High-volume Pancreatic Centers Research Articles

Optimizing the Management Strategies of Delayed Post-Pancreaticoduodenectomy Hemorrhage

Objective: To optimize the management strategies of delayed post-pancreaticoduodenectomy hemorrhage (PPH) by evaluating data from a high-volume pancreatic center. Summary Background Data: Delayed PPH is a potentially lethal complication. The management of delayed PPH remains controversial. Methods: Patients who underwent pancreaticoduodenectomy between July 2018 and June 2023 were identified from an institutional database. The clinical scenarios, management, and outcomes of patients with delayed PPH (>5 d postoperatively) were analyzed. Results: Out of the 2013 patients who underwent elective pancreaticoduodenectomy, 130 (6.5%) with delayed PPH were identified. The overall mortality was 15.4%. The success rates of endoscopy, angiographic intervention, and relaparotomy in treating delayed PPH were 54.5%, 56.5%, and 68.8%, respectively. For PPH from the hepatic arteries or their branches, complete blockade of the common or proper hepatic artery (C/PHA) was performed in 17 patients, either by coil embolization (n=7) or surgical ligation (n=10). Coil embolization of the C/PHA resulted in significant infarction of the left liver in 2 patients. No postoperative liver infarction occurred in patients who underwent ligation of the C/PHA during relaparotomy. Ten patients underwent suture repair of the C/PHA 13 times during relaparotomy. Arterial ligation achieved a significantly higher success rate of hemostasis than suture repair of the C/PHA during relaparotomy (100% vs. 30.8%, P<0.001). Conclusions: Angiography should be attempted first in managing hemodynamically stable delayed PPH. Arterial ligation was preferred for bleeding from the hepatic arteries during relaparotomy with minor consequences for the liver.

The Effect of Perioperative Dexamethasone on Postoperative Complications after Pancreaticoduodenectomy: A Multicenter Randomized Controlled Trial.

This study aimed to evaluate the effect of perioperative dexamethasone on postoperative complications after pancreaticoduodenectomy. The glucocorticoid dexamethasone has been shown to improve postoperative outcomes in surgical patients, but its effects on postoperative complications after pancreaticoduodenectomy are unclear. This multicenter, double-blind, randomized controlled trial was conducted in four Chinese high-volume pancreatic centers. Adults undergoing elective pancreaticoduodenectomy were randomized to receive either 0.2mg/kg dexamethasone or a saline placebo as an intravenous bolus within 5 minutes after anesthesia induction. The primary outcome was the Comprehensive Complication Index (CCI) score within 30 days after the operation, analyzed using the modified intention-to-treat principle. Among 428 patients for eligibility, 300 participants were randomized and 265 were included in the modified intention-to-treat analyses. 134 patients received dexamethasone and 131 patients received a placebo. The mean (SD) CCI score was 14.0 (17.5) in the dexamethasone group and 17.9 (20.3) in the placebo group (mean difference, -3.8; 95% CI, -8.4 to 0.7; P=0.100). The incidence of major complications (Clavien-Dindo grade ≥III) (12.7% vs. 16.0%, risk ratio 0.79; 95% CI, 0.44 to 1.43; P=0.439) and postoperative pancreatic fistula (25.4% vs. 31.3%, risk ratio 0.81; 95% CI, 0.55 to 1.19; P=0.286) were not significantly different between the two groups. In the stratum of participants with a main pancreatic duct ≤3mm (n=202), the CCI score was significantly lower in the dexamethasone group (mean difference, -6.4; 95% CI, -11.2 to -1.6; P=0.009). Perioperative dexamethasone did not significantly reduce postoperative complications within 30 days after pancreaticoduodenectomy.

Improved Clinical Staging System for Localized Pancreatic Cancer Using the ABC Factors: A TAPS Consortium Study.

Previous studies suggest that besides anatomy (A: resectable, borderline resectable [BR], or locally advanced [LA]) also biologic (B: carbohydrate antigen 19-9 [CA 19-9]) and conditional (C: performance status) factors should be considered when staging patients with localized pancreatic ductal adenocarcinoma (PDAC). The prognostic value of the combined ABC factors has not been quantitatively validated. In this retrospective cohort study, we evaluated patients with localized PDAC treated with initial (modified) fluorouracil with leucovorin, irinotecan, and oxaliplatin ([m]FOLFIRINOX) at five high-volume pancreatic cancer centers in the United States and the Netherlands (2012-2019). Multivariable Cox proportional hazards analysis was used to investigate the impact of the ABC factors for overall survival (OS). Overall, 1,835 patients with localized PDAC were included. Tumor stage at diagnosis was potentially resectable in 346 (18.9%), BR in 531 (28.9%), and LA in 958 (52.2%) patients. The baseline CA 19-9 was >500 U/mL in 559 patients (32.5%). Performance status was ≥1 in 1,110 patients (60.7%). Independent poor prognostic factors for OS were BR disease (hazard ratio [HR], 1.26 [95% CI, 1.06 to 1.50]), LA disease (HR, 1.71 [95% CI, 1.45 to 2.02]), CA 19-9 >500 U/mL (HR, 1.36 [95% CI, 1.21 to 1.52]), and WHO performance status ≥1 (HR, 1.31 [95% CI, 1.16 to 1.47]). Patients were assigned 1 point for each poor ABC factor and 2 points for LA disease. The median OS for patients with score 0-4 was 49.7, 29.9, 22.0, 19.1, and 14.9 months with corresponding 5-year OS rates of 47.0%, 28.9%, 19.2%, 9.3%, and 4.8%, respectively. The ABC factors of tumor anatomy, CA 19-9, and performance status at diagnosis were independent prognostic factors for OS in patients with localized PDAC treated with initial (m)FOLFIRINOX. Staging of patients with localized PDAC at diagnosis should be based on anatomy, CA 19-9, and performance status.

