OBJECTIVE:We evaluated the prognostic significance and implications of a major pathologic response (MPR) after preoperative treatment for pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA:Preoperative treatment is increasingly used for PDAC to improve oncologic outcomes. The pathologic response represents a potential indicator of treatment efficacy; however, its prognostic value in PDAC remains unclear. METHODS:We retrospectively analyzed 739 patients who underwent pancreatectomy for PDAC after preoperative treatment at 21 institutions in Japan. The pathologic response was graded using Evans' classification, with MPR defined as Evans grade III/IV. Survival outcomes and prognostic factors were evaluated, and factors associated with achieving MPR were analyzed to develop a predictive model. RESULTS:MPR was achieved in 11.5% of patients. The MPR group had a significantly longer median overall survival (71.5 vs. 40.9 mo) and recurrence-free survival (55.5 vs. 15.2 mo) than the non-MPR group. Multivariate analysis identified MPR as an independent prognostic factor for overall survival. In the MPR subgroup, neither overall nor recurrence-free survival differed according to adjuvant chemotherapy administration; multivariate analysis did not identify adjuvant therapy as an independent prognostic factor. Predictive factors for achieving MPR included chemoradiotherapy, preoperative duration ≥6 months, normal carbohydrate antigen 19-9 after preoperative treatment, and complete or partial radiologic response. Finally, we developed a simplified predictive model for achieving MPR. CONCLUSIONS:MPR was independently associated with favorable survival in PDAC. The prognostic impact of adjuvant chemotherapy was not observed among patients who achieved MPR, suggesting that MPR may inform individualized postoperative management and warrants prospective validation.
Fukuoka and colleagues, with accompanying videos, described single-arm robotic pancreaticoduodenectomy using the da Vinci SP Surgical System. Combining a right posterior approach with external traction using an internal organ retractor provided stable exposure while preserving robotic arm availability, facilitating secure dissection around the superior mesenteric artery and improving procedural reproducibility.
Nanoliposomal irinotecan (nal-IRI) plus fluorouracil/leucovorin (5-FU/LV) has become an established regimen for pancreatic ductal adenocarcinoma (PDAC) after gemcitabine-based therapy; however, complete response remains exceptionally rare. Here, we describe a 70-year-old female patient under surveillance for branch-duct intraductal papillary mucinous neoplasm who developed a new hypovascular pancreatic head mass ( 30 mm) with > 180° contact to the portal vein, consistent with borderline resectable PDAC. Adenocarcinoma was confirmed by endoscopic ultrasound-guided tissue acquisition. Initial therapy comprised gemcitabine plus nab-paclitaxel, but the patient showed radiographic and biochemical progression. Modified FOLFIRINOX (oxaliplatin, irinotecan, leucovorin (LV), and 5-fluorouracil (5-FU)) was attempted as second-line therapy, but discontinued after one cycle due to Grade 3 myelosuppression and severe fatigue. Subsequently, nal-IRI + 5-FU/LV was administered as third-line therapy for 10 cycles and toxicity was manageable. Follow-up contrast-enhanced computed tomography revealed marked tumor regression and resolution of previously observed right lower-lobe pulmonary opacity. Following multidisciplinary reassessment and with informed consent, subtotal stomach-preserving pancreaticoduodenectomy was performed. The resected specimen showed a 13 mm fibrotic scar without residual viable carcinoma and no lymph node metastasis was identified, meeting criteria for pathological complete response. At 25-month follow-up, the patient remained disease-free. This case provides evidence that nal-IRI + 5-FU/LV may induce profound tumor regression in carefully selected patients with preserved performance status and favorable baseline factors, enabling potentially curative resection after failure or intolerance to standard first-line regimens.
