Magnetic resonance imaging short protocols for intraductal papillary mucinous neoplasm (IPMN) surveillance: The time has come.

BACKGROUND/OBJECTIVES: To analyze the diagnostic performance of three short magnetic resonance imaging (MRI) protocols for the follow-up of pancratic intraductal papillary mucinous neoplasms (IPMN). METHODS: Follow-up MRI examinations of 287 patients with IPMN performed in two centers were retrospectively retrieved. Four MRI protocols were identified as follows: T1-weighted (T1w), T2-weighted (T2w), and MRCP sequences (protocol 1); T1w, T2w, MRCP, and diffusion-weighted (DWI) sequences (protocol 2); T1w, T2w, MRCP, and post-contrast T1w-sequences (protocol 3); and a comprehensive protocol including all previous sequences (protocol 4). Three radiologists with different experience in abdominal imaging expressed their opinion upon the optimal patient's management upon the evaluation of each protocol. Intra-and inter-observer agreement and concordance with the clinical decision expressed by a pancreatic surgeon were calculated with Cohen's kappa test. RESULTS: 223 patients were included (66±10 years; 92 men, 131 women). 143 patients had branch-duct-IPMNs, 25 main-duct-IPMNs and 55 mixed-type-IPMNs. 79 patients underwent surgery, resulting in 52 high-grade dysplasia (HGD) and 27 low-grade dysplasia (LGD). Concordance for the expert reader between protocols 1, 2 and 3 and the actual clinical decision were 0.63, 0.72, and 0.74 respectively (95% CI, 0.53-0.73, 0.63-0.81, and 0.65-0.83). Inter-observer agreement between reader 1 and reader 2, reader 1 and reader 3, and reader 2 and reader 3 were: 0.71, 0.50, and 0.75 for protocol 1 (95% CI, 0.63-0.81, 0.40-0.60, and 0.66-0.84);0.68, 0.54, and 0.84 for protocol 2 (95% CI, 0.59-0.77, 0.44-0.64, and 0.76-0.91); and 0.77, 0.65, and 0.86 for protocol 3 (95% CI, 0.69-0.86, 0.55-0.74, and 0.80-0.93). CONCLUSIONS: Short MRI protocol is suitable for IPMN surveillance.

Prophylactic abdominal drainage after distal pancreatectomy (PANDORINA): an international, multicentre, open-label, randomised controlled, non-inferiority trial.