Microbiome Dysbiosis with Enterococcus Presence in the Upper Gastrointestinal Tract is A Risk Factor for Mortality in Patients Undergoing Surgery for Pancreatic Cancer.

Recent retrospective studies suggest a role for distinct microbiota in the perioperative morbidity and mortality of pancreatic head resections. We aimed to prospectively investigate the microbial colonization of critical operative sites of pancreatic head resections to identify microbial stratification factors for surgical and long-term oncologic outcomes. Prospective biomarker study applying 16S rRNA sequencing and microbial culturing to samples collected from various sites of the GI tract and surgical sites of patients during pancreatic head resections at a German single high-volume pancreatic center. A total of 101 patients were included (38 non-cancer, 63 cancer patients [50 PDAC patients]) in the study. In a first data analysis series, 16S rRNA sequencing data were utilized from 96 patients to assess associations of microbiome profiles with clinical parameters and outcomes. In general, microbiome composition varied according to sampling site, cancer, age or preoperative ERCP intervention, notably for the bile microbiome. In the PDAC subcohort, compositional variance of the bile or periampullary microbiome was significantly associated with postoperative complications such as ICU admission; on a taxonomic level we observed Enterococcus spp. to be significantly more abundant in patients developing deep or organ-space surgical site infections (SSI). Elevated Enterococcus relative abundances in the upper GI tract, in turn, were associated with 6-months mortality rates. In a second step, we focused on microbiological cultures collected from bile aspirates during surgery and investigated associations with perioperative complications and long-term survival. Notably, Enterococcus spp. were among the most prevalent pathobiont isolates observed in cancer patient bile specimens that were associated with severe SSIs, and thereby elevated mortality rates up to 24 months. Clinically relevant postoperative pancreatic fistulas or severe SSI were found as other major variables determining short-term mortality in this cancer patient cohort. In the context of adverse microbiological factors, a preoperative ERCP was also observed to segregate long-term survival, and it appeared to interact with the presence of Enterococcus spp. as highest mortality rates were observed in PDAC patients with both preoperative ERCP and presence of E. faecalis in bile aspirates. The presence of Enterococcus spp. in bile ducts of PDAC patients undergoing pancreatic surgery represents a significant risk factor for perioperative infections and, thereby, elevated postoperative and long-term mortality. This finding supports previous data on the use of the antibiotic drug piperacillin-tazobactam as appropriate perioperative antibiotic prophylaxis for preventing adverse outcomes after pancreatoduodenectomy.

Minimally invasive versus open pancreatoduodenectomy for pancreatic and peri-ampullary neoplasm (DIPLOMA-2): study protocol for an international multicenter patient-blinded randomized controlled trial

BackgroundMinimally invasive pancreatoduodenectomy (MIPD) aims to reduce the negative impact of surgery as compared to open pancreatoduodenectomy (OPD) and is increasingly becoming part of clinical practice for selected patients worldwide. However, the safety of MIPD remains a topic of debate and the potential shorter time to functional recovery needs to be confirmed. To guide safe implementation of MIPD, large-scale international randomized trials comparing MIPD and OPD in experienced high-volume centers are needed. We hypothesize that MIPD is non-inferior in terms of overall complications, but superior regarding time to functional recovery, as compared to OPD.Methods/designThe DIPLOMA-2 trial is an international randomized controlled, patient-blinded, non-inferiority trial performed in 14 high-volume pancreatic centers in Europe with a minimum annual volume of 30 MIPD and 30 OPD. A total of 288 patients with an indication for elective pancreatoduodenectomy for pre-malignant and malignant disease, eligible for both open and minimally invasive approach, are randomly allocated for MIPD or OPD in a 2:1 ratio. Centers perform either laparoscopic or robot-assisted MIPD based on their surgical expertise. The primary outcome is the Comprehensive Complication Index (CCI®), measuring all complications graded according to the Clavien-Dindo classification up to 90 days after surgery. The sample size is calculated with the following assumptions: 2.5% one-sided significance level (α), 80% power (1-β), expected difference of the mean CCI® score of 0 points between MIPD and OPD, and a non-inferiority margin of 7.5 points. The main secondary outcome is time to functional recovery, which will be analyzed for superiority. Other secondary outcomes include post-operative 90-day Fitbit™ measured activity, operative outcomes (e.g., blood loss, operative time, conversion to open surgery, surgeon-reported outcomes), oncological findings in case of malignancy (e.g., R0-resection rate, time to adjuvant treatment, survival), postoperative outcomes (e.g., clinically relevant complications), healthcare resource utilization (length of stay, readmissions, intensive care stay), quality of life, and costs. Postoperative follow-up is up to 36 months.DiscussionThe DIPLOMA-2 trial aims to establish the safety of MIPD as the new standard of care for this selected patient population undergoing pancreatoduodenectomy in high-volume centers, ultimately aiming for superior patient recovery.Trial registrationISRCTN27483786. Registered on August 2, 2023

