Intra-splenic ovarian cystadenoma.

Splenic cysts are relatively common and usually involve post-traumatic or infective aetiologies. The management of splenic cysts varies in its aetiology, symptomology and size. Surgical intervention is warranted for symptomatic, larger sized cysts > 5 cm and can involve spleen-preserving laparoscopic cyst fenestrations, marsupialization or potentially a splenectomy. In this case report, we review a rare case of an ectopic ovarian cystadenoma presenting as a large recurrent splenic cyst.

Bi-national Review of Phaeochromocytoma Care: Is ICU Admission Always Necessary?

BACKGROUND: Post-operative management after phaeochromocytoma resection includes monitoring of blood pressure and blood sugar, and vigilance for haemorrhage. Guidelines recommend 24 h of continuous blood pressure monitoring, usually necessitating HDU/ICU admission. We hypothesised that most patients undergoing phaeochromocytoma resection do not require post-operative HDU/ICU admission. We aim to describe current Australian and New Zealand perioperative management of phaeochromocytoma and determine whether it is safe to omit HDU/ICU care for most patients. METHODS: We collected retrospective data on patients undergoing excision of phaeochromocytoma in 12 centres around Australia and New Zealand between 2007 and 2019. Data collected included preoperative medical management, anaesthetic management, vasopressor support, HDU/ICU admission and complications. RESULTS: A total of 223 patients were included in the study, 173 (77%) of whom were admitted to HDU/ICU post-operatively. The group of patients treated in ICU was similar to the group of patients treated on the ward in terms of demographic and tumour characteristics, and there were significant differences in the proportion of patients admitted to HDU/ICU between centres. Of patients admitted to ICU, 71 (41%) received vasopressor support. This was weaned within 24 h in 55 (77%) patients. Patients with larger tumours (> 6 cm) and a transfusion requirement are more likely to require prolonged inotropic support. Among patients admitted to the ward, there were no complications that required escalation of care. CONCLUSIONS: Although not widespread practice in Australia and New Zealand, it appears safe for the majority of patients undergoing minimally invasive resection of phaeochromocytoma to be admitted to the ward post-operatively.

Cohort study of 1241 patients to identify predictors of negative appendicectomy.

BACKGROUND: Acute Appendicitis is the most common surgical presentation within Australia. Despite the increasing use of radiological investigations to aid clinical diagnosis, many appendectomies result in a histologically normal appendix. This study examines the histological negative appendicectomy rate (NAR) in a metropolitan hospital and determine factors associated with a negative appendicectomy (NA). METHODS: Patients who underwent emergency appendicectomy for suspected acute appendicitis at Logan Hospital, Australia, between February 2016 and March 2019 inclusive were included. Clinicopathologic and imaging variables were analysed for associations with NA. RESULTS: A total of 1241 patients underwent emergency appendicectomy of which 121 patients (9.8%) had a NA. The NAR for clinical diagnosis alone (no imaging) was 9.9%, 14.5% for ultrasonography alone and computed tomography scan alone was 4.9%. Univariate analysis revealed age <27 years (P < 0.001), absence of hypertension (P = 0.008), symptoms >48 hours (P < 0.001), absence of leucocytosis (P < 0.001), undergoing ultrasonography only (P < 0.001), undergoing computed tomography scan only (P < 0.001), macroscopically normal appendix (P < 0.001) and time to operation >24 hours (P < 0.001) were associated with NA. Multivariate analysis identified symptoms >48 h at presentation (odds ratio (OR) 1.98, 95% confidence interval (CI) 1.20-3.24; P = 0.007), absence of leucocytosis (OR 2.41, 95% CI 1.52-3.81; P < 0.001) and macroscopically normal appendix (OR 5.70, 95% CI 3.49-9.33; P < 0.001) to be associated with a NA. CONCLUSION: The NAR reported is lowest in an Australian institution. The identified predictors of NA will be useful in identifying patients who would truly benefit from an appendicectomy versus those would have a higher rate of NA who may be suitable to be treated non-operatively to be spared the unnecessary morbidity of surgery.

Early outcomes of emergency ventral hernia repair in a cohort of poorly optimized patients.