BACKGROUND: Prophylactic passive abdominal drainage is standard practice after distal pancreatectomy. This approach aims to mitigate the consequences of postoperative pancreatic fistula (POPF) but its added value, especially in patients at low risk of POPF, is currently being debated. We aimed to assess the non-inferiority of a no-drain policy in patients after distal pancreatectomy. METHODS: In this international, multicentre, open-label, randomised controlled, non-inferiority trial, we recruited patients aged 18 years or older undergoing open or minimally invasive elective distal pancreatectomy for all indications in 12 centres in the Netherlands and Italy. We excluded patients with an American Society of Anesthesiology (ASA) physical status of 4-5 or WHO performance status of 3-4, added by amendment following the death of a patient with ASA 4 due to a pre-existing cardiac condition. Patients were randomly assigned (1:1) intraoperatively by permuted blocks (size four to eight) to either no drain or prophylactic passive drain placement, stratified by annual centre volume (<40 or ≥40 distal pancreatectomies) and low risk or high risk of grade B or C POPF. High-risk was defined as a pancreatic duct of more than 3 mm in diameter, a pancreatic thickness at the neck of more than 19 mm, or both, based on the Distal Pancreatectomy Fistula Risk Score. Other patients were considered low-risk. The primary outcome was the rate of major morbidity (Clavien-Dindo score ≥III), and the most relevant secondary outcome was grade B or C POPF, grading per the International Study Group for Pancreatic Surgery. Outcomes were assessed up to 90 days postoperatively and analysed in the intention-to-treat population and per-protocol population, which only included patients who received the allocated treatment. A prespecified non-inferiority margin of 8% was compared with the upper limit of the two-sided 95% CI (Wald) of unadjusted risk difference to assess non-inferiority. This trial is closed and registered in the Netherlands Trial Registry, NL9116. FINDINGS: Between Oct 3, 2020, and April 28, 2023, 376 patients were screened for eligibility and 282 patients were randomly assigned to the no-drain group (n=138; 75 [54%] women and 63 [46%] men) or the drain group (n=144; 73 [51%] women and 71 [49%] men). Seven patients in the no-drain group received a drain intraoperatively; consequently, the per-protocol population included 131 patients in the no-drain group and 144 patients in the drain group. The rate of major morbidity was non-inferior in the no-drain group compared with the drain group in the intention-to-treat analysis (21 [15%] vs 29 [20%]; risk difference -4·9 percentage points [95% CI -13·8 to 4·0]; pnon-inferiority=0·0022) and the per-protocol analysis (21 [16%] vs 29 [20%]; risk difference -4·1 percentage points [-13·2 to 5·0]; pnon-inferiority=0·0045). Grade B or C POPF was observed in 16 (12%) patients in the no-drain group and in 39 (27%) patients in the drain group (risk difference -15·5 percentage points [95% CI -24·5 to -6·5]; pnon-inferiority<0·0001) in the intention-to-treat analysis. Three patients in the no-drain group died within 90 days; the cause of death in two was not considered related to the trial. The third death was a patient with an ASA score of 4 who died after sepsis and a watershed cerebral infarction at second admission, leading to multiple organ failure. No patients in the drain group died within 90 days. INTERPRETATION: A no-drain policy is safe in terms of major morbidity and reduced the detection of grade B or C POPF, and should be the new standard approach in eligible patients undergoing distal pancreatectomy. FUNDING: Ethicon UK (Johnson & Johnson Medical, Edinburgh, UK).

Association of high-risk stigmata and worrisome features with advanced neoplasia in intraductal papillary mucinous neoplasms (IPMN): A systematic review.

BACKGROUND: This systematic review aimed to assess the diagnostic accuracy of the International Consensus Fukuoka Guidelines (ICG2017) in identifying high-risk lesions of Intraductal Papillary Mucinous Neoplasms (IPMNs). METHODS: The ICG2017 revision committee conducted a comprehensive literature review to establish evidence-based statements on IPMNs. The review focused on articles examining the diagnostic value of imaging features (e.g., cyst or main pancreatic duct diameter), clinical symptoms associated with IPMN, and serum biomarkers. Five clinical questions regarding high-risk stigmata (HRS) and worrisome features (WF) in the ICG2017 guidelines were addressed. RESULTS: A total of 210 articles were reviewed. The findings revealed a significant association between the presence of mural nodules ≥5 mm in diameter or solid components with contrast enhancement and the diagnosis of high-grade dysplasia or invasive carcinoma. Contrast-enhanced diagnostic tools, such as CT, MRI, or EUS, demonstrated the highest prediction rate and were recommended. Positive cytology was identified as an HRS, while symptoms like acute pancreatitis and cyst diameter growth ≥2.5 mm per year were considered WFs. The use of nomograms and multiple diagnostic factors was recommended for optimal IPMN management. CONCLUSIONS: This systematic review provides evidence supporting the improved diagnostic accuracy of ICG2017 in identifying high-risk lesions of IPMN. The multidisciplinary incorporation of HRS and WF based on imaging findings and clinical symptoms is crucial. These findings should inform the revision of ICG2017, enhancing the evaluation and management of IPMN patients. By implementing these recommendations, clinicians can make more informed decisions, leading to better diagnosis and treatment outcomes for high-risk IPMN cases.

Radiomics preoperative-Fistula Risk Score (RAD-FRS) for pancreatoduodenectomy: development and external validation.

