Surgical Outcomes of Pancreatectomy with Resection of the Portal Vein and/or Superior Mesenteric Vein and Jejunal Vein for Pancreatic Head Cancer: A Multicenter Study.

OBJECTIVE: The aim of this study was to investigate the safety and survival benefits of portal vein and/or superior mesenteric vein (PV/SMV) resection with jejunal vein resection (JVR) for pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA: Few studies have shown the surgical outcome and survival of pancreatic resection with JVR, and treatment strategies for patients with PDAC suspected of jejunal vein (JV) infiltration remain unclear. METHODS: In total, 1260 patients who underwent pancreatectomy with PV/ SMV resection between 2013 and 2016 at 50 facilities were included; treatment outcomes were compared between the PV/SMV group (PV/ SMV resection without JVR; n = 824), PV/SMV-J1 V group (PV/SMV resection with first jejunal vein resection; n = 394), and PV/SMV-J2,3 V group (PV/SMV resection with second jejunal vein or later branch resection; n = 42). RESULTS: Postoperative complications and mortality did not differ between the three groups. The postoperative complication rate associated with PV/ SMV reconstruction was 11.9% in PV/SMV group, 8.6% in PV/SMV-J1 V group, and 7.1% in PV/SMV-J2,3V group; there were no significant differences among the three groups. Overall survival did not differ between PV/SMV and PV/SMV-J1 V groups (median survival; 29.2 vs 30.9 months, P = 0.60). Although PV/SMV-J2,3 V group had significantly shorter survival than PV/SMV group who underwent upfront surgery ( P = 0.05), no significant differences in overall survival of patients who received preoperative therapy. Multivariate survival analysis revealed that adjuvant therapy and R0 resection were independent prognostic factors in all groups. CONCLUSION: PV/SMV resection with JVR can be safely performed and may provide satisfactory overall survival with the pre-and postoperative adjuvant therapy.

A nomogram to preoperatively predict 1-year disease-specific survival in resected pancreatic cancer following neoadjuvant chemoradiation therapy.

OBJECTIVE: This study aimed to develop a nomogram to predict the 1-year survival of patients with pancreatic cancer who underwent pancreatectomy following neoadjuvant treatment with preoperatively detectable clinical parameters. Extended pancreatectomy is necessary to achieve complete tumor removal in borderline resectable and locally advanced pancreatic cancer. However, it increases postoperative morbidity and mortality rates, and should be balanced with potential benefit of long-term survival. METHODS: The medical records of patients who underwent pancreatectomy following neoadjuvant treatment from January 2005 to December 2016 at Severance Hospital were retrospectively reviewed. Medical records were collected from five international institutions from Japan and Singapore for external validation. RESULTS: A total of 113 patients were enrolled. The nomogram for predicting 1-year disease-specific survival was created based on 5 clinically detectable preoperative parameters as follows: age (year), symptom (no/yes), tumor size at initial diagnostic stage (cm), preoperative serum carbohydrate antigen (CA) 19-9 level after neoadjuvant treatment (<34/≥34 U/mL), and planned surgery [pancreaticoduodenectomy (PD) (pylorus-preserving PD)/distal pancreatectomy (DP)/total pancreatectomy]. Model performance was assessed for discrimination and calibration. The calibration plot showed good agreement between actual and predicted survival probabilities; the the Greenwood-Nam-D'Agostino (GND) goodness-of-fit test showed that the model was well calibrated (χ2=8.24, P=0.5099). A total of 84 patients were used for external validation. When correlating actual disease-specific survival and calculated 1-year disease-specific survival, there were significance differences according to the calculated probability of 1-year survival among the three groups (P=0.044). CONCLUSIONS: The developed nomogram had quite acceptable accuracy and clinical feasibility in the decision-making process for the management of pancreatic cancer.

Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP05).

