Radical Pancreatectomy Research Articles

Predictors of occult metastases in potentially Resectable pancreatic ductal adenocarcinoma

BackgroundPatients with resectable (R) or borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) sometimes show unexpected liver, peritoneal, and para-aortic lymph node metastases intraoperatively. Despite radical pancreatectomy, a nonnegligible number of patients relapse within 6 months after surgery. The aim of this study was to identify the preoperative predictors of occult metastases (OM), defined as intraoperative distant metastases or within 6 months after pancreatectomy. Materials and methodsThis study included patients with R and BR PDAC who underwent curative-intent pancreatectomy or staging laparoscopy between 2006 and 2021. Multivariate logistic regression and Cox hazard analyses were performed to identify the preoperative predictors of OM and to assess the impact of these factors on prognosis after pancreatectomy. ResultsOf the 279 patients, OM was observed intraoperatively in 47 and postoperatively in 34. In the OM group, there were no differences in prognosis between patients who had intraoperative metastases and recurrence within 6 months (median survival time [MST], 18.1 vs. 12.9 months), and between patients who underwent pancreatectomy and those who did not (MST, 13.9 vs. 18.1 months). Preoperative tumor size ≥22 mm (odds ratio [OR], 2.03; 95 % confidence interval [CI], 1.16–3.53; p = 0.013) and preoperative CA19–9 level ≥ 118.8 U/mL (OR, 2.64; 95 % CI, 1.22–5.73; p = 0.014) were significant predictors of OM. Additionally, positive OM predictors were strong independent prognostic factors for overall survival after pancreatectomy (hazard ratio, 2.47; 95 % CI, 1.54–3.98; p < 0.001). ConclusionMultidisciplinary treatment strategies should be considered for patients with predictors of OM to avoid inappropriate surgical interventions.

Evaluating the efficacy of laparoscopic radical antegrade modular pancreatosplenectomy in selected early-stage left-sided pancreatic cancer: a propensity score matching study

BackgroundLaparoscopic radical pancreatectomy is safe and beneficial for recectable pancreatic cancer, but the extent of resection for early-stage tumors remains controversial.MethodsConsecutive patients with left-sided pancreatic cancer who underwent either laparoscopic radical antegrade modular pancreatosplenectomy (LRAMPS, n = 54) or laparoscopic distal pancreatosplecnectomy (LDP, n = 131) between October 2020 and December 2022 were reviewed. The preoperative radiological selection criteria were as follows: (1) tumor diameter ≤ 4 cm; (2) located ≥ 1 cm from the celiac trunk; (3) didn’t invade the fascial layer behind the pancreas.ResultsAfter 1:1 propensity score matching (LRAMPS, n = 54; LDP, n = 54), baseline data were well-balanced with no differences. LRAMPS resulted in longer operation time (240.5 vs. 219.0 min, P = 0.020) and higher intraoperative bleeding volume (200 vs. 150 mL, P = 0.001) compared to LDP. Although LRAMPS harvested more lymph nodes (16 vs. 13, P = 0.008), there were no statistically significant differences in lymph node positivity rate (35.2% vs. 33.3%), R0 pancreatic transection margin (94.4% vs. 96.3%), and retroperitoneal margin (83.3% vs. 87.0%) rate. Postoperative complications did not significantly differ between the two groups. However, LRAMPS was associated with increased drainage volume (85.0 vs. 40.0 mL, P = 0.001), longer time to recover semi-liquid diet compared to LDP (5 vs. 4 days, P < 0.001) and increased daily bowel movement frequency. Tumor recurrence pattern and recurrence-free survival were comparable between the two groups, but the adjuvant chemotherapy regimens varied, and the completion rate of the 6-month intravenous chemotherapy was lower in the LRAMPS group compared to the LDP group (51.9% vs. 75.9%, P = 0.016).ConclusionsLRAMPS did not provide oncological benefits over LDP for left-sided pancreatic cancer within the selection criteria, but it increased operation time, intraoperative bleeding, and postoperative bowel movement frequency. These factors impacted the regimen selection and completion of adjuvant chemotherapy, consequently compromising the potential benefits of LRAMPS in achieving better local control.Graphical

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

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. 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. 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). The combination of PMI and CONUT scores may be useful for predicting the prognosis of patients with PDAC after radical surgery.

