The preliminary analysis of lymphatic flow around the connective tissues surrounding SMA and SpA elucidates patients' oncological condition in borderline-resectable pancreatic cancer.

BACKGROUND: In pancreatic ductal adenocarcinoma (PDAC), invasion of connective tissues surrounding major arteries is a crucial prognostic factor after radical resection. However, why the connective tissues invasion is associated with poor prognosis is not well understood. MATERIALS AND METHODS: From 2018 to 2020, 25 patients receiving radical surgery for PDAC in our institute were enrolled. HyperEye Medical System (HEMS) was used to examine lymphatic flow from the connective tissues surrounding SMA and SpA and which lymph nodes ICG accumulated in was examined. RESULTS: HEMS imaging revealed ICG was transported down to the paraaortic area of the abdominal aorta along SMA. In pancreatic head cancer, 9 paraaortic lymph nodes among 14 (64.3%) were ICG positive, higher positivity than LN#15 (25.0%) or LN#18 (50.0%), indicating lymphatic flow around the SMA was leading directly to the paraaortic lymph nodes. Similarly, in pancreatic body and tail cancer, the percentage of ICG-positive LN #16a2 was very high, as was that of #8a, although that of #7 was only 42.9%. CONCLUSIONS: Our preliminary result indicated that the lymphatic flow along the connective tissues surrounding major arteries could be helpful in understanding metastasis and improving prognosis in BR-A pancreatic cancer.

The impact of vascular margin invasion on local recurrence after pancreatoduodenectomy in pancreatic adenocarcinoma.

PURPOSE: Pancreatic ductal adenocarcinoma (PADC) still has nowadays a very impaired long-term survival. Most studies are focused on overall survival; however, local recurrence occurs about up to 50% of cases and seems to be highly related with margin resection status. We aim to analyze the impact of vascular resection margins on local recurrence (LR) and to assess its impact on overall and disease-free survival. METHODS: Eighty out of 191 patients who underwent pancreatoduodenectomy in a university hospital between 2006 and 2021 with PDAC diagnosis were analyzed and vascular margin status specifically addressed. Univariate and multivariate were performed. Time to LR was compared by using the Kaplan-Meier method and prognostic factors assessed using Cox regression hazards model. RESULTS: LR appeared in 10 (50%) of the overall R1 resections in the venous margin and 9 (60%) in the arterial one. Time to LR was significantly shorter when any margin was overall affected (23.2 vs 44.7 months, p = 0.01) and specifically in the arterial margin involvement (13.7 vs 32.1 months, p = 0.009). Overall R1 resections (HR 2.61, p = 0.013) and a positive arterial margin (HR 2.84, p = 0.012) were associated with local recurrence on univariate analysis, whereas arterial positive margin remained significant on multivariate analysis (HR 2.70, p = 0.031). CONCLUSIONS: Arterial margin invasion is correlated in our cohort with local recurrence. Given the limited ability to modify this margin intraoperatively, preoperative therapies should be considered to improve local margin clearance.

Current considerations on intraductal papillary neoplasms of the bile duct and pancreatic duct.

Pancreatobiliary intraductal papillary neoplasms (IPNs) represent precursors of pancreatic cancer or bile duct cholangiocarcinoma that can be detected and treated. Despite advances in diagnostic methods, identifying these premalignant lesions is still challenging for treatment providers. Modern imaging, biomarkers and molecular tests for genomic alterations can be used for diagnosis and follow-up. Surgical intervention in combination with new chemotherapeutic agents is considered the optimal treatment for malignant cases. The balance between the risk of malignancy and any risk of resection guides management policy; therefore, treatment should be individualized based on a meticulous preoperative assessment of high-risk stigmata. IPN of the bile duct is more aggressive; thus, early diagnosis and surgery are crucial. The conservative management of low-risk pancreatic branch-duct lesions is safe and effective.

Preoperative pancreatic stent placement before the enucleation of insulinoma located in the head and neck of the pancreas in proximity to the main pancreatic duct: study protocol for a multicentre randomised clinical trial in Chinese tertiary medical centres.