BACKGROUND: Strangulated and obstructed ventral hernias require emergent repair to mitigate the risk of life-threatening complications. Emergency ventral hernia repairs are associated with a higher rate of surgical complications and recurrence compared to elective repairs. The purpose of this study was to explore the impact of patient factors, hernia and operative characteristics on post-operative outcomes in patients requiring emergency ventral hernia repairs. METHODS: Data were collected from a prospectively held database on 86 consecutive patients undergoing emergency ventral hernia repairs between January 2016 and January 2019 at Logan Hospital. Patient, hernia and operative characteristics were collected for reporting and analysis. RESULTS: Of the 86 patients, 29 (34%) developed a surgical complication, of which 17 patients (59%) had surgical site infections. We identified obesity (P = 0.017), history of smoking (P = 0.008), American Society of Anesthesiologists class of III-IV (P = 0.008), hernia defect size ≥3 cm (P = 0.048) and concomitant small bowel resection (P = 0.028) to be associated with post-operative surgical complication. Multivariate analysis identified smoking (P = 0.005) and concomitant small bowel resection (P = 0.026) as independent predictors for developing surgical complications. Seven patients (8%) recurred at a median of 221 days. Incisional hernias (P = 0.001), recurrent hernias (P < 0.001), greater than one defect (P < 0.001) and bowel involvement (P = 0.049) were associated with higher rates of hernia recurrence. CONCLUSION: Patient factors significantly influence outcomes in the emergency setting. Given that this is not modifiable at the time of surgery, greater emphasis needs to be placed on optimizing the physical and behavioural factors of patients with early symptomatic hernias for an elective repair.

Management of patients with hepatocellular adenoma: a single-institution experience.

BACKGROUND: Hepatocellular adenoma (HCA) is a rare benign liver tumour that may cause diagnostic and management dilemmas. This study describes the clinical and histopathological characteristics of patients who were treated for HCA in a tertiary referral hospital over a 17-year period. METHODS: A retrospective review was performed of prospectively collected data of all patients treated for HCA within the Northern Upper GI Surgical unit between 2002 and 2018. Immunohistochemical ß-catenin expression was evaluated. RESULTS: Thirty-two patients had histological or radiologically confirmed HCA. Twenty-eight patients underwent 30 operations and four patients were treated conservatively. The median age of the operative group was 43 years (range 19-83) and most patients were female (95%). The median body mass index was 28.7 (range 20-51), and nine patients (33%) were obese. Seven patients (25%) had multifocal HCA. Evidence of prior bleed or rupture or a perceived risk of either a bleed or malignant change (i.e. tumours ≥50 mm) were the most common indications for resection. There were no perioperative mortalities. Nuclear expression of ß-catenin by immunohistochemical staining was negative in all cases and there was no malignancy identified in any of the resected lesions. Two patients required transarterial embolization and two patients required a second liver resection for residual HCA. CONCLUSION: HCA is a rare lesion predominantly affecting females. Haemorrhage is seen frequently on imaging studies, occasionally requiring urgent angioembolization and/or surgical intervention. Malignant transformation and immunohistochemical ß-catenin expression are uncommon. HCA may be multifocal and residual tumours usually require ongoing surveillance and occasionally further intervention.

Management of recurrent bleeding after pancreatoduodenectomy.

BACKGROUND: Re-bleeding after management of a first haemorrhage following pancreatic surgery is an ever-present danger and often presents diagnostic and management dilemmas. METHODS: All cases of post-pancreatectomy haemorrhage (PPH) following pancreatoduodenectomy were identified from a tertiary referral, clinical database (April 2004-April 2013). Only those suffering a second re-bleeding episode were included in the final case notes review. RESULTS: A total of 301 patients underwent pancreatoduodenectomy during the study period (most common indication: pancreatic adenocarcinoma; 49.5%). Twenty-two (7.3%) patients suffered a PPH (five early). Of these cases, three suffered a re-bleeding event (one mortality). Endoscopy, interventional radiology and surgery were employed in each case. CONCLUSION: PPH presents major clinical challenges and is associated with significant morbidity and mortality. Early detection of the site and type of bleeding are critical and multimodal therapy is usually required. Interventional radiology techniques are making a major contribution to overall management.

Gallbladder mucosal lesions associated with high biliary amylase irrespective of pancreaticobiliary maljunction.