A randomized, controlled trial has begun to compare neoadjuvant chemotherapy using gemcitabine and S-1 with upfront surgery for patients planned resection of pancreatic cancer. Patients were enrolled after the diagnosis of resectable or borderline resectable by portal vein involvement pancreatic cancer with histological confirmation. They were randomly assigned to either neoadjuvant chemotherapy or upfront surgery. Adjuvant chemotherapy using S-1 was administered for 6 months to patients with curative resection who fully recovered within 10 weeks after surgery in both arms. The primary endpoint is overall survival; secondary endpoints include adverse events, resection rate, recurrence-free survival, residual tumor status, nodal metastases and tumor marker kinetics. The target sample size was required to be at least 163 (alpha-error 0.05; power 0.8) in both arms. A total of 360 patients were required after considering ineligible cases. This trial began in January 2013 and was registered with the UMIN Clinical Trials Registry (UMIN000009634).

Diffusion-weighted MR imaging of pancreatic cancer and inflammation: Prognostic significance of pancreatic inflammation in pancreatic cancer patients.

BACKGROUND: Pancreatic cancer often accompanies chronic obstructive pancreatitis (COP) due to obstruction of the main pancreatic duct, and the inflammatory environment may enhance cancer progression. The purpose of this study is to evaluate COP using the apparent diffusion coefficient (ADC) value measured by diffusion-weighted MR imaging (DWI), and to assess its prognostic significance in pancreatic cancer. METHODS: Twenty-eight patients (16 men, 12 women; mean age 67.1 years) with pancreatic cancers who underwent DWI followed by curative surgery were evaluated. The ADC value of pancreatic parenchyma upstream to the tumor (upstream pancreas) was measured and compared with the upstream pancreatic duct dilatation to assess whether DWI could reflect COP. The ADC values of tumor and upstream portion were compared with overall survival (OS) using Cox regression and Kaplan-Meier analysis. RESULTS: The ADC value of upstream pancreas was significantly lower in patients with greater dilated pancreatic duct than those with less (P = 0.03). In univariate Cox regression analysis, the ADC value of upstream pancreas showed a significant association with OS (P = 0.01), but that of tumor did not (P = 0.06). In Kaplan-Meier analysis, patients with lower ADC value of upstream pancreas (<1.36 × 10(-3) mm(2)/s) were significantly associated with poor OS (P = 0.0006). In multivariate analysis, the ADC value of upstream pancreas was identified as an independent prognostic factor (P = 0.01; hazards ratio, 0.05; 95% CI, 0.004-0.59). CONCLUSIONS: The ADC value of upstream pancreas was an independent prognostic factor for OS in pancreatic cancer patients. Inflammatory environment may play an important role in pancreatic cancer progression.

Is it possible to define early distal cholangiocarcinoma?

PURPOSE: The feasibility of defining early cholangiocarcinoma has not been adequately evaluated. The surgical outcomes of patients who had undergone pancreatoduodenectomy (PD) for pathological T1 (pT1) distal cholangiocarcinoma (DCC) were evaluated to determine whether it is possible to define early DCC. METHODS: The clinicopathological data of 18 patients with pT1 DCC who had undergone PD were reviewed retrospectively. Depth of fibromuscular (fm) layer invasion was divided into two categories: fm1 and fm2 (without adventitia fascia invasion and with adventitia fascia invasion). Comparative analyses were performed according to the depth of invasion. RESULTS: Disease-specific survival rates of patients with five mucosal tumors and 13 fm-invasive tumors were 80 and 61.9 % at 5 years and 80 and 41.2 % at 10 years, respectively. There was no significant difference in disease-specific survival rates between the two groups (P = 0.244). Disease-specific survival rates of patients with 7 fm1-invasive tumors and 6 fm2-invasive tumors were 85.7 and 40 % at 5 years and 85.7 and 0 % at 10 years. A significant difference in disease-specific survival rates was observed between mucosal tumors and fm2-invasive tumors (P = 0.043), and disease-specific survival rates of mucosal tumors and fm1-invasive tumors were similar (P = 0.968). CONCLUSIONS: Defining early DCC as carcinoma confined to the fm of the bile duct might be inappropriate; early DCC should be limited to the mucosal carcinoma.

