Adjuvant chemotherapy omission after pancreatic cancer resection: a French nationwide study.

BACKGROUND: Adjuvant chemotherapy (AC) improves the prognosis after pancreatic ductal adenocarcinoma (PDAC) resection. However, previous studies have shown that a large proportion of patients do not receive or complete AC. This national study examined the risk factors for the omission or interruption of AC. METHODS: Data of all patients who underwent pancreatic surgery for PDAC in France between January 2012 and December 2017 were extracted from the French National Administrative Database. We considered "omission of adjuvant chemotherapy" (OAC) all patients who failed to receive any course of gemcitabine within 12 postoperative weeks and "interruption of AC" (IAC) was defined as less than 18 courses of AC. RESULTS: A total of 11 599 patients were included in this study. Pancreaticoduodenectomy was the most common procedure (76.3%), and 31% of the patients experienced major postoperative complications. OACs and IACs affected 42% and 68% of the patients, respectively. Ultimately, only 18.6% of the cohort completed AC. Patients who underwent surgery in a high-volume centers were less affected by postoperative complications, with no impact on the likelihood of receiving AC. Multivariate analysis showed that age ≥ 80 years, Charlson comorbidity index (CCI) ≥ 4, and major complications were associated with OAC (OR = 2.19; CI95%[1.79-2.68]; OR = 1.75; CI95%[1.41-2.18] and OR = 2.37; CI95%[2.15-2.62] respectively). Moreover, age ≥ 80 years and CCI 2-3 or ≥ 4 were also independent risk factors for IAC (OR = 1.54, CI95%[1.1-2.15]; OR = 1.43, CI95%[1.21-1.68]; OR = 1.47, CI95%[1.02-2.12], respectively). CONCLUSION: Sequence surgery followed by chemotherapy is associated with a high dropout rate, especially in octogenarian and comorbid patients.

Clinical impact of high-quality testing for peritoneal lavage cytology in pancreatic cancer.

In pancreatic ductal adenocarcinoma (PDAC) patients, the importance of peritoneal lavage cytology, which indicates unresectability, remains controversial. This study sought to determine whether positive peritoneal lavage cytology (CY+) precludes pancreatectomy. Furthermore, we propose a novel liquid biopsy using peritoneal lavage fluid to detect viable peritoneal tumor cells (v-PTCs) with TelomeScan F35, a telomerase-specific replication-selective adenovirus engineered to express green fluorescent protein. Resectable cytologically or histologically proven PDAC patients (n = 53) were enrolled. CY was conducted immediately following laparotomy. The resulting fluid was examined by conventional cytology (conv-CY; Papanicolaou staining and MOC-31 immunostaining) and by the novel technique (Telo-CY; using TelomeScan F35). Of them, 5 and 12 were conv-CY+ and Telo-CY+, respectively. All underwent pancreatectomy. The two double-CY+ (conv-CY+ and Telo-CY+) patients showed early peritoneal recurrence (P-rec) postoperatively, despite adjuvant chemotherapy. None of the three conv-CY+ Telo-CY- patients exhibited P-rec. Six of the 10 Telo-CY+ conv-CY- patients (60%) relapsed with P-rec. Of the remaining 38 double-CY- [conv-CY-, Telo-CY-, conv-CY± (Class III)] patients, 3 (8.3%) exhibited P-rec. Although conv-CY+ status predicted poor prognosis and a higher risk of P-rec, Telo-CY was more sensitive for detecting v-PTC. Staging laparoscopy and performing conv-CY and Telo-CY are needed to confirm the indication for pancreatectomy.

Successful surgical management of pancreatic torsion in a 3-month-old Bernese Mountain dog without evidence of long-term pancreatic dysfunction.

To describe the clinical presentation, diagnosis, perioperative management and the short- and long-term outcomes of a dog diagnosed with pancreatic torsion. A 3-month-old female intact Bernese Mountain dog presented for an acute onset of vomiting, anorexia and abdominal pain. Abdominal ultrasonography showed a hypoechoic mass effect cranial to the stomach. A pancreatic torsion was diagnosed during exploratory laparotomy and treated with partial pancreatectomy. Histopathology confirmed pancreatic torsion. The patient recovered uneventfully and pancreatic function and inflammation testing that was performed 14 months postoperatively showed no evidence of ongoing dysfunction. This is the first report that demonstrates long-term follow-up with pancreatic function testing in a patient who had a partial pancreatectomy due to pancreatic torsion. There was no evidence of long-term pancreatic dysfunction due to partial pancreatectomy secondary to pancreatic torsion. Additionally, this is the youngest patient with pancreatic torsion to be described in the veterinary literature.