Pancreatic cancer is a highly intractable malignancy that necessitates personalized treatment strategies. Conventional patient-derived models, such as three-dimensional organoids, are often limited by intellectual property constraints and high costs. In this study, we developed an affordable adherent culture system for patient-derived pancreatic cancer cells using a proprietary medium and laminin-coated dishes. Primary cultures were successfully established from 28 patients with pancreatic ductal adenocarcinoma, exceeding a 90% success rate. Validation of eight samples confirmed maintenance of epithelial cell adhesion molecule expression and preservation of oncogenic KRAS mutations. Transcriptomic profiling revealed consistent upregulation of a six-gene signature (FAP, IGFBP5, PRRX1, SPARC, WNT5A, and ADAMTS12), which is associated with malignancy. In vitro drug sensitivity assays revealed interpatient heterogeneity with preliminary clinical associations. In conclusion, this simplified platform provides high-purity cancer cells and serves as a functional precision medicine tool. Beyond conventional chemotherapy, this platform has the potential to support applications ranging from biomarker validation and exploratory preclinical testing of novel therapeutics, including immune checkpoint inhibitors and antibody–drug conjugates. This optimization can lead to personalized therapeutic strategies for pancreatic cancer.
BACKGROUND:Although several prophylactic strategies have been developed for postoperative pancreatic fistula (POPF), research on its severe form is few. Recently, it has been reported that severe POPF can be caused by intraabdominal lipolysis. This study aimed to establish a rat model of severe POPF by combining pancreatic juice leakage and lipolysis and to develop a prophylactic strategy for POPF. METHODS:Sprague-Dawley rats were subjected to pancreatic transection to induce pancreatic juice leakage (PT group). Autologous fat tissue was thermally treated to prepare a fat solution, which was intraperitoneally administered to the rats in the PT group (PT + F group). A water-solubilized lipase inhibitor (cetilistat) was administered intraperitoneally to the rats in the PT + F group. A polyethylene glycol-based hydrogel (PEG-HG) formulation of water-solubilized cetilistat was equally administered. Ascitic and serum biochemical tests, including free fatty acids (FFA) levels, macroscopic or microscopic examinations, and survival analyses, were performed. RESULTS:In the PT + F group, significantly elevated ascitic and serum FFA levels and serum inflammatory cytokine levels were observed 24 h postoperatively (p < .001), and the survival rate was significantly exacerbated (p < .0001). Intraperitoneal administration of water-solubilized cetilistat resulted in reduced inflammation and improved outcomes. Although PEG hydrogel itself did not improve blood parameters or survival outcomes, the incorporation of water-solubilized cetilistat into the PEG-HG enabled similar improvement. CONCLUSION:Intraperitoneal administration of water-solubilized cetilistat prevented severe inflammation and multiple failures associated with severe POPF. The incorporation of water-solubilized cetilistat into the PEG-HG is a promising delivery system for clinical application.
BACKGROUND:Partial pancreatectomies for intraductal papillary mucinous neoplasms (IPMN) often leave a dilated main pancreatic duct (MPD). However, its impact on the development of remnant pancreatic lesions is unknown. METHODS:Medical records of consecutive patients who underwent partial pancreatectomy for noninvasive or microinvasive IPMN with dilated MPD on preoperative imaging between April 2007 and March 2023 at two tertiary referral centers in Japan were retrospectively reviewed. A dilated remnant MPD (DRM) was defined as an MPD diameter of the expected remnant pancreas of ≥5 mm. The clinically significant remnant pancreatic lesion (CSRPL) was defined as a remnant pancreatic lesion which requires intervention. RESULTS:A total of 172 patients (106 males and 66 females) were analyzed. Preoperatively, 132 patients (76.7 %) had mixed-type IPMN and 40 (23.1 %) had main duct IPMN. Among them, 16 patients (9.3 %) had CSRPL at 1569 days (median; range, 120-5503 days) after the initial surgery. In the preoperative imaging analysis, 104 patients (60.5 %) had DRM. The univariate analysis revealed that high-grade or micro-invasive pathology (p = 0.013) was significantly associated with CSRPL, whereas DRM was inversely associated with CSRPL (p = 0.021). The multivariate analysis revealed that the trends of DRM (p = 0.002) and high-grade/micro-invasive pathology (p = 0.003) remained significant. CONCLUSIONS:Leaving a dilated MPD did not increase but instead inversely associated with the incidence of CSRPL after IPMN resection. It was suggested that preserving the pancreas, including the dilated MPD, is oncologically safe if the lesion of interest can be resected.
