The Difficulty of Detecting Occult Metastases in Patients with Potentially Resectable Pancreatic Cancer: Development and External Validation of a Preoperative Prediction Model.

Occult metastases are detected in 10-15% of patients during exploratory laparotomy for pancreatic cancer. This study developed and externally validated a model to predict occult metastases in patients with potentially resectable pancreatic cancer. Model development was performed within the Dutch Pancreatic Cancer Audit, including all patients operated for pancreatic cancer (January 2013-December 2017). Multivariable logistic regression analysis based on the Akaike Information Criteria was performed with intraoperative pathologically proven metastases as the outcome. The model was externally validated with a cohort from the University Hospital of Verona (January 2013-December 2017). For model development, 2262 patients were included of whom 235 (10%) had occult metastases, located in the liver (n = 143, 61%), peritoneum (n = 73, 31%), or both (n = 19, 8%). The model included age (OR 1.02, 95% CI 1.00-1.03), BMI (OR 0.96, 95% CI 0.93-0.99), preoperative nutritional support (OR 1.73, 95% CI 1.01-2.74), tumor diameter (OR 1.60, 95% CI 1.04-2.45), tumor composition (solid vs. cystic) (OR 2.33, 95% CI 1.20-4.35), and indeterminate lesions on preoperative imaging (OR 4.01, 95% CI 2.16-7.43). External validation showed poor discrimination with a C-statistic of 0.56. Although some predictor variables were significantly associated with occult metastases, the model performed insufficiently at external validation.

Early experience with robotic pancreatoduodenectomy versus open pancreatoduodenectomy: nationwide propensity-score-matched analysis.

BACKGROUND: Although robotic pancreatoduodenectomy has shown promising outcomes in experienced high-volume centres, it is unclear whether implementation on a nationwide scale is safe and beneficial. The aim of this study was to compare the outcomes of the early experience with robotic pancreatoduodenectomy versus open pancreatoduodenectomy in the Netherlands. METHODS: This was a nationwide retrospective cohort study of all consecutive patients who underwent robotic pancreatoduodenectomy or open pancreatoduodenectomy who were registered in the mandatory Dutch Pancreatic Cancer Audit (18 centres, 2014-2021), starting from the first robotic pancreatoduodenectomy procedure per centre. The main endpoints were major complications (Clavien-Dindo grade greater than or equal to III) and in-hospital/30-day mortality. Propensity-score matching (1 : 1) was used to minimize selection bias. RESULTS: Overall, 701 patients who underwent robotic pancreatoduodenectomy and 4447 patients who underwent open pancreatoduodenectomy were included. Among the eight centres that performed robotic pancreatoduodenectomy, the median robotic pancreatoduodenectomy experience was 86 (range 48-149), with a 7.3% conversion rate. After matching (698 robotic pancreatoduodenectomy patients versus 698 open pancreatoduodenectomy control patients), no significant differences were found in major complications (40.3% versus 36.2% respectively; P = 0.186), in-hospital/30-day mortality (4.0% versus 3.1% respectively; P = 0.326), and postoperative pancreatic fistula grade B/C (24.9% versus 23.5% respectively; P = 0.578). Robotic pancreatoduodenectomy was associated with a longer operating time (359 min versus 301 min; P < 0.001), less intraoperative blood loss (200 ml versus 500 ml; P < 0.001), fewer wound infections (7.4% versus 12.2%; P = 0.008), and a shorter hospital stay (11 days versus 12 days; P < 0.001). Centres performing greater than or equal to 20 robotic pancreatoduodenectomies annually had a lower mortality rate (2.9% versus 7.3%; P = 0.009) and a lower conversion rate (6.3% versus 11.2%; P = 0.032). CONCLUSION: This study indicates that robotic pancreatoduodenectomy was safely implemented nationwide, without significant differences in major morbidity and mortality compared with matched open pancreatoduodenectomy patients. Randomized trials should be carried out to verify these findings and confirm the observed benefits of robotic pancreatoduodenectomy versus open pancreatoduodenectomy.

Long-term follow-up study of necrotising pancreatitis: interventions, complications and quality of life.