The clinical value of radical resection of retroperitoneal lipo-lymphatic layer for pancreatic head cancer

Objective: To investigate the clinical value of the novel approach,radical resection of the retroperitoneal lipo-lymphatic layer (RRRLLL),in the surgical treatment of resectable pancreatic head cancer. Methods: Between June 2020 and June 2022,a total of 221 patients with pancreatic head cancer underwent surgical treatment using the RRRLLL approach(RRRLLL group),while 107 patients received traditional surgical treatment(traditional group) in five high-volume pancreatic centers in China. Data from surgical technique and clinical perioperative outcomes,including lymph node harvested,surgical time,and complications,were analyzed. The RRRLLL group consisted of 144 males and 77 females with an age of (67.5±9.0) years(range:41.3 to 81.1 years). The traditional group included 71 males and 36 females,with an age of (66.3±8.1) years(range:45.1 to 79.2 years). Statistical analysis was performed using the K-S test,Z test,or χ2 test. Results: Pancreaticoduodenectomy was performed successfully in all patients,achieving R0 resection. RRRLLL group surgery required mobilization of retroperitoneal adipose and lymphatic tissues starting from the right edge of the inferior vena cava and extending to the left side,up to the superior mesenteric artery,down to the inferior mesenteric artery,and left to the left side of the aorta,including the perineural and lymphatic tissues around the superior mesenteric artery and the sheath of the mesenteric artery. However,the traditional group did not include the areas mentioned above in the scope of clearance. There were no statistically significant differences between the RRRLLL group and the traditional group in terms of age,sex,tumor size,T stage,and vascular invasion (all P>0.05). However,the number of lymph nodes harvested in the RRRLLL group was significantly higher at 28.7±9.0 (range: 18 to 39) compared to 18.2±8.0 (range: 12 to 21) in the traditional group (Z=-10.691,P<0.05). There were no statistically significant differences in the number of positive lymph nodes,N staging,and postoperative complications between the two groups. Conclusion: The RRRLLL approach improved lymph node dissection compared to the traditional approach,potentially leading to reduced recurrence rates.

Clinical outcomes of minimally invasive duodenum-preserving pancreatic head resection

BackgroundThe procedure of total duodenum-preserving pancreatic head resection (DPPHRt) has been reported frequently, but rare in minimally invasive procedure, especially robotic-assisted operation. Here we share our experience and analyze the clinical outcomes of minimally invasive DPPHRt in the treatment of benign lesions or low-grade malignant tumors of the pancreatic head in this study.Materials and methodsFrom October 2016 to January 2022, three patients received robot-assisted DPPHRt(RA-DPPHRt), and seventeen patients received laparoscopic DPPHRt(LDPPHRt). Data were retrospectively collected in terms of demographic characteristics (age, gender, body mass index, and pathological diagnosis), intraoperative variables (operative time, estimated blood loss), and post-operative variables (post-operative hospital stay, and complications).ResultsAll 20 patients received minimally invasive total duodenum-preserving pancreatic head resection successfully without conversion, including 8 males and 12 females. Pathological diagnosis suggested 1 case of serous cystadenoma (SCA), 4 cases of intraductal papillary mucinous neoplasm (IPMN) ,5 cases of mucinous cystic neoplasm (MCN), 4 cases of pancreatic neuroendocrine neoplasm (PNET), 2 cases of chronic pancreatitis (CP),4 case of solid pseudopapillary tumor (SPT). The average operation time was (285.35 ± 95.13 min), ranging from 95 to 420 min. The average estimate blood loss was (196.50 ± 174.45ml) ,ranging from 10 to 600ml.The average post-operative hospital stay was(20.90 ± 14.44days),ranging from 8 to 54 days. Postoperative complications occurred in 10 patients (50%). A total of 5 patients (20%) suffered grade B or C pancreatic fistula. Two patients (10%) suffered from biliary fistula. Two patients (10%) suffered from delayed gastric emptying. One patient (5%) suffered from abdominal bleeding. The 90-day mortality was 0. No patient was observed tumor recurrence and new-onset diabetes but one developed diarrhea.ConclusionRA-DPPHRt or LDPPHRt provided a minimally invasive approach with good organ-preservation for patients with benign and low-grade malignant pancreatic head tumor. It is only recommended to be performed in high-volume pancreatic centers by experienced pancreatic surgeons.