BACKGROUND:The use of the hinotori™ Surgical System (hinotori) in distal pancreatectomy (DP) is new compared to the da Vinci™ Surgical System (DVSS). The hinotori is equipped with mechanisms distinct from those of DVSS, and comprehensive reports detailing the surgical techniques and outcomes associated with hinotori in DP (hinotori-DP) are lacking. This study aimed to compare the outcomes of DP using the hinotori and DVSS (Xi system), focusing on differences in settings and techniques between the two methods. METHODS:This study retrospectively investigated consecutive patients who underwent robotic DP from April 2010 (the introduction of robotic DP at our institute) to July 2024. The analysis excluded patients who underwent spleen-preserving procedures or procedures performed using robotic platform other than hinotori or daVinci Xi. The hinotori-DP cases were compared with those performed using DVSS (DVSS-DP). The techniques used in hinotori-DP were examined in more detail. RESULTS:A total of 75 robotic DP cases (11 with hinotori and 64 with DVSS) were analyzed in this study. Different port configurations and techniques, including a lesser curvature approach, were used in the hinotori-DP compared to DVSS-DP. The operation time was relatively shorter in the hinotori-DP group (299 vs. 366 min, p = 0.095), and the postoperative complication rates were comparable (pancreatic fistula: 27 % vs. 30 %, p = 0.871; Clavien-Dindo Grade ≥3a complications: 18 % vs. 19 %, p = 0.964) between the two groups. CONCLUSION:The hinotori-DP can be safely performed by focusing on the unique characteristics of the hinotori surgical system.
Background/Objectives: Due to the increasing incidence of pancreatic and periampullary cancers with advancing age, coupled with the growing evidence supporting minimally invasive pancreatectomy, the demand for such procedures is rising. However, data on the feasibility of robotic pancreatectomy in octogenarian patients remain scant. This study aimed to investigate overall outcomes of robotic pancreatectomy and evaluate its safety and feasibility in octogenarian patients. Methods: A multicenter, retrospective study was conducted, including 380 patients who underwent robotic pancreatectomy at two high-volume centers in Japan from April 2020 to December 2024. Using prospectively collected data, we compared outcomes between younger patients (<80 years) and octogenarian patients (≥80 years). Multivariable logistic regression analyses were performed to assess the impact of age on postoperative outcomes. Results: Among the 380 patients, with a median age of 72 (interquartile range: 61–77) years, 213 underwent robotic pancreatoduodenectomy (RPD), and 167 underwent robotic distal pancreatectomy (RDP). Octogenarian patients were found to have more comorbidities and a higher incidence of malignant diseases. Octogenarians experienced significantly longer hospital stays post-RPD (22 [octogenarian; n = 36] vs. 14 [younger; n = 177] days, p < 0.001) and post-RDP (14 [n = 23] vs. 10.5 [n = 144] days, p = 0.02), yet their perioperative outcomes were comparable. Multivariable analyses indicated that age (≥80 years) was not a significant risk factor for major complications following robotic pancreatectomy (odds ratio, 1.33; 95% confidence interval, 0.59–2.84; p = 0.479). Conclusions: This multicenter study conducted at high-volume centers suggests that robotic pancreatectomy can be safely performed in carefully selected octogenarian patients.