INTRODUCTION: The surgical intervention approach to insulinomas in proximity to the main pancreatic duct remains controversial. Standard pancreatic resection is recommended by several guidelines; however, enucleation (EN) still attracts surgeons with less risk of late exocrine/endocrine insufficiency, despite a higher postoperative pancreatic fistula (POPF) rate. Recently, the efficacy and safety of preoperative pancreatic stent placement before the EN have been demonstrated. Thus, a multicentre open-label study is being conducted to evaluate the efficacy and safety of stent placement in improving the outcome of EN of insulinomas in proximity to the main pancreatic duct. METHODS AND ANALYSIS: This is a prospective, randomised, open-label, superiority clinical trial conducted at multiple tertiary centres in China. The major eligibility criterion is the presence of insulinoma located in the head and neck of the pancreas in proximity (≤2 mm) to the main pancreatic duct. Blocked randomisation will be performed to allocate patients into the stent EN group and the direct EN group. Patients in the stent EN group will go through stent placement by the endoscopist within 24 hours before the EN surgery, whereas other patients will receive EN surgery directly. The primary outcome is the assessment of the superiority of stent placement in reducing POPF rate measured by the International Study Group of Pancreatic Surgery standard. Both interventions will be performed in an inpatient setting and regular follow-up will be performed. The primary outcome (POPF rate) will be tested for superiority with the Χ2 test. The difference in secondary outcomes between the two groups will be analysed using appropriate tests. ETHICS AND DISSEMINATION: The study has been approved by the Peking Union Medical College Hospital Institutional Review Board (K23C0195), Ruijin Hospital Ethics Committee (2023-314), Peking University First Hospital Ethics Committee (2024033-001), Institutional Review Board of Xuanwu Hospital of Capital Medical University (2023223-002), Ethics Committee of the First Affiliated Hospital of Xi'an Jiaotong University (XJTU1AF2023LSK-473), Institutional Review Board of Tongji Medical College Tongji Hospital (TJ-IRB202402059), Ethics Committee of Tongji Medical College Union Hospital (2023-0929) and Shanghai Cancer Center Institutional Review Board (2309282-16). The results of the study will be published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05523778.

Prognostic value of combined psoas muscle mass and controlling nutritional status in patients with pancreatic ductal adenocarcinoma: a retrospective cohort study.

BACKGROUND: Pancreatic ductal carcinoma (PDAC) is an extremely poor prognostic disease. Even though multidisciplinary treatment for PDAC has developed, supportive therapies, such as nutritional therapy or perioperative rehabilitation to sustain and complete aggressive treatment, have not yet been well-established in PDAC. The aim of this study was to elucidate the relationship between the combined index using psoas muscle mass index (PMI) values and controlling nutritional status (CONUT) score and prognosis. METHODS: We included 101 patients diagnosed with PDAC who underwent radical pancreatectomy with regional lymphadenectomy. The cut-off value was set at the first quartile (male, 6.3 cm2/m2; female 4.4 cm2/m2), and patients were classified into high PMI and low PMI groups. A CONUT score of 0 to 1 was classified as the normal nutritional status group, and 2 or more points as the malnutritional status group. Patients were further divided into three groups: high PMI and normal nutrition (good general condition group), low PMI and low nutrition (poor general condition group), and none of the above (moderate general condition group). We performed a prognostic analysis of overall survival (OS), stratified according to PMI values and CONUT scores. RESULTS: In the poor general condition group, the proportion of elderly people over 70 years of age was significantly higher than that in the other groups (p < 0.001). The poor general condition group had a significantly worse prognosis than the good and moderate general condition groups (p = 0.012 and p = 0.037). The 5-year survival rates were 10.9%, 22.3%, and 36.1% in the poor, moderate, and good general condition groups, respectively. In multivariate analysis, poor general condition, with both low PMI and malnutrition status, was an independent poor prognostic factor for postoperative OS (hazard ratio 2.161, p = 0.031). CONCLUSIONS: The combination of PMI and CONUT scores may be useful for predicting the prognosis of patients with PDAC after radical surgery.

Pancreatic head resection for carcinoma of the ampulla vateri - better long-term prognosis, but more postoperative complications.