OBJECTIVE: To describe the long-term consequences of necrotising pancreatitis, including complications, the need for interventions and the quality of life. DESIGN: Long-term follow-up of a prospective multicentre cohort of 373 necrotising pancreatitis patients (2005-2008) was performed. Patients were prospectively evaluated and received questionnaires. Readmissions (ie, for recurrent or chronic pancreatitis), interventions, pancreatic insufficiency and quality of life were compared between initial treatment groups: conservative, endoscopic/percutaneous drainage alone and necrosectomy. Associations of patient and disease characteristics during index admission with outcomes during follow-up were assessed. RESULTS: During a median follow-up of 13.5 years (range 12-15.5 years), 97/373 patients (26%) were readmitted for recurrent pancreatitis. Endoscopic or percutaneous drainage was performed in 47/373 patients (13%), of whom 21/47 patients (45%) were initially treated conservatively. Pancreatic necrosectomy or pancreatic surgery was performed in 31/373 patients (8%), without differences between treatment groups. Endocrine insufficiency (126/373 patients; 34%) and exocrine insufficiency (90/373 patients; 38%), developed less often following conservative treatment (p<0.001 and p=0.016, respectively). Quality of life scores did not differ between groups. Pancreatic gland necrosis >50% during initial admission was associated with percutaneous/endoscopic drainage (OR 4.3 (95% CI 1.5 to 12.2)), pancreatic surgery (OR 3.2 (95% CI 1.1 to 9.5) and development of endocrine insufficiency (OR13.1 (95% CI 5.3 to 32.0) and exocrine insufficiency (OR6.1 (95% CI 2.4 to 15.5) during follow-up. CONCLUSION: Acute necrotising pancreatitis carries a substantial disease burden during long-term follow-up in terms of recurrent disease, the necessity for interventions and development of pancreatic insufficiency, even when treated conservatively during the index admission. Extensive (>50%) pancreatic parenchymal necrosis seems to be an important predictor of interventions and complications during follow-up.

Nationwide use and Outcome of Minimally Invasive Distal Pancreatectomy in IDEAL Stage IV following a Training Program and Randomized Trial.

OBJECTIVE: To assess the nationwide long-term uptake and outcomes of minimally invasive distal pancreatectomy (MIDP) after a nationwide training program and randomized trial. BACKGROUND: Two randomized trials demonstrated the superiority of MIDP over open distal pancreatectomy (ODP) in terms of functional recovery and hospital stay. Data on implementation of MIDP on a nationwide level are lacking. METHODS: Nationwide audit-based study including consecutive patients after MIDP and ODP in 16 centers in the Dutch Pancreatic Cancer Audit (2014 to 2021). The cohort was divided into three periods: early implementation, during the LEOPARD randomized trial, and late implementation. Primary endpoints were MIDP implementation rate and textbook outcome. RESULTS: Overall, 1496 patients were included with 848 MIDP (56.5%) and 648 ODP (43.5%). From the early to the late implementation period, the use of MIDP increased from 48.6% to 63.0% and of robotic MIDP from 5.5% to 29.7% ( P <0.001). The overall use of MIDP (45% to 75%) and robotic MIDP (1% to 84%) varied widely between centers ( P <0.001). In the late implementation period, 5/16 centers performed >75% of procedures as MIDP. After MIDP, in-hospital mortality and textbook outcome remained stable over time. In the late implementation period, ODP was more often performed in ASA score III-IV (24.9% vs. 35.7%, P =0.001), pancreatic cancer (24.2% vs. 45.9%, P <0.001), vascular involvement (4.6% vs. 21.9%, P <0.001), and multivisceral involvement (10.5% vs. 25.3%, P <0.001). After MIDP, shorter hospital stay (median 7 vs. 8 d, P <0.001) and less blood loss (median 150 vs. 500 mL, P <0.001), but more grade B/C postoperative pancreatic fistula (24.4% vs. 17.2%, P =0.008) occurred as compared to ODP. CONCLUSION: A sustained nationwide implementation of MIDP after a successful training program and randomized trial was obtained with satisfactory outcomes. Future studies should assess the considerable variation in the use of MIDP between centers and, especially, robotic MIDP.

Uptake of robot-assisted colon cancer surgery in the Netherlands.

BACKGROUND: The robot-assisted approach is now often used for rectal cancer surgery, but its use in colon cancer surgery is less well defined. This study aims to compare the outcomes of robotic-assisted colon cancer surgery to conventional laparoscopy in the Netherlands. METHODS: Data on all patients who underwent surgery for colon cancer from 2018 to 2020 were collected from the Dutch Colorectal Audit. All complications, readmissions, and deaths within 90 days after surgery were recorded along with conversion rate, margin and harvested nodes. Groups were stratified according to the robot-assisted and laparoscopic approach. RESULTS: In total, 18,886 patients were included in the analyses. The operative approach was open in 15.2%, laparoscopic in 78.9% and robot-assisted in 5.9%. The proportion of robot-assisted surgery increased from 4.7% in 2018 to 6.9% in 2020. There were no notable differences in outcomes between the robot-assisted and laparoscopic approach for Elective cT1-3M0 right, left, and sigmoid colectomy. Only conversion rate was consistently lower in the robotic group. (4.6% versus 8.8%, 4.6% versus 11.6%, and 1.6 versus 5.9%, respectively). CONCLUSIONS: This nationwide study on surgery for colon cancer shows there is a gradual but slow adoption of robotic surgery for colon cancer up to 6.9% in 2020. When comparing the outcomes of right, left, and sigmoid colectomy, clinical outcomes were similar between the robotic and laparoscopic approach. However, conversion rate is consistently lower in the robotic procedures.

