SCANPatient: study protocol for a multi-centre, batched, stepped wedge, comparative effectiveness, randomised clinical trial of synoptic reporting of computerised tomography (CT) scans assessing cancers of the pancreas.

BACKGROUND: Complete surgical removal of pancreatic ductal adenocarcinoma (PDAC) is central to all curative treatment approaches for this aggressive disease, yet this is only possible in patients technically amenable to resection. Hence, an accurate assessment of whether patients are suitable for surgery is of paramount importance. The SCANPatient trial aims to test whether implementing a structured synoptic radiological report results in increased institutional accuracy in defining surgical resectability of non-metastatic PDAC. METHODS: SCANPatient is a batched, stepped wedge, comparative effectiveness, cluster randomised clinical trial. The trial will be conducted at 33 Australian hospitals all of which hold regular multi-disciplinary team meetings (MDMs) to discuss newly diagnosed patients with PDAC. Each site is required to manage a minimum of 20 patients per year (across all stages). Hospitals will be randomised to begin synoptic reporting within a batched, stepped wedge design. Initially all hospitals will continue to use their current reporting method; within each batch, after each 6-month period, a randomly selected group of hospitals will commence using the synoptic reports, until all hospitals are using synoptic reporting. Each hospital will provide data from patients who (i) are aged 18 or older; (ii) have suspected PDAC and have an abdominal CT scan, and (iii) are presented at a participating MDM. Non-metastatic patients will be documented as one of the following categories: (1) locally advanced and surgically unresectable; (2) borderline resectable; or (3) anatomically clearly resectable (Note: Metastatic disease is treated as a separate category). Data collection will last for 36 months in each batch, and a total of 2400 patients will be included. DISCUSSION: Better classifying patients with non-metastatic PDAC as having tumours that are either clearly resectable, borderline or locally advanced and unresectable may improve patient outcomes by optimising care and treatment planning. The borderline resectable group are a small but important cohort in whom surgery with curative intent may be considered; however, inconsistencies with definitions and an understanding of resectability status means these patients are often incorrectly classified and hence overlooked for curative options. TRIAL REGISTRATION: The SCANPatient trial was registered on 17th May 2023 in the Australian New Zealand Clinical Trials Registry (ANZCTR) (ACTRN12623000508673).

Safety and feasibility of instituting a robotic pancreas program in the Australian setting: a case series and narrative review.

BACKGROUND: Minimally invasive pancreatic resection has been gathering interest over the last decade due to the technical demands and high morbidity associated with these typically open procedures. We report our experience with robotic pancreatectomy within an Australian context. METHODS: All patients undergoing robotic distal pancreatectomy (DP) and pancreaticoduodenectomy (PD) at two Australian tertiary academic hospitals between May 2014 and December 2020 were included. RESULTS: Sixty-two patients underwent robotic pancreatectomy during the study period. Thirty-four patients with a median age of 68 years (range 42-84) were in the PD group whilst the DP group included 28 patients with a median age of 60 years (range 18-78). Thirteen patients (46.4%) in the DP group had spleen-preserving procedures. There were 13 conversions (38.2%) in the PD group whilst 0 conversions occurred in the DP group. The Clavien-Dindo grade ≥III complication rate was 26.4% and 17.9% in the PD and DP groups, respectively. Two deaths (5.9%) occurred within 90-days in the PD group whilst none were observed in the DP group. The median length of hospital stay was 11.5 days (range 4-56) in the PD group and 6 days (range 2-22) in the DP group. CONCLUSION: Robotic pancreatectomy outcomes at our institution are comparable with international literature demonstrating it is both safe and feasible to perform. With improved access to this platform, robotic pancreas surgery may prove to be the turning point for patients with regards to post-operative complications as more experience is obtained.

Robotic enucleation & uncinectomy of complex lesions of the proximal pancreas.

