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.

Predictors of long-term survival after resection of adenocarcinoma arising from intraductal papillary mucinous neoplasm and derivation of a prognostic model: An international multicenter study (ADENO-IPMN study).

BACKGROUND: Predictors of long-term survival after resection of adenocarcinoma arising from intraductal papillary mucinous neoplasms are unknown. This study determines predictors of long-term (>5 years) disease-free survival and recurrence in adenocarcinoma arising from intraductal papillary mucinous neoplasms and derives a prognostic model for disease-free survival. METHODS: Consecutive patients who underwent pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasms in 18 academic pancreatic centers in Europe and Asia between 2010 to 2017 with at least 5-year follow-up were identified. Factors associated with disease-free survival were determined using Cox proportional hazards model. Internal validation was performed, and discrimination and calibration indices were assessed. RESULTS: In the study, 288 patients (median age, 70 years; 52% male) were identified; 140 (48%) patients developed recurrence after a median follow-up of 98 months (interquartile range, 78.4-123), 57 patients (19.8%) developed locoregional recurrence, and 109 patients (37.8%) systemic recurrence. At 5 years after resection, the overall and disease-free survival was 46.5% (134/288) and 35.0% (101/288), respectively. On Cox proportional hazards model analysis, multivisceral resection (hazard ratio, 2.20; 95% confidence interval, 1.06-4.60), pancreatic tail location (hazard ratio, 2.34; 95% confidence interval, 1.22-4.50), poor tumor differentiation (hazard ratio, 2.48; 95% confidence interval, 1.10-5.30), lymphovascular invasion (hazard ratio, 1.74; 95% confidence interval, 1.06-2.88), and perineural invasion (hazard ratio, 1.83; 95% confidence interval, 1.09-3.10) were negatively associated with long-term disease-free survival. The final predictive model incorporated 8 predictors and demonstrated good predictive ability for disease-free survival (C-index, 0.74; calibration, slope 1.00). CONCLUSION: A third of patients achieve long-term disease-free survival (>5 years) after pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasms. The predictive model developed in the current study can be used to estimate the probability of long-term disease-free survival.

Management and outcomes of splenic injuries secondary to blunt trauma in patients presenting to major trauma hospitals in Aotearoa New Zealand.

BACKGROUND: Non-operative management of splenic injuries has significantly increased in the last decade with an increased emphasis on splenic preservation. This shift was assisted by increased availability of angioembolization, however, potential geographical variability in access exists in Aotearoa New Zealand (AoNZ). The aim of this study was to assess the management of splenic injury across AoNZ. METHOD: Five-year retrospective study of all patients admitted to AoNZ hospitals with blunt major trauma and a splenic injury. Patients were identified using the National Trauma Registry and cross-referenced with the National Minimum Data Set to determine their management. The primary outcome was the non-operative rate. RESULTS: Seven hundred seventy-three patients were included. Four hundred sixty-nine presented to a tertiary major trauma hospital and 304 to a secondary major trauma hospital. A difference was found in the rate of non-operative management between tertiary and secondary hospitals (P = 0.019). The rate of non-operative management was similar in mild (P = 0.814) and moderate (P = 0.825) injuries, however, significantly higher in severe injuries in tertiary hospitals (P = 0.009). No difference in mortality rate was found. CONCLUSION: This study found a difference in the management of splenic injuries between tertiary and secondary major trauma hospitals; predominantly due to a higher rate of operative management in patients with severe injuries at secondary hospitals. Despite this, no difference in mortality rate was found between tertiary and secondary hospitals.

Long-term Outcomes following Resection of Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasm (A-IPMN) versus Pancreatic Ductal Adenocarcinoma (PDAC): A Propensity-score Matched Analysis.

OBJECTIVE: The aim of the present study was to compare long-term post-resection oncological outcomes between A-IPMN and PDAC. SUMMARY BACKGROUND DATA: Knowledge of long term oncological outcomes (e.g recurrence and survival data) comparing between adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) and pancreatic ductal adenocarcinoma (PDAC) is scarce. METHODS: Patients undergoing pancreatic resection (2010-2020) for A-IPMN were identified retrospectively from 18 academic pancreatic centres and compared with PDAC patients from the same time-period. Propensity-score matching (PSM) was performed and survival and recurrence were compared between A-IPMN and PDAC. RESULTS: 459 A-IPMN patients (median age,70; M:F,250:209) were compared with 476 PDAC patients (median age,69; M:F,262:214). A-IPMN patients had lower T-stage, lymphovascular invasion (51.4%vs. 75.6%), perineural invasion (55.8%vs. 71.2%), lymph node positivity (47.3vs. 72.3%) and R1 resection (38.6%vs. 56.3%) compared to PDAC(P<0.001). The median survival and time-to-recurrence for A-IPMN versus PDAC were 39.0 versus19.5months (P<0.001) and 33.1 versus 14.8months (P<0.001), respectively (median follow-up,78 vs.73 months). Ten-year overall survival for A-IPMN was 34.6%(27/78) and PDAC was 9%(6/67). A-IPMN had higher rates of peritoneal (23.0 vs. 9.1%, P<0.001) and lung recurrence (27.8% vs. 15.6%, P<0.001) but lower rates of locoregional recurrence (39.7% vs. 57.8%; P<0.001). Matched analysis demonstrated inferior overall survival (P=0.005), inferior disease-free survival (P=0.003) and higher locoregional recurrence (P<0.001) in PDAC compared to A-IPMN but no significant difference in systemic recurrence rates (P=0.695). CONCLUSIONS: PDACs have inferior survival and higher recurrence rates compared to A-IPMN in matched cohorts. Locoregional recurrence is higher in PDAC but systemic recurrence rates are comparable and constituted by their own distinctive site-specific recurrence patterns.