C-Reactive Protein-to-Albumin Ratio to Predict Tolerability of S-1 as an Adjuvant Chemotherapy in Pancreatic Cancer.

Adjuvant chemotherapy (AC) with S-1 after radical surgery for resectable pancreatic cancer (PC) has shown a significant survival advantage over surgery alone. Consequently, ensuring that patients receive a consistent, uninterrupted S-1 regimen is of paramount importance. This study aimed to investigate whether the C-reactive protein-to-albumin ratio (CAR) could predict S-1 AC completion in PC patients without dropout due to adverse events (AEs). We retrospectively enrolled 95 patients who underwent radical pancreatectomy and S-1 AC for PC between January 2010 and December 2022. A statistical analysis was conducted to explore the correlation of predictive markers with S-1 completion, defined as continuous oral administration for 6 months. Among the 95 enrolled patients, 66 (69.5%) completed S-1, and 29 (30.5%) failed. Receiver operating characteristic curve analysis revealed 0.05 as the optimal CAR threshold to predict S-1 completion. Univariate and multivariate analyses further validated that a CAR ≥ 0.05 was independently correlated with S-1 completion (p < 0.001 and p = 0.006, respectively). Furthermore, a significant association was established between a higher CAR at initiation of oral administration and acceptable recurrence-free and overall survival (p = 0.003 and p < 0.001, respectively). CAR ≥ 0.05 serves as a predictive marker for difficulty in completing S-1 treatment as AC for PC due to AEs.

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

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. 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. The radio-clinical model may be clinically useful for successfully predicting PC prognosis.

Prognostic significance of grade of malignancy based on histopathological differentiation and Ki-67 in pancreatic ductal adenocarcinoma.

Tumor cell malignancy is indicated by histopathological differentiation and cell proliferation. Ki-67, an indicator of cellular proliferation, has been used for tumor grading and classification in breast cancer and neuroendocrine tumors. However, its prognostic significance in pancreatic ductal adenocarcinoma (PDAC) remains uncertain. Patients who underwent radical pancreatectomy for PDAC were retrospectively enrolled, and relevant prognostic factors were examined. Grade of malignancy (GOM), a novel index based on histopathological differentiation and Ki-67, is proposed, and its clinical significance was evaluated. The optimal threshold for Ki-67 was determined to be 30%. Patients with a Ki-67 expression level > 30% rather than ≤ 30% had significantly shorter 5-year overall survival (OS) and recurrence-free survival (RFS). In multivariate analysis, both histopathological differentiation and Ki-67 were identified as independent prognostic factors for OS and RFS. The GOM was used to independently stratify OS and RFS into 3 tiers, regardless of TNM stage and other established prognostic factors. The tumor-node-metastasis-GOM stage was used to stratify survival into 5 distinct tiers, and surpassed the predictive performance of TNM stage for OS and RFS. Ki-67 is a valuable prognostic indicator for PDAC. Inclusion of the GOM in the TNM staging system may potentially enhance prognostic accuracy for PDAC.

Evaluating the benefits of adjuvant chemotherapy in patients with pancreatic cancer undergoing radical pancreatectomy after neoadjuvant therapy-a systematic review and meta-analysis.