BACKGROUND: Malignant tumours within the proximal pancreas traditionally require pancreaticoduodenectomy (PD) for cure. For smaller lesions with borderline malignant potential the risk/benefit of PD becomes difficult to justify. Robotic approaches to these lesions allow for parenchymal preserving resection with reduced complication profile without oncological compromise. METHODS: A review of a single surgeons prospectively collated database across two institutions of consecutive robotic enucleations or parenchyma preserving resections of the proximal pancreas was performed between July 2018 and October 2021. Standard demographic data, preoperative variables, intraoperative parameters, post-operative outcomes, morbidity and mortality were recorded. RESULTS: Thirteen patients (8 female and 5 male) underwent robotic enucleation (EN) (8) and/or uncinectomy (UN) (5) in the proximal pancreas. Mean BMI was 32(kg/m2 ). Three patients (21%) underwent preoperative prophylactic pancreatic duct stenting. One patient required conversion to open. The median operative time in the EN group was 170 min (108-224 min) and the UN group was 160 min (110-204 min). The majority (8) of lesions were pNETs. Three lesions were IPMNs, with 1 solitary fibrous tumour and a serous cystic neoplasm (SCN) respectively. Median tumour size was 23 mm (11-58 mm) in the EN group, and 27 mm (17-38 mm) in the UN group. Ten of 13 patients had an R0 resection. There was no mortality in our series. Four (31%) patients across both groups developed clinically relevant POPF while none developed new endocrine or exocrine insufficiency. Average outpatient follow-up has been 6 months (1-18 months). CONCLUSION: A robotic approach in proximal parenchymal preserving pancreatectomy is expanding, safe and feasible.

High SUVmax on routine pre-operative FDG-PET predicts early recurrence in pancreatic and peri-ampullary cancer.

BACKGROUND: SUVmax of a primary pancreatic tumour on FDG-PET/CT (SUVmax-p) may predict early post-operative recurrence. This has not been tested in the context of routine pre-operative FDG-PET/CT. It is also unknown whether this association exists independent of local residual tumour. METHODS: FDG-PET/CT was performed routinely prior to resection of pancreatic or peri-ampullary adenocarcinoma between 2008 and 2012 as part of a previous prospective study. We compared SUVmax-p according to whether recurrence was diagnosed within 6 months of resection. We also determined the odds ratio for recurrence within 6 months for multiple cut-points of SUVmax-p. This analysis was repeated exclusively for patients who had resection with clear surgical margins (R0). RESULTS: Of 56 patients from the initial study 23 underwent resection and were eligible. Recurrence within 6 months was associated with higher median SUVmax-p (5.9 vs 3.5; p = 0.04). This was also observed in 12 patients who underwent R0 resection (6.5 vs 2.2; p = 0.05). The cut-point with the highest odds for recurrence within 6 months for both groups was SUVmax-p ≥ 5.5 (OR = 10.8, CI = 1.56-109; OR[R0] = 24.0, CI = 1.64-1020). CONCLUSION: SUVmax-p on routine FDG-PET/CT is useful for identifying patients likely to benefit from additional pre-operative staging or neoadjuvant therapy, even where clear margins can confidently be achieved.

Portal vein thrombosis following elective laparoscopic splenectomy: incidence and analysis of risk factors.

BACKGROUND: Minimally invasive splenectomy is now well established for a wide range of pathologies. Portal vein thrombosis (PVT) is increasingly being recognised as a complication of splenectomy. The aim was to determine the incidence and risk factors for PVT after laparoscopic splenectomy. METHODS: All cases of elective laparoscopic splenectomy performed from 1993 to 2020 were reviewed. Parameters recorded included demographics, diagnostic criterion and post-operative outcomes. Data were analysed using Minitab V18 with a p < 0.05 considered significant. RESULTS: 210 patients (103 female, 107 male) underwent laparoscopic splenectomy (14 to 85 years). A major proportion of cases were performed for ITP (n = 77, p = 0.012) followed by lymphoma (n = 28), indeterminate lesions (n = 21) and myelofibrosis (n = 19). Ten patients developed symptomatic portal vein thrombosis (4.8%). Patients presented most commonly with pain and fever and diagnosis was confirmed by computed tomography (CT) or ultrasonography (USS). There were 10 conversions (4.8%) to open and two postoperative deaths, one from PVT and one from pneumonia. The remaining nine patients were successfully treated with anticoagulation. Of 19 patients with myelofibrosis, six patients developed PVT (p = 0.0002). Patients who developed PVT had significantly greater specimen weights (1773 g vs 348 g, p < 0.001). Forty-three patients had a specimen weight of 1 kg or greater, and of these 9 developed portal vein thrombosis (21%), versus one with PVT of 155 with a specimen weight of less than 1 kg (p < 0.0001). Myelofibrosis (p = 0.0039), specimen weight (p < 0.001) and mean platelet count (p = 0.0049) were predictive of PVT. CONCLUSION: A high index of suspicion for this complication should be maintained and prompt treatment with anticoagulation. High-risk patients should be considered for prophylactic anticoagulation and routine imaging of the portal vein.

