The Revo-i Robotic Surgical System in Advanced Pancreatic Surgery: A Second Non-Randomized Clinical Trial and Comparative Analysis to the da Vinci™ System.

PURPOSE: Numerous robot-assisted pancreatic surgery are being performed worldwide. This study aimed to evaluate the feasibility and safety of the Revo-i robot system (Meerecompany, Seoul, Republic of Korea) for advanced pancreatic surgery, and also compare this new system with the existing da Vinci™ robot system (Intuitive Surgical, Sunnyvale, CA, USA) in the context of robot-assisted pancreaticoduodenectomy (RPD). MATERIALS AND METHODS: This study was a one-armed prospective clinical trial that assessed the Revo-i robot system for advanced pancreatic surgery. Ten patients aged 30 to 73 years were enrolled between December 2019 and August 2020. Postoperative outcomes were retrospectively compared with those of the da Vinci™ surgical system. From March 2017 to August 2020, a total of 47 patients who underwent RPD were analyzed retrospectively. RESULTS: In the prospective clinical trial, pancreaticoduodenectomy was performed in nine patients and one patient underwent central pancreatectomy. Among the 10 study participants, the incidence of major complications was 0% in hospital stay. There were eight postoperative pancreatic fistula (POPF) biochemical leaks (80%). In the retrospective analysis that compared the Revo-i and da Vinci™ robotic systems, 10 patients underwent Revo-i RPD and 37 patients underwent da Vinci™ RPD, with no significant differences in complication or POPF incidence rates between the two groups (p=0.695, p=0.317). CONCLUSION: In this single-arm prospective study with short-term follow-up at a single institution, the Revo-i robotic surgical system was safe and effective for advanced pancreatic surgery. Revo-i RPD is comparable to the da Vinci™ RPD and is expected to have wide clinical application.

Impact of adjuvant therapy in patients with invasive intraductal papillary mucinous neoplasms of the pancreas: an international multicenter cohort study.

BACKGROUND: Adjuvant therapy prolongs survival in patients with pancreatic ductal adenocarcinoma. However, no clear guidelines are available regarding the oncologic effects of adjuvant therapy (AT) in resected invasive intraductal papillary mucinous neoplasms (IPMN). The aim was to investigate the potential role of AT in patients with resected invasive IPMN. MATERIALS AND METHODS: From 2001 to 2020, 332 patients with invasive pancreatic IPMN were retrospectively reviewed in 15 centres in eight countries. Propensity score-matched and stage-matched survival analyses were conducted. RESULTS: A total of 289 patients were enroled in the study after exclusion (neoadjuvant therapy, unresectable disease, uncertain AT status, and stage IV). A total of 170 patients were enroled in a 1:1 propensity score-matched analysis according to the covariates. In the overall cohort, disease-free survival was significantly better in the surgery alone group than in the AT group ( P =0.003), but overall survival (OS) was not ( P =0.579). There were no significant differences in OS in the stage-matched analysis between the surgery alone and AT groups (stage I, P =0.402; stage II, P =0.179). AT did not show a survival benefit in the subgroup analysis according to nodal metastasis (N0, P =0.481; N+, P =0.705). In multivariate analysis, node metastasis (hazard ratio, 4.083; 95% CI, 2.408-6.772, P <0.001), and cancer antigen 19-9 greater than or equal to 100 (hazard ratio, 2.058; 95% CI, 1.247-3.395, P =0.005) were identified as adverse prognostic factors in resected invasive IPMN. CONCLUSION: The current AT strategy may not be recommended to be performed with resected invasive IPMN in stage I and II groups, unlike pancreatic ductal adenocarcinoma. Further investigations of the potential role of AT in invasive IPMN are recommended.

Development of a metabolite calculator for diagnosis of pancreatic cancer.