Long-term surgical outcomes of patients with type 1 autoimmune pancreatitis.

BACKGROUND: Although pancreatectomy has sometimes been performed for patients with autoimmune pancreatitis (AIP) presenting atypical radiologic findings under the diagnosis of pancreatobiliary malignancy, the long-term surgical outcome of these patients had not yet been fully elucidated. METHODS: The long-term surgical outcomes of 13 patients with pathologically diagnosed type 1 AIP with immunohistochemical staining for immunoglobulin G4 (IgG4) were retrospectively compared with those of 34 patients with conventional chronic pancreatitis to evaluate the residual pancreatic function. RESULTS: A definite relapse of AIP in terms of the clinical manifestations and diagnostic imaging was not found in any of the patients, although one patient experienced an attack of acute pancreatitis caused by pancreatic stones, and stricture of the hepaticojejunostomy occurred in one patient. The overall body weight decreased significantly more in patients with AIP than in patients with conventional chronic pancreatitis (p < 0.05); however, there was no difference in the preoperative nondiabetic patients. Refractory diarrhea occurred in only one patient with AIP. The cumulative new-onset rates of diabetes mellitus of the ten patients with AIP and 24 patients with conventional chronic pancreatitis at 5 years after the surgery were 32.5 and 26.1 %, respectively (p = 0.70). CONCLUSIONS: Careful long-term follow-up is needed for patients undergoing pancreatectomy for type 1 AIP because remnant pancreatic function can deteriorate as severely as that of patients who undergo pancreatectomy for conventional chronic pancreatitis. In the present series, however, there were few definite manifestations indicating relapse or the persistent existence of AIP.

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.

Single-incision laparoscopic enucleation for pancreatic insulinoma with preoperative nasopancreatic stent placement: A case report.

INTRODUCTION AND IMPORTANCE: Most insulinomas are benign and solitary, with a tumor diameter less than 2 cm; therefore, laparoscopic enucleation, which is a minimally invasive procedure that can preserve the pancreatic parenchyma, is considered an optimal procedure. The key to enucleation is to avoid injury to the main pancreatic duct (MPD). Herein, we present a case in which single-incision laparoscopic enucleation (SILE) was performed for insulinomas, with preoperative nasopancreatic stent (NPS) placement. CASE PRESENTATION: A male patient in his fifties underwent SILE for insulinomas. To prevent injury to the MPD, an NPS was preoperatively placed. All surgical procedures were performed through a single mini-laparotomy site in the umbilicus. NPS placement facilitated identification of the MPD under laparoscopic ultrasonography. Enucleation was successfully completed without any injury to the MPD, and the NPS was removed immediately after confirming that there was no injury to the MPD by the NPS via pancreatography. The postoperative course was uneventful. CLINICAL DISCUSSION: This report serves to highlight the maximum safety and minimal invasiveness of SILE with the preoperative NPS placement. Preoperative NPS placement is useful for avoiding injury to the MPD during enucleation and has the merit of helping to recognize whether leakage occurs by intraoperative pancreatography via the NPS. CONCLUSION: Preoperative NPS placement helps to ensure the safe enucleation of pancreatic insulinomas even in single-incision laparoscopic surgery, with minimal invasiveness and better cosmetic outcomes.

Tumor-to-tumor metastasis: an extremely rare combination with renal cell carcinoma as the donor and a pancreatic neuroendocrine tumor as the recipient.

