Precursor Epithelial Subtypes of Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasms (A-IPMN): Clinicopathological Features, Recurrence and Response to Adjuvant Chemotherapy.

BACKGROUND: The clinico-oncological outcomes of precursor epithelial subtypes of adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) are limited to small cohort studies. Differences in recurrence patterns and response to adjuvant chemotherapy between A-IPMN subtypes are unknown. METHODS: Clincopathological features, recurrence patterns and long-term outcomes of patients undergoing pancreatic resection (2010-2020) for A-IPMN were reported from 18 academic pancreatic centres worldwide. Precursor epithelial subtype groups were compared using uni- and multivariate analysis. RESULTS: In total, 297 patients were included (median age, 70 years; male, 78.9%), including 54 (18.2%) gastric, 111 (37.3%) pancreatobiliary, 80 (26.9%) intestinal and 52 (17.5%) mixed subtypes. Gastric, pancreaticobiliary and mixed subtypes had comparable clinicopathological features, yet the outcomes were significantly less favourable than the intestinal subtype. The median time to recurrence in gastric, pancreatobiliary, intestinal and mixed subtypes were 32, 30, 61 and 33 months. Gastric and pancreatobiliary subtypes had worse overall recurrence (p = 0.048 and p = 0.049, respectively) compared with the intestinal subtype but gastric and pancreatobiliary subtypes had comparable outcomes. Adjuvant chemotherapy was associated with improved survival in the pancreatobiliary subtype (p = 0.049) but not gastric (p = 0.992), intestinal (p = 0.852) or mixed subtypes (p = 0.723). In multivariate survival analysis, adjuvant chemotherapy was associated with a lower likelihood of death in pancreatobiliary subtype, albeit with borderline significance [hazard ratio (HR) 0.56; 95% confidence interval (CI) 0.31-1.01; p = 0.058]. CONCLUSIONS: Gastric, pancreatobiliary and mixed subtypes have comparable recurrence and survival outcomes, which are inferior to the more indolent intestinal subtype. Pancreatobiliary subtype may respond to adjuvant chemotherapy and further research is warranted to determine the most appropriate adjuvant chemotherapy regimens for each subtype.

Invasive intraductal oncocytic papillary neoplasms (IOPN) and adenocarcimoma arising from intraductal papillary mucinous neoplasms (A-IPMN) of the pancreas: comparative analysis of clinicopathological features, patterns of recurrence and survival: a multicentre study.

BACKGROUND: Intraductal oncocytic papillary neoplasms (IOPNs) of the pancreas are now considered a separate entity to intraductal papillary mucinous neoplasms (IPMN). Invasive IOPNs are extremely rare, and their recurrence patterns, response to adjuvant chemotherapy and long-term survival outcomes are unknown. METHODS: Consecutive patients undergoing pancreatic resection (2010-2020) for invasive IOPNs or adenocarcinoma arising from IPMN (A-IPMN) from 18 academic pancreatic centers worldwide were included. Outcomes of invasive IOPNs were compared with A-IPMN invasive subtypes (ductal and colloid A-IPMN). RESULTS: 415 patients were included: 20 invasive IOPN, 331 ductal A-IPMN and 64 colloid A-IPMN. After a median follow-up of 6-years, 45% and 60% of invasive IOPNs had developed recurrence and died, respectively. There was no significant difference in recurrence or overall survival between invasive IOPN and ductal A-IPMN. Overall survival of invasive IOPNs was inferior to colloid A-IPMNs (median time of survival 24.4 months vs. 86.7, months, p = 0.013), but the difference in recurrence only showed borderline significance (median time to recurrence, 22.5 months vs. 78.5 months, p = 0.132). Adjuvant chemotherapy, after accounting for high-risk features, did not reduce rates of recurrence in invasive IOPN (p = 0.443), ductal carcinoma (p = 0.192) or colloid carcinoma (p = 0.574). CONCLUSIONS: Invasive IOPNs should be considered an aggressive cancer with a recurrence rate and prognosis consistent with ductal type A-IPMN.