Assessing quality of hepato-pancreato-biliary surgery: nationwide benchmarking.

BACKGROUND: Clinical auditing is a powerful tool to evaluate and improve healthcare. Deviations from the expected quality of care are identified by benchmarking the results of individual hospitals using national averages. This study aimed to evaluate the use of quality indicators for benchmarking hepato-pancreato-biliary (HPB) surgery and when outlier hospitals could be identified. METHODS: A population-based study used data from two nationwide Dutch HPB audits (DHBA and DPCA) from 2014 to 2021. Sample size calculations determined the threshold (in percentage points) to identify centres as statistical outliers, based on current volume requirements (annual minimum of 20 resections) on a two-year period (2020-2021), covering mortality rate, failure to rescue (FTR), major morbidity rate and textbook/ideal outcome (TO) for minor liver resection (LR), major LR, pancreaticoduodenectomy (PD) and distal pancreatectomy (DP). RESULTS: In total, 10 963 and 7365 patients who underwent liver and pancreatic resection respectively were included. Benchmark and corresponding range of mortality rates were 0.6% (0 -3.2%) and 3.3% (0-16.7%) for minor and major LR, and 2.7% (0-7.0%) and 0.6% (0-4.2%) for PD and DP respectively. FTR rates were 5.4% (0-33.3%), 14.2% (0-100%), 7.5% (1.6%-28.5%) and 3.1% (0-14.9%). For major morbidity rate, corresponding rates were 9.8% (0-20.5%), 28.1% (0-47.1%), 36% (15.8%-58.3%) and 22.3% (5.2%-46.1%). For TO, corresponding rates were 73.6% (61.3%-94.4%), 54.1% (35.3-100), 46.8% (25.3%-59.4%) and 63.3% (30.7%-84.6%). Mortality rate thresholds indicating a significant outlier were 8.6% and 15.4% for minor and major LR and 14.2% and 8.6% for PD and DP. For FTR, these thresholds were 17.9%, 31.6%, 22.9% and 15.0%. For major morbidity rate, these thresholds were 26.1%, 49.7%, 57.9% and 52.9% respectively. For TO, lower thresholds were 52.5%, 32.5%, 25.8% and 41.4% respectively. Higher hospital volumes decrease thresholds to detect outliers. CONCLUSION: Current event rates and minimum volume requirements per hospital are too low to detect any meaningful between hospital differences in mortality rate and FTR. Major morbidity rate and TO are better candidates to use for benchmarking.

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries.

BACKGROUND: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide. METHODS: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters. RESULTS: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 per cent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 per cent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 per cent; however, it was 41 per cent in low-to-middle- compared with 19 per cent in very high-HDI countries. CONCLUSION: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761).

Pancreatic surgery can sometimes lead to health problems afterwards. Although some top hospitals report good results, it is not clear how patients are doing all over the world. The aim was to find out how people are recovering after pancreatic surgery in different countries, and to see whether where they live affects their health outcomes after pancreatic surgery. The health records of 4223 patients from 67 countries who had pancreatic surgery in a 3-month interval in 2021 were studied, especially looking at how many people faced serious complications or passed away within 90 days of the surgery. Almost 7 in 10 patients faced some health problems after operation. The chance of having a major health issue or dying after the surgery was higher in countries with fewer resources and less developed healthcare. For example, 10 of 100 patients died after the surgery in these countries, but only 5 of 100 patients did in richer countries. What stands out is that countries with fewer resources have a tougher time getting patients back to health when things go wrong after surgery. It is hoped that doctors and medical groups worldwide can work together to improve these outcomes and give everyone the best chance of recovering well after pancreatic surgery.

Textbook outcome after pancreatoduodenectomy and distal pancreatectomy with postoperative hyperamylasemia-a propensity score matching analysis.