BACKGROUND: Accurately predicting the risk of clinically relevant postoperative pancreatic fistula after pancreatoduodenectomy before surgery may assist surgeons in making more informed treatment decisions and improved patient counselling. The aim was to evaluate the predictive accuracy of a radiomics-based preoperative-Fistula Risk Score (RAD-FRS) for clinically relevant postoperative pancreatic fistula. METHODS: Radiomic features were derived from preoperative CT scans from adult patients after pancreatoduodenectomy at a single centre in the Netherlands (Amsterdam, 2013-2018) to develop the radiomics-based preoperative-Fistula Risk Score. Extracted radiomic features were analysed with four machine learning classifiers. The model was externally validated in a single centre in Italy (Verona, 2020-2021). The radiomics-based preoperative-Fistula Risk Score was compared with the Fistula Risk Score and the updated alternative Fistula Risk Score. RESULTS: Overall, 359 patients underwent a pancreatoduodenectomy, of whom 89 (25 per cent) developed a clinically relevant postoperative pancreatic fistula. The radiomics-based preoperative-Fistula Risk Score model was developed using CT scans of 118 patients, of which three radiomic features were included in the random forest model, and externally validated in 57 patients. The model performed well with an area under the curve of 0.90 (95 per cent c.i. 0.71 to 0.99) and 0.81 (95 per cent c.i. 0.69 to 0.92) in the Amsterdam test set and Verona data set respectively. The radiomics-based preoperative-Fistula Risk Score performed similarly to the Fistula Risk Score (area under the curve 0.79) and updated alternative Fistula Risk Score (area under the curve 0.79). CONCLUSION: The radiomics-based preoperative-Fistula Risk Score, which uses only preoperative CT features, is a new and promising radiomics-based score that has the potential to be integrated with hospital CT report systems and improve patient counselling before surgery. The model with underlying code is readily available via www.pancreascalculator.com and www.github.com/PHAIR-Consortium/POPF-predictor.

It is not necessary to resect all mucinous cystic neoplasms of the pancreas: current guidelines do not reflect the actual risk of malignancy.

BACKGROUND: Mucinous Cystic Neoplasms (MCN) of the pancreas are premalignant cysts for which current guidelines support pancreatic resection. The primary aim of this systematic review and meta-analysis is to define the pooled rate of malignancy for MCN. METHODS: A systematic review of eligible studies published between 2000 and 2021 was performed on PubMed and Embase. Primary outcome was rate of malignancy. Data regarding high-risk features, including cyst size and mural nodules, were collected and analyzed. RESULTS: A total of 40 studies and 3292 patients with resected MCN were included in the final analysis. The pooled rate of malignancy was 16.1% (95%CI 13.1-19.0). The rate of malignant MCN in studies published before 2012 was significantly higher than that of studies published after recent guidelines were published (21.0% vs 14.9%, p < 0.001). Malignant MCN were larger than benign (mean difference 25.9 mm 95%CI 14.50-37.43, p < 0.001) with a direct correlation between size and presence of malignant MCN (R2 = 0.28, p = 0.020). A SROC identified a threshold of 65 mm to be associated with the diagnosis of malignant MCN. Presence of mural nodules was associated with the diagnosis of a malignant MCN (OR = 4.34, 95%CI 3.00-6.29, p < 0.001). CONCLUSION: Whereas guidelines recommend resection of all MCN, the rate of malignancy in resected MCN is 16%, implying that surveillance has a role in most cases, and that surgical selection criteria are warranted. Size and presence of mural nodules are significantly associated with an increased risk of malignant degeneration, small MCN and without mural nodules can be considered for surveillance.

Early and Sustained Elevation in Serum Pancreatic Amylase Activity: A Novel Predictor of Morbidity After Pancreatic Surgery.