BACKGROUND: Tumor-to-tumor metastasis is a rare phenomenon in which primary tumor cells metastasize hematogenously into another tumor. Herein, we report an extremely rare case of a renal cell carcinoma metastasis into a pancreatic neuroendocrine tumor exhibiting a tumor-to-tumor metastasis. Ours is the third reported case worldwide. CASE PRESENTATION: The patient, a 72-year-old male, was referred to our hospital for further examination and treatment due to high levels of prostate-specific antigen. A left renal tumor and pancreatic head tumor were revealed incidentally on screening computed tomography. There were suspected to be a renal cell carcinoma and primary pancreatic neuroendocrine tumor or pancreatic metastasis from the renal cell carcinoma according to preoperative examination. The left nephrectomy and subtotal stomach-preserving pancreaticoduodenectomy were performed because of the pancreatic tumor indicated for operation in either case of diagnosis. Postoperative pathological examination showed a diagnosis of clear cell renal cell carcinoma for the left renal tumor. The pancreatic tumor was diagnosed with clear cell renal cell carcinoma metastasis into the pancreatic neuroendocrine tumor, that is to say tumor-to-tumor metastasis. CONCLUSION: In some cases, conservative approach is selected for pancreatic neuroendocrine tumor patients who meet some requirements. However, if such patients exhibit tumor-to-tumor metastasis which combines with renal cell carcinoma and pancreatic neuroendocrine tumor as this case, conservative approach leads to progression of renal cell carcinoma. Therefore, conceiving the possibility of tumor-to-tumor metastasis, it is necessary to carefully choose a treatment plan for pancreatic neuroendocrine tumor patients associated with renal cell carcinoma, not easily choosing conservative approach.

Production of a recombinant full-length prion protein in a soluble form without refolding or detergents.

Recombinant prion protein has been produced in insoluble form and refolded following solubilization with denaturants. It is, however, preferable to use a soluble recombinant protein prepared without artificial solubilization. In this study, a soluble recombinant prion protein was produced in Escherichia coli cells by coexpression of neuregulin I-ß1 and purified to high purity.

A case with massive hemobilia long-term after internal drainage surgery for congenital biliary dilation.

BACKGROUND: Currently, there is an unwavering consensus that the standard surgery for congenital biliary dilation (CBD) is extrahepatic bile duct resection and choledochojejunostomy. However, decades prior, choledochocyst-gastrointestinal anastomosis without extrahepatic bile duct resection (internal drainage surgery, IDS) was preferred for CBD because of its simplicity. Currently, there is almost no chance of a surgeon encountering a patient who has undergone old-fashioned IDS, which has been completely obsolete due to the risk of carcinogenesis from the remaining bile duct. Moreover, the pathological condition long after IDS is unclear. Herein, we report a case of life-threatening bile duct bleeding as well as carcinoma of the bile duct 62 years after IDS in a patient with CBD. CASE PRESENTATION: An 82-year-old Japanese woman with hemorrhagic shock due to gastrointestinal bleeding was transferred to our hospital. She had a medical history of unspecified surgery for CBD at the age of 20. Based on imaging findings and an understanding of the historical transition of the surgical procedure for CBD, the cause of gastrointestinal bleeding was determined to be rupture of the pseudoaneurysm of the dilated bile duct that remained after IDS. Hemostasis was successfully performed by transcatheter arterial embolization (TAE) in an emergency setting. Then, elective surgery for extrahepatic bile duct resection and choledochojejunostomy was performed to prevent rebleeding. Pathological examination revealed severely and chronically inflamed mucosa of the bile duct. Additionally, cholangiocarcinoma (Tis, N0, M0, pStage 0) was incidentally revealed. CONCLUSION: It has been indicated that not only carcinogenesis, but also a risk of life-threatening bleeding exists due to long-lasting chronic inflammation to the remnant bile duct after IDS for CBD. Additionally, both knowledge of which CBD operation was performed, and an accurate clinical history are important for the diagnosis of hemobilia.

Clinical practice guidelines for the management of liver metastases from extrahepatic primary cancers 2021.