The utility of synoptic operation reports in colorectal surgery: a systematic review.

PURPOSE: Accurate documentation is crucial in surgical patient care. Synoptic reports (SR) are structured checklist-based reports that offer a standardised alternative to traditional narrative reports (NR). This systematic review aims to assess the completeness of SR compared to NR in colorectal cancer (CRC) surgery. Secondary outcomes include the time to completion, surgeon satisfaction, educational value, research value, and barriers to implementation. METHODS: Prospective or retrospective studies that assessed SR compared to NR in colorectal cancer surgery procedures were identified through a systematic search of Ovid MEDLINE, Embase (Ovid), CIHNAL Plus with Full Text (EBSCOhost), and Cochrane. One thousand two articles were screened, and eight studies met the inclusion criteria after full-text review of 17 papers. RESULTS: Analysis included 1797 operative reports (NR, 729; SR, 1068). Across studies reporting this outcome, the completeness of documentation was significantly higher in SR (P < 0.001). Reporting of secondary outcomes was limited, with a predominant focus on research value. Several studies demonstrated significantly reduced data extraction times when utilising SR. Surgeon satisfaction with SR was high, and these reports were seen as valuable tools for research and education. Barriers to implementation included integrating SR into existing electronic medical records (EMR) and surgeon concerns regarding increased administrative burden. CONCLUSIONS: SR offer advantages in completeness, data extraction, and communication compared to NR. Surgeons perceive them as beneficial for research, quality improvement, and teaching. This review supports the necessity for development of user-friendly SR that seamlessly integrate into pre-existing EMRs, optimising patient care and enhancing the quality of CRC surgical documentation.

Standardizing process in acute biliary disease.

INTRODUCTION: The perioperative management of biliary disease (BD) is variable across institutions with suboptimal outcomes for patients and health care systems. This results in inefficient utilization of limited resources. The aim of the current study was to identify modifiable factors impacting patients' time to theater, intraoperative time, and time to discharge as the constituents of length of stay to guide creation of a perioperative management protocol to address this variability. METHODS: Data were prospectively captured at Christchurch Hospital for all adult patients presenting for cholecystectomy between May 2015 and May 2022. Pre, post, and intraoperative factors were assessed for their impact on time to theater, operative time, and postoperative hours to discharge. RESULTS: Four thousand five hundred seventy-seven patients underwent cholecystectomy during the study period, of which 2807 (61%) were acute presentations and made up the cohort for analysis. Time to theater was significantly impacted by preoperative imaging type, while operative grade and the procedure type had the most clinically significant impact on operative time. Postoperatively time to discharge was significantly impacted by drain placement. CONCLUSIONS: Standardizing management of BD would likely result in significant savings for the health care system and improved outcomes for patients. The data seen here evidence the importance of appropriate imaging selection, intraoperative difficulty operative grade identification, and low suction drain selection. These data have been incorporated in a perioperative management protocol as standardization of care across the patient workflow in BD is a sensible approach for ensuring optimal use of scarce resources.

Adjuvant chemotherapy for adenocarcinoma arising from intraductal papillary mucinous neoplasia: multicentre ADENO-IPMN study.