BACKGROUND: Carbohydrate antigen (CA) 19-9 is a known pancreatic cancer (PC) biomarker, but is not commonly used for general screening due to its low sensitivity and specificity. This study aimed to develop a serum metabolites-based diagnostic calculator for detecting PC with high accuracy. METHODS: A targeted quantitative approach of direct flow injection-tandem mass spectrometry combined with liquid chromatography-tandem mass spectrometry was employed for metabolomic analysis of serum samples using an Absolute IDQ™ p180 kit. Integrated metabolomic analysis was performed on 241 pooled or individual serum samples collected from healthy donors and patients from nine disease groups, including chronic pancreatitis, PC, other cancers, and benign diseases. Orthogonal partial least squares discriminant analysis (OPLS-DA) based on characteristics of 116 serum metabolites distinguished patients with PC from those with other diseases. Sparse partial least squares discriminant analysis (SPLS-DA) was also performed, incorporating simultaneous dimension reduction and variable selection. Predictive performance between discrimination models was compared using a 2-by-2 contingency table of predicted probabilities obtained from the models and actual diagnoses. RESULTS: Predictive values obtained through OPLS-DA for accuracy, sensitivity, specificity, balanced accuracy, and area under the receiver operating characteristic curve (AUC) were 0.9825, 0.9916, 0.9870, 0.9866, and 0.9870, respectively. The number of metabolite candidates was narrowed to 76 for SPLS-DA. The SPLS-DA-obtained predictive values for accuracy, sensitivity, specificity, balanced accuracy, and AUC were 0.9773, 0.9649, 0.9832, 0.9741, and 0.9741, respectively. CONCLUSIONS: We successfully developed a 76 metabolome-based diagnostic panel for detecting PC that demonstrated high diagnostic performance in differentiating PC from other diseases.

Multidimensional Nomogram to Predict Postoperative Pancreatic Fistula after Minimally Invasive Pancreaticoduodenectomy.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is an inherently severe risk of pancreatic resection. Previous research has proposed models that identify risk factors and predict CR-POPF, although these are rarely applicable to minimally invasive pancreaticoduodenectomy (MIPD). This study aimed to evaluate the individual risks of CR-POPF and to propose a nomogram for predicting POPF in MIPD. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 429 patients who underwent MIPD. In the multivariate analysis, the Akaike information criterion stepwise logistic regression method was used to select the final model to develop the nomogram. RESULTS: Of 429 patients, 53 (12.4%) experienced CR-POPF. On multivariate analysis, pancreatic texture (p = 0.001), open conversion (p = 0.008), intraoperative transfusion (p = 0.011), and pathology (p = 0.048) were identified as independent predictors of CR-POPF. The nomogram was developed based on patient, pancreatic, operative, and surgeon factors by using the following four additional clinical factors as variables: American Society of Anesthesiologists class ≥ III, size of pancreatic duct, type of surgical approach, and < 40 cases of MIPD experience. CONCLUSIONS: A multidimensional nomogram was developed to predict CR-POPF after MIPD. This nomogram and calculator can help surgeons anticipate, select, and manage critical complications.

Which one is better? Laparoscopic versus robotic reconstruction in the remnant soft pancreas with a small pancreatic duct following pancreaticoduodenectomy: a multicenter study with propensity score matching analysis.

BACKGROUND: Evidence of the advantages of robotic pancreaticoduodenectomy (RPD) over laparoscopic pancreaticoduodenectomy (LPD) is limited. Thus, this study aimed to compare the surgical outcomes of laparoscopic reconstruction L-recon) versus robotic reconstruction (R-recon) in patients with soft pancreas and small pancreatic duct. METHOD: Among 429 patients treated with minimally invasive pancreaticoduodenectomy (MIPD) between October 2012 and June 2020 by three surgeons at three institutions, 201 patients with a soft pancreas and a small pancreatic duct (< 3 mm) were included in this study. RESULTS: Sixty pairs of patients who underwent L-recon and R-recon were selected after propensity score matching. The perioperative outcomes were comparable between the reconstruction approaches, with comparable clinically relevant postoperative pancreatic fistula (CR-POPF) rates (15.0% [L-recon] vs. 13.3% [R-recon]). The sub-analysis according to the type of MIPD procedure also showed comparable outcomes, but only a significant difference in postoperative hospital stay was identified. During the learning curve analysis using the cumulative summation by operation time (CUSUMOT), two surgeons who performed both L-recon and R-recon procedures reached their first peak in the CUSUMOT graph earlier for the R-recon group than for the L-recon group (i.e., 20th L-recon case and third R-recon case of surgeon A and 43rd L-recon case and seventh R-recon case of surgeon B). Surgeon C, who only performed R-recon, demonstrated the first peak in the 22nd case. The multivariate regression analysis for risk factors of CR-POPF showed that the MIPD procedure type, as well as other factors, did not have any significant effect. CONCLUSION: Postoperative pancreatic fistula rates and the overall perioperative outcomes of L-recon and R-recon were comparable in patients with soft-textured pancreas and small pancreatic duct treated by experienced surgeons.