Efficacy of adjuvant chemoradiotherapy in patients with pancreatic ductal adenocarcinoma after surgery: A real-world study in high-volume pancreatic cancer center.

e16308 Background: Whether adjuvant chemoradiotherapy provides survival benefit for pancreatic ductal adenocarcinoma (PDAC) patients remains unknown. Methods: This prospective real-world study recruited PDAC patients receiving surgical treatment in Zhongshan Hospital Fudan University, Shanghai, China from June 2020 to December 2021. Patients with carcinoma in situ, distant metastases, synchronous cancers within 5 years, and receiving neoadjuvant therapy were excluded. Patients were then categorized into three groups according to their adjuvant treatment: C- (without adjuvant chemotherapy), C+R- (with adjuvant chemotherapy only), and C+R+ (with adjuvant chemoradiotherapy). Overall survival (OS) and disease free survival (DFS) were compared between groups. Results: A total of 216 patients were included in the final analyses. Median follow time for three groups ranged from 18 to 21.9 months. OS and DFS were significantly different between groups (OS, p value = 0.0088; DFS, p value = 0.0037). Median OS (mOS) for C- and C+R- were 24.3 (95% confidence interval [CI], 18 - not available [NA]) and 29.5 (24.9 – NA). Patients in C+R+ groups did not reach mOS (27.2 - NA). Median DFS (mDFS) for C-, C+R-, and C+R+ were 8.42 (5.72 - NA), 16.9 (13.91 - NA) and 19.66 (16.83 - NA), respectively. Conclusions: Adjuvant treatment significantly increased survival outcomes of pancreatic cancer patients after surgical treatment. In order to find out whom might benefit from additional radiotherapy and which is the best therapy combination, more detail information, including chemotherapy regimen, staging, resection margin, etc., were needed to include in the survival analyses. Clinical trial information: NCT04737551 . [Table: see text]

Comment on: Are Parenchyma-Sparing Resections Really Appropriate for Small (

Comment on: Are Parenchyma-Sparing Resections Really Appropriate for Small (<3 cm) Nonfunctional Pancreatic Neuroendocrine Tumors?

Pancreaticoduodenectomies in a Low Volume, Small Island Eastern Caribbean State: A Retrospective Cohort Study

Background: Although pancreaticoduodenectomy (PD) is safe when performed in high-volume hospitals, many patients in low-income countries cannot access these hospitals. Barbados is a small island that does not have a high-volume pancreatic center. We sought to document peri-operative outcomes when PD was performed in Barbados. Methods: We carried out a retrospective cohort study of all consecutive patients who underwent PDs over from August 1, 2016 to October 30, 2022. Therapeutic outcomes, post-operative morbidity and mortality were evaluated. Statistical analyses were performed using SPSS ver 16.0. Results: Six patients at a mean age of 54.8 years underwent PD (mean annual case volume of 1). Two patients underwent planned vein resections and reconstruction. In this subset, the mean operating time was 325 minutes (Range 300-250; Median 325; SD ±35.4), mean estimated blood loss was 825mls (Range 750-900; Median 825; SD±106.1), and the mean transfusion requirement was 1 unit of packed cells (Range 0-2; Median 1; SD±1.41). In the four patients without vein resection, mean operating time was 308 minutes (Range 280-350; Median 300; SD±24.01), median blood loss was 575 ml (Range 150-900; Median 700; SD±320.6) and mean transfusion requirements were 0.5 units of packed cells (Range 0-2; Median 0; SD ±0.84). The mean ICU stay was 2.17 days (Range 1-3; Median 2.5; SD±0.98), and the mean duration of hospitalization was 9.3 days (Range 7-11; Median 9.5; SD±1.37). There were no recorded peri-operative deaths, but there was 1 (17%) minor complication (delayed gastric emptying) and 1 (17%) major complication (myocardial infarction). Conclusion: In Barbados, there are good peri-operative outcomes after PD despite the low volume and challenging healthcare environment. We believe that (1) surgeon experience (2) continuous adaptive hospital learning and (3) regular audit of hospital data are better indicators of PD quality than volume data alone.