PURPOSE: Postoperative serum hyperamylasemia (POH) is a part of the new, increasingly highlighted, definition for postpancreatectomy pancreatitis (PPAP). This study aimed to analyze whether the biochemical changes of PPAP are differently associated with postoperative complications after distal pancreatectomy (DP) compared with pancreatoduodenectomy (PD). The textbook outcome (TO) was used as a summary measure to capture real-world data. METHODS: The data were retrospectively extracted from a prospective clinical database. Patients with POH, defined as levels above our institution's upper limit of normal on postoperative day 1, after DP and the corresponding propensity score-matched cohort after PD were evaluated on postoperative complications by using logistic regression analyses. RESULTS: We analyzed 723 patients who underwent PD and DP over a period of 9 years. After propensity score matching, 384 patients (192 patients in each group) remained. POH was observed in 78 (41.1%) and 74 (39.4%) after PD and DP correspondingly. There was a significant increase of postoperative complications in the PD group: Clavien-Dindo classification system ≥3 (P < .01 vs P = .71), clinically relevant postoperative pancreatic fistula (P < .001 vs P = .2), postpancreatectomy hemorrhage (P < .001 vs P = .11), and length of hospital stay (P < .001 vs P = .69) if POH occurred compared with in the DP group. TO was significantly unlikely in cases with POH after PD compared with DP (P > .001 vs P = .41). Furthermore, POH was found to be an independent predictor for missing TO after PD (odds ratio [OR], 0.29; 95% CI, 0.14-0.60; P < .001), whereas this was not observed in patients after DP (OR, 0.53; 95% CI, 0.21-1.33; P = .18). CONCLUSION: As a part of the definition for PPAP, POH is a predictive indicator associated with postoperative complications after PD but not after DP.

Influence of aberrant right hepatic artery on survival after pancreatic resection for ductal adenocarcinoma of the pancreatic head.

PURPOSE: The presence of an aberrant right hepatic artery (aRHA), arising from the superior mesenteric artery, is a common variant of the liver vascular anatomy. Considering that tumor spread occurs along vessels, the question arises, whether the presence of an aRHA influences the oncologic outcome after resection for cancer of the pancreatic head. METHODS: Patients with ductal adenocarcinoma of the pancreatic head, who underwent resection from 2011 to 2020 at the Frankfurt University Hospital, Germany, were analyzed retrospectively. Surgical records and computed tomography imaging were reviewed for the presence of aRHA. Overall and disease-free survival as well as hepatic recurrence were analyzed according to the presence of aRHA. RESULTS: aRHA was detected in 21 out of 145 patients (14.5%). The median overall survival was 26 months (95%CI 20.8-34.4), median disease-free survival was 12.1 months (95%CI 8.1-17.3). There was no significant difference in overall survival (26.1 versus 21.4 months, adjusted hazard ratio 1.31, 95%CI 0.7-2.46, p = 0.401) or disease-free survival (14.5 months versus 12 months, adjusted hazard ratio 0.98, 95%CI 0.57-1.71, p = 0.957) without and with aRHA. The hepatic recurrence rate was 24.4.% with conventional anatomy versus 30.8% with aRHA (adjusted odds ratio 1.36, 95%CI 0.3-5.38, p = 0.669). In the multivariable analysis, only lymphatic vessel invasion was an independent prognostic factor for hepatic recurrence. CONCLUSIONS: The presence of an aRHA does not seem to influence the long-term survival and hepatic recurrence after resection for ductal adenocarcinoma of the pancreatic head.

Optimizing prediction models for pancreatic fistula after pancreatectomy: Current status and future perspectives.

Postoperative pancreatic fistula (POPF) is a frequent complication after pancreatectomy, leading to increased morbidity and mortality. Optimizing prediction models for POPF has emerged as a critical focus in surgical research. Although over sixty models following pancreaticoduodenectomy, predominantly reliant on a variety of clinical, surgical, and radiological parameters, have been documented, their predictive accuracy remains suboptimal in external validation and across diverse populations. As models after distal pancreatectomy continue to be progressively reported, their external validation is eagerly anticipated. Conversely, POPF prediction after central pancreatectomy is in its nascent stage, warranting urgent need for further development and validation. The potential of machine learning and big data analytics offers promising prospects for enhancing the accuracy of prediction models by incorporating an extensive array of variables and optimizing algorithm performance. Moreover, there is potential for the development of personalized prediction models based on patient- or pancreas-specific factors and postoperative serum or drain fluid biomarkers to improve accuracy in identifying individuals at risk of POPF. In the future, prospective multicenter studies and the integration of novel imaging technologies, such as artificial intelligence-based radiomics, may further refine predictive models. Addressing these issues is anticipated to revolutionize risk stratification, clinical decision-making, and postoperative management in patients undergoing pancreatectomy.