Systemic inflammation response index correlates with survival and predicts oncological outcome of resected pancreatic cancer following neoadjuvant chemotherapy.

BACKGROUND: The Systemic Inflammation Response Index (SIRI) has been used to predict the prognosis of various cancers. This study examined SIRI as a prognostic factor in the neoadjuvant setting and determined whether it changing after chemotherapy is related to patient prognosis. METHODS: Patients who underwent pancreatic surgery following neoadjuvant chemotherapy for pancreatic cancer were retrospectively analyzed. To establish the cut-off values, SIRIpre-neoadjuvant, SIRIpost-neoadjuvant, and SIRIquotient (SIRIpost-neoadjuvant/SIRIpre-neoadjuvant) were calculated and significant SIRI values were statistically determined to examine their effects on survival rate. RESULTS: The study included 160 patients. Values of SIRIpost-neoadjuvant ≥ 0.8710 and SIRIquotient <0.9516 affected prognosis (hazard ratio [HR], 1.948; 95% confidence interval [CI], 1.210-3.135; ∗∗P = 0.006; HR, 1.548; 95% CI, 1.041-2.302; ∗∗P = 0.031). Disease-free survival differed significantly at values of SIRIpost-neoadjuvant < 0.8710 and SIRIpost-neoadjuvant ≥ 0.8710 (P = 0.0303). Overall survival differed significantly between SIRIquotient <0.9516 and SIRIquotient ≥0.9516 (P = 0.0368). CONCLUSIONS: SIRI can predict the survival of patients with pancreatic ductal adenocarcinoma after resection and neoadjuvant chemotherapy. Preoperative SIRI value was correlated with disease-free survival, while changes in SIRI values were correlated with overall survival.

Total laparoscopic versus robotic-assisted laparoscopic pancreaticoduodenectomy: which one is better?

BACKGROUND: Minimally invasive pancreaticoduodenectomy (MIPD) is a challenging procedure. Laparoscopic pancreaticoduodenectomy (LPD) is feasible and safe. Since the development of robotic platforms, the number of reports on robot-assisted pancreatic surgery has increased. We compared the technical feasibility and safety between LPD and robot-assisted LPD (RALPD). METHODS: From September 2012 to August 2020, 257 patients who underwent MIPD for periampullary tumors were enrolled. Of these, 207 underwent LPD and 50 underwent RALPD. We performed a 1:1 propensity score-matched (PSM) analysis and retrospectively analyzed the demographics and surgical outcomes. RESULTS: After PSM analysis, no difference was noted in demographics. Operation times and estimated blood loss were similar, as was the incidence of complications (p > 0.05). In subgroup analysis in patients with soft pancreas with pancreatic duct ≤ 2 mm, no significant between-group difference was noted regarding short-term surgical outcomes, including clinically relevant POPF (CR-POPF) (p > 0.05). In multivariable analysis, the only soft pancreatic texture was a predictive factor (HR 3.887, 95% confidence interval 1.121-13.480, p = 0.032). CONCLUSION: RALPD and LPD are safe and effective for MIPD and can compensate each other to achieve the goal of minimally invasive surgery.

