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We herein reported a case of advanced gastric cancer (GC) with para-aortic lymph node (PALN) metastases who successful achieved downstaging following systemic chemotherapy and underwent curative laparoscopic conversion surgery. A 74-year-old male patient diagnosed with advanced GC and PALN metastases [cT4N3M1(LYM), stage IVA] was administered chemotherapy and immunotherapy for 28 months. After 27 courses of nivolumab as third-line chemotherapy, PALN enlargement was resolved, for which conversion surgery was planned. Subsequently, laparoscopic distal D2 gastrectomy with sampling para-aortic lymphadenectomy was performed, after which a pathological diagnosis of type V moderately differentiated tubular adenocarcinoma with mucinous adenocarcinoma, stage ypT3 (SS), ly1c, and v0, was established. The pathological proximal and distal tumor margins were negative. One lymph node metastasis was observed (No. 6; 1/25). The sampled lymph nodes were negative (No. 16a1: 0/2). The therapeutic effect was categorized as Grade 1a. The postoperative course was uneventful, with the patient receiving nivolumab to control for potential PALN metastases. Postoperatively, no recurrence was observed over 11 months. Laparoscopic conversion gastrectomy was successfully performed in a patient with advanced GC that was originally unresectable, suggesting that minimally invasive surgery may be a good option for originally unresectable advanced GC that becomes resectable.

Diaphragmatic resection may be required beneath the diaphragm in some patients with liver tumors. Laparoscopic diaphragmatic resection is technically difficult to secure in the surgical field and in suturing. We report a case of successful laparoscopic hepatectomy with diaphragmatic resection. A 48-year-old man who underwent laparoscopic partial hepatectomy for liver metastasis of rectal cancer 20 months ago underwent surgery because of a new hepatic lesion that invaded the diaphragm. The patient was placed in the left hemilateral decubitus position. The liver and diaphragm attachment areas were encircled using hanging tape. Liver resection preceded diaphragmatic resection with the hanging tape in place. Two snake retractors were used to secure the surgical field for the inflow of CO2 into the pleural space after diaphragmatic resection. The defective part of the diaphragm was repaired using continuous or interrupted sutures. Both ends of the suture were tied with an absorbable suture clip without ligation. In laparoscopic liver resection with diaphragmatic resection, the range of diaphragmatic resection can be minimized by performing liver resection using the hanging method before diaphragmatic resection. The surgical field can be secured using snake retractors. Suturing with an absorbable suture clip is conveniently feasible. Supplementary Information The online version contains supplementary material available at 10.1007/s13691-021-00506-x.

Lenvatinib is reported to have a stronger angiogenesis-inhibiting effect in hepatocellular carcinoma(HCC)than sorafenib, but in many cases dose reduction and withdrawal are required due to the occurrence of adverse events. We report 12 cases of using lenvatinib for advanced HCC in our hospital together with a case of rapid re-growth due to withdrawal of lenvatinib. In 2 cases, metastases of HCC were controlled and radically resected. All patients required lenvatinib withdrawal due to Grade 3 adverse event, except for 2 cases that started with dose reduction. There were 3 cases in which drug withdrawal was required for 2 weeks or more, and in 2 of them, rapid re-growth of tumor was observed during the drug withdrawal and the treatment could not be continued. Although the use of lenvatinib may results in tumor shrinkage, suggesting that prolonged drug withdrawal may make disease management difficult. It is important to manage adverse events and minimize days of drug withdrawal by reducing the dose and systematically discontinuing the drug.

BACKGROUND Prevention of bile duct injury and vasculo-biliary injury while performing laparoscopic cholecystectomy (LC) is an unsolved problem. Clarifying the surgical difficulty using intraoperative findings can greatly contribute to the pursuit of best practices for acute cholecystitis. In this study, multiple evaluators assessed surgical difficulty items in unedited videos and then constructed a proposed surgical difficulty grading. METHODS We previously assembled a library of typical video clips of the intraoperative findings for all LC surgical difficulty items in acute cholecystitis. Fifty-one experts on LC assessed unedited surgical videos. Inter-rater agreement was assessed by Fleiss's κ and Gwet's agreement coefficient (AC). RESULTS Except for one item ("edematous change"), κ or AC exceeded 0.5, so the typical videos were judged to be applicable. The conceivable surgical difficulty gradings were analyzed. According to the assessment of difficulty factors, we created a surgical difficulty grading system (agreement probability = 0.923, κ = 0.712, 90% CI: 0.587-0.837; AC2 = 0.870, 90% CI: 0.768-0.972). CONCLUSION The previously published video clip library and our novel surgical difficulty grading system should serve as a universal objective tool to assess surgical difficulty in LC.