OBJECTIVE: To characterize early postoperative serum pancreatic amylase (spAMY) trends after pancreatic resections. SUMMARY BACKGROUND DATA: A postoperative spAMY elevation is a common finding but uncertainties remain about its meaning and prognostic implications. METHODS: Analysis of patients who consecutively underwent pancreatectomy from 2016 to 2019. spAMY activity was assessed from postoperative day (POD) 0 to 3. Different patterns of spAMY have been identified based on the spAMY standard range (10-52 U/l). RESULTS: Three patterns were identified: (#1) spAMY values always < the lower limit of normal/within the reference range /a single increase in spAMY > upper limit of normal at any POD; (#2) Sustained increase in spAMY activity on POD 0 + 1; (#3) Sustained increase in spAMY activity including POD 1 + 2. Shifting through spAMY patterns was associated with increase morbidity (21% in #1 to 68% in #3 at POD 7; log rank < 0.001). Almost all severe complications (at least Clavien-Dindo ≥3) occurred in patients with pattern #3 (15% vs 3% vs 5% in #1 and #2 at POD 7, P = 0.006), without difference considering >3-times or >the spAMY normal limit ( P = 0.85). POPF (9% in #1 vs 48% in #3, P < 0.001) progressively increased across patterns. Pre-operative diabetes (OR 0.19), neoadjuvant therapy (OR 0.22), pancreatic texture (OR 8.8), duct size (OR 0.78), and final histology (OR 2.2) were independent predictors of pattern #3. CONCLUSIONS: A sustained increase in spAMY activity including POD 1 + 2 (#3) represents an early postoperative predictor of overall and severe early morbidity. An early and dynamic evaluation of spAMY could crucially impact the subsequent clinical course with relevant prognostic implications.

Distal Pancreatectomy Fistula Risk Score (D-FRS): Development and International Validation.

OBJECTIVE: To develop 2 distinct preoperative and intraoperative risk scores to predict postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP) to improve preventive and mitigation strategies, respectively. BACKGROUND: POPF remains the most common complication after DP. Despite several known risk factors, an adequate risk model has not been developed yet. METHODS: Two prediction risk scores were designed using data of patients undergoing DP in 2 Italian centers (2014-2016) utilizing multivariable logistic regression. The preoperative score (calculated before surgery) aims to facilitate preventive strategies and the intraoperative score (calculated at the end of surgery) aims to facilitate mitigation strategies. Internal validation was achieved using bootstrapping. These data were pooled with data from 5 centers from the United States and the Netherlands (2007-2016) to assess discrimination and calibration in an internal-external validation procedure. RESULTS: Overall, 1336 patients after DP were included, of whom 291 (22%) developed POPF. The preoperative distal fistula risk score (preoperative D-FRS) included 2 variables: pancreatic neck thickness [odds ratio: 1.14; 95% confidence interval (CI): 1.11-1.17 per mm increase] and pancreatic duct diameter (OR: 1.46; 95% CI: 1.32-1.65 per mm increase). The model performed well with an area under the receiver operating characteristic curve of 0.83 (95% CI: 0.78-0.88) and 0.73 (95% CI: 0.70-0.76) upon internal-external validation. Three risk groups were identified: low risk (<10%), intermediate risk (10%-25%), and high risk (>25%) for POPF with 238 (18%), 684 (51%), and 414 (31%) patients, respectively. The intraoperative risk score (intraoperative D-FRS) added body mass index, pancreatic texture, and operative time as variables with an area under the receiver operating characteristic curve of 0.80 (95% CI: 0.74-0.85). CONCLUSIONS: The preoperative and the intraoperative D-FRS are the first validated risk scores for POPF after DP and are readily available at: http://www.pancreascalculator.com . The 3 distinct risk groups allow for personalized treatment and benchmarking.

Surgical and Oncological Outcomes After Preoperative FOLFIRINOX Chemotherapy in Resected Pancreatic Cancer: An International Multicenter Cohort Study.