Predictive value of baseline serum carbohydrate antigen 19-9 level on treatment effect of neoadjuvant chemoradiotherapy in patients with resectable and borderline resectable pancreatic cancer in two randomized trials.

BACKGROUND: Guidelines suggest that the serum carbohydrate antigen (CA19-9) level should be used when deciding on neoadjuvant treatment in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (hereafter referred to as pancreatic cancer). In patients with resectable pancreatic cancer, neoadjuvant therapy is advised when the CA19-9 level is 'markedly elevated'. This study investigated the impact of baseline CA19-9 concentration on the treatment effect of neoadjuvant chemoradiotherapy (CRT) in patients with resectable and borderline resectable pancreatic cancers. METHODS: In this post hoc analysis, data were obtained from two RCTs that compared neoadjuvant CRT with upfront surgery in patients with resectable and borderline resectable pancreatic cancers. The effect of neoadjuvant treatment on overall survival was compared between patients with a serum CA19-9 level above or below 500 units/ml using the interaction test. RESULTS: Of 296 patients, 179 were eligible for analysis, 90 in the neoadjuvant CRT group and 89 in the upfront surgery group. Neoadjuvant CRT was associated with superior overall survival (HR 0.67, 95 per cent c.i. 0.48 to 0.94; P = 0.019). Among 127 patients (70, 9 per cent) with a low CA19-9 level, median overall survival was 23.5 months with neoadjuvant CRT and 16.3 months with upfront surgery (HR 0.63, 0.42 to 0.93). For 52 patients (29 per cent) with a high CA19-9 level, median overall survival was 15.5 months with neoadjuvant CRT and 12.9 months with upfront surgery (HR 0.82, 0.45 to 1.49). The interaction test for CA19-9 level exceeding 500 units/ml on the treatment effect of neoadjuvant CRT was not significant (P = 0.501). CONCLUSION: Baseline serum CA19-9 level defined as either high or low has prognostic value, but was not associated with the treatment effect of neoadjuvant CRT in patients with resectable and borderline resectable pancreatic cancers, in contrast with current guideline advice.

Feasibility, safety, and efficacy of stereotactic body radiotherapy combined with intradermal heat-killed mycobacterium obuense (IMM-101) vaccination for non-progressive locally advanced pancreatic cancer, after induction chemotherapy with (modified)FOLFIRINOX - The LAPC-2 trial.

BACKGROUND AND PURPOSE: In this phase I/II trial, non-progressive locally advanced pancreatic cancer (LAPC) patients after (modified)FOLFIRINOX therapy were treated with stereotactic body radiotherapy (SBRT) combined with heat-killed mycobacterium (IMM-101) vaccinations. We aimed to assess safety, feasibility, and efficacy of this treatment approach. MATERIALS AND METHODS: On five consecutive days, patients received a total of 40 Gray (Gy) of SBRT with a dose of 8 Gy per fraction. Starting two weeks prior to SBRT, they in addition received six bi-weekly intradermal vaccinations with one milligram of IMM-101. The primary outcomes were the number of grade 4 or higher adverse events and the one-year progression free-survival (PFS) rate. RESULTS: Thirty-eight patients were included and started study treatment. Median follow-up was 28.4 months (95 %CI 24.3 - 32.6). We observed one grade 5, no grade 4 and thirteen grade 3 adverse events, none related to IMM-101. The one-year PFS rate was 47 %, the median PFS was 11.7 months (95 %CI 11.0 - 12.5) and the median overall survival was 19.0 months (95 %CI 16.2 - 21.9). Eight (21 %) tumors were resected, of which 6 (75 %) were R0 resections. Outcomes were comparable with the outcomes of the patients from the previous LAPC-1 trial, in which LAPC patients were treated with SBRT, without IMM-101. CONCLUSION: Combination treatment with IMM-101 and SBRT was safe and feasible for non-progressive locally advanced pancreatic cancer patients after (modified)FOLFIRINOX. No improvement in the progression-free survival could be demonstrated by adding IMM-101 to SBRT.

Outcome of Pancreatic Surgery During the First 6 Years of a Mandatory Audit Within the Dutch Pancreatic Cancer Group.