BackgroundPancreatic ductal adenocarcinoma (PDAC) is a lethal disease, and multimodal strategies, such as surgery plus neoadjuvant chemotherapy (NAC)/adjuvant chemotherapy, have been attempted to improve survival in patients with localized PDAC. To date, there is one prospective study providing evidence for the superiority of a neoadjuvant strategy over upfront surgery for localized PDAC. However, which NAC regimen is optimal remains unclear.MethodsA randomized, exploratory trial is performed to examine the clinical benefits of two chemotherapy regimens, gemcitabine plus S-1 (GS) and gemcitabine plus nab-paclitaxel (GA), as NAC for patients with planned PDAC resection. Patients are enrolled after the diagnosis of resectable or borderline resectable PDAC. They are randomly assigned to either NAC regimen. Adjuvant chemotherapy after curative resection is highly recommended for 6 months in both arms. The primary endpoint is tumor progression-free survival time, and secondary endpoints include the rate of curative resection, the completion rate of protocol therapy, the recurrence type, the overall survival time, and safety. The target sample size is set as at least 100.DiscussionThis study is the first randomized phase II study comparing GS combination therapy with GA combination therapy as NAC for localized pancreatic cancer.Trial registrationUMIN Clinical Trials RegistryUMIN000021484. This trial began in April 2016.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, and multimodal strategies, such as surgery plus neoadjuvant chemotherapy (NAC)/adjuvant chemotherapy, have been attempted to improve survival in patients with localized PDAC. To date, there is one prospective study providing evidence for the superiority of a neoadjuvant strategy over upfront surgery for localized PDAC. However, which NAC regimen is optimal remains unclear.Methods: A randomized, exploratory trial was performed to examine the clinical benefits of two chemotherapy regimens, gemcitabine plus S-1 (GS) and gemcitabine plus nab-paclitaxel (GA), as NAC for patients with planned PDAC resection. Patients were enrolled after the diagnosis of resectable or borderline resectable PDAC. They were randomly assigned to either NAC regimen. Adjuvant chemotherapy after curative resection was highly recommended for 6 months in both arms. The primary endpoint was tumor progression-free survival time, and secondary endpoints included the rate of curative resection, the completion rate of protocol therapy, the recurrence type, the overall survival time and safety. The target sample size was set as at least 100.Discussion: This study is the first randomized phase II study comparing GS combination therapy with GA combination therapy as NAC for localized pancreatic cancer.Trial registration: This trial began in April 2016 and was registered with the UMIN Clinical Trials Registry (UMIN000021484).

Neoadjuvant therapy reportedly shows only marginal clinical benefit in pancreatic ductal adenocarcinoma (PDAC), especially in resectable cases. However, with more effective regimens, neoadjuvant therapy may become a standard of care for resectable cases. A prospective, open-label, multicenter phases 1 and 2 trial of neoadjuvant therapy was conducted using full-dose gemcitabine and S-1 concurrently with 50.4 Gy of radiation therapy (GSRT) for resectable PDAC. This report describes the phase 2 results. The phase 2 part of this study enrolled 57 patients with cytologically or histologically proven PDAC deemed resectable based on imaging before neoadjuvant therapy. These patients received GSRT. After reevaluation by computed tomography scan, surgical exploration was performed, followed by adjuvant therapy. According to the prescribed protocol of the clinical trial, statistical analyses included 57 phase 2 patients and 6 phase 1 patients who received the same dosage as in phase 2. This trial enrolled 63 patients (42 men and 21 women) with a median age of 70 years. Leukopenia or neutropenia of grade 3 or higher occurred for 79% of the patients, but no other severe adverse events were observed. Among the 63 patients, 54 underwent surgical resection. Intention-to-treat analysis of the 63 patients showed an excellent median survival time lasting as long as 55.3 months. The patients who completed neoadjuvant therapy, surgery, and adjuvant therapy had a 5-year survival rate of 56.6%. This regimen showed outstanding clinical efficacy with acceptable tolerability for patients with resectable PDAC.

Here, we report a case of ascending colon cancer successfully treated with laparoscopic right hemicolectomy in a 74- year-old man with a medical history of hemophilia A. He was admitted to our hospital because of bloody stool and diagnosed with type 2 ascending colon cancer based on colonoscopy findings. Preoperatively, blood transfusion and administration of recombinant factor Ⅷ products were performed. Surgery involved laparoscopic right hemicolectomy plus group 3 lymph node dissection. No complications, such as bleeding, occurred during hospitalization. The patient was discharged on postoperative day 8. There have been a few reports of laparoscopic surgery for patients with hemophilia. However, this case suggests that it can be safely performed with planned factor Ⅷ supplementation in the perioperative period.

