Minimally invasive versus open distal pancreatectomy: an individual patient data meta-analysis of two randomized controlled trials

Background: Minimally invasive distal pancreatectomy (MIDP) has been suggested to reduce postoperative outcomes as compared to open distal pancreatectomy (ODP). Recently, the first randomized controlled trials (RCTs) comparing MIDP to ODP were published. This individual patient data meta-analysis compared outcomes after MIDP versus ODP combining data from both RCTs. Methods: A systematic literature search was performed to identify RCTs on MIDP vs. ODP, and individual patient data were harmonized. Primary endpoint was the rate of major (Clavien-Dindo ≥ III) complications. Sensitivity analyses were performed in high-risk subgroups. Results: A total of 166 patients from the LEOPARD and LAPOP RCTs were included. The rate of major complications was 21% after MIDP vs. 35% after ODP (adjusted odds ratio 0.54; p = 0.148). MIDP significantly reduced length of hospital stay (6 vs. 8 days, p = 0.036), and delayed gastric emptying (4% vs. 16%, p = 0.049), as compared to ODP. A trend towards higher rates of postoperative pancreatic fistula was observed after MIDP (36% vs. 28%, p = 0.067). Outcomes were comparable in high-risk subgroups. Conclusion: This individual patient data meta-analysis showed that MIDP, when performed by trained surgeons, may be regarded as the preferred approach for distal pancreatectomy. Outcomes are improved after MIDP as compared to ODP, without obvious downsides in high-risk subgroups

Diploma approach for standardized pathology assessment of distal pancreatectomy specimens

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant cancers. A minority (20%) of PDACs are found in the pancreatic body and tail. Accurate pathology assessment of the pancreatic specimen is essential for providing prognostic information and it may guide further treatment strategies. The recent 8th edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/ UICC) staging system for pancreatic tumors has incorporated significant changes to tumor (pT) stage, which is predominantly based on tumor size. This change emphasizes the importance of careful block selection. Owing to the greater prevalence of tumors in the head of the pancreas, efforts are made to standardize the assessment of pancreatoduodenectomy specimens. However, consensus regarding the macroscopic assessment of distal (i.e., left) pancreatectomy specimens is lacking. The DIPLOMA approach includes the standardized measurement of pancreas and other resected organs, inking of relevant surgical margins and anatomical surfaces without removing covering layers of fat, measurement of tumor size (for T-stage), together with assessment of splenic vessel involvement (and other organs if present). All relevant margins are assessed, and relevant blocks are selected to confirm these parameters microscopically. The current protocol describes a standardized approach to the macroscopic assessment of distal pancreatectomy specimens. This approach was developed during several meetings with pathologists and surgeons during the preparation phase for an international multicenter trial (DIPLOMA, ISRCTN44897265), which focuses on radicality of distal pancreatectomy for pancreatic ductal adenocarcinoma. This standardized approach can be instrumental in the design of studies and will uniform reporting on the outcomes of distal pancreatectomy. The described technique is used in the DIPLOMA trial for pancreatic ductal adenocarcinoma but may also be useful for other indications

The role of 18F-FDG PET/CT in retroperitoneal sarcomas—A multicenter retrospective study

Background: The role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the evaluation of retroperitoneal sarcomas is poorly defined. We evaluated the correlation of maximum standardized uptake value (SUVmax) with pathologic tumor grade in the surgical specimen of primary retroperitoneal dedifferentiated liposarcoma (DDLPS) and leiomyosarcoma (LMS). Methods: Patients with the above histological subtypes in three participating institutions with preoperative 18F-FDG PET/CT scan and histopathological specimen available for review were included. The association between SUVmax and pathological grade was assessed. Correlation between SUVmax and relapse-free survival (RFS) and overall survival (OS) were also studied. Results: Of the total 58 patients, final pathological subtype was DDLPS in 44 (75.9%) patients and LMS in 14 (24.1%) patients. The mean SUVmax was 8.7 with a median 7.1 (range, 2.2–33.9). The tumors were graded I, II, III in 6 (10.3%), 35 (60.3%), and 17 (29.3%) patients, respectively. There was an association of higher histological grade with higher SUVmax (rs = 0.40, p =.002). Increasing SUVmax was associated with worse RFS (p =.003) and OS (p =.003). Conclusion: There is a correlation between SUVmax and pathologic tumor grade; increasing SUVmax was associated with worse OS and RFS, providing a preoperative noninvasive surrogate marker of tumor grade and biological behavior

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

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

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

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 (&lt;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]; p non-inferiority=0·0022) and the per-protocol analysis (21 [16%] vs 29 [20%]; risk difference –4·1 percentage points [–13·2 to 5·0]; p non-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]; p non-inferiority&lt;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 &amp; Johnson Medical, Edinburgh, UK).</p

Prophylactic abdominal drainage after distal pancreatectomy (PANDORINA): an international, multicentre, randomised controlled trial

Background: Prophylactic abdominal drainage is standard practice after distal pancreatectomy (DP). 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 DP. Methods: In this international, multicentre, randomised controlled non-inferiority trial, we recruited patients undergoing elective DP in 12 centres in the Netherlands and Italy. Patient were randomly assigned to either no drain or drain placement. Stratification was performed for patients at low or high risk of POPF, based on the DP fistula risk score (D-FRS). Primary outcome was major morbidity (Clavien-Dindo score ≥3) and the most relevant secondary outcome was grade B/C POPF. Analyses were performed by intention-to-treat. The predefined non-inferiority margin of 8% was compared with the upper limit of the two-sided 95% confidence interval (CI) of absolute difference in both the primary and most relevant secondary outcome. Subgroup analyses were based on the D-FRS. This trial is registered with the Netherlands Trial Registry (NL9116). Findings: Between October 3, 2020 and April 28, 2023, 282 patients undergoing DP were randomised: 138 in the no-drain group and 144 in the drain group. Major morbidity was comparable between groups (21 [15·2%] vs 29 [20·1%], difference -4·9%, 95% CI -13·77 to 3·97, pnon-inferiority = 0·002). The rates of grade B/C POPF (16 [11·6%] vs 39 [27·1%], difference -15·5%, 95% CI -24·51 to -6·49, psuperiority &lt;0·001) and overall complications (46 patients, 33·3% vs 73 patients, 50·7%, p=0·003) were both lower in the no-drain group. The rates of postoperative radiological and endoscopic interventions (14 patients, 10·1% vs 24 patients, 16·7%, p=0·109) and reoperations (6 patients, 4·4% vs 4 patients, 2·8%, p=0·476) were comparable between groups. In the low-risk POPF group (n=81), the no-drain group had a lower major morbidity rate (2 [4·5%] vs 7 [18·9%], difference -14·4, 95% CI -28·42 to -0·38, p=0·040). In the intermediate- and high-risk POPF groups, major morbidity did not differ between the groups. Interpretation: A no-drain policy after DP is non-inferior to drain placement in terms of major morbidity and superior in terms of grade B/C POPF which was reduced by over 50%

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 (&lt;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]; p non-inferiority=0·0022) and the per-protocol analysis (21 [16%] vs 29 [20%]; risk difference –4·1 percentage points [–13·2 to 5·0]; p non-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]; p non-inferiority&lt;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 &amp; Johnson Medical, Edinburgh, UK).</p