Can the presence of KRAS mutations guide the type of liver resection during simultaneous resection of colorectal liver metastasis?

Backgrounds/Aims: It is generally accepted that non-anatomical resection (NAR) in colorectal liver metastasis (CRLM) has comparable safety and efficacy compared to anatomical resection (AR); however, there are reports that AR may have better outcomes in KRAS mutated CRLM. This study aimed to determine the effects of KRAS mutations and surgical techniques on survival outcomes in CRLM patients. Methods: Two hundred fifty patients who underwent hepatic resection of CRLM with known KRAS mutational status between 2007 and 2018 were analyzed. A total of 94 KRAS mutated CRLM and 156 KRAS wild-type CRLM were subdivided by surgical approach and compared for short- and long-term outcomes. Results: In both KRAS wild-type and mutated type, there was no difference in estimated blood loss, postoperative complications, and 30-day mortality. There was no difference in disease-free survival (DFS) between AR and NAR in both groups (p = 0.326, p = 0.954, respectively). Finally, there was no difference in intrahepatic DFS between AR and NAR groups in both the KRAS groups (p = 0.165, p = 0.516, respectively). Conclusions: The presence of KRAS mutation may not be a significant factor when deciding the approach in simultaneous resection of CRLM.

Safety and feasibility of laparoscopic pancreaticoduodenectomy in octogenarians.

INTRODUCTION: With continued technical advances in surgical instruments and growing surgical expertise, many laparoscopic pancreaticoduodenectomies (LPDs) have been safely performed with favorable outcomes, and this approach is being used more frequently. With an increase in the life expectancy, interest in treatments for elderly patients has increased. In this study, we investigated the safety and feasibility of LPD in octogenarians. METHODS: From September 2005 to February 2020, resectable/borderline resectable periampullary tumors (PATs) were diagnosed in 71 octogenarians at Sincheon Severance Hospital and CHA Bundang Medical Center. Patients were divided into two groups: those who underwent surgery (PD, N = 38) and those who did not (NPD, N = 33). The group that underwent surgery was further divided into two groups: those who underwent open PD (OPD, N = 19), and those who underwent LPD (LPD, N = 19). Perioperative outcomes, including long-term survival, were retrospectively compared between these groups. RESULTS: There was no significant difference in age, sex, comorbidities, diagnosis, and chemo-radiotherapy between the surgery and non-surgery groups. The PD group had a better survival rate than the NPD group (p < 0.05). The baseline characteristics and postoperative outcomes were not significantly different between the OPD and LPD groups. Only three and two patients in the OPD and LPD groups had a biochemical leak (p > 0.999). There was no significant difference in overall survival and disease-free survival between the OPD and LPD groups (p = 0.816, p = 0.446, respectively). CONCLUSIONS: LPD is a good alternative for octogenarians with PAT requiring PD.

Multicenter comparison of totally laparoscopic and totally robotic pancreaticoduodenectomy: Propensity score and learning curve-matching analyses.

BACKGROUND: Few studies have compared laparoscopic pancreaticoduodenectomy (LPD) and robotic pancreaticoduodenectomy (RPD) despite emerging use of minimally invasive pancreaticoduodenectomy (MIPD). The present study therefore compares perioperative outcomes of LPD and RPD patients, and evaluates safety and feasibility of MIPD. METHODS: This retrospective multicenter analysis evaluated MIPD patients through June 2020 performed by three experienced pancreatic surgeons at three different institutions. Perioperative outcomes were compared before and after propensity score-matching analyses, and learning curves based on operation time were used for additional matching analysis. RESULTS: Of 362 patients, 282 underwent LPD and 80 underwent RPD. Open conversion rate was significantly higher in LPD (P = .001). There were no significant differences in rates of major complications (Clavien-Dindo ≥III) and clinically relevant postoperative pancreatic fistula (CR-POPF). After matching, operation time (P = .001) and hospital stay (P = .027) were significantly shorter in RPD, but there were no differences in major complications and CR-POPF. Propensity score-matched comparison after learning curve attainment showed shorter operation time (P = .037) and hospital stay (P = .014) in RPD, and no differences in major complications and CR-POPF. CONCLUSION: RPD had several advantages compared with LPD, including shorter operative time and hospital stay, and lower open conversion rate. Postoperative complications including CR-POPF showed comparable results in two groups. Both LPD and RPD seemed to be feasible and safe approaches in experienced hands.