BACKGROUND: Previous studies have focused on the presence of reflux in selected cohorts with pancreaticobiliary maljunction (PBM), but little is known regarding the wider incidence of occult reflux and associated mucosal changes. We aimed to correlate gallbladder mucosal abnormalities with objective evidence of PBM and occult pancreaticobiliary reflux (PBR) in an Australian population undergoing cholecystectomy. METHODS: Patients undergoing cholecystectomy between September 2010 and September 2012 were eligible for inclusion. Demographic and pre-operative clinical data were collated and entered into a pre-defined database. Operative cholangiograms were routinely performed and the presence of PBM noted. Gallbladder bile samples were analysed for bilirubin (<20 µmol/L), amylase (<100 U/L) and lipase (<70 U/L) levels. Evidence of PBR was correlated with gallbladder mucosal findings. RESULTS: A total of 305 cholecystectomies were performed for biliary colic (73%), choledocholithiasis (9%), cholecystitis (8.4%) and pancreatitis (6.4%). A total of 12.7% had cholangiographic evidence of PBM and 11.9% possessed gallbladder mucosal changes. Overall, 7.7% had increased biliary amylase, which was associated with significantly higher rates of gallbladder intestinal metaplasia (33% versus 8.6%; P = 0.012). Elevated biliary amylase was also higher in patients with prior pancreatitis (P = 0.02) or choledocholithiasis (P < 0.01). The presence of PBM did not predict for the presence of PBR. CONCLUSION: PBR is associated with an increased frequency of gallbladder mucosal metaplasia, irrespective of the presence of PBM. Objectively identified reflux represents an additional indication for cholecystectomy but the long-term consequences for extra-hepatic biliary malignancy remain unknown and warrant further investigation. Methods of objectively identifying PBR pre-operatively require further investigation.

Dictating genomic destiny: Epigenetic regulation of pancreatic neuroendocrine tumours.

Pancreatic neuroendocrine tumours are a diverse group of neoplasms with an increasingly well-defined genomic basis. Despite this, much of what drives this disease is still unknown and epigenetic influences represent the next tier of gene, and hence disease modifiers that are of unquestionable importance. Moreover, they are of arguably more significance than the genes themselves given their malleable nature and potential to be exploited for not only diagnosis and prognosis, but also therapy. This review summarises what is known regarding the key epigenetic modifiers of disease through the domains of diagnosis, prognosis and treatment.

Cholangiocarcinoma following external beam radiotherapy: A report of two cases.

Cholangiocarcinoma (CCA) is a relatively rare primary malignancy, with established risk factors that include primary sclerosing cholangitis, choledochal cysts and hepatolithiasis. In the present study, two cases of CCA, which occurred following abdominal external beam radiotherapy (EBRT) for non-Hodgkin's lymphoma, are reported. Case 1 and 2 were diagnosed with cholangiocarcinoma 30 and 4 years following treatment with combined chemotherapy and abdominal radiotherapy treatment, respectively. The patients received chemotherapy as treatment of cholangiocarcinoma; however, whilst their symptoms improved, they succumbed within 12 and 2 months respectively following the diagnosis with cholangiocarcinoma. Currently, the association between radiation exposure and hepatobiliary malignancy remains unclear, however, we hypothesize that biliary epithelium sensitivity to ionizing radiation may have contributed to the etiology of the secondary malignancies observed in these two patients. This study indicates that patients treated with abdominal EBRT may benefit from a heightened index of suspicion and more intensive surveillance for secondary biliary malignancies.

Systematic review of peri-operative prognostic biomarkers in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) continues to be associated with a poor prognosis. This systematic review aimed to summarize the literature regarding potential prognostic biomarkers to facilitate validation studies and clinical application. METHODS: A systematic review was performed (2004-2014) according to PRISMA guidelines. Studies were ranked using REMARK criteria and the following outcomes were examined: overall/disease free survival, nodal involvement, tumour characteristics, metastasis, recurrence and resectability. RESULTS: 256 biomarkers were identified in 158 studies. 171 biomarkers were assessed with respect to overall survival: urokinase-type plasminogen activator receptor, atypical protein kinase C and HSP27 ranked the highest. 33 biomarkers were assessed for disease free survival: CD24 and S100A4 were the highest ranking. 17 biomarkers were identified for lymph node involvement: Smad4/Dpc4 and FOXC1 ranked highest. 13 biomarkers were examined for tumour grade: mesothelin and EGFR were the highest ranking biomarkers. 10 biomarkers were identified for metastasis: p16 and sCD40L were the highest ranking. 4 biomarkers were assessed resectability: sCD40L, s100a2, Ca 19-9, CEA. CONCLUSION: This review has identified and ranked specific biomarkers that should be a primary focus of ongoing validation and clinical translational work in PDAC.