BACKGROUND: Hepatectomy is standard treatment for colorectal liver metastases; however, it is unclear whether liver metastases from other primary cancers should be resected or not. The Japanese Society of Hepato-Biliary-Pancreatic Surgery therefore created clinical practice guidelines for the management of metastatic liver tumors. METHODS: Eight primary diseases were selected based on the number of hepatectomies performed for each malignancy per year. Clinical questions were structured in the population, intervention, comparison, and outcomes (PICO) format. Systematic reviews were performed, and the strength of recommendations and the level of quality of evidence for each clinical question were discussed and determined. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations. RESULTS: The eight primary sites were grouped into five categories based on suggested indications for hepatectomy and consensus of the guidelines committee. Fourteen clinical questions were devised, covering five topics: (1) diagnosis, (2) operative treatment, (3) ablation therapy, (4) the eight primary diseases, and (5) systemic therapies. The grade of recommendation was strong for one clinical question and weak for the other 13 clinical questions. The quality of the evidence was moderate for two questions, low for 10, and very low for two. A flowchart was made to summarize the outcomes of the guidelines for the indications of hepatectomy and systemic therapy. CONCLUSIONS: These guidelines were developed to provide useful information based on evidence in the published literature for the clinical management of liver metastases, and they could be helpful for conducting future clinical trials to provide higher-quality evidence.

Is pancreatectomy with arterial reconstruction a safe and useful procedure for locally advanced pancreatic cancer?

BACKGROUND/PURPOSE: We often encounter unresectable pancreatic cancer due to invasions of the major vessels. Vascular resection for locally advanced pancreatic cancers has an advantage in en block local resection. There are potential cases in which good outcomes can be achieved by arterial resection. METHODS: Pancreatectomy (including total pancreatectomy in 15 cases, pancreatoduodenectomy in 7 cases and distal pancreatectomy in one case) was performed in 23 cases of invasive ductal carcinoma of the pancreas, in combination with resection and reconstruction of the hepatic artery in 15 cases, the superior mesenteric artery in 12 cases (there are overlaps) and the portal vein in 20 cases. RESULTS: The median operating time was 686 min (416-1,190 min) and the median blood loss was 2,830 ml (440-19,800 ml). This shows that the surgery was highly-invasive. The operative mortality rate was 4.3%. On the basis of the UICC classification, there were 2 cases of Stage IIa, 4 cases of Stage IIb, 9 cases of Stage III, 8 cases of Stage IV, while there were 18 cases (78.3%) of R0 resection. On the other hand, the final histological findings showed that there were 8 cases (34.8%) of M1 (liver and non-regional lymph node metastases), so it is thought that decisions on operative indications should be not be made slightly. As for the overall survival rate, the 1-year survival rate was 51.2% and the 3-year survival rate was 23.1% while the median survival time (MST) was 12 months. As for 15 cases of M0, the 1-year survival rate was 61.9% and the 4-year survival rate was 38.7% while the MST was 16 months. On the other hand, the MST was poor (10 months) in 8 cases of M1, showing that a statistically significant difference was observed depending upon the degree of metastasis (log-rank P = 0.0409). In 18 cases of R0, the 1-year survival rate was 67.2%, the 4-year survival rate 30.2% and the MST 13 months, respectively, while in 5 cases of R1 and R2, the MST was 6 months, showing that there was a statistically significant difference between R0 cases and R1, R2 cases (log-rank P = 0.0002). CONCLUSIONS: Further discussion is required concerning surgical indications and significance. However, it is thought that resection is useful only when surgery of R0 has taken place for selected locally advanced pancreatic cancer (M0).

In situ surgical procedures for locally advanced pancreatic cancer: partial abdominal evisceration and intestinal autotransplantation.