More and more patients with pancreatic cancer (PC) received neoadjuvant therapy (NAT) and then underwent radical pancreatectomy. However, the benefit of adjuvant chemotherapy (AC) for these patients is still controversial. This study is designed to determine the benefits of postoperative AC for patients with PC undergoing NAT and radical resection. We conducted a comprehensive search of the PubMed, Embase, Web of Science, and Cochrane Library databases, covering the period from their inception until 10 September 2023. Our analysis focused on the assessment of overall survival (OS) and recurrence-free survival (RFS) through meta-analysis. The fixed-effects model and the random-effects model were used to process the data. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were employed to determine the necessary of administering AC for patients with PC who have undergone NAT and radical resection. We retrieved 3,063 search results, of which 3,048 were excluded because of duplication or after applying our inclusion and exclusion criteria. A total of 15 studies with 21,113 patients (7,794 patients in the AC group and 13,319 in the non-AC group) were included, all of which reported OS, and three studies reported disease-free survival (DFS)/tumor-specific survival (CSS)/RFS. The final results showed that AC significantly improved OS and DFS/CSS/RFS in patients with PC who underwent pancreatectomy after NAT [OS: HR = 0.80, 95% CI (0.75∼0.86), P < 0.00001, I2 = 48%; DFS/CSS/RFS: HR = 0.53, 95% CI (0.41~0.69), P < 0.00001, I2 = 0%]. Furthermore, we performed subgroup analyses and demonstrated that AC provided a significant survival benefit for patients with PC after NAT and resection regardless of the tumor size [<2-cm subgroup: HR = 0.72, 95% CI (0.5∼0.94), P = 0.01; ≥2-cm subgroup: HR = 0.79, 95% CI (0.65∼0.96), P = 0.02] and the margin status [R0 subgroup: HR = 0.83, 95% CI (0.77∼0.88), P < 0.00001; R2 subgroup: HR = 0.75, 95% CI (0.61∼0.92), P = 0.007]. AC also benefited the patients with a stage N0 [HR = 0.79, 95% CI (0.74~0.84), P < 0.00001], N1 [HR = 0.78, 95% CI (0.72∼0.85), P < 0.00001], or poorly/undifferentiated tumor [HR = 0.76, 95% CI (0.66∼0.87), P < 0.0001] in survival but not in patients with a stage N2 [HR = 0.69, 95% CI (0.43∼1.09), P = 0.11] or well/moderately differentiated tumor [HR = 0.97, 95% CI (0.66∼1.42), P = 0.87]. Although AC showed survival benefit for patients with PC undergoing radical pancreatectomy after NAT, we still need to consider the lymph node stage and the degree of differentiation of the tumor when we gave AC to a patient. High-quality prospective randomized controlled studies are required to well disclose the value of AC in patients with PC undergoing radical pancreatectomy after NAT. https://www.crd.york.ac.uk/prospero/ PROSPERO, identifier CRD42023461365.

The application of radiofrequency ablation in pancreatic cancer liver-only recurrence after radical pancreatectomy.

To evaluate the safety, feasibility, and survival benefit of radiofrequency ablation in liver-only recurrence pancreatic cancer patients after radical pancreatectomy. The data and follow-up of pancreatic cancer patients who suffered liver-only recurrence after radical pancreatectomy from 2015 to 2021 were retrospectively collected. Finally, 19 liver metastases radiofrequency ablation patients were assigned to radiofrequency ablation group, and 41 patients were to systemic treatment group. (1) the baseline, perioperative characteristics, and pathological outcomes were well-balanced. (2) Recurrence pattern showed there were more multiple (> 3) recurrence tumors in systemic treatment patients (multiple one vs. 19, P = 0.005). (3) Median radiofrequency ablation operation time was 30.0min, median blood loss was 1.0ml, 4 (21.05%) patients suffered postoperative complications, and 94.74% liver metastases tumors got complete necrosis. The first efficacy evaluation showed a significantly better effect of radiofrequency ablation, complete and partial response rate 72.22% vs. 27.78%, P < 0.001. Overall survival from the initial surgery and after liver recurrence was significantly longer in the radiofrequency ablation group (43.0 vs. 22.0months, 29.0 vs. 14.0months, P = 0.003, 0.006, respectively). Progression-free survival after treatment was longer in the radiofrequency ablation group (6.0 vs. 5.0months, P = 0.029). For liver recurrence tumor ≤ 3, overall survival from the initial surgery and after liver recurrence was significantly longer in radiofrequency ablation patients (43.0 vs. 22.0months, 29.0 vs. 14.0months, P = 0.011, 0.013, respectively). Progression-free survival after treatment was longer in the radiofrequency ablation group (7.0 vs. 4.0months, P = 0.042). Radiofrequency ablation could get a curative purpose for patients with liver-only recurrence after pancreatectomy, improve progression-free survival and overall survival, and with minor surgery damage and risk.