Current Practice Patterns among Radiation Oncologists at High-Volume Pancreatic Cancer Centers Participating in the Canopy Cancer Collective Learning Health Network

<h3>Purpose/Objective(s)</h3> Radiation therapy (RT) for localized pancreatic ductal adenocarcinoma (PDAC) remains controversial, with conflicting data likely resulting in variable practice patterns. The Canopy Cancer Collective (CCC) is a learning health network of 14 institutions with high-volume multidisciplinary PDAC teams. To characterize the current state of RT for PDAC at high-volume, academic centers, radiation oncology faculty at CCC member institutions were surveyed. <h3>Materials/Methods</h3> A survey focusing on RT practice patterns for localized PDAC was distributed to 18 faculty with expertise in gastrointestinal RT at CCC sites. Survey results are descriptively reported. <h3>Results</h3> The survey was completed by 17/18 (94%) faculty. Among respondents, the number of localized PDAC patients treated per year with RT included >50 (n=5, 29%), 26-50 (n=8, 47%), 10-25 (n=3, 18%), and <10 (n=1, 6%). Two (12%) respondents reported that they routinely offer pre-operative RT for resectable PDAC. Majority of respondents (n=15, 88%) indicated that pre-operative RT is offered to certain patients with borderline resectable pancreatic cancer (BPRC), but the specific proportion of BRPC patients receiving pre-operative RT was variable across respondents (median 70%, range: 10-100%). Similarly, majority of respondents (n=16, 94%) indicated that RT is offered as definitive treatment for certain patients with locally advanced pancreatic cancer (LAPC), but the specific proportion of LAPC patients receiving RT was also variable (median 80%, range: 20-100%), as was the estimated proportion of LAPC patients who eventually undergo resection (median 25%, range 2-50%). Table 1 summarizes the distribution of preferred planning techniques and target volumes used by respondents in both the pre-operative and definitive settings. Variation was also seen in use of fiducials (n=12, 71%), preferred motion management strategy (breath-hold: n=12, 71%; gating: n=5, 29%), systematic use of adjunctive imaging beyond CT for target delineation (MRI: n=6, 35%; PET: n=3, 18%), and use of prophylactic anti-emetics (n=5, 29%) and proton pump inhibitors (n=11, 65%). <h3>Conclusion</h3> RT practice patterns for the treatment of localized PDAC remain disparate, with significant variation in institutional standards across stage of disease as well as in basic treatment parameters such as prescription dose and target volume design. A better understanding of the basis for such variation may help guide future avenues of study.

Long-term Outcomes of Parenchyma-sparing and Oncologic Resections in Patients With Nonfunctional Pancreatic Neuroendocrine Tumors

The role of parenchyma-sparing resections (PSR) and lymph node dissection in small (<3cm) nonfunctional pancreatic neuroendocrine tumors (PNET) is unlikely to be studied in a prospective randomized clinical trial. By combining data from 4 high-volume pancreatic centers we compared postoperative and long-term outcomes of patients who underwent PSR with patients who underwent oncologic resections. Retrospective review of prospectively collected clinicopathologic data of patients who underwent pancreatectomy between 2000 and 2021 was collected from 4 high-volume institutions. PSR and lymph node-sparing resections (enucleation and central pancreatectomy) were compared to those who underwent oncologic resections with lymphadenectomy (pancreaticoduodenectomy, distal pancreatectomy). Statistical testing was performed using χ 2 test and t test, survival estimates with Kaplan-Meier method and multivariate analysis using Cox proportional hazard model. Of 810 patients with small sporadic nonfunctional PNETs, 121 (14.9%) had enucleations, 100 (12.3%) had central pancreatectomies, and 589 (72.7%) patients underwent oncologic resections. The median age was 59 years and 48.2% were female with a median tumor size of 2.5cm. After case-control matching for tumor size, 221 patients were selected in each group. Patients with PSR were more likely to undergo minimally invasive operations (32.6% vs 13.6%, P <0.001), had less intraoperative blood loss (358 vs 511ml, P <0.001) and had shorter operative times (180 vs 330 minutes, P <0.001) than patients undergoing oncologic resections. While the mean number of lymph nodes harvested was lower for PSR (n=1.4 vs n=9.9, P <0.001), the mean number of positive lymph nodes was equivalent to oncologic resections (n=1.1 vs n=0.9, P =0.808). Although the rate of all postoperative complications was similar for PSR and oncologic resections (38.5% vs 48.2%, P =0.090), it was higher for central pancreatectomies (38.5% vs 56.6%, P =0.003). Long-term median disease-free survival (190.5 vs 195.2 months, P =0.506) and overall survival (197.9 vs 192.6 months, P =0.372) were comparable. Of the 810 patients 136 (16.7%) had no lymph nodes resected. These patients experienced less blood loss, shorter operations ( P <0.001), and lower postoperative complication rates as compared to patients who had lymphadenectomies (39.7% vs 56.9%, P =0.008). Median disease-free survival (197.1 vs 191.9 months, P =0.837) and overall survival (200 vs 195.1 months, P =0.827) were similar for patients with no lymph nodes resected and patients with negative lymph nodes (N0) after lymphadenectomy. In small <3cm nonfunctional PNETs, PSRs and lymph node-sparing resections are associated with lower blood loss, shorter operative times, and lower complication rates when compared to oncologic resections, and have similar long-term oncologic outcomes.