Late biliary complications, consisting of anastomotic stricture and cholangitis, are known to impair long-term quality of life and significantly impact patient outcomes following robot-assisted pancreaticoduodenectomy (RPD). The role of stent placement in HJ remains debatable. This study aimed to investigate the incidence of late biliary complications and the impact of stent placement on long-term outcomes after RPD. This retrospective observational study included patients who underwent RPD from November 2009 to April 2024 at two institutions. Patients were categorized into no-stent, internal stent, and external stent groups. The incidence of late biliary complications was analyzed with Kaplan–Meier estimates and Cox proportional hazards models. The analysis included 157 patients. Late biliary stricture occurred in 20 (13
Stapler transection during robotic distal pancreatectomy (RDP) has limitations, including device cost, difficulty in thick pancreas, and challenges in pathological assessment of the margin. We developed the crush and clip (CC) technique, in which the parenchyma is crushed using Maryland forceps and the main pancreatic duct is clipped without stump reinforcement. This study aimed to describe the CC technique and assess its non-inferiority to stapler transection regarding postoperative pancreatic fistula (POPF). We retrospectively analyzed 127 RDP cases at a high-volume center (CC: 23; stapler: 104) between 2010 and 2025. Procedures used included da Vinci Xi, da Vinci SP, or hinotori™ systems. The primary endpoint includes clinically relevant POPF (ISGPS grade B/C). Body mass index, stump thickness, and robotic platform were used to estimate the propensity score, and overlap weighting was applied. Non-inferiority was prespecified as a risk difference (CC − stapler) of less than + 5
The da Vinci SP, a robotic surgical platform capable of single-port surgery, offers cosmetic advantages; however, its use in pediatric patients has been limited. This report presents the first da Vinci SP operation for a choledochal cyst in a 7-year-old girl with Type Ic disease. The procedure was completed in 300 min, including 192 min of console time, with no intraoperative complications. Postoperative recovery was uneventful, and the patient was discharged on postoperative day 7. The SP robot enables precise surgical interventions within small anatomical spaces without the need for extensive planning of port placement to avoid forceps interference. Additionally, its ability to adjust the position of the remote center expands the potential for a wide range of pediatric operations, particularly for surgeries in close proximity to target organs.
Robotic pancreaticoduodenectomy (RPD) is technically demanding, and 20–50 cases are required to surpass the learning curve. This study aimed to show our experience of 76 cases from the introduction of RPD and report the changes in surgical results owing to the accumulation of cases and optimization of surgical techniques. A total of 76 patients who underwent RPD between November 2009 and May 2023 at the Fujita Health University Hospital were divided into three groups: competency (n = 23, Nov 2009–Mar 2020), proficiency (n = 31, Apr 2020–Jun 2022), and mastery (n = 22, Jul 2022–May 2023) phases. In the mastery phase, for the education of new surgeons and maintenance of surgical quality, optimization of the procedure, including hanging maneuver with or without stapling transection of the retropancreatic tissue was implemented. The surgical outcomes were compared between the groups. The mean operation time decreased over time despite of the participation of newly started operators in mastery phase [competency: 921.5 min (IQR 775–996 min) vs. proficiency: 802.8 min (IQR 715–887 min) vs. mastery: 609.2 min (IQR 514–699 min), p < 0.001]. Additionally, Clavien–Dindo ≥ grade IIIa complications decreased from 52.2
BackgroundsPancreatojejunostomy is a technically demanding procedure during robotic pancreaticoduodenectomy (RPD). Modified Blumgart anastomosis (mBA) is a common method for the pancreatojejunostomy; however, the technical details for robotic mBA are not well established. During RPD, we performed a mBA for the pancreatojejunostomy using thread manipulation with gauze and an additional assist port.MethodsPatients who underwent robotic pancreatoduodenectomy at Fujita Health University from November 2009 to May 2023 were retrospectively investigated, and technical details for the robotic-modified Blumgart anastomosis were demonstrated.ResultsAmong 78 patients who underwent RPD during the study period, 33 underwent robotic mBA. Postoperative pancreatic fistula (POPF) occurred in six patients (18%). None of the patients suffered POPF Grade C according to the international study group of pancreatic surgery definition. The anastomotic time for mBA was 80 min (54-125 min).ConclusionRobotic mBA resulted in reasonable outcomes. We propose that mBA could be used as one of the standard methods for robotic pancreatojejunosotomy.