Geriatric nutritional risk index as a potential prognostic marker for patients with resectable pancreatic cancer: a single-center, retrospective cohort study

In pancreatic cancer, postoperative complications (POCs) are associated with disease outcomes. The geriatric nutritional risk index (GNRI) is known to predict POCs after pancreatoduodenectomy (PD) or distal pancreatectomy (DP) in patients with hepatobiliary pancreatic tumors, including pancreatic cancer. Through POC occurrence risk, we aimed to determine whether GNRI could predict prognosis in patients who underwent PD or DP for resectable pancreatic cancer. This retrospective study examined 139 patients who underwent radical pancreatectomy for resectable pancreatic cancer at Ehime University. All patients were subjected to nutritional screening using GNRI and were followed up for POC diagnosis and patient outcomes such as overall survival (OS). Patients were divided based on the GNRI value of 99 (Low group: N = 74, GNRI < 99; High group: N = 65, GNRI ≥ 99), which was determined by receiver operating characteristic curve analysis. Multivariate analysis showed that GNRI < 99 was statistically correlated with POCs after curative pancreatic resection (p = 0.02). Univariate and multivariate analyses confirmed that GNRI < 99 was significantly associated with long OS (p = 0.04). GNRI could be a potential prognostic marker for resectable pancreatic cancer after curative pancreatic resection despite being a simple and noninvasive approach.

Clinical features and postoperative survival in patients with sporadic versus multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors: An international cohort study

BackgroundThe optimal surgical management of pancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1 is controversial. This study sought to compare clinicopathologic characteristics and outcomes of multiple endocrine neoplasia type 1–associated and sporadic pancreatic neuroendocrine tumors from a large multi-national database. MethodsA multi-institutional, international database of patients with surgically resected pancreatic neuroendocrine tumors was analyzed. The cohort was divided into 2 groups: those with multiple endocrine neoplasia type 1 versus those with sporadic disease. Clinicopathologic comparisons were made. Overall and disease-free survival were analyzed. Propensity score matching was used to reduce bias. ResultsOf 651 patients included, 45 (6.9%) had multiple endocrine neoplasia type 1 and 606 sporadic pancreatic neuroendocrine tumors. Multiple endocrine neoplasia type 1–associated pancreatic neuroendocrine tumors were more common in younger patients and associated with multifocal disease at the time of surgery and higher T-stage. Lymph node involvement and the presence of metastasis were similar. Total pancreatectomy rate was 5-fold higher in the multiple endocrine neoplasia type 1 cohort. Median survival did not differ (disease-free survival 126 months multiple endocrine neoplasia type 1 vs 198 months sporadic, P > .5). After matching, survival remained similar (overall survival not reached in either cohort, disease-free survival 126 months multiple endocrine neoplasia type 1 vs 198 months sporadic, P > .5). Equivalence in overall survival and disease-free survival persisted even when patients who underwent subtotal and total pancreatectomy were excluded. ConclusionMultiple endocrine neoplasia type 1–associated pancreatic neuroendocrine tumors are more common in younger patients and are associated with multifocality and higher T-stage. Survival for patients with multiple endocrine neoplasia type 1–associated pancreatic neuroendocrine tumors is comparable to those with sporadic pancreatic neuroendocrine tumors, even in the absence of radical pancreatectomy. Consideration should be given to parenchymal-sparing surgery to preserve pancreatic function.