BACKGROUND: Pancreatoduodenectomies are complex surgical procedures with a considerable morbidity and mortality even in high-volume centers. However, postoperative morbidity and long-term oncological outcome are not only affected by the surgical procedure itself, but also by the underlying disease. The aim of our study is an analysis of pancreatoduodenectomies for patients with pancreatic ductal adenocarcinoma (PDAC) and ampullary carcinoma (CAMP) concerning postoperative complications and long-term outcome in a tertiary hospital in Germany. METHODS: The perioperative and oncological outcome of 109 pancreatic head resections performed for carcinoma of the ampulla vateri was compared to the outcome of 518 pancreatic head resections for pancreatic ductal adenocarcinoma over a 20 year-period from January 2002 until December 2021. All operative procedures were performed at the University Hospital Freiburg, Germany. Patient data was analyzed retrospectively, using a prospectively maintained SPSS database. Propensity score matching was performed to adjust for differences in surgical and reconstruction technique. Primary outcome of our study was long-term overall survival, secondary outcomes were postoperative complications and 30-day postoperative mortality. Postoperative complications like pancreatic fistula (POPF), postpancreatectomy hemorrhage (PPH) and delayed gastric emptying (DGE) were graded following current international definitions. Survival was estimated using Kaplan Meier curves and log-rank tests. A p-value < 0.05 was considered statistically significant. RESULTS: Operation time was significantly longer in PDAC patients (432 vs. 391 min, p < 0.001). The rate of portal vein resections was significantly higher in PDAC patients (p < 0.001). In CAMP patients, a pancreatogastrostomy as reconstruction technique was performed more frequently compared to PDAC patients (48.6% vs. 29.9%, p < 0.001) and there was a trend towards more laparoscopic surgeries in CAMP patients (p = 0.051). After propensity score matching, we found no difference in DGE B/C and PPH B/C (p = 0.389; p = 0.517), but a significantly higher rate of clinically relevant pancreatic fistula (CR-POPF) in patients with pancreatoduodenectomies due to ampullary carcinoma (30.7% vs. 16.8%, p < 0.001). Long-term survival was significantly better in CAMP patients (42 vs. 24 months, p = 0.003). CONCLUSION: Patients with pancreatoduodenectomies due to ampullary carcinomas showed a better long-term oncological survival, by reason of the better prognosis of this tumor entity. However, these patients often needed a more elaborated postoperative treatment due to the higher rate of clinically relevant pancreatic fistula in this group.

Predicting postoperative prognosis of pancreatic cancer using a computed tomography-based radio-clinical model: exploring biologic functions.

Computed tomography (CT) imaging has the potential to assist in predicting the prognosis and treatment strategies for pancreatic cancer (PC). This study aimed to develop and validate a radio-clinical model based on preoperative multiphase CT assessments to predict the overall survival (OS) of PC and identify differentially expressed genes associated with OS. METHODS: Patients with PC who had undergone radical pancreatectomy (R0 resection) were divided into development and external validation sets. Independent predictors of OS were identified using Cox regression analyses and included in the nomogram, which was externally validated. The area under the curve was used to measure the model's accuracy in estimating OS probability. RNA sequencing data from The Cancer Genome Atlas were used for gene expression analysis. RESULTS: In the development and external validation sets, survival was estimated respectively for 132 and 27 patients. Multivariate Cox regression analysis identified 5 independent OS predictors: age (P = .049), sex (P = .001), bilirubin level (P = .005), tumor size (P = .020), and venous invasion (P = .041). These variables were incorporated into the nomogram. Patients were divided into high- and low-risk groups for OS and survival curves showed that all patients in the low-risk group had better OS than that of those in the high-risk group (P < .001). Differentially expressed genes in patients with a poor prognosis were involved in neuroactive ligand-receptor interaction. CONCLUSION: The radio-clinical model may be clinically useful for successfully predicting PC prognosis.

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.

Defining distal splenopancreatectomy by the mesopancreas.

BACKGROUND: The implementation of the pathologic CRM (circumferential resection margin) staging system for pancreatic head ductal adenocarcinomas (hPDAC) resulted in a dramatic increase of R1 resections at the dorsal resection margin, presumably because of the high rate of mesopancreatic fat (MP) infiltration. Therefore, mesopancreatic excision (MPE) during pancreatoduodenectomy has recently been promoted and has demonstrated better local disease control, fueling the discussion of neoadjuvant downsizing regimes in MP + patients. However, it is unknown to what extent the MP is infiltrated in patients with distal pancreatic (tail/body) carcinomas (dPDAC). It is also unknown if the MP infiltration status affects surgical margin control in distal pancreatectomy (DP). The aim of our study was to histopathologically analyze MP infiltration and elucidate the influence of resection margin clearance on recurrence and survival in patients with dPDAC. Furthermore, the results were compared to a collective receiving MPE for hPDAC. METHOD: Clinicopathological and survival parameters of 295 consecutive patients who underwent surgery for PDAC (n = 63 dPDAC and n = 232 hPDAC) were evaluated. The CRM evaluation was performed in a standardized fashion and the specimens were examined according to the Leeds pathology protocol (LEEPP). The MP area was histopathologically evaluated for cancerous infiltration. RESULTS: In 75.4% of dPDAC patients the MP fat was infiltrated by vital tumor cells. The rates of MP infiltration and R0CRM- resections were similar between dPDAC and hPDAC patients (p = 0.497 and 0.453 respectively). MP- infiltration status did not correlate with CRM implemented resection status in dPDAC patients (p = 0.348). In overall survival analysis, resection status and MP status remained prognostic factors for survival. In follow up analysis. surgical margin clearance in dPDAC patients was associated with a significant improvement in local recurrence rates (5.2% in R0CRM- resected vs. 33.3 in R1/R0CRM + resected, p = 0.002). CONCLUSION: While resection margin status was not affected by the MP status in dPDAC patients, the high MP infiltration rate, as well as improved survival in MP- dPDAC patients after R0CRM- resection, justify mesopancreatic excision during splenopancreatectomy. Larger scale studies are urgently needed to validate our results and to study the effect on neoadjuvant treatment in dPDAC patients.