Robotic distal pancreatectomy (RDP) has emerged as a minimally invasive approach to left-sided pancreatic tumors. This study aimed to evaluate the efficacy of the robot-assisted approach (RAA) using a laparoscopic articulating vessel-sealing device (LAVSD) during RDP by comparing it with the pure-robotic approach (PRA). Among 62 patients who underwent RDP between April 2020 and December 2023 at Fujita Health University, 22 underwent RAA (the RAA group). In RAA, console surgeons mainly prepared the surgical fields, and assistant surgeons actively dissected the adipose and connective tissues using LAVSD. The surgical outcomes of these patients were compared with those of 40 consecutive patients who underwent RDP with PRA. In total, 28 males and 34 females with a median age of 71 years were analyzed. The console surgeon’s prior experience of performing RDP was similar between the groups (RAA; median, 6 [range, 0–36], PRA; median, 5.5 [range, 0–34] cases). The operation time was significantly shorter in the TST group (median, 300.5 [range, 202–557] vs. 363.5 [range, 230–556] min, p = 0.015). Major complications (Clavien–Dindo ≥ grade 3a) occurred less frequently in the RAA group (4.6
Background/Purpose Gut microbiota status after pancreaticoduodenectomy (PD) is unclear, and postoperative fatty liver is an important complication after PD. This study evaluated the relationship between postoperative fatty liver and gut microbiota after PD. Methods Fecal samples were collected from patients who had undergone PD and remained stable after 6 months of follow-up. A comprehensive bacterial analysis using 16S rRNA gene amplicon sequencing was performed. The results were compared with those of 85 healthy volunteers. The association between perioperative factors, gut microbiota, and development of fatty liver was investigated. Results Twenty-four patients after PD, including 10 in the fatty liver (FL) group and 14 in the normal liver (NL) group were investigated. The β-diversity of the gut microbiota was significantly different between the healthy volunteers and patients after PD, with more Escherichia coli and Streptococcus gallolyticus and less Bifidobacterium catenulatum and Faecalibacterium prausnitzii in the patients with PD. Lactobacillus gasseri was significantly less abundant in the FL group than in the healthy volunteers, although this change was not observed in the NL group. Conclusions The gut microbiota of patients after PD was in dysbiosis at postoperative ≥6 months. Development of fatty liver might be associated with significant differences in gut microbiota.
Background: Posthepatectomy liver failure (PHLF) remains a severe complication after liver resection. This retrospective study investigated the correlation of three hepatic functional tests and whether 99mTc-galactosyl human serum albumin (99mTc-GSA) scintigraphy and modified albumin–bilirubin (ALBI) score are useful for predicting PHLF. Methods: A total of 413 consecutivepatients undergoing hepatectomies between January 2017 and December 2020 at our institution were enrolled in this retrospective cohort study. To evaluate preoperative hepatic functional reserve, modified ALBI grade, indocyanine green clearance (ICG-R15), and 99mTc-GSA scintigraphy (LHL15) were routinely examined before the scheduled hepatectomy. Based on the retrospective chart review, multivariate logistic regression analysis adjusted for confounding factors was performed to confirm that ALBI, ICG-R15, and LHL15 are independent risk factors for PHLF. Results: ICG-R15 and LHL15 were moderately correlated ( r = −0.61). However, the correlation with LHL15 weakened when ICG-R15 was about ³20. Weak correlations were observed between LHL15 and ALBI score ( r = −0.269) and ALBI score and ICG-R15 ( r = 0.339). Of 413 patients, 66 (19%) developed PHLF (grade A: n = 20, grade B: n = 44, grade C: n = 2). Multivariable logistic regression analyses, mALBI grade ( P = .014) and ICG-R15 ( P < .001) were significant independent risk factors for PHLF. Subgroup analysis showed that ICG-R15 <19, major hepatectomy, and mALBI grade and ICG-R15 ³19, major hepatectomy, and LHL15 were significant independent risk factors for PHLF ( P =.036,.020,.043, and.013, respectively). Conclusion: LHL15 and mALBI grade would be complementary to ICG-R15 for predicting PHLF risk.