Laparoscopic pancreatectomy for pancreatic cancer with advanced energy device (LigaSure Maryland jaw device)

Pancreatic cancer is well known to be one of the most lethal malignant diseases in gastrointestinal tract. As a monotherapy, margin-negative radical pancreatectomy is regarded as the most potent anticancer treatment. However, to enhance the oncologic efficacy of curative resection, postoperative chemotherapy should be considered. As a matter of fact, it is estimated that pancreatic cancer will be the second most common cancer-related human mortality in 2030, which will be main theme regarding human health issue. With advance of pancreatic surgery, developing method for early diagnosis, understanding tumor biology, and introduction of new potent chemotherapeutic agents, pancreatic cancer is expected to face new paradigm in near future. Especially in treating pancreatic cancer, surgical extirpation is very important. Due to anatomical complexity, and surgical difficulty, laparoscopic radical pancreatectomy in treating pancreatic cancer is still controversial. However, currently available data are showing its feasibility, safety, and equivalent oncologic outcomes comparing with open surgical approach in well selected patients. There are potential theoretical advantages of laparoscopic pancreatectomy. Early recovery with less surgical stress is expected to provide the patients with appropriate patients' condition to receive the postoperative adjuvant chemotherapy, which is inevitable requirement for the long-term survival. Therefore, in performing laparoscopic radical pancreatectomy for pancreatic cancer, surgeons need for effective energy device in dissecting the pancreas for safe and effective margin-negative resection. It is thought that LigaSure Maryland jaw device can be appropriate in performing laparoscopic radical pancreatectomy for pancreatic cancer due to following several reasons; 1) Burst pressure 2) Temperature 3) Nano-coating 4) Blunt dissection. Obtaining superior mesenteric artery (SMA) lateral margin is crucial in pancreatic head cancer. Very narrow space is allowed for securing SMA lateral margin. Alternative advanced energy device, Sonicision curved jaw cordless ultrasonic dissection system, can enhance the surgical performance and safety. Thin and small curved blade (0.8 mm-1.7 mm) can provide easy access to the tight space with less potential thermal damage near the major vascular structure. In this presentation, I would like to discuss our clinical practice of laparoscopic pancreatectomy for pancreatic cancer with advanced energy device.

Validation of difficulty scoring system for laparoscopic distal pancreatectomy

Laparoscopic distal pancreatectomy (LDP) is gaining acceptance as a standard approach for removal of various benign and malignant pancreatic diseases. There are several methods of LDP which includes classic LDP with splenectomy for benign diseases, laparoscopic spleen and vessel preserving distal pancreatectomy, and laparoscopic radical pancreatectomy for invasive pancreatic cancers for pancreatic cancer. Several conditions may contribute to the difficulty of LDP based on type of operation, characteristics of the disease, patients' body habitus and tumor location. We have previously developed a difficulty scoring (DS) system to quantify the degree of difficulty in LDP to aid surgeons who would like to learn or teach this procedure in a stepwise manner. The aim of this study is to validate the DS system in LDP, proposed by the study group of Japan Society for Hepato-Biliary-Pancreatic Surgery/Asian-Pacific Hepato-Pancreato-Biliary Association in 2018 (J Hepatobiliary Pancreato Sci 2018;25:489-497). Effect of score assessed by DS system on surgical outcomes including conversion rate, operation time and blood loss was validated in both Korean and Japanese cohort. We found significant difference of operation time and conversion rates in both Japanese and Korean cohort. However, the DS was not related with blood loss in both cohorts. We observed associations between the DS system and operative outcomes, to some extent, and the trend seems to be same in both Korean and Japanese. To make the DS system for more useful one, we would like to modify the system in the future.