Comparison of lipid-normalised concentrations of persistent organic pollutants (POPs) between serum and adipose tissue.

Human biomonitoring of persistent organic pollutants (POPs) is typically based on serum analysis and for comparison and modelling purposes, data are often normalised to the lipid content of the serum. Such approach assumes a steady state of the compound between the serum lipids and for example lipid-rich adipose tissue. Few published data are available to assess the validity of this assumption. The aim of this study was to measure concentrations of POPs in both serum and adipose tissue samples from 32 volunteers and compare the lipid-normalised concentrations between serum and adipose tissue. For p,p'-DDE, PCB-138, PCB-153 and PCB-180, lipid-normalised adipose tissue concentrations were positively correlated to the respective serum concentrations but generally were more highly concentrated in adipose tissue. These results suggest that the investigated legacy POPs that were consistently found in paired samples may often not be in a steady state between the lipid compartments of the human body. Consequently, the analysis of serum lipids as a surrogate for adipose tissue exposure may more often than not underestimate total body burden of POPs. Further research is warranted to confirm the findings of this study.

Body mass index and surgical outcomes in laparoscopic liver resections: a systematic review.

BACKGROUND: Laparoscopic liver resection is gaining momentum; however, there is limited evidence on its efficacy and safety in obese patients. The aim of this study was to examine the relationship between BMI and outcomes after laparoscopic liver resection (LLR) using a systematic review of the existing literature. METHODS: A systematic search of Medline (Ovid 1946-present), PubMed (NCBI), Embase (Ovid 1966-present) and Cochrane Library was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement for parameters of LLR and BMI. Operative, post-operative and oncological outcomes were recorded. RESULTS: Of 1460 abstracts, seven retrospective studies were analysed, published between 2015 and 2017 (study periods 1998-2017). Total patient cohort were classified as 481 obese and 1180 non-obese with a median age range of 42.5-69.4 years. Variations existed in definitions of obesity (Asia BMI >25 kg/m2 , Western BMI >30 kg/m2 ). Rates of conversion were examined in four studies (0-31%) with one reporting BMI >28 kg/m2 as an independent risk factor. Estimated blood loss and transfusion rates were similar. Operative time was increased in obese patients in one study (P = 0.02). Mortality rates ranged from 0% to 4.3% with no difference between BMI classes. No difference in major morbidity was demonstrated. Bile leak rates were increased in obese groups in one study (0-3.44%, P < 0.05). Wound infections were reported in five studies, with higher rates in obese patients (0-5.8% versus 0-1.9%). Tumour size was comparable in both groups. Completeness of resection was analysed in four studies with one study reporting increased R0 rates in obese patients (P = 0.012). CONCLUSION: This systematic review highlights that current evidence shows LLR in obese patients is safe, however, further studies are required.

Consensus Guidelines for the Use of Fluorescence Imaging in Hepatobiliary Surgery.

OBJECTIVE: To establish consensus recommendations for the use of fluorescence imaging with indocyanine green (ICG) in hepatobiliary surgery. BACKGROUND: ICG fluorescence imaging has gained popularity in hepatobiliary surgery in recent years. However, there is varied evidence on the use, dosage, and timing of administration of ICG in clinical practice. To standardize the use of this imaging modality in hepatobiliary surgery, a panel of pioneering experts from the Asia-Pacific region sought to establish a set of consensus recommendations by consolidating the available evidence and clinical experiences. METHODS: A total of 13 surgeons experienced in hepatobiliary surgery and/or minimally invasive surgery formed an expert consensus panel in Shanghai, China in October 2018. By the modified Delphi method, they presented the relevant evidence, discussed clinical experiences, and derived consensus statements on the use of ICG in hepatobiliary surgery. Each statement was discussed and modified until a unanimous consensus was achieved. RESULTS: A total of 7 recommendations for the clinical applications of ICG in hepatobiliary surgery were formulated. CONCLUSIONS: The Shanghai consensus recommendations offer practical tips and techniques to augment the safety and technical feasibility of ICG fluorescence-guided hepatobiliary surgery, including laparoscopic cholecystectomy, liver segmentectomy, and liver transplantation.