Prognostic impact of osteosarcopenia in patients undergoing pancreatic resection for pancreatic ductal adenocarcinoma.

BACKGROUND: We investigated the prognostic impact of osteosarcopenia, defined as the combination of osteopenia and sarcopenia, in patients undergoing pancreatic resection for pancreatic ductal adenocarcinoma (PDAC). METHODS: The relationship of osteosarcopenia with disease-free survival and overall survival was analyzed in 183 patients who underwent elective pancreatic resection for PDAC. Computed tomography was used to measure the pixel density in the midvertebral core of the 11th thoracic vertebra for evaluation of osteopenia and in the psoas muscle area of the 3rd lumbar vertebra for evaluation of sarcopenia. Osteosarcopenia was defined as the simultaneous presence of both osteopenia and sarcopenia. The study employed a retrospective design to examine the relationship between osteosarcopenia and survival outcomes. RESULTS: Osteosarcopenia was identified in 61 (33%) patients. In the univariate analysis, disease-free survival was significantly worse in patients with male sex (p = 0.031), pathological stage ≥ III PDAC (p = 0.001), NLR, ≥ 2.71 (p = 0.041), sarcopenia (p = 0.027), osteopenia (p = 0.001), and osteosarcopenia (p < 0.001), and overall survival was significantly worse in patients with male sex (p = 0.001), pathological stage ≥ III PDAC (p = 0.001), distal pancreatectomy (p = 0.025), sarcopenia (p = 0.003), osteopenia (p < 0.001), and osteosarcopenia (p < 0.001). In the multivariate analysis, the independent predictors of disease-free survival were osteosarcopenia (p < 0.001) and pathological stage ≥ III PDAC (p = 0.002), and the independent predictors of overall survival were osteosarcopenia (p < 0.001), male sex (p = 0.006) and pathological stage ≥ III PDAC (p = 0.001). CONCLUSION: Osteosarcopenia has an adverse prognostic impact on long-term outcomes in patients undergoing pancreatic resection for PDAC.

Is the robotic approach the future of distal pancreatectomy with splenectomy? A propensity score matched analysis.

Our study provides a comparative analysis of the Laparo-Endoscopic Single Site (LESS) and robotic surgical approaches for distal pancreatectomy and splenectomy, examining their cosmetic advantages, patient outcomes, and operative efficiencies through propensity score matching (PSM). We prospectively followed 174 patients undergoing either the LESS or robotic procedure, matched by cell type, tumor size, age, sex, and BMI from 2012 to 2023. Propensity score matching (PSM) was utilized for data adjustment, with results presented as median (mean ± SD). Post-PSM analysis showed no significant differences in age or BMI between the two groups. LESS approach exhibited a shorter operative duration (180(180 ± 52.0) vs. 248(262 ± 78.5) minutes, p = 0.0002), but increased estimated blood loss (200(317 ± 394.4) vs. 100 (128 ± 107.2) mL, p = 0.04). Rates of intraoperative and postoperative complications, length of hospital stay, readmissions within 30 days, in-hospital mortalities, and costs were comparably similar between the two procedures. While the robotic approach led to lower blood loss, LESS was more time-efficient. Patient outcomes were similar in both methods, suggesting that the choice between these surgical techniques should balance cosmetic appeal with technical considerations.

Preoperative anaemia in distal pancreatectomy: a propensity-score matched analysis.

BACKGROUND: Preoperative anaemia is a prevalent morbidity predictor that adversely affects short- and long-term outcomes of patients undergoing surgery. This analysis aimed to investigate preoperative anaemia and its detrimental effects on patients after distal pancreatectomy. MATERIAL AND METHODS: The present study was a propensity-score match analysis of 286 consecutive patients undergoing distal pancreatectomy. Patients were screened for preoperative anaemia and classified according to WHO recommendations. The primary outcome measure was overall morbidity. The secondary endpoints were in-hospital mortality and rehospitalization. RESULTS: The preoperative anaemia rate before matching was 34.3% (98 patients), and after matching a total of 127 patients (non-anaemic 42 vs. anaemic 85) were included. Anaemic patients had significantly more postoperative major complications (54.1% vs. 23.8%; p < 0.01), a higher comprehensive complication index (26.2 vs. 4.3; p < 0.01), and higher in-hospital mortality rate (14.1% vs. 2.4%; p = 0.04). Multivariate regression analysis confirmed these findings and identified preoperative anaemia as a strong independent risk factor for postoperative major morbidity (OR 4.047; 95% CI: 1.587-10.320; p < 0.01). CONCLUSION: The current propensity-score matched analysis strongly considered preoperative anaemia as a risk factor for major complications following distal pancreatectomy. Therefore, an intense preoperative anaemia workup should be increasingly prioritised.