Exposure to Blood Components and Inflammation Contribute to Pancreatic Cancer Progression

Pancreatectomy is a highly invasive procedure with extensive intraoperative blood loss (IBL) and high risk of postoperative pancreatic fistula (POPF). We conducted an experimental and retrospective clinical study to determine whether the malignant behaviors of pancreatic cancer cells were enhanced by exposure to blood components in vitro and to evaluate the oncological significance of high IBL and POPF in pancreatic cancer. This study included 107 patients undergoing radical pancreatectomy in the University of Yamanashi Hospital between 2011 and 2017, classified into high (n = 29) and low (n = 78) IBL groups. In vitro experiments included functional analyses of Panc-1 pancreatic cancer and normal mesothelial cells exposed to patient blood components, and clinical data were used to assess the contribution of IBL and POPF to patient outcomes. The migration (p = 0.007), invasion (p < 0.001), and proliferation (p < 0.01) of Panc-1 cells were enhanced with platelet coculture. The ability of Panc-1 cells to adhere mesothelial cells was enhanced by plasma coincubation, especially in the presence of inflammation (p < 0.001). High IBL was associated with worse overall survival (p = 0.007) and increased locoregional recurrence (p = 0.003) in patients. POPF enhanced the negative prognostic significance of high IBL (p < 0.001 for overall survival, p = 0.001 for locoregional recurrence), indicating the oncological negative effects of high IBL and POPF. Blood components, especially platelets, and inflammation enhance the malignant behaviors of pancreatic cancer cells, potentially contributing to poor prognosis for pancreatic cancer patients.

Nomogram and competing risk model to predict recurrence after curative surgical resection of PDAC

BackgroundSurgical resection remains the only potentially curative treatment for pancreatic ductal adenocarcinoma (PDAC). However, a number of patients get disease recurred in a short time post-operation. Few studies have focused on the predictors of different recurrence patterns of PDAC. ObjectiveTo try to establish and verify a nomogram to predict recurrence free survival (RFS) in PDAC patients, and to distinguish the risk factors of local recurrence first and distant metastasis first via competing risk model. MethodsPatients who underwent radical pancreatectomy for PDAC in our center from 2010 to 2018 were reviewed retrospectively. Kaplan-Meier methods and multivariate Cox regression analyses were used to identify the clinicopathological predictors of recurrence post-operation. And then, a nomogram was constructed and validated. Competing risk regression model was used to compare the predictors between local recurrence group and distant metastasis group. ResultsA total of 200 patients were included into the final analysis, and 153 patients got disease relapsed post-operation. CA19-9 level, vascular resection, tumor differentiation, lymph node ratio (LNR) and adjuvant chemotherapy were identified as independent risk factors for recurrence free survival (RFS) and incorporated into the nomogram. The C-index of the nomogram was 0.650. Competing risk model indicated that the status of lymph-node metastasis was significantly associated the patterns of first relapse. ConclusionsNomogram and competing risk model were constructed to quantify the risk of recurrence following surgery for PDAC. Our findings may be useful for predicting RFS and recurrence pattern in clinical work.

A nomogram of preoperative predictors for occult metastasis in patients with PDAC during laparoscopic exploration.

Surgical resection is the only potentially curative treatment for pancreatic ductal adenocarcinoma (PDAC). However, most of patients lose the chance of surgery due to the unresectable disease at the time of diagnosis. Despite the improvement of radiological imaging, a portion of patients intended for radical resection were proven to be unresectable at surgical exploration due to occult metastasis. Patients who were aimed to undergo radical pancreatectomy for PDAC from 2010 to 2019 were reviewed retrospectively. All patients included underwent diagnostic laparoscopic exploration. Patients were divided into two groups depending on whether distant metastasis were encountered during exploration. Univariate and multivariate logistic regression analyses were used to identify risk factors for occult metastasis. A nomogram to predict occult metastasis of PDAC on exploration was developed and evaluated. A total of 273 patients who underwent diagnostic laparoscopic exploration were included in this study. Nineteen (7.0%) patients were found with distant metastasis during exploration. Multivariate logistic regression analysis showed that ALT>40U/L, CA19-9, CA125 and regional nodes enlargement were independent predictors for occult metastasis. Incorporating these four factors, the nomogram achieved concordance index of 0.799, with a well-fitted calibration curve. Occult metastasis is not unusual during surgical exploration in patients with resectable or borderline resectable PDAC. The nomogram could achieve a personal prediction of unexpected distant metastasis on exploration. It may help to sift through patients with PDAC who would benefit from laparoscopic exploration.