The Impact of the COVID-19 Pandemic on Multidisciplinary Clinics: A High-Volume Pancreatic Cancer Center Experience

The unprecedented impact of the Sars-CoV-2 pandemic (COVID-19) has strained the healthcare system worldwide. The impact is even more profound on diseases requiring timely complex multidisciplinary care such as pancreatic cancer. Multidisciplinary care teams have been affected significantly in multiple ways as healthcare teams collectively acclimate to significant space limitations and shortages of personnel and supplies. As a result, many patients are now receiving suboptimal remote imaging for diagnosis, staging, and surgical planning for pancreatic cancer. In addition, the lack of face-to-face interactions between the physician and patient and between multidisciplinary teams has challenged patient safety, research investigations, and house staff education. In this study, we discuss how the COVID-19 pandemic has transformed our high-volume pancreatic multidisciplinary clinic, the unique challenges faced, as well as the potential benefits that have arisen out of this situation. We also reflect on its implications for the future during and beyond the pandemic as we anticipate a hybrid model that includes a component of virtual multidisciplinary clinics as a means to provide accessible world-class healthcare for patients who require complex oncologic management.

Multiagent Chemotherapy and Stereotactic Body Radiation Therapy in Patients with Unresectable Pancreatic Adenocarcinoma: A Prospective Nonrandomized Controlled Trial

PurposeIn a prospective multicenter study, gemcitabine monotherapy followed by stereotactic body radiation therapy (SBRT) was well tolerated with outcomes comparable to chemoradiation for locally advanced pancreatic cancer (LAPC). Recent trials have reported improved survival with multiagent chemotherapy (MA-CTX) alone. This prospective trial explored whether SBRT could be safely delivered after MA-CTX. Herein, we report the long-term outcomes of adding SBRT after MA-CTX in LAPC patients and evaluate whether genetic profiles of specimens obtained before SBRT influence outcomes. Methods and MaterialsThis prospective nonrandomized controlled phase 2 trial enrolled 44 LAPC and 4 locally recurrent patients after multidisciplinary evaluation between 2012 and 2015 at a high-volume pancreatic cancer center. For induction CTX, most received modified FOLFIRINOX (mFFX), or gemcitabine and nab-paclitaxel (GnP) followed by 5-fraction SBRT for all. During fiducial placement, biopsies were obtained with DNA extracted for targeted sequencing using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets platform. ResultsMedian induction CTX duration was ≥4 months, and 31 patients received mFFX (65%). Among 44 LAPC patients, 17 (39%) were surgically explored, and 12 of 16 (75%) achieved a R0 resection. Median overall survival (mOS) was 20.2 and 14.6 months from diagnosis and SBRT, respectively. One- and 2-year OS from SBRT was 58% and 28%. The mOS after resection was 28.6 and 22.4 months from diagnosis and SBRT, respectively. Median local progression-free survival was 23.9 and 15.8 months from diagnosis and SBRT, respectively. The mOS for pre-SBRT CA 19-9 ≤180 U/mL versus >180 was 23.1 and 11.3 months, respectively (hazard ratio, 0.53; P = .04). Only 1 patient (2.1%) had late grade ≥2 gastrointestinal toxic effects attributable to SBRT. Despite significant pretreatment with chemotherapy, 88% of tumor specimens were effectively sequenced; survival outcomes were not significantly associated with specific mutational patterns. Quality of life was prospectively collected pre- and post-SBRT with the EORTC QLQ-C30 and PAN26 questionnaires showing no significant change. ConclusionsSBRT was safely administered with MA-CTX with minimal toxicity. A high proportion of LAPC patients underwent R0 resection with favorable survival outcomes.

Real-world study of surgical treatment of pancreatic cancer in China: annual report of China Pancreas Data Center (2016–2020)

Abstract Objective: In 2015, the Chinese Pancreatic Association of the Chinese Society of Surgery of the Chinese Medical Association launched a national multicenter online system for registration of surgical treatment of pancreatic cancer in China, called China Pancreas Data Center (CPDC). With continued effort, the CPDC has developed over time. Herein, we report the general results of the CPDC from January 2016 to January 2020 to present the real-world situation of surgical treatment of pancreatic cancer in China. Methods: The data of the CPDC from January 2016 to January 2020 were retrieved and analyzed in this real-world study, including the data on patient demographics, comorbidities, diagnostic modalities, neoadjuvant treatment, surgical procedures, postoperative complications and treatment, pathological examinations, postoperative adjuvant treatment, survival, and risk factors. Results: A total of 13,595 cases from 70 centers in 28 provinces were retrieved for analysis. This study reported the largest cohort of patients who underwent surgical treatment for pancreatic cancer in China to date. More cases were derived from the Eastern regions, among which Shanghai, Beijing, and Zhejiang ranked in the top three. The peak age of the patients ranged from 60 to 69 years. The ratio of males to females was 1.5:1. Overall, 64.3% of the tumors were located in the head and neck of the pancreas, and 35.7% in the body and tail of the pancreas. Of the patients, 23.0% underwent positron-emission tomography-computed tomography, 21.6% underwent endoscopic ultrasound, and 4.8% underwent preoperative biopsy. Two percent of the patients underwent neoadjuvant treatment, while 68.9% underwent R0 surgical resection (margin free of tumor cells). Of the latter, 78.6% of the operations were open procedures, 12.6% were laparoscopic procedures, 2.9% were robotic procedures, and 3.7% were converted to open procedures. The in-hospital mortality rate after surgery was 0.4%. The incidence of grade 2 and grade 3 postoperative pancreatic fistulas was 25.5% and 2.5%, respectively. The incidence of complications based on the Clavien-Dindo classification was 17.9% of grade II, 4.3% of grade IIIa, 1% of grade IIIb, and 0.6% of grade IV. Of the patients, 28.9% underwent postoperative adjuvant chemotherapy. The 1-year, 2-year, and 3-year overall survival of these patients were 77%, 51%, and 38%, respectively. In the 8542 patients who underwent R0 resection, the 1-year, 2-year, and 3-year overall survival and disease-free survival were 77%, 54%, and 43%, and 68%, 49%, and 41%, respectively. The factors related to the prognosis of these patients were also identified after uni- and multi-variate analyses. Conclusion: The surgical quality, safety, and long-term survival of the patients in CPDC are similar to those of international high-volume pancreatic centers. However, neoadjuvant and postoperative adjuvant chemotherapy should be improved.