Cavitron ultrasonic surgical aspirator (CUSA) compared with conventional pancreatic transection in distal pancreatectomy: study protocol for the randomised controlled CUSA-1 pilot trial.

BACKGROUND: Postoperative pancreatic fistula (POPF) remains the most common and serious complication after distal pancreatectomy. Many attempts at lowering fistula rates have led to unrewarding insignificant results as still up to 30% of the patients suffer from clinically relevant POPF. Therefore, the development of new innovative methods and procedures is still a cornerstone of current surgical research.The cavitron ultrasonic surgical aspirator (CUSA) device is a well-known ultrasound-based parenchyma transection method, often used in liver and neurosurgery which has not yet been thoroughly investigated in pancreatic surgery, but the first results seem very promising. METHODS: The CUSA-1 trial is a randomised controlled pilot trial with two parallel study groups. This single-centre trial is assessor and patient blinded. A total of 60 patients with an indication for open distal pancreatectomy will be intraoperatively randomised after informed consent. The patients will be randomly assigned to either the control group with conventional pancreas transection (scalpel or stapler) or the experimental group, with transection using the CUSA device. The primary safety endpoint of this trial will be postoperative complications ≥grade 3 according to the Clavien-Dindo classification. The primary endpoint to investigate the effect will be the rate of POPF within 30 days postoperatively according to the ISGPS definition. Further perioperative outcomes, including postpancreatectomy haemorrhage, length of hospital stay and mortality will be analysed as secondary endpoints. DISCUSSION: Based on the available literature, CUSA may have a beneficial effect on POPF occurrence after distal pancreatectomy. The rationale of the CUSA-1 pilot trial is to investigate the safety and feasibility of the CUSA device in elective open distal pancreatectomy compared with conventional dissection methods and gather the first data on the effect on POPF occurrence. This data will lay the groundwork for a future confirmatory multicentre randomised controlled trial. ETHICS AND DISSEMINATION: The CUSA-1 trial protocol was approved by the ethics committee of the University of Heidelberg (No. S-098/2022). Results will be published in an international peer-reviewed journal and summaries will be provided in lay language to study participants and their relatives. TRIAL REGISTRATION NUMBER: DRKS00027474.

Short- and long-term outcomes after distal pancreatectomy with radiologic infiltration of splenic vessels for pancreatic ductal adenocarcinoma.

BACKGROUND: The effect of radiologic splenic vessels involvement (RSVI) on the survival of patients with pancreatic adenocarcinoma (PAC) located in the body and tail of the pancreas is controversial, and its influence on postoperative morbidity after distal pancreatectomy (DP) is unknown. This study aimed to determine the influence of RSVI on postoperative complications, overall survival (OS), and disease-free survival (DFS) in patients undergoing DP for PAC. METHODS: A multicenter retrospective study of DP was conducted at 7 hepatopancreatobiliary units between January 2008 and December 2018. Patients were classified according to the presence of RSVI. A Clavien-Dindo grade of >II was considered to represent a major complication. RESULTS: A total of 95 patients were included in the analysis. Moreover, 47 patients had vascular infiltration: 4 had arterial involvement, 10 had venous involvement, and 33 had both arterial and venous involvements. The rates of major complications were 20.8% in patients without RSVI, 40.0% in those with venous RSVI, 25.0% in those with arterial RSVI, and 30.3% in those with both arterial and venous RSVIs (P = .024). The DFS rates at 3 years were 56% in the group without RSVI, 50% in the group with arterial RSVI, and 16% in the group with both arterial and venous RSVIs (P = .003). The OS rates at 3 years were 66% in the group without RSVI, 50% in the group with arterial RSVI, and 29% in the group with both arterial and venous RSVIs (P < .0001). CONCLUSION: RSVI increased the major complication rates after DP and reduced the OS and DFS. Therefore, it may be a useful prognostic marker in patients with PAC scheduled to undergo DP and may help to select patients likely to benefit from neoadjuvant treatment.