Curative intent radical cholecystectomy followed by hyperthermic intraperitoneal chemotherapy in ruptured intraductal papillary neoplasm of gallbladder with invasive carcinoma.

Gallbladder cancer has a poor prognosis, especially in peritoneal carcinomatosis related to perforation of the gallbladder followed by bile spillage. Previously, curative-intent treatment was not considered in carcinomatosis from cancer of the biliary tract. A 72-year-old male was referred to the hospital with a perforated gallbladder cancer. Intraoperatively, the tumor was confined to the gallbladder and liver. We presented a case of intention-to-curative resection of perforated gallbladder cancer followed by intraoperative hyperthermic intraperitoneal chemotherapy.

Surgical Outcomes and Comparative Analysis of Transduodenal Ampullectomy and Pancreaticoduodenectomy: A Single-Center Study.

BACKGROUND: Transduodenal ampullectomy (TDA) is performed for adenoma or early cancer of the ampulla of Vater (AoV). This study aimed to analyze the short- and long-term outcomes of TDA (TDA group) when compared with conventional pancreaticoduodenectomy (PD) or pylorus-preserving pancreaticoduodenectomy (PD group). METHODS: Patients who underwent TDA between January 2006 and December 2019, and PD cases performed for AoV malignancy with carcinoma in-situ (Tis) (high-grade dysplasia, HGD) and T1 and T2 stage from January 2010 to December 2019 were reviewed. RESULTS: Forty-six patients underwent TDA; 21 had a benign tumor, and 25 cases with malignant tumors were compared with PD cases (n = 133). Operation time (p < 0.001), estimated blood loss (p < 0.001), length of hospital stays (p = 0.003), and overall complication rate (p < 0.001) were lower in the TDA group than in the PD group. Lymph node metastasis rates were 14.6% in pT1 and 28.9% in pT2 patients. The 5-year disease-free survival and 5-year overall survival rates for HGD/Tis and T1 tumor between the two groups were similar (TDA group vs PD group, 72.2% vs 77.7%, p = 0.550; 85.6% vs 79.2%, p = 0.816, respectively). CONCLUSION: TDA accompanied with lymph node dissection is advisable in HGD/Tis and T1 AoV cancers in view of superior perioperative outcomes and similar long-term survival rates compared with PD.

Pancreaticoduodenectomy with combined hepatic artery and portal vein resection after laparoscopic division of pancreaticosplenic ligament due to FOLFIRINOX-induced hepatic toxicity related secondary hypersplenism.

Pancreatic cancer is one of the dismal malignant disease in gastrointestinal tract. However, since the recent literature reporting median survival of FOLFIRINOX (leucovorin clcium, fluorouracil, irinotecan hydrochloride, oxaliplatin) chemotherapy was more than 12 months in metastatic pancreatic cancer was published, the positive attitude toward the treatment of the advanced pancreatic cancer is gradually expanded among the medical and surgical oncologists. Due to multiple combination of potent chemotherapeutic agents, potential adverse side effects should be concerned when considering FOLFIRINOX. Herein, we report a 55-year old male patient with locally advanced pancreatic cancer who successfully underwent curative resection following by laparoscopic division of pancreaticosplenic ligament due to long-term preoperative use of FOLFIRINOX related hepatic toxicity associated with secondary hypersplenism. The present case suggests the extended radical PD with combined major vascular resection following laparoscopic division of pancreaticosplenic ligament containing splenic artery and vein can improve the safety of curative resection and may expand the potential indication of pancreatic cancer in well-selected long-term use of preoperative FOLFIRINOX induced hepatic toxicity associated with secondary hypersplenism.