Diagnostic and therapeutic considerations in biopsy-proven type 2 autoimmune pancreatitis: comparative analysis with biopsy-proven type 1 autoimmune pancreatitis.

BACKGROUND: Autoimmune processes are now an increasingly recognized cause of acute and chronic pancreatitis. Autoimmune pancreatitis is a rare, benign pathology with two distinct clinicopathologic subtypes. The aim of this study was to compare the presentation, diagnostic considerations and outcomes of patients with biopsy-proven type 1 and 2 autoimmune pancreatitis (AIP). METHODS: A retrospective review of the Queensland Health pathology database of histologically proven AIP was conducted. Parameters compared included demographics, diagnostic criterion and post-treatment outcomes. RESULTS: Twenty-three patients had a confirmed histological diagnosis of AIP (type 1 = 13, type 2 = 10). Patients with type 2 AIP were younger (median age 49 versus 59 years, P < 0.05). There was no significant difference in gender distribution of disease at presentation. Type 2 AIP presented with significant increased focal pancreatic changes on cross-sectional imaging (80% versus 54%, P < 0.05). Serum IgG4 levels were raised (>1.40 g/L) in 69% of patients with type 1 AIP and not detected in type 2 (P < 0.01). Concurrent underlying inflammatory bowel disease was present in a higher proportion of type 2 AIP (40% versus 15%, P < 0.05). A significantly increased proportion of patients with type 2 AIP underwent surgical resection (70% versus 30%, P < 0.05). Conservative management was utilized in more patients with type 1 disease (54% versus 30%). On follow-up, two patients have experienced symptomatic relapse at 6-18 months. CONCLUSIONS: Diagnostic challenges do exist and clinicians must suspect 2 type AIP in young, serum IgG4-negative inflammatory bowel disease patients with recurrent pancreatitis.

Management of primary hepatic malignancies during the COVID-19 pandemic: recommendations for risk mitigation from a multidisciplinary perspective.

Around the world, recommendations for cancer treatment are being adapted in real time in response to the pandemic of COVID-19. We, as a multidisciplinary team, reviewed the standard management options, according to the Barcelona Clinic Liver Cancer classification system, for hepatocellular carcinoma. We propose treatment recommendations related to COVID-19 for the different stages of hepatocellular carcinoma (ie, 0, A, B, and C), specifically in relation to surgery, locoregional therapies, and systemic therapy. We suggest potential strategies to modify risk during the pandemic and aid multidisciplinary treatment decision making. We also review the multidisciplinary management of intrahepatic cholangiocarcinoma as a potentially curable and incurable diagnosis in the setting of COVID-19.

Large size and haemorrhage are not contraindications to laparoscopic resection of hepatocellular adenoma.

BACKGROUND: Hepatocellular adenoma (HCA) is a hepatocyte derived neoplastic lesion with an increasing incidence and a strong association with oestrogen therapy. Laparoscopic resection has proven safe for small, non-ruptured lesions whilst its use for large adenomas (≥10 cm) and cases of haemorrhage requires further investigation. METHODS: All patients undergoing liver resection for HCA at the Royal Brisbane Hospital between January 2003 and April 2018 were analysed. Ethics approval was obtained. RESULTS: Thirty-three laparoscopic and three open resections were performed in 35 patients, all female, with a median age of 35 years (range 14-75). Nine laparoscopic resections were performed for large adenomas (≥10 cm) and 17 laparoscopic resections were performed for adenomas of intermediate size (5-9.9 cm). Only one conversion to open surgery was required for an intermediate sized tumour. Haemorrhage, either intratumoural, intraparenchymal or free intraperitoneal was the indication for resection in six of the 33 laparoscopic cases. Median operative time was 143 and 266 min for laparoscopically resected intermediate and large lesions, respectively. The median length of stay was 5 days (range 4-9) and no major complications were observed in the laparoscopic group. ß-catenin mutation was seen in four of nine large adenomas whereas the inflammatory subtype constituted 11 of 17 intermediate sized lesions. CONCLUSION: Laparoscopic surgery has been demonstrated to be safe for the resection of HCA in this group of patients. Importantly, haemorrhage and/or large size were not barriers to laparoscopic resection.

Subclassification of hepatocellular adenomas: practical considerations in the implementation of the Bordeaux criteria.