The optimal approach for the safe implementation and education of robotic pancreaticoduodenectomy (RPD) remains unclear. Prolonged operation time may cause surgeon fatigue and result in perioperative complications. To solve this issue, our department adopted task division by the console surgeon turnover between resection and reconstruction in 2022. This study retrospectively investigated consecutive patients who underwent RPD from November 2009 (initial introduction of RPD) to December 2023. The analysis excluded patients who underwent concomitant resection of other organs. The cases performed by a single console surgeon (single approach) were compared with those performed by two or more console surgeons (multiple approach). This study analyzed 85 consecutive RPD cases, including 51 with the single approach and 34 with the multiple approach. The operation time was significantly shorter (832 vs. 618 min, p < 0.001), and the postoperative major complication was less frequent (45
AbstractAimEvidence regarding the reliability of endoscopic ultrasound‐guided tissue acquisition (EUS‐TA) for assessing histological proliferation and WHO grading of small (≤20 mm) pancreatic neuroendocrine tumors (PanNETs) is limited.MethodsIn this multicenter retrospective study, we analyzed data from 122 patients with small PanNETs who underwent EUS‐TA followed by surgical resection between 2006 and 2022. We compared the histopathological proliferation assessment and WHO grading between preoperative EUS‐TA and surgical definitive specimens.ResultsAmong the 122 patients with small PanNETs (80% with surgical definitive WHO grade G1 and 20% with G2), EUS‐TA histology identified neuroendocrine tumors in 101 (83%) patients and provided WHO grading in 85 (70%) patients. Histopathological WHO grading for EUS‐TA was concordant with surgical definitive grading in 86% (73/85) of cases, overstaged in 4% (3/85), and understaged in 11% (9/85). Moderate, severe, and fatal adverse events associated with EUS‐TA, as classified by the lexicon, were not reported in this cohort.ConclusionEUS‐TA is a reliable method for assessing histopathological proliferation and WHO grading of small PanNETs. However, grading discordance may occur, and a risk–benefit evaluation on a per‐patient basis is recommended.
Background: Although minimally invasive distal pancreatectomy (MIDP) is considered a standard approach it still presents a non-negligible rate of conversion to open that is mainly related to some difficulty factors, as obesity. The aim of this study is to analyze the preoperative factors associated with conversion in obese patients with MIDP. Methods: In this multicenter study, all obese patients who underwent MIDP at 18 international expert centers were included. The preoperative factors associated with conversion to open surgery were analyzed. Results: Out of 436 patients, 91 (20.9%) underwent conversion to open, presenting higher blood loss, longer operative time and similar rate of major complications. Twenty (22%) patients received emergent conversion. At univariate analysis, the type of approach, radiological invasion of adjacent organs, preoperative enlarged lymphnodes and ASA > III were significantly associated with conversion to open. At multivariate analysis, robotic approach showed a significantly lower conversion rate (14.6 % vs 27.3%, OR = 2.380, p = 0.001). ASA > III (OR = 2.391, p = 0.002) and preoperative enlarged lymphnodes (OR = 3.836, p = 0.003) were also independently associated with conversion. Conclusion: Conversion rate is significantly lower in patients undergoing robotic approach. Radiological enlarged lymphnodes and ASA > III are also associated with conversion to open. Conversion is associated with poorer perioperative outcomes, especially in case of intraoperative hemorrhage.