Role of postoperative adjuvant therapy in resected invasive intraductal papillary mucinous neoplasm of the pancreas: A multicenter external validation.

BACKGROUND: Adjuvant therapy is beneficial in prolonging survival in patients with pancreatic ductal adenocarcinoma (PDAC). However, no clear guidelines are available on the oncologic effect of adjuvant therapy in resected invasive intraductal papillary mucinous neoplasms (inv-IPMN). METHODS: In total, 551 patients with PDAC and 67 patients with inv-IPMN of the pancreas were reviewed. For external validation, 46 patients with inv-IPMN from six other Korean institutions were enrolled. Propensity score-matched analysis and stage-matched survival analysis were conducted. RESULTS: The mean follow-up durations in the inv-IPMN and PDAC groups were 43.36 months (SD, 42.34 months) and 43.35 months (SD, 35.62 months), respectively. The 5-year overall survival (OS) was significantly better in the resected inv-IPMN group than in the PDAC group in the overall stage-matched analysis (P < .001). In the inv-IPMN cohort, OS was better in the surgery alone group (P = .042). In subgroup analysis, no significant survival difference was found between the adjuvant therapy and surgery alone groups according to the stage (stage I; P = .285, stage II or III; P = .077). Multicenter external validation did not show a better OS in the adjuvant therapy group (P = .531). On multivariable analysis, only perineural invasion (PNI) was identified as an adverse prognostic factor in resected inv-IPMN (HR 4.844; 95% CI 1.696-13.838, P = .003). CONCLUSIONS: inv-IPMN has a more indolent course than PDAC. Current strategy of adjuvant therapy may not improve the OS in patients with resected inv-IPMN. Further investigations on the potential role of adjuvant therapy in inv-IPMN are mandatory.

Laparoscopic pancreaticoduodenectomy in pancreatic ductal adenocarcinoma.

Laparoscopic pancreatoduodenectomy (LPD) in pancreatic cancer is primarily criticized for its technical and oncological safety. Although solid evidence has not yet been established, many institutions are performing LPD for pancreatic cancer patients, with continuous efforts to ensure oncologic safety. In this video, we demonstrated a case of standard LPD combined with vascular resection in pancreatic cancer.

Laparoscopic pancreaticoduodenectomy with excision of aberrant right hepatic artery after preoperative segmental embolization in mid-bile duct cancer.

Laparoscopic pancreaticoduodenectomy has proven to be a safe and effective alternative to open pancreaticoduodenectomy with similar oncologic outcomes. Cases including excision of the hepatic artery with or without reconstruction during pancreaticoduodenectomy have been reported for periampullary cancer. Here we present a case of an 82-year-old patient who underwent laparoscopic pancreaticoduodenectomy following preoperative arterial embolization of an aberrant right hepatic artery arising from the superior mesenteric artery.

Total laparoscopic pancreaticoduodenectomy in patients with periampullary tumors: a learning curve analysis.

BACKGROUND: With continued technical advances in surgical instruments and growing expertise, many surgeons have safely performed laparoscopic pylorus-preserving pancreaticoduodenectomies (LPDs) with good results, and the laparoscopic approach is being performed more frequently. However, this complex procedure requires a relatively long training period to ensure technical competence. The present study aimed to analyze the learning curve for LPD. METHODS: From September 2012 to May 2019, LPDs were performed for 171 patients at the Yonsei University Severance Hospital by a single surgeon. We retrospectively analyzed the demographic and surgical outcomes. The learning curve for LPD was evaluated using both the cumulative sum (CUSUM) and risk-adjusted CUSUM (RA-CUSUM) methods. All variables among the learning curve phases were compared. RESULTS: Based on the CUSUM and the RA-CUSUM analyses, the learning curve for LPD was grouped into three phases: phase I was the initial learning period (cases 1-40), phase II represented the technical competence period (cases 41-100), and phase III was regarded as the challenging period (cases 101-171). CONCLUSIONS: According to the learning curve analysis, 40 cases are required to achieve technical competence in LPD and 100 cases are required to address highly challenging cases.