BACKGROUND: The clinical impact of adjuvant chemotherapy after resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia is unclear. The aim of this study was to identify factors related to receipt of adjuvant chemotherapy and its impact on recurrence and survival. METHODS: This was a multicentre retrospective study of patients undergoing pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia between January 2010 and December 2020 at 18 centres. Recurrence and survival outcomes for patients who did and did not receive adjuvant chemotherapy were compared using propensity score matching. RESULTS: Of 459 patients who underwent pancreatic resection, 275 (59.9%) received adjuvant chemotherapy (gemcitabine 51.3%, gemcitabine-capecitabine 21.8%, FOLFIRINOX 8.0%, other 18.9%). Median follow-up was 78 months. The overall recurrence rate was 45.5% and the median time to recurrence was 33 months. In univariable analysis in the matched cohort, adjuvant chemotherapy was not associated with reduced overall (P = 0.713), locoregional (P = 0.283) or systemic (P = 0.592) recurrence, disease-free survival (P = 0.284) or overall survival (P = 0.455). Adjuvant chemotherapy was not associated with reduced site-specific recurrence. In multivariable analysis, there was no association between adjuvant chemotherapy and overall recurrence (HR 0.89, 95% c.i. 0.57 to 1.40), disease-free survival (HR 0.86, 0.59 to 1.30) or overall survival (HR 0.77, 0.50 to 1.20). Adjuvant chemotherapy was not associated with reduced recurrence in any high-risk subgroup (for example, lymph node-positive, higher AJCC stage, poor differentiation). No particular chemotherapy regimen resulted in superior outcomes. CONCLUSION: Chemotherapy following resection of adenocarcinoma arising from intraductal papillary mucinous neoplasia does not appear to influence recurrence rates, recurrence patterns or survival.

Best supportive care in advanced pancreas cancer: a systematic review to define a patient-care bundle.

BACKGROUND: The majority of patients with pancreatic adenocarcinoma (PDAC) have advanced disease at presentation, preventing treatment with curative intent. Management of these patients is often provided by surgical teams for whom there are a lack of widely accepted strategies for care. The aim of this study was to conduct a systematic review to identify key issues in patients with advanced PDAC and integrate the evidence to form a care bundle checklist for use in surgical clinics. METHODS: A systematic review of the literature was performed regarding best supportive care for advanced PDAC according to the PRISMA guidelines. Interventions pertaining to supportive care were included whilst preventative and curative treatments were excluded. A narrative review was planned. RESULTS: Forty-four studies were assessed and four themes were developed: (i) Pain is an undertreated symptom, requiring escalating analgesics and sometimes invasive modalities. (ii) Health-related quality of life necessitates optimisation by involving family, carers and multi-disciplinary teams. (iii) Malnutrition and weight loss can be mitigated with early assessment, replacement therapies and resistance exercise. (iv) Biliary and duodenal obstruction can often be relieved by endoscopic/radiological interventions with surgery rarely required. CONCLUSION: This is the first systematic review to evaluate the different types of interventions utilized during best supportive care in patients with advanced PDAC. It provides a comprehensive care bundle for surgeons that informs management of the common issues experienced by patients within a multidisciplinary environment.

Textbook outcomes for liver resection: can a medium sized centre have acceptable outcomes?

BACKGROUND: Textbook outcome (TO) is an objective, composite measure of clinical outcomes in surgery. TO in liver surgery has been used in previous international studies to define and compare performance across centres. This study aimed to review TO rates following liver resection at a single institution. The secondary aim was to use a CuSum analysis to evaluate monitoring of performance quality over time for colorectal cancer liver metastases (CRCLM). METHODS: All patients undergoing liver resection for benign and malignant causes from Christchurch Hospital hepatobiliary unit between 2005 and 2022 were included. Textbook outcomes measures were the absence of; intraoperative incidents, Clavien-Dindo >3 complication, 90 day re-admission, 90 day mortality, R1 resection, and post-operative bile leak/liver failure. Sequential CuSum analysis was performed to review achievement of TO in liver resections for colorectal cancer liver metastases (CRCLM). RESULTS: Four hundred and seventy-eight patients were included in this study, 54 had resection for benign pathology, 290 for CRCLM and 134 for other malignancies. TO was achieved in 74% of cases overall, with rates for benign, CRCLM and other malignancy being 82%, 73% and 74% respectively (P = 0.405). CuSum analysis documented a deterioration in performance after patient 60, with return to baseline by end of study period. CONCLUSIONS: TO for liver resection in a medium sized centre in New Zealand are comparable to published rates. It is possible to use process control techniques like CuSum with the binary result of TO to monitor performance, providing opportunity for continuous improvement in surgical units.