OBJECTIVE: To describe outcome after pancreatic surgery in the first 6 years of a mandatory nationwide audit. BACKGROUND: Within the Dutch Pancreatic Cancer Group, efforts have been made to improve outcome after pancreatic surgery. These include collaborative projects, clinical auditing, and implementation of an algorithm for early recognition and management of postoperative complications. However, nationwide changes in outcome over time have not yet been described. METHODS: This nationwide cohort study included consecutive patients after pancreatoduodenectomy (PD) and distal pancreatectomy from the mandatory Dutch Pancreatic Cancer Audit (January 2014-December 2019). Patient, tumor, and treatment characteristics were compared between 3 time periods (2014-2015, 2016-2017, and 2018-2019). Short-term surgical outcome was investigated using multilevel multivariable logistic regression analyses. Primary endpoints were failure to rescue (FTR) and in-hospital mortality. RESULTS: Overall, 5345 patients were included, of whom 4227 after PD and 1118 after distal pancreatectomy. After PD, FTR improved from 13% to 7.4% [odds ratio (OR) 0.64, 95% confidence interval (CI) 0.50-0.80, P <0.001] and in-hospital mortality decreased from 4.1% to 2.4% (OR 0.68, 95% CI 0.54-0.86, P =0.001), despite operating on more patients with age >75 years (18%-22%, P =0.006), American Society of Anesthesiologists score ≥3 (19%-31%, P <0.001) and Charlson comorbidity score ≥2 (24%-34%, P <0.001). The rates of textbook outcome (57%-55%, P =0.283) and major complications remained stable (31%-33%, P =0.207), whereas complication-related intensive care admission decreased (13%-9%, P =0.002). After distal pancreatectomy, improvements in FTR from 8.8% to 5.9% (OR 0.65, 95% CI 0.30-1.37, P =0.253) and in-hospital mortality from 1.6% to 1.3% (OR 0.88, 95% CI 0.45-1.72, P =0.711) were not statistically significant. CONCLUSIONS: During the first 6 years of a nationwide audit, in-hospital mortality and FTR after PD improved despite operating on more high-risk patients. Several collaborative efforts may have contributed to these improvements.

Outcomes of a Multicenter Training Program in Robotic Pancreatoduodenectomy (LAELAPS-3).

OBJECTIVE: To assess feasibility and safety of a multicenter training program in robotic pancreatoduodenectomy (RPD) adhering to the IDEAL framework for implementation of surgical innovation. BACKGROUND: Good results for RPD have been reported from single center studies. However, data on feasibility and safety of implementation through a multicenter training program in RPD are lacking. METHODS: A multicenter training program in RPD was designed together with the University of Pittsburgh Medical Center, including an online video bank, robot simulation exercises, biotissue drills, and on-site proctoring. Benchmark patients were based on the criteria of Clavien. Outcomes were collected prospectively (March 2016-October 2019). Cumulative sum analysis of operative time was performed to distinguish the first and second phase of the learning curve. Outcomes were compared between both phases of the learning curve. Trends in nationwide use of robotic and laparoscopic PD were assessed in the Dutch Pancreatic Cancer Audit. RESULTS: Overall, 275 RPD procedures were performed in seven centers by 15 trained surgeons. The recent benchmark criteria for low-risk PD were met by 125 (45.5%) patients. The conversion rate was 6.5% (n = 18) and median blood loss 250ml [interquartile range (IQR) 150-500]. The rate of Clavien-Dindo grade ≥III complications was 44.4% (n = 122), postoperative pancreatic fistula (grade B/C) rate 23.6% (n = 65), 90-day complication-related mortality 2.5% (n = 7) and 90-day cancer-related mortality 2.2.% (n = 6). Median postoperative hospital stay was 12 days (IQR 8-20). In the subgroup of patients with pancreatic cancer (n = 80), the major complication rate was 31.3% and POPF rate was 10%. Cumulative sum analysis for operative time found a learning curve inflection point at 22 RPDs (IQR 10-35) with similar rates of Clavien-Dindo grade ≥III complications in the first and second phase (43.4% vs 43.8%, P = 0.956, respectively). During the study period the nationwide use of laparoscopic PD reduced from 15% to 1%, whereas the use of RPD increased from 0% to 25%. CONCLUSIONS: This multicenter RPD training program in centers with sufficient surgical volume was found to be feasible without a negative impact of the learning curve on clinical outcomes.

The risk of not receiving adjuvant chemotherapy after resection of pancreatic ductal adenocarcinoma: a nationwide analysis.

BACKGROUND: The relation between type of postoperative complication and not receiving chemotherapy after resection of pancreatic ductal adenocarcinoma (PDAC) is unclear. The aim was to investigate which patient factors and postoperative complications were associated with not receiving adjuvant chemotherapy. METHODS: Patients who underwent resection (2014-2017) for PDAC were identified from the nationwide mandatory Dutch Pancreatic Cancer Audit. The association between patient-, tumor-, center-, treatment characteristics, and the risk of not receiving adjuvant chemotherapy was analyzed with multivariable logistic regression. RESULTS: Overall, of 1306 patients, 24% (n = 312) developed postoperative Clavien Dindo ≥3 complications. In-hospital mortality was 3.5% (n = 46). Some 433 patients (33%) did not receive adjuvant chemotherapy. Independent predictors (all p < 0.050) for not receiving adjuvant chemotherapy were older age (odds ratio (OR) 0.96), higher ECOG performance status (OR 0.57), postoperative complications (OR 0.32), especially grade B/C pancreatic fistula (OR 0.51) and post-pancreatectomy hemorrhage (OR 0.36), poor tumor differentiation grade (OR 0.62), and annual center volume of <40 pancreatoduodenectomies (OR 0.51). CONCLUSIONS: This study demonstrated that a third of patients do not receive chemotherapy after resection of PDAC. Next to higher age, worse performance status and lower annual surgical volume, this is mostly related to surgical complications, especially postoperative pancreatic fistula and post-pancreatectomy hemorrhage.