BACKGROUND/PURPOSE: Pancreatic cancers in which invasion to the root of the mesentery are suspected have been regarded as unresectable in general. We report the surgical techniques in two cases of locally advanced pancreatic cancer for which in situ surgical procedures including partial abdominal evisceration and intestinal autotransplantation were performed. METHODS: The patients were a woman 57 years of age and a man 64 years of age. Both cases had a locally advanced cancer that had originated in the pancreatic uncus and was found to have invaded the root of the mesentery, as well as the superior mesenteric artery (SMA) and the superior mesenteric vein (SMV). The cancers in both patients were assessed as resectable because the jejunal artery and vein were secured intact at a site peripheral from the root of the mesentery, and the origin of the SMA along with the portal and splenic veins was intact at a proximal site, so pancreatectomy and resection of the transverse and ascending colons were performed. The SMA and the SMV were ablated just below each origin at a site proximal to the root of the mesentery. At a distal site, two jejunal arteries and one jejunal vein were kept intact and all the remaining arteries and veins were ablated. The remaining small intestine had become a free autograft. As for the portal and jejunal veins, end-to-end anastomosis was performed. Reconstruction of the SMA was achieved with an end-to-end anastomosis, using the right internal iliac artery as a graft. Reconstruction of the alimentary tract was achieved using small intestine as an autograft. RESULTS: Both patients survived the major operative procedures. Warm ischemia time was 84 min for the SMA and 12 min for the SMV-portal system in Case 1 while it was 30 min for the SMA and 25 min for the SMV-portal system in Case 2. No ex-vivo resection technique was used. Leakage occurred in both cases at the anastomotic lesion between the small intestine and the left colon. Abdominal drainage and conservative treatment were applied in both cases. Cure was achieved within 3 months postoperatively in Case 1 and within 2.5 months in Case 2. Subsequently, the patients returned to their preoperative lives. Case 1 died 11 months and Case 2 died 12 months after the operation due to abdominal dissemination and liver metastases. CONCLUSIONS: We were able to perform in situ procedures including partial abdominal evisceration and intestinal autotransplantation for two cases of pancreatic cancer with possible invasion to the root of the mesentery. There are few reports of such procedures. There has been one report of a case which applied an ex vivo technique. It is expected that the development of adequate adjuvant therapy will lead to further improvement in the prognosis of pancreatic cancers.

Pancreatectomy with reconstruction of the right and left hepatic arteries for locally advanced pancreatic cancer.

BACKGROUND/PURPOSE: The resectability of locally advanced pancreatic cancer depends upon, before anything else, the relationship between the tumor and the adjacent arterial structure. Pancreatic cancer that has developed at the caudal side of the pancreas can invade the common hepatic artery (CHA). Pancreatic cancers with CHA involvement can become candidates for surgery in selected cases. Pancreatic cancer arising at the caudal side of the pancreas head may sometimes invade the right and left hepatic arteries (RLHA) as well as the CHA. Pancreatic cancer with RLHA involvement may be assessed as unresectable unless complex vascular reconstruction is performed. METHODS: We have experienced 3 cases of successfully resected pancreatic cancer with RLHA and portal vein (PV) invasion. Pancreatectomy (including total pancreatectomy in two cases and pancreatoduodenectomy in one case) with RLHA and PV reconstruction was performed. Three different techniques of arterial reconstruction that were suitable for the individual cases were used. They were: (1) end-to-end anastomosis between the CHA and the left hepatic artery (LHA) and end-to-end anastomosis between the middle hepatic artery (MHA) and the right hepatic artery (RHA), (2) end-to-end anastomosis between the left gastric artery (LGA) and the RHA and end-to-end anastomosis between the right gastroepiploic artery and the LHA, and (3) end-to-side anastomosis between the splenic artery (SA) and the LHA and end-to-end anastomosis between the SA and the RHA. RESULTS: The mean operating time was 735 min (range 686-800 min) and the mean blood loss was 1726 ml (range 1140-2230 ml). Microscopic curative resection (R0) was possible in all cases even if their International Union Against Cancer (UICC) stage was IIb. There was one case of wound infection, although no serious complications, including hepatic artery thrombosis, liver failure, or biliary fistula were observed. By follow-up three-dimensional computed tomography (3D-CT) angiography, the patency of the anastomosed artery was confirmed to be maintained in all three cases. CONCLUSIONS: R0 operation with 3 different arterial reconstruction techniques was able to be performed without presenting any risk.

Management of postoperative arterial hemorrhage after pancreato-biliary surgery according to the site of bleeding: re-laparotomy or interventional radiology.