Risk of Recurrence after Surgical Resection for Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasia (IPMN) with Patterns of Distribution and Treatment: An International, Multicentre, Observational Study.

OBJECTIVE: This international multicentre cohort study aims to identify recurrence patterns and treatment of first and second recurrence in a large cohort of patients after pancreatic resection for adenocarcinoma arising from IPMN. SUMMARY BACKGROUND DATA: Recurrence patterns and treatment of recurrence post resection of adenocarcinoma arising from IPMN are poorly explored. METHOD: Patients undergoing pancreatic resection for adenocarcinoma from IPMN between January 2010 to December 2020 at 18 pancreatic centres were identified. Survival analysis was performed by the Kaplan-Meier log rank test and multivariable logistic regression by Cox-Proportional Hazards modelling. Endpoints were recurrence (time-to, location, and pattern of recurrence) and survival (overall survival and adjusted for treatment provided). RESULTS: Four hundred and fifty-nine patients were included (median, 70 y; IQR, 64-76; male, 54 percent) with a median follow-up of 26.3 months (IQR, 13.0-48.1 mo). Recurrence occurred in 209 patients (45.5 percent; median time to recurrence, 32.8 months, early recurrence [within 1 y], 23.2 percent). Eighty-three (18.1 percent) patients experienced a local regional recurrence and 164 (35.7 percent) patients experienced distant recurrence. Adjuvant chemotherapy was not associated with reduction in recurrence (HR 1.09;P=0.669) One hundred and twenty patients with recurrence received further treatment. The median survival with and without additional treatment was 27.0 and 14.6 months (P<0.001), with no significant difference between treatment modalities. There was no significant difference in survival between location of recurrence (P=0.401). CONCLUSION: Recurrence after pancreatic resection for adenocarcinoma arising from IPMN is frequent with a quarter of patients recurring within 12 months. Treatment of recurrence is associated with improved overall survival and should be considered.

Clinical validation of the international study group of pancreatic surgery (ISGPS) definition for post-pancreatectomy acute pancreatitis.

BACKGROUND: The diagnosis of postoperative or post-pancreatectomy acute pancreatitis (PPAP) is controversial. In 2021, the International Study Group of Pancreatic Surgery (ISGPS) published the first unifying definition and grading system for PPAP. This study sought to validate recent consensus criteria, using a cohort of patients undergoing pancreaticoduodenectomy (PD) in a high-volume pancreaticobiliary specialty unit. METHODS: All consecutive patients undergoing PD at a tertiary referral centre between January 2016 and December 2021 were retrospectively reviewed. Patients with serum amylase recorded within 48h from surgery were included for analysis. Postoperative data were extracted and evaluated against the ISGPS criteria, including the presence of postoperative hyperamylasaemia, radiologic features consistent with acute pancreatitis, and clinical deterioration. RESULTS: A total of 82 patients were evaluated. The overall incidence of PPAP was 32% (26/82) in this cohort, of which 3/26 demonstrated postoperative hyperamylasaemia and 23/26 had clinically relevant PPAP (Grade B or C) when correlated radiologic and clinical criteria. CONCLUSIONS: This study is among the first to apply the recently published consensus criteria for PPAP diagnosis and grading to clinical data. While the results support their utility in establishing PPAP as a distinct post-pancreatectomy complication, there remains a need for future large-scale validation studies.

The artery first technique: re-examining the critical view of safety during laparoscopic cholecystectomy.