Textbook Outcome: Nationwide Analysis of a Novel Quality Measure in Pancreatic Surgery.

BACKGROUND: Textbook outcome (TO) is a multidimensional measure for quality assurance, reflecting the "ideal" surgical outcome. METHODS: Post-hoc analysis of patients who underwent pancreatoduodenectomy (PD) or distal pancreatectomy (DP) for all indications between 2014 and 2017, queried from the nationwide prospective Dutch Pancreatic Cancer Audit. An international survey was conducted among 24 experts from 10 countries to reach consensus on the requirements for TO in pancreatic surgery. Univariable and multivariable logistic regression was performed to identify TO predictors. Between-hospital variation in TO rates was compared using observed-versus-expected rates. RESULTS: Based on the survey (92% response rate), TO was defined by the absence of postoperative pancreatic fistula, bile leak, postpancreatectomy hemorrhage (all ISGPS grade B/C), severe complications (Clavien-Dindo ≥III), readmission, and in-hospital mortality. Overall, 3341 patients were included (2633 (79%) PD and 708 (21%) DP) of whom 60.3% achieved TO; 58.3% for PD and 67.4% for DP. On multivariable analysis, ASA class 3 predicted a worse TO rate after PD (ASA 3 OR 0.59 [0.44-0.80]), whereas a dilated pancreatic duct (>3 mm) and pancreatic ductal adenocarcinoma (PDAC) were associated with a better TO rate (OR 2.22 [2.05-3.57] and OR 1.36 [1.14-1.63], respectively). For DP, female sex and the absence of neoadjuvant therapy predicted better TO rates (OR 1.38 [1.01-1.90] and OR 2.53 [1.20-5.31], respectively). When comparing institutions, the observed-versus-expected rate for achieving TO varied from 0.71 to 1.46 per hospital after casemix-adjustment. CONCLUSIONS: TO is a novel quality measure in pancreatic surgery. TO varies considerably between pancreatic centers, demonstrating the potential benefit of quality assurance programs.

Alternative Fistula Risk Score for Pancreatoduodenectomy (a-FRS): Design and International External Validation.

OBJECTIVE: The aim of this study was to develop an alternative fistula risk score (a-FRS) for postoperative pancreatic fistula (POPF) after pancreatoduodenectomy, without blood loss as a predictor. BACKGROUND: Blood loss, one of the predictors of the original-FRS, was not a significant factor during 2 recent external validations. METHODS: The a-FRS was developed in 2 databases: the Dutch Pancreatic Cancer Audit (18 centers) and the University Hospital Southampton NHS. Primary outcome was grade B/C POPF according to the 2005 International Study Group on Pancreatic Surgery (ISGPS) definition. The score was externally validated in 2 independent databases (University Hospital of Verona and University Hospital of Pennsylvania), using both 2005 and 2016 ISGPS definitions. The a-FRS was also compared with the original-FRS. RESULTS: For model design, 1924 patients were included of whom 12% developed POPF. Three predictors were strongly associated with POPF: soft pancreatic texture [odds ratio (OR) 2.58, 95% confidence interval (95% CI) 1.80-3.69], small pancreatic duct diameter (per mm increase, OR: 0.68, 95% CI: 0.61-0.76), and high body mass index (BMI) (per kg/m increase, OR: 1.07, 95% CI: 1.04-1.11). Discrimination was adequate with an area under curve (AUC) of 0.75 (95% CI: 0.71-0.78) after internal validation, and 0.78 (0.74-0.82) after external validation. The predictive capacity of a-FRS was comparable with the original-FRS, both for the 2005 definition (AUC 0.78 vs 0.75, P = 0.03), and 2016 definition (AUC 0.72 vs 0.70, P = 0.05). CONCLUSION: The a-FRS predicts POPF after pancreatoduodenectomy based on 3 easily available variables (pancreatic texture, duct diameter, BMI) without blood loss and pathology, and was successfully validated for both the 2005 and 2016 POPF definition. The online calculator is available at www.pancreascalculator.com.

Preoperative Oral Antibiotic Prophylaxis Reduces Surgical Site Infections After Elective Colorectal Surgery: Results From a Before-After Study.