BACKGROUND: Preoperative FOLFIRINOX chemotherapy is increasingly administered to patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) to improve overall survival (OS). Multicenter studies reporting on the impact from the number of preoperative cycles and the use of adjuvant chemotherapy in relation to outcomes in this setting are lacking. This study aimed to assess the outcome of pancreatectomy after preoperative FOLFIRINOX, including predictors of OS. METHODS: This international multicenter retrospective cohort study included patients from 31 centers in 19 European countries and the United States undergoing pancreatectomy after preoperative FOLFIRINOX chemotherapy (2012-2016). The primary end point was OS from diagnosis. Survival was assessed using Kaplan-Meier analysis and Cox regression. RESULTS: The study included 423 patients who underwent pancreatectomy after a median of six (IQR 5-8) preoperative cycles of FOLFIRINOX. Postoperative major morbidity occurred for 88 (20.8%) patients and 90-day mortality for 12 (2.8%) patients. An R0 resection was achieved for 243 (57.4%) patients, and 259 (61.2%) patients received adjuvant chemotherapy. The median OS was 38 months (95% confidence interval [CI] 34-42 months) for BRPC and 33 months (95% CI 27-45 months) for LAPC. Overall survival was significantly associated with R0 resection (hazard ratio [HR] 1.63; 95% CI 1.20-2.20) and tumor differentiation (HR 1.43; 95% CI 1.08-1.91). Neither the number of preoperative chemotherapy cycles nor the use adjuvant chemotherapy was associated with OS. CONCLUSIONS: This international multicenter study found that pancreatectomy after FOLFIRINOX chemotherapy is associated with favorable outcomes for patients with BRPC and those with LAPC. Future studies should confirm that the number of neoadjuvant cycles and the use adjuvant chemotherapy have no relation to OS after resection.

Routine prophylactic abdominal drainage versus no-drain strategy after distal pancreatectomy: A multicenter propensity score matched analysis.

BACKGROUND: /Objectives Postoperative pancreatic fistula (POPF) remains the most common complication after distal pancreatectomy (DP). Traditionally, surgical drains are placed routinely after DP, but some question its efficacy and postulate that the use of drains may convert a self-limiting postoperative collection into a POPF. This study aimed to compare outcomes between three institutions with varying drainage strategies. METHODS: The study is a retrospective propensity score-matched analysis of intraoperative prophylactic drain placement during DP (2010-2019). The primary outcome is major morbidity. Propensity score matching was used to obtain comparable groups. RESULTS: Overall, 963 patients after DP were included. One center did not place a surgical drain routinely, but decided to place a drain when unsatisfactory pancreatic closure occurred. Prophylactic abdominal drains were placed in 805 patients (84%) of which 74 could be matched to 74 patients without a drain. The rate of major morbidity (8% vs 19%, p = 0.054) and radiological interventions (5% vs 12%, p = 0.147) were non-significantly lower in the no-drain group as compared to the prophylactic drain group, respectively. The rates of POPF (4% vs 16%, p = 0.014) were lower in the no-drain group. CONCLUSION: In this international retrospective multicenter study, a selective no-drain strategy after DP was not associated with higher rates major morbidity or radiological interventions as compared to routine prophylactic abdominal drainage. Although the rate of POPF was lower in the no-drain group, randomized trials should confirm the safety and outcome of a no-drain strategy after DP.

Bioethics in an oncological surgery unit during the COVID-19 pandemic: the Verona experience.

The spread of COVID-19 has overwhelmed medical facilities across the globe, with patients filling beds in both regular wards and in intensive care units. The repurposing of hospital facilities has resulted in a dramatic decrease in the capacity of hospitals-in terms of available beds, surgical facilities, and medical and nursing staff- to care for oncology patients. The Italian National Board of Bioethics provided precise and homogeneous guidelines for the allocation of the scarce resources available. In our experience, strictly following these general guidelines and not considering the clinical vocation of each single health care center did not allow us to resume usual activities but generated further confusion in resource allocation. To face the scarcity of available resources and guarantee our patients fair access to the health care system we created a surgical triage with four fundamental steps. We took into consideration " well defined and widely accepted clinical prognostic factors " as stated by the Italian Society of Anesthesia and Resuscitation. We were able to draw up a list of patients giving priority to those who theoretically should have a greater chance of overcoming their critical situation. The age criterion has also been used in the overall evaluation of different cure options in each case, but it has never been considered on its own or outside the other clinical parameters. Although not considered acceptable by many we had to forcefully adopt the criterion of comparison between patients to give priority to those most in need of immediate care.