INTRODUCTION: Significant discrepancies exist between surgeon-documented and actual rates of critical view of safety (CVS) achievement on retrospective review following laparoscopic cholecystectomy. This discrepancy may be due to surgeon utilisation of the artery first technique (AFT), an exception to the CVS first described by Strasberg et al. The present study aims to characterise the use of the AFT, hypothesising it is used as an adjunct in difficult dissections to maximise exposure of the hepato-cystic triangle ensuring safe cholecystectomy. METHODS: Prospective digital recording of the operative procedure of patients' undergoing laparoscopic cholecystectomy were undertaken at Christchurch Public Hospital, New Zealand and North Shore Private Hospital, Sydney, Australia. Videos were uploaded to Touch Surgery™ Enterprise. Difficulty was graded, annotated and indications for the AFT quantified using a standardised protocol. RESULTS: A total of 275 annotated procedures were included in this study. The AFT was employed in 54 (20%) patients; in 13 (24%) patients for bleeding, in 35 (65%) patients where windows one and two were visible, and in 6 (11%) patients no windows were visible within the hepato-cystic triangle. There were significant differences in utilisation across operative grade and by seniority of operator (p < 0.005). CONCLUSIONS: The data presented here demonstrate the AFT is frequently used, particularly with Grade 3 cholecystectomy. However, more data are needed to confirm the utility and safety of this approach. Analysis of the AFT shows that to understand and improve safety in laparoscopic cholecystectomy appreciating how the operation was undertaken and not just that the CVS was achieved is crucial.

Usability survey of an inpatient electronic clinical communication platform at a large New Zealand tertiary hospital.

BACKGROUND: Internationally, there is significant published literature indicating low levels of clinical satisfaction with the digital electronic clinical record. Many New Zealand hospitals are currently undergoing a process of digitisation. The aim of the current study was to determine the usability of the inpatient clinical documentation and communication platform known as Cortex approximately one year after full deployment at Christchurch Hospital. METHODS: Te Whatu Ora - Health New Zealand Waitaha Canterbury staff were invited via their work email to complete an online questionnaire. It was comprised of the System Usability Scale (SUS) survey (industry standard mean scores: 50-69 marginal, and ≥70 acceptable) and one additional question about the participant's clinical profession within the organisation. RESULTS: A total of 144 responses were received during the study period. The median SUS score was 75 with an interquartile range (IQR) of 60-87.5. The median IQR SUS scores did not significantly differ among the different occupation groups: 78 (65-90) for doctors; 70 (57.5-82.5) for nurses; and 73 (55.6-84.4) for allied health staff (p=0.268). Additionally, 70 qualitative responses were recorded. Three themes were identified through the analysis of the participants' responses. These were: the need for integration with other electronic systems; implementation issues; and fine-tuning the functionality of Cortex. CONCLUSIONS: The current study revealed good usability of Cortex. The user experience was equivalent among the various professions of the study's participants (doctors, nurses, and allied health staff). The present study provides a useful benchmark for Cortex at a point-of-time, and it sets up potential to periodically repeat this survey to see how new functionality has added to (or detracted from) its usability.

Use of prospective video analysis to understand the impact of technical difficulty on operative process during laparoscopic cholecystectomy.

BACKGROUND: An understanding of the impact of operative difficulty on operative process in laparoscopic cholecystectomy is lacking. The aim of the present study was to prospectively analyse digitally recorded laparoscopic cholecystectomy to assess the impact of operative technical difficulty on operative process. METHODS: Video of laparoscopic cholecystectomy procedures performed at Christchurch Hospital, NZ and North Shore Private Hospital, Sydney Australia were prospectively recorded. Using a framework derived from a previously published standard process video was annotated using a standardized template and stratified by operative grade to evaluate the impact of grade on operative process. RESULTS: 317 patients had their laparoscopic cholecystectomy operations prospectively recorded. Seventy one percent of these videos (n = 225) were annotated. Single ICC of operative grade was 0.760 (0.663-0.842 p < 0.010). Median operative time, rate of operative errors significantly increased and rate of CVS decreased with increasing operative grade. Significant differences in operative anatomy, operative process and instrumentation were seen with increasing grade. CONCLUSION: Operative technical difficulty is accurately predicted by operative grade and this impacts on operative process with significant implications for both surgeons and patients. Consequently operative grade should be documented routinely as part of a culture of safe laparoscopic cholecystectomy.