BACKGROUND: Surgical site infections (SSIs) are common complications after colorectal procedures and remain an important source of morbidity and costs. Preoperative oral antibiotic prophylaxis is a potential infection control strategy, but its effectiveness without simultaneous use of mechanical bowel preparation (MBP) is unclear. In this study, we aimed to determine whether preoperative oral antibiotics reduce the risk of deep SSIs in elective colorectal surgery. METHODS: We performed a before-after analysis in a teaching hospital in the Netherlands. Patients who underwent surgery between January 2012 and December 2015 were included. On 1 January 2013, oral antibiotic prophylaxis with tobramycin and colistin was implemented as standard of care prior to colorectal surgery. The year before implementation was used as the control period. The primary outcome was a composite of deep SSI and/or mortality within 30 days after surgery. RESULTS: Of the 1410 patients, 352 underwent colorectal surgery in the control period and 1058 in the period after implementation of the antibiotic prophylaxis. We observed a decrease in incidence of the primary endpoint of 6.2% after prophylaxis implementation. When adjusted for confounders, the risk ratio for development of the primary outcome was 0.58 (95% confidence interval, 0.40-0.79). Other findings included a decreased risk of anastomotic leakage and a reduction in the length of postoperative stay. CONCLUSIONS: Preoperative oral antibiotic prophylaxis prior to colorectal surgery is associated with a significant decrease in SSI and/or mortality in a setting without MBP. Preoperative oral antibiotics can therefore be considered without MBP for patients who undergo colorectal surgery.

Superiority of Step-up Approach vs Open Necrosectomy in Long-term Follow-up of Patients With Necrotizing Pancreatitis.

BACKGROUND & AIMS: In a 2010 randomized trial (the PANTER trial), a surgical step-up approach for infected necrotizing pancreatitis was found to reduce the composite endpoint of death or major complications compared with open necrosectomy; 35% of patients were successfully treated with simple catheter drainage only. There is concern, however, that minimally invasive treatment increases the need for reinterventions for residual peripancreatic necrotic collections and other complications during the long term. We therefore performed a long-term follow-up study. METHODS: We reevaluated all the 73 patients (of the 88 patients randomly assigned to groups) who were still alive after the index admission, at a mean 86 months (±11 months) of follow-up. We collected data on all clinical and health care resource utilization endpoints through this follow-up period. The primary endpoint was death or major complications (the same as for the PANTER trial). We also measured exocrine insufficiency, quality of life (using the Short Form-36 and EuroQol 5 dimensions forms), and Izbicki pain scores. RESULTS: From index admission to long-term follow-up, 19 patients (44%) died or had major complications in the step-up group compared with 33 patients (73%) in the open-necrosectomy group (P = .005). Significantly lower proportions of patients in the step-up group had incisional hernias (23% vs 53%; P = .004), pancreatic exocrine insufficiency (29% vs 56%; P = .03), or endocrine insufficiency (40% vs 64%; P = .05). There were no significant differences between groups in proportions of patients requiring additional drainage procedures (11% vs 13%; P = .99) or pancreatic surgery (11% vs 5%; P = .43), or in recurrent acute pancreatitis, chronic pancreatitis, Izbicki pain scores, or medical costs. Quality of life increased during follow-up without a significant difference between groups. CONCLUSIONS: In an analysis of long-term outcomes of trial participants, we found the step-up approach for necrotizing pancreatitis to be superior to open necrosectomy, without increased risk of reinterventions.

Long-term Oncological and Functional Outcomes of Chemoradiotherapy Followed by Organ-Sparing Transanal Endoscopic Microsurgery for Distal Rectal Cancer: The CARTS Study.

Importance: Treatment of rectal cancer is shifting toward organ preservation aiming to reduce surgery-related morbidity. Short-term outcomes of organ-preserving strategies are promising, but long-term outcomes are scarce in the literature. Objective: To explore long-term oncological outcomes and health-related quality of life (HRQL) in patients with cT1-3N0M0 rectal cancer who underwent neoadjuvant chemoradiotherapy (CRT) followed by transanal endoscopic microsurgery (TEM). Design, Setting, and Participants: In this multicenter phase II feasibility study, patients with cT1-3N0M0 rectal cancer admitted to referral centers for rectal cancer throughout the Netherlands between February 2011 and September 2012 were prospectively included. These patients were to be treated with neoadjuvant CRT followed by TEM in case of good response. An intensive follow-up scheme was used to detect local recurrences and/or distant metastases. Data from validated HRQL questionnaires and low anterior resection syndrome questionnaires were collected. Data were analyzed from February 2011 to April 2017. Main Outcomes and Measures: The primary study outcome of the study was the number of ypT0-1 specimens by performing TEM. Secondary outcome parameters were locoregional recurrences and HRQL. Results: Of the 55 included patients, 30 (55%) were male, and the mean (SD) age was 64 (39-82) years. Patients were followed up for a median (interquartile range) period of 53 (39-57) months. Two patients (4%) died during CRT, 1 (2%) stopped CRT, and 1 (2%) was lost to follow-up. Following CRT, 47 patients (85%) underwent TEM, of whom 35 (74%) were successfully treated with local excision alone. Total mesorectal excision was performed in 16 patients (4 with inadequate responses, 8 with completion after TEM, and 4 with salvage for local recurrence). The actuarial 5-year local recurrence rate was 7.7%, with 5-year disease-free and overall survival rates of 81.6% and 82.8%, respectively. Health-related quality of life during follow-up was equal to baseline, with improved emotional well-being in patients treated with local excision (mean score at baseline, 72.0; 95% CI, 67.1-80.1; mean score at follow-up, 86.9; 95% CI, 79.2-94.7; P = .001). Major, minor, and no low anterior resection syndrome was experienced in 50%, 28%, and 22%, respectively, of patients with successful organ preservation. Conclusions and Relevance: In early-stage rectal cancer (cT1-3N0M0), CRT enables organ preservation with additional TEM surgery in approximately two-thirds of patients with good long-term oncological outcome and HRQL. This multimodality treatment triggers a certain degree of bowel dysfunction, and one-third of patients still undergo radical surgery and are overtreated by CRT.