Effectiveness and stability of robot-assisted anastomosis on minimally invasive pancreaticoduodenectomy

Reconstruction using robot in pancreaticoduodenectomy (PD) was expected to be an effective means to overcome the limitation of laparoscopic surgery. To our knowledge, a few comparative reports exist on the outcomes of totally laparoscopic pancreaticoduodenectomy (TLPD) and robot-assisted laparoscopic pancreaticoduodenectomy (RLPD). This retrospective study aimed to analyze the surgical results of TLPD and RLPD in a high-volume pancreatic center. We analyzed surgical results on consecutive patients between January 2016 and May 2020 who underwent minimally invasive pancreaticoduodenectomy (MIPD) for malignant or benign periampullary lesions. Forty-three patients of TLPD and 49 patients of RLPD were enrolled. There were no significant differences in demographics characteristics between the two groups except tumor size, which was significantly larger in the RLPD group than in the TLPD group (mean 3.1 cm vs. 2.5 cm, p = 0.035). RLPD had the shorter whole operative time (mean 400.4 minutes vs. 352.2 minutes, p = 0.003) and the shorter anastomosis time than TLPD (mean 94.5 minutes vs. 54.9 minutes, p < 0.001). There was no significant difference between the two groups in the rate of pancreatic fistula, morbidity, and mortality. But a significantly lower rate of wound infection was found in the RLPD group relative to the TLPD group (0% vs. 9.3%, p = 0.038). RLPD shows the advantage of reducing the operation time compared to TLPD as well as technical feasibility and safety.

Is Improved Survival in Early-Stage Pancreatic Cancer Worth the Extra Cost at High-Volume Centers?

Volume of operative cases may be an important factor associated with improved survival for early-stage pancreatic cancer. Most high-volume pancreatic centers are also academic institutions, which have been associated with additional healthcare costs. We hypothesized that at high-volume centers, the value of the extra survival outweighs the extra cost. This retrospective cohort study used data from the California Cancer Registry linked to the Office of Statewide Health Planning and Development database from January 1, 2004 through December 31, 2012. Stage I-II pancreatic cancer patients who underwent resection were included. Multivariable analyses estimated overall survival and 30-day costs at low- vs high-volume pancreatic surgery centers. The incremental cost-effectiveness ratio (ICER) and incremental net benefit (INB) were estimated, and statistical uncertainty was characterized using net benefit regression. Of 2,786 patients, 46.5% were treated at high-volume centers and 53.5% at low-volume centers. There was a 0.45-year (5.4 months) survival benefit (95% CI 0.21-0.69) and a $7,884 extra cost associated with receiving surgery at high-volume centers (95% CI $4,074-$11,694). The ICER was $17,529 for an additional year of survival (95% CI $7,997-$40,616). For decision-makers willing to pay more than $20,000 for an additional year of life, high-volume centers appear cost-effective. Although healthcare costs were greater at high-volume centers, patients undergoing pancreatic surgery at high-volume centers experienced a survival benefit (5.4 months). The extra cost of $17,529 per additional year is quite modest for improved survival and is economically attractive by many oncology standards.

Nomogram based on albumin and neutrophil-to-lymphocyte ratio for predicting postoperative complications after pancreaticoduodenectomy.