Germline ESR2 mutation predisposes to medullary thyroid carcinoma and causes up-regulation of RET expression.

Familial medullary thyroid cancer (MTC) and its precursor, C cell hyperplasia (CCH), is associated with germline RET mutations causing multiple endocrine neoplasia type 2. However, some rare families with apparent MTC/CCH predisposition do not have a detectable RET mutation. To identify novel MTC/CCH predisposition genes we undertook exome resequencing studies in a family with apparent predisposition to MTC/CCH and no identifiable RET mutation. We identified a novel ESR2 frameshift mutation, c.948delT, which segregated with histological diagnosis following thyroid surgery in family members and demonstrated loss of ESR2-encoded ERß expression in the MTC tumour. ERα and ERß form heterodimers binding DNA at specific oestrogen-responsive elements (EREs) to regulate gene transcription. ERß represses ERα-mediated activation of the ERE and the RET promoter contains three EREs. In vitro, we showed that ESR2 c.948delT results in unopposed ERα mediated increased cellular proliferation, activation of the ERE and increased RET expression. In vivo, immunostaining of CCH and MTC using an anti-RET antibody demonstrated increased RET expression. Together these findings identify germline ESR2 mutation as a novel cause of familial MTC/CCH and provide important insights into a novel mechanism causing increased RET expression in tumourigenesis.

Efficacy of primary tumour volume as a predictor of survival compared with size alone in pancreatic ductal adenocarcinoma.

Tumour size (TSize) predicts outcome in pancreatic ductal adenocarcinoma (PDAC), but little is known regarding three-dimensional tumour volume (TVol) associations. We hypothesised that TVol would more accurately predict outcome following pancreatoduodenectomy (PD) for PDAC. Clinicopathological and outcome data was reviewed for all PDs performed in the Royal North Shore Hospital (St. Leonards, NSW, Australia), between April 2004 and November 2010, in patients whose three tumour dimensions were recorded (n=103). TVol was quantified using the ellipsoidal volume formula, 4/3π(r1×r2×r3), and was correlated with clinicopathological indices/outcome. Over a median follow-up time of 20.5 months, TVol failed to significantly predict post-resection mortality [odds ratio (OR), 1.0; 95% confidence interval (CI), 0.99-1.00; P=0.438)]. Neural invasion remained an overall independent predictor of mortality following multivariate analysis (OR, 3.94; 95% CI, 1.36-11.40; P=0.011). Patients with higher TVol were more likely to require a vascular resection (P=0.007), had longer surgical times (P<0.001), larger intraoperative blood losses (P=0.007) and a trend toward worse survival (P=0.068). TVol inclusion in a multivariate model resulted in a small improvement in mortality prediction versus TSize (14.9 vs. 14.7%). A higher TVol results in a more complex perioperative course. Although TVol improved the mortality prediction beyond simple TSize alone, this difference was not significant. Studies normalising TVol for body composition are required.

Acute Gastric Rupture in a Giant Inguinoscrotal Hernia.

Inguinoscrotal gastric herniation is a rare occurrence and generally presents with obstruction when encountered. We present a case of acute spontaneous gastric rupture in a giant inguinoscrotal hernia which was managed surgically in a one-stage procedure with primary gastric and hernia repair. A subtotal colectomy was performed due to risk of volvulus as well as allowing for primary closure of the abdominal wall. This case illustrates the possibilities in terms of hernia size and contents, in addition to the potential complications that may ensue. Moreover, this case illustrates that adherence to the principles of hernia repair can equip the surgeon to deal with rare and unfamiliar presentations.

Use of the Nerve Integrity Monitor during Thyroid Surgery Aids Identification of the External Branch of the Superior Laryngeal Nerve.