Hepatocellular adenomas are benign liver lesions with a risk of rupture and malignant transformation. Various molecular subgroups have been identified which appear to have characteristic morphological and immunohistochemical features. We examined the morphology and immunohistochemical profile of a series of 121 HCA from 97 patients to identify the HCA subtypes present and determine the number at risk for malignant transformation according to the World Health Organization (WHO) criteria for hepatocellular adenomas. There were 34 HNF1α inactivated HCA (28%), 61 inflammatory HCA (50%), 15 ß-catenin activated HCA (12%) and 11 unclassified adenomas (9%). This proportion of cases was similar to that seen in other series utilising molecular classification. The morphological features of the adenomas were suggestive but not definite indicators of the subtypes present. Morphological features that showed overlap between the subtypes included steatosis within the lesion, a ductular reaction and focal atypia, so that immunohistochemical typing was required for accurate classification. In conclusion, immunohistochemistry is a clinically useful surrogate for identifying underlying molecular changes in the HCA subtypes.

Laparoscopic pancreaticoduodenectomy in Brisbane, Australia: an initial experience.

BACKGROUND: The role of minimally invasive approach for pancreaticoduodenectomy has not yet been well defined in Australia. We present our early experience with laparoscopic pancreaticoduodenectomy (LPD) from Brisbane, Australia. METHODS: Retrospective review in a prospectively collected database of patients undergoing LPD between 2006 and 2016 was performed. Patients who underwent a hybrid LPD (HLPD) mobilization approach and resection followed by open reconstruction and totally LPD (TLPD) approach were included in this study. Operative characteristics, perioperative outcomes, pathological and survival data were collected. RESULTS: Twenty-seven patients underwent LPD including 17 HLPD (63%) and 10 TLPD (37%) patients. HLPD patients were mostly converted to open for planned reconstruction or vascular resection. With increasing experience, more TLPDs were performed, including laparoscopic anastomoses. Median operating time was 462 min (504 min for TLPD). Median length of hospital stay was 10 days. Histology showed 21 invasive malignancies, two neuroendocrine tumours, two intraductal papillary mucinous neoplasms and two benign lesions. Median nodal harvest was 22. Margin negative resection was achieved in 84% of patients. Twenty-two percent of patients developed a Grade 3/4 complication, including 19% clinically significant pancreatic fistula. There was one perioperative mortality (4%) due to pancreatic fistula, post-operative haemorrhage and sepsis. CONCLUSIONS: LPD is a technically challenging operation with a steep learning curve. The early oncological outcomes appear satisfactory. It remains to be determined whether the minimally invasive approach to pancreaticoduodenectomy offers benefits to patients.

Synchronous colorectal liver metastases in pregnancy and post-partum.

BACKGROUND: Metastatic colorectal cancer (mCRC) in pregnancy and post-partum is rare, but represents significant diagnostic and therapeutic challenges for clinicians. A multidisciplinary team (MDT) approach is essential. This study reports the first series in the Australasian literature, describing our experience with and management of pregnant and post-partum patients diagnosed with synchronous colorectal liver metastases (sCRLM). METHOD: A retrospective review of prospectively collected data for patients with sCRLM diagnosed during pregnancy or post-partum, presenting to a tertiary referral hospital between 2009 and 2014, was performed. Data regarding patient presentation, imaging, management, histopathology and survival were analysed. Patient characteristics and outcomes were reviewed, including age, presenting complaint and median survival. RESULTS: Five patients were identified with sCRLM: three patients were diagnosed antepartum and two post-partum. Median age was 31 years (range 26-34). All patients were diagnosed with colorectal primary and synchronous liver lesions. All patients received folinic acid, fluorouracil, oxaliplatin chemotherapy, two intrapartum. One patient had both the primary lesion and liver metastases excised early post-partum. Second-line chemotherapy with folinic acid, fluorouracil, irinotecan and other biological agents was used in some cases post-partum. One patient suffered a fetal loss, while the other four had uncomplicated live births. Median survival was 7.6 months, with two patients dying shortly after delivery. CONCLUSION: The diagnosis of mCRC in pregnancy is challenging and survival is poor. A MDT approach to management is essential. Chemotherapy remains the mainstay of treatment from the second trimester. Rapid confirmation of diagnosis and early chemotherapy, followed by post-partum colorectal and liver resection may improve survival.