Does robotic rectal cancer surgery improve the results of experienced laparoscopic surgeons? An observational single institution study comparing 168 robotic assisted with 184 laparoscopic rectal resections.

BACKGROUND: The role of robotic assistance in colorectal cancer surgery has not been established yet. We compared the results of robotic assisted with those of laparoscopic rectal resections done by two surgeons experienced in laparoscopic as well as in robotic rectal cancer surgery. METHODS: Two surgeons who were already experienced laparoscopic colorectal surgeons in 2005 started robotic surgery with the daVinci SI system in 2012. All their rectal cancer resections between 2005 and 2015 were retrieved from a prospectively recorded colorectal database of routinely collected patient data. Multi-organ resections were excluded. Patient data, diagnostic data, data on preceding operations and neoadjuvant treatment, perioperative and operative data, logistic data, and short-term outcomes were gathered. Multivariable analyses (multiple linear and logistic regression) were used to assess differences in several outcomes between the two resection methods while adjusting for all potential confounders we could identify. Results are presented as adjusted mean differences for continuous outcome variables or as adjusted odds ratios (OR) for dichotomous outcome variables. RESULTS: Three hundred and fifty-two patients with rectal cancers were identified: 168 robotic and 184 conventional laparoscopic cases, 178 operated by surgeon A and 174 operated by surgeon B. Adjusted mean operation time was 215 min in the robotic group which was 40 min (95% CI 24-56; p < 0.0005) longer than the 175 min in the laparoscopic group. Robotic treatment had significantly lesser numbers of conversions (OR 0.09 (0.03-0.32); p < 0.0005) and other complications (SSI and anastomic leakage excluded) (OR 0.32 (0.15-0.69); p = 0.004), adjusted for potential confounders. CONCLUSIONS: Our study suggests that robotic surgery in the hands of experienced laparoscopic rectal cancer surgeons improves the conversion rate and complication rate drastically compared to conventional laparoscopic surgery, but operation time is longer.

Robot-assisted laparoscopic resection of clinical T4b tumours of distal sigmoid and rectum: initial results.

BACKGROUND: Radical resection by multivisceral resection of colorectal T4 tumours is important to reduce local recurrence and improve survival. Oncological safety of laparoscopic resection of T4 tumours is controversial. However, robot-assisted resections might have advantages, such as 3D view and greater range of motion of instruments. The aim of this study is to evaluate the initial results of robot-assisted resection of T4 rectal and distal sigmoid tumours. METHODS: This is a cohort study of a prospectively kept database of all robot-assisted rectal and sigmoid resections between 2012 and 2017. Patients who underwent a multivisceral resection for tumours appearing as T4 cancer during surgery were included. Rectal and sigmoid resections are routinely performed with the DaVinci robot, unless an indication for intra-operative radiotherapy exists. RESULTS: 28 patients with suspected T4 rectal or sigmoid cancer were included. Most patients (78%) were treated with neoadjuvant chemoradiotherapy (n = 19), short course radiotherapy with long waiting interval (n = 2) or chemotherapy (n = 1). En bloc resection was performed with the complete or part of the invaded organ (prostate, vesicles, bladder, abdominal wall, presacral fascia, vagina, uterus, adnex). In 3 patients (11%), the procedure was converted to laparotomy. Twenty-four R0-resections were performed (86%) and four R1-resections (14%). Median length of surgery was 274 min (IQR 222-354). Median length of stay was 6 days (IQR 5-11). Twelve patients (43%) had postoperative complications: eight (29%) minor complications and four (14%) major complications. There was no postoperative mortality. CONCLUSIONS: Robot-assisted laparoscopy seems to be a feasible option for the resection of clinical T4 cancer of the distal sigmoid and rectum in selected cases. Radical resections can be achieved in the majority of cases. Therefore, T4 tumours should not be regarded as a strict contraindication for robot-assisted surgery.