Quality of life after pancreatic surgery.

BACKGROUND: Pancreatic surgery is challenging owing to the anatomical characteristics of the pancreas. Increasing attention has been paid to changes in quality of life (QOL) after pancreatic surgery. AIM: To summarize and analyze current research results on QOL after pancreatic surgery. METHODS: A systematic search of the literature available on PubMed and EMBASE was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Relevant studies were identified by screening the references of retrieved articles. Studies on patients' QOL after pancreatic surgery published after January 1, 2012, were included. These included prospective and retrospective studies on patients' QOL after several types of pancreatic surgeries. The results of these primary studies were summarized inductively. RESULTS: A total of 45 articles were included in the study, of which 13 were related to pancreaticoduodenectomy (PD), seven to duodenum-preserving pancreatic head resection (DPPHR), nine to distal pancreatectomy (DP), two to central pancreatectomy (CP), and 14 to total pancreatectomy (TP). Some studies showed that 3-6 months were needed for QOL recovery after PD, whereas others showed that 6-12 months was more accurate. Although TP and PD had similar influences on QOL, patients needed longer to recover to preoperative or baseline levels after TP. The QOL was better after DPPHR than PD. However, the superiority of the QOL between patients who underwent CP and PD remains controversial. The decrease in exocrine and endocrine functions postoperatively was the main factor affecting the QOL. Minimally invasive surgery could improve patients' QOL in the early stages after PD and DP; however, the long-term effect remains unclear. CONCLUSION: The procedure among PD, DP, CP, and TP with a superior postoperative QOL is controversial. The long-term benefits of minimally invasive versus open surgeries remain unclear. Further prospective trials are warranted.

Defining the learning curve for robotic pancreaticoduodenectomy for a single surgeon following experience with laparoscopic pancreaticoduodenectomy.

Robotic pancreaticoduodenectomy (RPD) has a learning curve of approximately 30-250 cases to reach proficiency. The learning curve for laparoscopic pancreaticoduodenectomy (LPD) at Duke University was previously defined as 50 cases. This study describes the RPD learning curve for a single surgeon following experience with LPD. LPD and RPD were retrospectively analyzed. Continuous pathologic and perioperative metrics were compared and learning curve were defined with respect to operative time using CUSUM analysis. Seventeen LPD and 69 RPD were analyzed LPD had an inverted learning curve possibly accounting for proficiency attained during the surgeon's fellowship and acquisition of new skills coinciding with more complex patient selection. The learning curve for RPD had three phases: accelerated early experience (cases 1-10), skill consolidation (cases 11-40), and improvement (cases 41-69), marked by reduction in operative time. Compared to LPD, RPD had shorter operative time (379 vs 479 min, p < 0.005), less EBL (250 vs 500, p < 0.02), and similar R0 resection. RPD also had improved LOS (7 vs 10 days, p < 0.007), and lower rates of surgical site infection (10% vs 47%, p < 0.002), DGE (19% vs 47%, p < 0.03), and readmission (13% vs 41%, p < 0.02). Experience in LPD may shorten the learning curve for RPD. The gap in surgical quality and perioperative outcomes between LPD and RPD will likely widen as exposure to robotics in General Surgery, Hepatopancreaticobiliary, and Surgical Oncology training programs increase.

Nomogram model for predicting early recurrence for resectable pancreatic cancer: A multicenter study.