BACKGROUND/PURPOSE: Intra-abdominal arterial hemorrhage is still one of the most serious complications after pancreato-biliary surgery. We retrospectively analyzed our experiences with 15 patients in order to establish a therapeutic strategy for postoperative arterial hemorrhage following pancreato-biliary surgery. METHODS: Between August 1981 and November 2007, 15 patients developed massive intra-abdominal arterial bleeding after pancreato-biliary surgery. The initial surgery of these 15 patients were pylorus-preserving pancreatoduodenectomy (PPPD) (7 patients), hemihepatectomy and caudate lobectomy with extrahepatic bile duct resection or PPPD (4 patients), Whipple's pancreatoduodenectomy (PD) (3 patients), and total pancreatectomy (1 patient). Twelve patients were managed by transcatheter arterial embolization and three patients underwent re-laparotomy. RESULTS: Patients were divided into two groups according to the site of bleeding: SMA group, superior mesenteric artery (4 patients); HA group, stump of gastroduodenal artery, right hepatic artery, common hepatic artery, or proper hepatic artery (11 patients). In the SMA group, re-laparotomy and coil embolization for pseudoaneurysm were performed in three and one patients, respectively, but none of the patients survived. In the HA group, all 11 patients were managed by transcatheter arterial embolization. None of four patients who had major hepatectomy with extrahepatic bile duct resection survived. Six of seven patients (85.7%) who had pancreatectomy survived, although hepatic infarction occurred in four. CONCLUSIONS: Management of postoperative arterial hemorrhage after pancreato-biliary surgery should be done according to the site of bleeding and the initial operative procedure. Careful consideration is required for indication of interventional radiology for bleeding from SMA after pancreatectomy and hepatic artery after major hepatectomy with bilioenteric anastomosis.

Exosome-encapsulated microRNA-4525, microRNA-451a and microRNA-21 in portal vein blood is a high-sensitive liquid biomarker for the selection of high-risk pancreatic ductal adenocarcinoma patients.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with poor prognosis. This is due to late diagnosis and lack of reliable prognostic biomarkers. In this study, we focused on exosomal microRNA (miRNA) in portal vein blood (PVB) as a potential biomarker to identify patients at high-risk for recurrence and poor postoperative outcome. METHODS: Exosomal miR-4525, miR-451a and miR-21 expressions were assessed using PVB and peripheral blood (PB) collected from 55 PDAC patients during curative pancreatectomy. Correlation between the miRNA expressions and clinical outcomes, and target genes expressions was investigated. RESULTS: Exosomal miR-4525, miR-451a and miR-21 levels were upregulated in PVB, which were higher than those in the PB. High expression of miR-4525, miR-451a and miR-21 in PVB was associated with recurrence with a higher sensitivity, specificity, and accuracy than that in PB. Cox regression analysis showed miR-4525, miR-451a and miR-21 levels in PVB were independent prognostic factors for overall survival and disease-free survival. There was a negative correlation between the expressions of miR-4525 and MEN1 mRNA, miR-451a and CAB39 mRNA, and t miR-21 and PDCD4 mRNA. CONCLUSIONS: miR-4525, miR-451a and miR-21 in PVB are potential biomarkers identifying patients at high-risk for recurrence and poor survival in resected PDAC patients.

A single-arm, phase II trial of neoadjuvant gemcitabine and S1 in patients with resectable and borderline resectable pancreatic adenocarcinoma: PREP-01 study.

BACKGROUND: Neoadjuvant chemotherapy (NAC) represents a promising alternative to pancreatic ductal adenocarcinoma (PDAC) planned resection, but the survival impact remains undefined. To assess the feasibility and survival outcomes of NAC with gemcitabine and S1 (GS) for PDAC planned resection by prospective study. METHODS: Patients with resectable or borderline resectable PDAC received 2 cycles of NAC-GS and were offered curative resection followed by gemcitabine adjuvant. The primary endpoint was 2-year overall survival (OS). Adverse events during NAC, radiological and tumor marker responses, resection rate, and surgical safety were evaluated as secondary endpoints (UMIN000004148). RESULTS: We enrolled 104 patients between 2010 and 2012, with 101 patients treated using NAC-GS as the full analysis set (FAS). Of the 101 patients, 88% received the planned 2 cycles of NAC. Grade 3 neutropenia was common (35%). Radiological partial response and decreased carbohydrate antigen 19-9 concentration (> 50% decrease) were noted in 13% and 41%, respectively. R0/1 resections with M0 were performed in 65 patients without surgical mortality. Of the 65 patients, 44 received planned gemcitabine adjuvant for 6 months as the on-protocol cohort. The primary endpoint for the 2-year OS rate was 55.9% in the FAS (n = 101) and 74.6% in the on-protocol cohort (n = 44). CONCLUSIONS: NAC-GS was feasible and actively prolonged survival following PDAC planned resection. Randomized control trials are needed to further clarify the survival benefit of NAC-GS in addition to surgery followed by adjuvant therapy.

