that have been genetically engineered to express self-Ag. Here we have tested this hypothesis in experimental autoimmune encephalomyelitis (EAE) induced by the self-Ag myelin oligodendrocyte glycoprotein (MOG). We show that, in mice, transplantation of BM genetically modified to express MOG prevented the induction and progression of EAE, and combined with antecedent corticosteroid treatment, induced long-term remission of established disease. Mice remained resistant to EAE development upon subsequent rechallenge with MOG. Transfer of BM from these mice rendered recipients resistant to EAE. Splenocytes from these mice failed to proliferate or produce IL-17, IFN-gamma, and GM-CSF in response to MOG(35-55) peptide stimulation and they failed to produce MOG autoantibody. Mechanistically, we demonstrated in vivo reduction in development of CD4(+) MOG(35-55)-specific thymocytes, indicative of clonal deletion with no evidence for selection of Ag-specific regulatory T cells. These findings validate our hypothesis that transplantation of genetically modified BM expressing disease-causative self-Ag provides a curative approach by clonal deletion of disease-causative self-reactive T cells.

Experimental autoimmune encephalomyelitis (EAE) is an animal model of human multiple sclerosis (MS). EAE, induced by immunisation with myelin-associated autoantigens, is characterised by an inflammatory infiltrate in the central nervous system (CNS) associated with axonal degeneration, demyelination and damage. We have recently shown in an experimental mouse model of autoimmune gastritis that methylprednisolone treatment induces a reversible remission of gastritis with regeneration of the gastric mucosa. Here, we examined the effect of oral methylprednisolone on the mouse EAE model of human MS induced by immunisation with myelin oligodendrocyte glycoprotein peptide (MOG(35-55)). We examined the clinical scores, CNS pathology and lymphocyte reactivity to MOG(35-55) following treatment and withdrawal of the steroid. Methylprednisolone remitted the clinical signs of EAE and the inflammatory infiltrate in the CNS, accompanied by loss of lymphocyte reactivity to MOG(35-55) peptide. Methylprednisolone withdrawal initiated relapse of the clinical features, a return of the CNS inflammatory infiltrate and lymphocyte reactivity to MOG(35-55) peptide. This is the first study to show that methylprednisolone induced a reversible remission in the clinical and pathological features of EAE in mice accompanied by loss of lymphocyte reactivity to the encephalitogen. This model will be useful for studies directed at a better understanding of mechanisms associated with steroid-induced disease remission, relapse and remyelination and also as an essential adjunct to an overall curative strategy.