Pancreatic cancer is a highly aggressive malignancy that is characterized by early metastasis, high recurrence, and therapy resistance. Early recurrence after surgery is one of the important reasons affecting the prognosis of pancreatic cancer. This study aimed to establish an accurate preoperative nomogram model for predicting early recurrence (ER) for resectable pancreatic adenocarcinoma. We retrospectively analyzed patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma between January 2011 and December 2020. The training set consisted of 604 patients, while the validation set included 222 patients. Survival was estimated using Kaplan-Meier curves. The factors influencing early recurrence of resectable pancreatic cancer after surgery were investigated, then the predictive model for early recurrence was established, and subsequently the predictive model was validated based on the data of the validation group. The preoperative risk factors for ER included a Charlson age-comorbidity index ≥ 4 (odds ratio [OR]: 0.628), tumor size > 3.0 cm on computed tomography (OR: 0.628), presence of clinical symptoms (OR: 0.515), carbohydrate antigen 19-9 > 181.3 U/mL (OR 0.396), and carcinoembryonic antigen > 6.01 (OR: 0.440). The area under the curve (AUC) of the predictive model in the training group was 0.711 (95% confidence interval: 0.669-0.752), while it reached 0.730 (95% CI: 0.663-0.797) in the validation group. The predictive model may enable the prediction of the risk of postoperative ER in patients with resectable pancreatic ductal adenocarcinoma, thereby optimizing preoperative decision-making for effective treatment.

Prognostic significance of systemic immune-inflammation index in patients with nonfunction pancreatic neuroendocrine tumor undergoing surgical resection.

PURPOSE: The purpose of our study was to investigate the clinical significance and prognostic role of the systemic immune-inflammation index (SII) in patients who underwent surgical resection for nonfunctioning pancreatic neuroendocrine tumors (pNETs). METHODS: We conducted a retrospective analysis of 364 patients with nonfunctioning pNETs. The association between the SII level and clinical parameters was investigated. The receiver operating characteristic (ROC) curve was used to calculate the optimal SII value. Cox proportional hazard analysis was performed to evaluate the prognostic factors. RESULTS: Our study included 364 patients with nonfunctioning pNETs who underwent surgery. The median age was 51.0 (43.0, 59.3), and 164 (45.1%) were male. The optimal threshold of SII determined by ROC analysis was 523.95. Higher SII levels were significantly associated with older age (p = 0.001), sex (p = 0.011), tumor size (p = 0.032), and tumor grade (p = 0.002). Recurrence was observed in 70 (19.2%) patients following a median follow-up of 98 months. Univariate analysis showed that higher SII (p < 0.0001), tumor size >4 cm (p = 0.015), and G2/G3 grade (p = 0.002) were significantly associated with disease-free survival (DFS). Multivariate analysis revealed that higher SII (HR: 7.35; 95% CI: 3.44, 15.70; p < 0.0001) and G2/G3 grade (HR: 3.11; 95% CI: 1.42, 6.82; p = 0.005) remained significantly associated with tumor recurrence. Furthermore, 46 (12.6%) patients died during the follow-up. Higher SII (HR: 8.43; 95% CI: 3.19, 22.72; p < 0.0001) and G2/G3 grade (HR: 3.16; 95% CI: 1.01, 9.86; p = 0.048) were independent predictors of overall survival (OS) by multivariate analysis. CONCLUSION: In conclusion, our study revealed that a higher SII level was associated with tumor-related features (larger tumor size and advanced grade) and subsequent shorter DFS and OS in patients with nonfunctioning pNETs. These results indicated that the SII could serve as an efficient prognostic biomarker for nonfunctioning pNETs.

Utility of gastrostomy tube placement at the time of pancreaticoduodenectomy.

PURPOSE: The aim of this study is to investigate the utility of gastrostomy tube (G-tube) placement in reducing delayed gastric emptying (DGE) among patients undergoing pancreaticoduodenectomy (PD). METHODS: We retrospectively reviewed consecutive patients undergoing PD from 2015 to 2020 at our institution. Thirty-day patient outcomes including DGE, length of stay (LOS), reoperation rates, and morbidity were analyzed in patients with or without G-tube placement. RESULTS: 128 patients with resectable pancreatic head cancer (54 females, median age 68.50 [59.00-74.00]) underwent PD (66 had G-tube placement and 62 did not). There was no significant difference in the incidence of DGE (n = 17 vs. n = 17, p = 0.612), and LOS between the groups. Postoperative ileus (p = 0.007) was significantly lower while atrial fibrillation (p = 0.037) was higher among the G-tube group. Gastrostomy-related complications (p = 0.001) developed in ten patients: skin-related complications (n = 6), tube dislodgement (n = 3) and clogging (n = 1). Nine patients required reoperation during index admission (n = 4 vs. n = 5, p = 1.000). There was no difference in 30-day readmissions (n = 7 vs. n = 5, p = 0.471) and no difference in 30 or 90-day mortality. CONCLUSION: Gastrostomy tube placement during index PD did not affect the incidence of DGE. However, patients experienced significant morbidities due to G-tube-related complications. Placement of gastrostomy tubes at the index PD offers no clinical benefits.