Establishing extracorporeal membrane oxygenation team increased number of patients and improved data recording.

BACKGROUND: For patients treated with extracorporeal membrane oxygenation (ECMO), employing a well-coordinated, multidisciplinary team specializing in ECMO has reportedly been effective in delivering better clinical outcomes. This study aims to assess the impact of establishing such a specialized team for patients treated with ECMO. METHOD: This retrospective cohort study was performed at a tertiary-care hospital in Japan. We reviewed medical records of all consecutive patients treated with ECMO during October 2010-September 2016. The results obtained in pre-ECMO team cases (PRE group; October 2011-September 2012) and post-ECMO team cases (POST group; October 2014-September 2015) were compared. RESULTS: The results obtained in pre-ECMO team cases (PRE group; October 2011-September 2012) and post-ECMO team cases (POST group; October 2014-September 2015) were compared. During the study period, 177 patients were treated with ECMO. Before the introduction of ECMO team, an average of 22.7 patients underwent ECMO treatment per year; after establishing ECMO team, this number increased to 36.3 patients per year. ECMO was applied mainly to cardiac arrest patients 52/69 (75%). The PRE (n = 27) and POST (n = 42) groups did not differ with regard to the survival rate to hospital discharge, ECMO duration, ventilator days, and length of hospital stay. However, PaO2 and positive end-expiratory pressure were significantly higher in the POST group at 6 h after ECMO initiation than those in the PRE group [367 (186-490) vs. 239 (113-430) mmHg, p = 0.047 and 8 (5-10) vs. 7 (5-8) cmH2O, p = 0.01, respectively]. In addition, data recording the detailed time points of ECMO initiation was conducted in significantly more cases in the POST group (28/126 (22%) than in the PRE group (6/81 (7%); p = 0.01). CONCLUSIONS: Following the establishment of an ECMO team, the survival rate of patients treated with ECMO, ECMO duration, and length of hospital stay were not improved. However, the number of ECMO cases increased and the recording of clinical data was improved.

Usefulness of exosome-encapsulated microRNA-451a as a minimally invasive biomarker for prediction of recurrence and prognosis in pancreatic ductal adenocarcinoma.

BACKGROUND: MicroRNAs (miRNAs) encapsulated in the exosomes of plasma is of interest as stable and minimally invasive biomarkers for recurrence and prognosis in cancer patients. The aim of this study was to clarify the predictive and prognostic value of plasma exosomal microRNA-451a (miR-451a) in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Microarray-based expression profiling of miRNAs derived from exosomes in the plasma of six PDAC patients with UICC stage II was employed to identify a biomarker to distinguish between patients with and without recurrence. For validation analysis, plasma exosome samples of other 50 PDAC patients were measured by TaqMan MicroRNA assays. RESULTS: In the miRNA microarray analyses, miR-451a showed the highest upregulation in the stage II patients who showed recurrence after surgery. In the relationship to pathological factors, exosomal miR-451a showed a significant association with tumor size and stage. The overall survival (OS) and disease-free survival rates (DFS) of the high exosomal miR-451a patients were significantly worse than those of the low miR-451a patients. In Cox proportional hazards model analysis, exsomal miR-451a showed significance to OS and DFS. CONCLUSIONS: Plasma exosomal miR-451a levels may be a useful minimally invasive biomarker for the prediction of recurrence and prognosis in PDAC patients.