BACKGROUND: The external branch of the superior laryngeal nerve (EBSLN) is at risk during thyroid surgery. Despite meticulous dissection and visualization, the EBSLN can be mistaken for other structures. The nerve integrity monitor (NIM) allows EBSLN confirmation with cricothyroid twitch on stimulation. AIMS: The aim of this study was to assess any difference in identification of EBSLN and its anatomical sub-types by dissection alone compared to NIM-aided dissection. METHODS: Routine intra-operative nerve monitoring (IONM) was used, when available, for 228 consecutive thyroid operations (129 total thyroidectomies, 99 hemi-thyroidectomies) over a 10-month period. EBSLN identification by dissection alone (with NIM confirmation of cricothyroid twitch) and by NIM-assisted dissection was recorded prospectively. Anatomical sub-types were defined by the Cernea classification. RESULTS: Of 357 nerves at risk, 97.2 % EBSLNs (95 % confidence interval [CI], 95.5-98.9) were identified by visualization and NIM-aided dissection compared to 85.7 % (95 % CI, 82.1-89.3) identified by dissection alone (<0.001). EBSLN frequency was 34 % for type 1, 55 % for type 2a, and 11 % for type 2b. All identified EBSLNs were stimulated to confirm a cricothyroid twitch after superior thyroid vessel ligation. CONCLUSION: Using the NIM and meticulous dissection of the upper thyroid pole improves EBSLN identification. As the EBSLN is at risk during thyroidectomy and can lead to voice morbidity, the NIM can aid identification of the EBSLN and provide a functional assessment of the EBSLN after thyroid resection.

Noncoding RNA blockade of autophagy is therapeutic in medullary thyroid cancer.

Micro-RNAs are dysregulated in medullary thyroid carcinoma (MTC) and preliminary studies have shown that miRNAs may enact a therapeutic effect through changes in autophagic flux. Our aim was to study the in vitro effect of miR-9-3p on MTC cell viability, autophagy and to investigate the mRNA autophagy gene profile of sporadic versus hereditary MTC. The therapeutic role of miR-9-3p was investigated in vitro using human MTC cell lines (TT and MZ-CRC-1 cells), cell viability assays, and functional mechanism studies with a focus on cell cycle, apoptosis, and autophagy. Post-miR-9-3p transfection mRNA profiling of cell lines was performed using a customized, quantitative RT-PCR gene array card. This card was also run on clinical tumor samples (sporadic: n = 6; hereditary: n = 6) and correlated with clinical data. Mir-9-3p transfection resulted in reduced in vitro cell viability; an effect mediated through autophagy inhibition. This was accompanied by evidence of G2 arrest in the TT cell line and increased apoptosis in both cell lines. Atg5 was validated as a predicted miR-9-3p mRNA target in TT cells. Post-miR-9-3p transfection array studies showed a significant global decline in autophagy gene expression (most notably in PIK3C3, mTOR, and LAMP-1). Autophagy gene mRNAs were generally overexpressed in sporadic (vs. hereditary MTC) and Beclin-1 overexpression was shown to correlate with residual disease. Autophagy is a tumor cell survival mechanism in MTC that when disabled, is of therapeutic advantage. Beclin-1 expression may be a useful prognostic biomarker of aggressive disease.

Laparoscopic stapled excision of non-parasitic splenic cysts.

BACKGROUND: A laparoscopic spleen preserving surgical approach is preferred for the management of symptomatic non-parasitic splenic cysts. The aim of this study was to review our experience with managing this rare presentation. METHODS: A retrospective review of all cases of splenic cysts was performed over a 10-year period (2001-2011). Demographic data, clinical history, investigations, operative details and the outcome of each case were reviewed with an emphasis on patients who underwent laparoscopic stapled cyst excision. RESULTS: Eleven cases were identified. Seven patients were managed surgically; six by laparoscopic stapled cyst excision and one by open excision of remnant splenic tissue. Laparoscopic management was successful in all six cases and radiological and clinical follow-up (median: 28 months) revealed no evidence of cyst recurrence in five of six cases. One patient developed an asymptomatic, non-progressing and small recurrent anterior cyst and she continues to be observed. CONCLUSION: Laparoscopic stapled splenic cyst excision can be performed safely and is particularly effective for large superficial non-parasitic cysts. This technique allows spleen preservation with a low cyst recurrence rate. However, it may not be suitable for deeper intraparenchymal splenic cysts. Further studies are required to refine the management of specific subtypes of non-parasitic splenic cysts.