Variation in hospital mortality after pancreatoduodenectomy is related to failure to rescue rather than major complications: a nationwide audit.

BACKGROUND: In the mandatory nationwide Dutch Pancreatic Cancer Audit, rates of major complications and Failure to Rescue (FTR) after pancreatoduodenectomy between low- and high-mortality hospitals are compared, and independent predictors for FTR investigated. METHODS: Patients undergoing pancreatoduodenectomy in 2014 and 2015 in The Netherlands were included. Hospitals were divided into quartiles based on mortality rates. The rate of major complications (Clavien-Dindo ≥3) and death after a major complication (FTR) were compared between these quartiles. Independent predictors for FTR were identified by multivariable logistic regression analysis. RESULTS: Out of 1.342 patients, 391 (29%) developed a major complication and in-hospital mortality was 4.2%. FTR occurred in 56 (14.3%) patients. Mortality was 0.9% in the first hospital quartile (4 hospitals, 327 patients) and 8.1% in the fourth quartile (5 hospitals, 310 patients). The rate of major complications increased by 40% (25.7% vs 35.2%) between the first and fourth hospital quartile, whereas the FTR rate increased by 560% (3.6% vs 22.9%). Independent predictors of FTR were male sex (OR = 2.1, 95%CI 1.2-3.9), age >75 years (OR = 4.3, 1.8-10.2), BMI ≥30 (OR = 2.9, 1.3-6.6), histopathological diagnosis of periampullary cancer (OR = 2.0, 1.1-3.7), and hospital volume <30 (OR = 3.9, 1.6-9.6). CONCLUSIONS: Variations in mortality between hospitals after pancreatoduodenectomy were explained mainly by differences in FTR, rather than the incidence of major complications.

Randomised controlled trial of transanal endoscopic microsurgery versus endoscopic mucosal resection for large rectal adenomas (TREND Study).

OBJECTIVE: Non-randomised studies suggest that endoscopic mucosal resection (EMR) is equally effective in removing large rectal adenomas as transanal endoscopic microsurgery (TEM), but EMR might be more cost-effective and safer. This trial compares the clinical outcome and cost-effectiveness of TEM and EMR for large rectal adenomas. DESIGN: Patients with rectal adenomas ≥3 cm, without malignant features, were randomised (1:1) to EMR or TEM, allowing endoscopic removal of residual adenoma at 3 months. Unexpected malignancies were excluded postrandomisation. Primary outcomes were recurrence within 24 months (aiming to demonstrate non-inferiority of EMR, upper limit 10%) and the number of recurrence-free days alive and out of hospital. RESULTS: Two hundred and four patients were treated in 18 university and community hospitals. Twenty-seven (13%) had unexpected cancer and were excluded from further analysis. Overall recurrence rates were 15% after EMR and 11% after TEM; statistical non-inferiority was not reached. The numbers of recurrence-free days alive and out of hospital were similar (EMR 609±209, TEM 652±188, p=0.16). Complications occurred in 18% (EMR) versus 26% (TEM) (p=0.23), with major complications occurring in 1% (EMR) versus 8% (TEM) (p=0.064). Quality-adjusted life years were equal in both groups. EMR was approximately €3000 cheaper and therefore more cost-effective. CONCLUSION: Under the statistical assumptions of this study, non-inferiority of EMR could not be demonstrated. However, EMR may have potential as the primary method of choice due to a tendency of lower complication rates and a better cost-effectiveness ratio. The high rate of unexpected cancers should be dealt with in further studies.

Nationwide prospective audit of pancreatic surgery: design, accuracy, and outcomes of the Dutch Pancreatic Cancer Audit.

BACKGROUND: Auditing is an important tool to identify practice variation and 'best practices'. The Dutch Pancreatic Cancer Audit is mandatory in all 18 Dutch centers for pancreatic surgery. METHODS: Performance indicators and case-mix factors were identified by a PubMed search for randomized controlled trials (RCT's) and large series in pancreatic surgery. In addition, data dictionaries of two national audits, three institutional databases, and the Dutch national cancer registry were evaluated. Morbidity, mortality, and length of stay were analyzed of all pancreatic resections registered during the first two audit years. Case ascertainment was cross-checked with the Dutch healthcare inspectorate and key-variables validated in all centers. RESULTS: Sixteen RCT's and three large series were found. Sixteen indicators and 20 case-mix factors were included in the audit. During 2014-2015, 1785 pancreatic resections were registered including 1345 pancreatoduodenectomies. Overall in-hospital mortality was 3.6%. Following pancreatoduodenectomy, mortality was 4.1%, Clavien-Dindo grade ≥ III morbidity was 29.9%, median (IQR) length of stay 12 (9-18) days, and readmission rate 16.0%. In total 97.2% of >40,000 variables validated were consistent with the medical charts. CONCLUSIONS: The Dutch Pancreatic Cancer Audit, with high quality data, reports good outcomes of pancreatic surgery on a national level.