The aim of this study was to identify a preoperative inflammatory marker with the most predictive value for postoperative complications after pancreaticoduodenectomy (PD). We then combined it with other perioperative variables to construct and validate a nomogram for complications after PD. A total of 223 patients who received PD from January 2014 to July 2019 at a high-volume (>60 PDs/year) pancreatic centers in China were included in this retrospective study. All of the PDs were performed by the same surgeon who is beyond the learning curve with more than 100 PDs over the previous 3 years before 2014. 15 preoperative inflammatory markers were collected, including neutrophils, lymphocytes, high-sensitivity C-reactive protein and lactic dehydrogenase. The inflammatory markers' predicting abilities for complications were analyzed by calculating the values of an area under the curve (AUC). The complications included surgical complications (such as pancreatic fistula, delayed gastric emptying and bile leakage) and medical complications (such as sepsis, pneumonia, urinary tract infection, acute heart failure and acute liver failure) in this study. Univariable and multivariable logistic regression analyses were performed to investigate the perioperative features for independent risk factors for complications after PD. Nomograms with or without the most predictive inflammatory for complications were subsequently developed based on multivariable logistic regression using Akaike information criterion. Nomograms' performance was quantified and compared in terms of calibration and discrimination. We studied the utility of the nomograms using decision curve analysis. The albumin/ NLR score (ANS) exhibited the highest AUC value (0.616) for predicting postoperative complications. ANS and approach method were identified as independent risk factors for complications. The nomogram with ANS had higher C-index (0.725) and better calibration. The NRI compared between nomograms was 0.160 (95% CI: 0.023-0.296; P=0.022). By decision curve analysis, the model with ANS had higher clinical value. The ANS is a useful predictor and an independent risk factor for postoperative complications after PD. The nomogram with ANS was constructed with better performance and more clinical benefit for predicting postoperative complications.

Long-term outcomes of a prospective single institution study with multiagent chemotherapy and stereotactic body radiation therapy in locally advanced or recurrent pancreatic adenocarcinoma.

440 Background: We previously reported a multi-center study in which gemcitabine and stereotactic body radiation therapy (SBRT) were shown to be safe with outcomes comparable to chemoradiation in locally advanced pancreatic cancer (LAPC). This prospective clinical trial was developed to evaluate the efficacy of adding SBRT to multi-agent chemotherapy in LAPC. Herein, we report on the long-term survival outcomes. Methods: From 2012 to 2015, 48 patients (pts) were prospectively enrolled after multidisciplinary evaluation at a single high-volume pancreatic center. Pts received multi-agent chemotherapy (CTX) with modified mFOLFIRINOX (mFFX) or gemcitabine/abraxane followed by 5 fractions of SBRT (median 33 Gy; range, 25-33 Gy). At the time of fiducial placement, biopsies were obtained and DNA extracted for targeted sequencing using MSK-IMPACT. Kaplan-Meier curves were generated to compare survival outcomes by sub-group. Multivariate analysis (MVA) was performed to identify factors prognostic for survival. Results: 44 pts (91.7%) had LAPC disease and 4 (8.3%) had locally recurrent disease. The median follow-up interval was 21.5 months (mo) from diagnosis. CTX consisted of mFFX in 25 pts (52.1%) with 24 pts (50.0%) receiving therapy for a duration ≥4 mo. Of 44 pts with LAPC, 15 (34.1%) were surgically explored, and 11 (73.3%) achieved a margin-negative resection. From diagnosis and after completion of SBRT, respectively, the median overall survival (OS) was 21.6 (95% CI 16-29.7 mo) and 14.6 mo (95% CI: 11.6-23.0 mo); median progression free survival (PFS) was 13.2 (95% CI 11.9-18.1mo) and 6.4 mo (95% CI: 5-12.7 mo); median local PFS (LPFS) was 23.9 (95% CI 18.9-56.9 mo) and 15.8 mo (95% CI: 12.9-27.6 mo); and median distant metastasis free survival (DMFS) was 18.4 (95% CI 12.6-29.3 mo) and 8.5 mo (95% CI: 6.3-17.2 mo). Resected pts experienced better DMFS at 1-year (78% vs. 34%, p= 0.004) with an improved trend for 1-year OS (73% vs. 52%, p= 0.331). If CTX duration was ≥4 mo, 1-year OS (75% vs. 42%, p= 0.018), PFS (50% vs. 21%, p= 0.022), and DMFS (72% vs. 29%, p= 0.031) were significantly improved. In 44 LAPC pts, MVA confirmed ≥4 mo duration of CTX was associated with OS, PFS, and DMFS. Surgical resection was associated with improved DMFS, and CA19-9 level prior to SBRT was associated with PFS and LPFS. The most common mutations detected from biopsy specimens were KRAS (64.3%) , TP53 (50%), and SMAD4 (16.7%). Conclusions: In a prospective trial of pts with LAPC receiving multiagent CTX and SBRT, clinical outcomes were improved with longer durations of CT ( &gt; 4 mo). A high proportion of LAPC pts underwent margin negative resection with favorable outcomes. Future studies should focus on which pts are most likely to benefit from SBRT and surgery following multiagent CTX. In pts who cannot undergo resection, escalated doses of SBRT may be indicated. Clinical trial information: NCT01781728.

Robotic versus laparoscopic distal pancreatectomy: a European comparison of short-term perioperative outcomes in high-volume pancreatic centers.

Robotic versus laparoscopic distal pancreatectomy: a European comparison of short-term perioperative outcomes in high-volume pancreatic centers.