Evidence for molecular subtyping in pancreatic ductal adenocarcinoma: a systematic review.

BACKGROUND: Pancreatic Ductal Adenocarcinoma (PDAC) patients exhibit varied responses to multimodal therapy. RNA gene sequencing has unravelled distinct tumour biology subtypes, forming the focus of this review exploring its impact on survival outcomes. METHODS: A systematic search across PubMed, Medline, Embase, and CINAHL databases targeted studies assessing long-term overall and disease-free survival in PDAC patients with molecular subtyping. RESULTS: Fifteen studies including 2731 patients were identified. Molecular subtyping was performed by RNA sequencing and Immunohistochemistry in 14 studies and by Mass Spectrometry in 1 study. Two main tumour subtypes were identified (classical and basal-like or squamous) with basal like associated with poorer outcomes. Further subtypes were identified in individual studies. Superior survival was seen with classical subtype in all other analyses that compared the classical and basal subtypes. High risk stromal subtypes were identified on further analysis of the stroma and were associated with a worse survival independent of the tumour subtype. CONCLUSION: Molecular subtyping of PDAC specimens can identify patients with high-risk tumour biology and poor survival outcomes. Routine subtyping is limited by the cost of RNA sequencing and the volume of raw data generated which has made its translation into routine clinical practice difficult.

A multicentre prospective evaluation of health-related quality of life and patient related outcomes in pancreatic and peripancreatic cancer: PROMCAN study.

BACKGROUND: The temporal evolution of HRQoL and the importance of other PROs to patients, following resection for pancreatic and peripancreatic malignancy remains unexplored. METHODS: Patients undergoing pancreatic resection between 2021 and 2022 were enrolled from 2 UK HPB centres. Patients completed the EORTC QLQ-C30, QLQ-PAN26 tools and rated 56 PROs preoperatively (T1), at discharge (T2), 6-weeks (T3), 3-months (T4) and 6-months (T5) postoperatively. ANOVA followed by post-hoc analysis was used to examine patterns in HRQoL through time. Multivariable ANOVA was used to identify impact of clinical factors on HRQoL. RESULTS: 63 patients were recruited [median age, 72 (IQR 41-85); 39/63 male]. Physical functioning declined from 70.4 (26.2) at T1 to 53.5 (20.9) at T2 (p = 0.016). Global QoL score increased significantly from 41.0 (23.0) at T2 to 60.0 (26.1) at T5 (p = 0.007), as did role functioning [21.1 (27.9) at T2 to 59.4 (32.8) at T5, p < 0.001]. Chemotherapy status and the postoperative complications did not significantly change HRQoL. General QoL and health were the only PROs rated as 'very important' (scores 7-9) by more than 80 % of participants at five time-points. CONCLUSION: Recuperation of HRQoL measures is seen at 6-months postoperative and was not affected by chemotherapy or postoperative complications. Notably, PROs important to patients varied over time.

A retrospective study of colonoscopic surveillance in the elderly.

BACKGROUND: Aotearoa New Zealand (AoNZ) guidelines suggest surveillance colonoscopy should be carefully considered after age 75. The authors noted a cluster of patients presenting in their 8th and 9th decade of life with a new colorectal cancer (CRC) having previously been declined surveillance colonoscopy. METHODS: A 7-year retrospective analysis was performed of patients who underwent a colonoscopy aged between 71 and 75 years in the period between 2006 and 2012. Kaplan-Meier graphs were created with survival measured from the time of index colonoscopy. Log rank tests were used to determine any difference in survival distribution. Relative risk (RR) was calculated, and 95% confidence intervals (CI) reported. RESULTS: A total of 623 patients met inclusion criteria; 461 (74%) had no indication for surveillance colonoscopy and 162 (26%) had an indication. Of the 162 patients with an indication, 91 (56.2%) underwent surveillance colonoscopies after the age of 75. Twenty-three (3.7%) patients were diagnosed with a new CRC. Eighteen (78.2%) patients diagnosed with a new CRC underwent surgery. The median survival overall was 12.9 years (95% CI 12.2-13.5). This did not differ between patients with (13.1, 95% CI 12.1-14.1) or without (12.6, 95% CI 11.2-14.0) an indication for surveillance. CONCLUSION: This study found one quarter of patients who had a colonoscopy between the ages of 71-75 had an indication for surveillance colonoscopy. Most patients with a new CRC underwent surgery. This study suggests it may be appropriate to update the AoNZ guidelines and consider adopting a risk stratification tool to aid decision making.