Repeated Pancreatectomy for Isolated Local Recurrence in the Remnant Pancreas Following Radical Pancreatectomy for Pancreatic Ductal Adenocarcinoma: A Pooled Analysis.

The mainstream treatment for recurrent pancreatic cancer is potent chemotherapy or chemoradiotherapy. However, recent clinical investigations have suggested a potential oncologic role of local resection of recurrent pancreatic cancer. This systemic review with a pooled analysis aimed to assess the potential role of local repeated pancreatectomy with respect to the survival outcomes for patients with recurrent pancreatic ductal adenocarcinoma (PDAC) in the remnant pancreas. The PubMed database was searched, and 15 articles reporting on repeated pancreatectomy for local recurrence of PDAC in the remnant pancreas were identified. The pooled individual data were examined for the clinical outcomes of repeated pancreatectomy for recurrent PDAC. The survival analysis was performed using the Kaplan–Meier method. In the pooled analysis, the mean time interval from initial pancreatectomy to repeated pancreatectomy was 41.3 months (standard deviation (SD), 29.09 months). Completion total pancreatectomy was most commonly performed as repeated pancreatectomy (46 patients, 92.0%), and partial pancreatic resection was performed for only 4 (10.3%) patients. Twenty (40.9%) patients received postoperative chemotherapy following repeated pancreatectomy. The median overall survival was 60 months (95% confidential interval (CI): 45.99–74.01) after repeated pancreatectomy for isolated local recurrence in the remnant pancreas. Overall survival was markedly longer considering the timing of the initial pancreatectomy for pancreatic cancer (median, 107 months (95% CI: 80.37–133.62). The time interval between the initial and subsequent repeated pancreatectomy for pancreatic cancer was not associated with long-term oncologic outcomes (p = 0.254). Repeated pancreatectomy cannot completely replace adjuvant chemotherapy but should be considered for patients with isolated local recurrent PDAC in the remnant pancreas.

Is Laparoscopic Pancreaticoduodenectomy Feasible for Pancreatic Ductal Adenocarcinoma?

Simple SummaryPancreatic cancer is known to be one of the most lethal malignant diseases in gastrointestinal tract. Margin-negative pancreatectomy followed by postoperative adjuvant chemotherapy is essential treatment for long-term survival. Due to anatomical complexity and technical difficulty, laparoscopic pancreaticoduodenectomy is still controversial. However, with the advance of laparoscopic surgery, laparoscopic pancreatic resection of pancreatic head cancer has been carefully applied in well selected patients. The accumulating data are suggesting its technical feasibility, safety, and potential equivalent long-term oncologic outcome. In this review, the current status of laparoscopic pancreaticoduodenectomy for pancreatic head cancer is summarized. In addition, potential surgical indications and future perspectives of laparoscopic pancreaticoduodenectomy for pancreatic cancer are discussed for safe implementation in our clinical practice.Margin-negative radical pancreatectomy is the essential condition to obtain long-term survival of patients with pancreatic cancer. With the investigation for early diagnosis, introduction of potent chemotherapeutic agents, application of neoadjuvnat chemotherapy, advancement of open and laparoscopic surgical techniques, mature perioperative management, and patients’ improved general conditions, survival of the resected pancreatic cancer is expected to be further improved. According to the literatures, laparoscopic pancreaticoduodenectomy (LPD) is also thought to be good alternative strategy in managing well-selected resectable pancreatic cancer. LPD with combined vascular resection is also feasible, but only expert surgeons should handle these challenging cases. LPD for pancreatic cancer should be determined based on surgeons’ proficiency to fulfil the goals of the patient’s safety and oncologic principles.

Pancreatoduodenectomy With Arterial Resection for Locally Advanced Pancreatic Cancer of the Head: A Systematic Review.