Perioperative interventions to reduce pancreatic fistula following pancreatoduodenectomy: meta-analysis.

BACKGROUND: Data on interventions to reduce postoperative pancreatic fistula (POPF) following pancreatoduodenectomy (PD) are conflicting. The aim of this study was to assimilate data from RCTs. METHODS: MEDLINE and Embase databases were searched systematically for RCTs evaluating interventions to reduce all grades of POPF or clinically relevant (CR) POPF after PD. Meta-analysis was undertaken for interventions investigated in multiple studies. A post hoc analysis of negative RCTs assessed whether these had appropriate statistical power. RESULTS: Among 22 interventions (7512 patients, 55 studies), 12 were assessed by multiple studies, and subjected to meta-analysis. Of these, external pancreatic duct drainage was the only intervention associated with reduced rates of both CR-POPF (odds ratio (OR) 0.40, 95 per cent c.i. 0.20 to 0.80) and all-POPF (OR 0.42, 0.25 to 0.70). Ulinastatin was associated with reduced rates of CR-POPF (OR 0.24, 0.06 to 0.93). Invagination (versus duct-to-mucosa) pancreatojejunostomy was associated with reduced rates of all-POPF (OR 0.60, 0.40 to 0.90). Most negative RCTs were found to be underpowered, with post hoc power calculations indicating that interventions would need to reduce the POPF rate to 1 per cent or less in order to achieve 80 per cent power in 16 of 34 (all-POPF) and 19 of 25 (CR-POPF) studies respectively. CONCLUSION: This meta-analysis supports a role for several interventions to reduce POPF after PD. RCTs in this field were often relatively small and underpowered, especially those evaluating CR-POPF.

Clinical features and postoperative survival in patients with sporadic versus multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors: An international cohort study.

BACKGROUND: The optimal surgical management of pancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1 is controversial. This study sought to compare clinicopathologic characteristics and outcomes of multiple endocrine neoplasia type 1-associated and sporadic pancreatic neuroendocrine tumors from a large multi-national database. METHODS: A multi-institutional, international database of patients with surgically resected pancreatic neuroendocrine tumors was analyzed. The cohort was divided into 2 groups: those with multiple endocrine neoplasia type 1 versus those with sporadic disease. Clinicopathologic comparisons were made. Overall and disease-free survival were analyzed. Propensity score matching was used to reduce bias. RESULTS: Of 651 patients included, 45 (6.9%) had multiple endocrine neoplasia type 1 and 606 sporadic pancreatic neuroendocrine tumors. Multiple endocrine neoplasia type 1-associated pancreatic neuroendocrine tumors were more common in younger patients and associated with multifocal disease at the time of surgery and higher T-stage. Lymph node involvement and the presence of metastasis were similar. Total pancreatectomy rate was 5-fold higher in the multiple endocrine neoplasia type 1 cohort. Median survival did not differ (disease-free survival 126 months multiple endocrine neoplasia type 1 vs 198 months sporadic, P > .5). After matching, survival remained similar (overall survival not reached in either cohort, disease-free survival 126 months multiple endocrine neoplasia type 1 vs 198 months sporadic, P > .5). Equivalence in overall survival and disease-free survival persisted even when patients who underwent subtotal and total pancreatectomy were excluded. CONCLUSION: Multiple endocrine neoplasia type 1-associated pancreatic neuroendocrine tumors are more common in younger patients and are associated with multifocality and higher T-stage. Survival for patients with multiple endocrine neoplasia type 1-associated pancreatic neuroendocrine tumors is comparable to those with sporadic pancreatic neuroendocrine tumors, even in the absence of radical pancreatectomy. Consideration should be given to parenchymal-sparing surgery to preserve pancreatic function.