The development of increasingly effective chemotherapy regimens and increasing tumor necrosis is allowing radical pancreatectomy to be re-evaluated. This systematic review examines the outcome of patients with locally advanced cancer of the pancreatic head after pancreatectomy with arterial resection. Electronic searches were performed on PubMed and Medline databases between January 2000 and December 2018. The end points were to determine the safety and overall survival after arterial resection in pancreatectomy. Thirteen studies with 467 patients were included. Celiac, hepatic, mesenteric, and splenic arteries were resected across all studies. The median overall morbidity was 52% (range, 37%-100%) and with major complications occurring in a median of 25% (range, 12%-54%) of patients. The median 90-day mortality was 5% (range, 0%-17%). R0 was achieved in 66% (range, 43%-100%) and R1 in 31% (range, 0%-74%). The median survival was 17 (range, 7-29) months with a 1- and 3-year survival of 59% (range, 16%-92%) and 17% (range, 0%-13%), respectively. Pancreatectomy with arterial resection may be safely performed in high-volume centers with acceptable survival results in highly selected patients. Pooling of data through a multi-institutional registry will allow a more accurate assessment of the safety and efficacy of this treatment strategy.

Developing a preoperative serum metabolome-based recurrence-predicting nomogram for patients with resected pancreatic ductal adenocarcinoma

We investigated the potential application of preoperative serum metabolomes in predicting recurrence in patients with resected pancreatic cancer. From November 2012 to June 2014, patients who underwent potentially curative pancreatectomy for pancreatic ductal adenocarcinoma were examined. Among 57 patients, 32 were men; 42 had pancreatic head cancers. The 57 patients could be clearly categorized into two main clusters using 178 preoperative serum metabolomes. Patients within cluster 2 showed earlier tumor recurrence, compared with those within cluster 1 (p = 0.034). A nomogram was developed for predicting the probability of early disease-free survival in patients with resected pancreatic cancer. Preoperative cancer antigen (CA) 19–9 levels and serum metabolomes PC.aa.C38_4, PC.ae.C42_5, and PC.ae.C38_6 were the most powerful preoperative clinical variables with which to predict 6-month and 1-year cancer recurrence-free survival after radical pancreatectomy, with a Harrell’s concordance index of 0.823 (95% CI: 0.750–0.891) and integrated area under the curve of 0.816 (95% CI: 0.736–0.893). Patients with resected pancreatic cancer could be categorized according to their different metabolomes to predict early cancer recurrence. Preoperative detectable parameters, serum CA 19–9, PC.aa.C38_4, PC.ae.C42_5, and PC.ae.C38_6 were the most powerful predictors of early recurrence of pancreatic cancer.

A Quantitative Clinicopathological Signature for Predicting Recurrence Risk of Pancreatic Ductal Adenocarcinoma After Radical Resection.

Recurrence and distant metastases were main reasons of unfavorable outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) after surgery. The aim of this study was to describe the patterns, timing, and predictors of recurrence or metastasis in PDAC patients after curative surgery. Patients with PDAC who underwent radical pancreatectomy were included. Associations between clinicopathological and radiological characteristics and specific pattern of progression were investigated. Least absolute shrinkage and selection operator (LASSO) and Cox regression were applied to assess the prognostic factors for overall survival (OS) and progression-free survival (PFS). A total of 302 patients were included into present study, and 173 patients were documented as recurrence after a median survival of 24.7 months. More than half of patients recurred after 12 months after surgery, and the liver was the most common metastatic site. Decreased time interval to progression, elevated carbohydrate antigen 19-9 (CA19-9) level, and lymph node (LN)16 metastasis were independent predictors for reduced OS. Independent prognostic factors for PFS included elevated carcinoembryonic antigen (CEA) level, local progression, liver or lung-only metastasis, local + distant progression, multiple metastases, LN16 metastasis, imaging tumor size, chemotherapy, and tumor–node–metastasis (TNM) stage. The predictive system showed valuable prediction performance with values of concordance indexes (C-indexes) and the area under the receiver operating characteristic curve (AUC) over 0.80. Different survival curves and predictive factors for specific patterns of disease progression suggested the biological heterogeneity, providing new versions into personal management of recurrence in PDAC patients after surgery.