Laparoscopic pancreaticoduodenectomy(LPD)is less invasive and provides better cosmetic outcomes than open pancreaticoduodenectomy( OPD). LPD without vascular excision and lymph node dissection has been covered by insurance since 2016 in Japan. On the other hand, secondary small bowel volvulus is a rare condition caused after abdominal operation. A 77-year-old woman underwent a laparoscopic pancreaticoduodenectomy with pancreatic cancer of pT2N0M0, pStageⅠB. She suffered from epigastric pain after meal. The abdominal CT revealed counterclockwise rotation of the SMV on SMA about 540 degree. Gastrointestinal endoscopy showed no abnormal findings in May 2017. Her abdominal pain was disappeared in July 2017. But the pain was recurred in May 2019. The abdominal CT revealed mesenteric edema and counterclockwise rotation about 810 degree. Her abdominal pain was disappeared again in February 2020. The counterclockwise rotation was decreased about 540 degree. Between May 2012 and February 2020, 50 patients underwent LPD at Kansai Rosai Hospital. 111 patients who received OPD between 2010 and February 2015 were included for comparison. No significant differences were noted between the LPD and OPD groups with respect to patient age(67.9 vs 70.3), gender(M/F: 31/19 vs 70/41). The intraoperative blood loss was lower(106 g vs 1,064 g, p0.0001)and the operation time was longer (624 vs 535 min, p0.0001)in the LPD group than the OPD group. Small bowel volvulus over 270 degree was 7/43 vs 5/106(p=0.0338), and over 360 degree was 6/44 vs 1/110(p=0.0014), respectively. Small bowel volvulus after pancreaticoduodenectomy was frequently observed in the laparoscopic group.

Rationale: Pancreatic cancer (PC) has the worst prognosis among all carcinomas. However, patients with carcinoma in situ (CIS) of the pancreas, usually, have a good prognosis. Many previous reports have mentioned the high frequency of fibrosis around CIS. In some cases, the fibrosis is detected on endoscopic ultrasonography (EUS), but there are few past reports of fibrosis detected on computed tomography (CT). Patient concerns: We encountered a case of fibrosis around CIS detected by CT. A 74-year-old man was being followed for chronic hepatitis C. On a contrast-enhanced CT (CE-CT), a space-occupied lesion (7 mm in size) in the pancreatic head was identified in the delayed phase. Diagnosis: It was shown to be a hypo echoic lesion in EUS, and EUS-fine-needle aspiration was performed. Cytological examination revealed abnormal cells suspicious for a neuroendocrine tumor. Interventions: Consequently, a pancreaticoduodenectomy was performed. Histopathological examination showed CIS in the branch duct with 10 mm of fibrosis around CIS. The fibrotic area corresponded to the mass detected by preoperative CE-CT. Outcomes: He had no relapse of PC but died 2 years later from another cause. Lessons: This case highlights the importance of identifying the enhanced area in the delayed phase on CE-CT, as this can be fibrosis around CIS.

416 Background: The NIVOLVE trial was designed to assess the efficacy and safety of nivolumab as an adjuvant therapy for HCC, and to identify biomarkers predictive of recurrence in patients after SR or RFA (Registration # UMIN 000026648). Methods: The trial involved 11 sites and was conducted in patients with HCC who showed a complete response after SR (n = 33) or RFA (n = 22) (ITT). Overall, 53 of 55 patients with Child-Pugh A received nivolumab (240 mg/body every 2 weeks (8 cycles)), followed by nivolumab (480 mg/body every 4 weeks [8 cycles]) within 6 weeks after SR or RFA. The primary endpoint was the 1-year recurrence-free survival rate (RFSR). The key secondary endpoint was RFS. Exploratory biomarker analysis included mutations, copy number alterations, and positivity of immune cells. Techniques included next generation sequencing, immunohistochemical staining (IHC) of formalin-fixed paraffin-embedded tissues (n = 31 [13 with recurrence and 18 without]) for CD8, PD-1, PD-L1, Foxp3, and β-catenin, and ctDNA analysis using pre-nivolumab whole blood by deep sequencing (CAPP-seq; Avenio). Results: The 1-year RFSR and median RFS were 78.6% and 26.3 months (95% confidence interval (CI), 16.8-NR), respectively, with no difference between SR and RFA. Copy number gains (CNGs) in WNT/β-catenin related genes ( APC, CTNNB1, TCF7L1, TCF7L2) (n = 30) correlated with shorter RFS (positive: 10.6 months vs. negative: not reached [NR]; p < 0.0001). IHC revealed that negative staining for PD-1 (p < 0.0001), a low combined positive score for PD-L1 (p = 0.005), a low number of CD8+ tumor infiltrating lymphocytes (TILs) (p < 0.001), and positivity for Foxp3+ cells (p = 0.015) correlated with recurrence. HCC cases with low numbers of CD8+ TILs or cases positive for Foxp3+ cells (n = 16) showed a significantly shorter RFS (16.8 months [95% CI, 8.7-25.2]) than those with high numbers of CD8+ TILs and those positive for PD-1/PD-L1 expression (n = 15) (NR [95% CI,26.2months–NR]) (p < 0.0001). HCC cases with activation of the WNT/β-catenin pathway assessed by IHC (n = 9) showed shorter RFS (17.0 months [95% CI,1.1–26.2]) than those without activation (n = 22) (NR [95% CI,23.0 months–NR]) (p = 0.014). Patients positive for ctDNA (n = 15) before nivolumab tended to have shorter RFS than those without ctDNA (n = 9) (26.3 vs. NR). There was no correlation between TMB and RFS. Treatment-emergent adverse events (AEs) (n = 53) were as follows: all grades, 93%; grades 3–4 (18.9%); and immune related AEs, 25%. Conclusions: The 1-year RFSR and RFS in the NIVOLVE trial were 78.6% and 26.3 months, respectively. No new safety signal was observed. CNG in WNT/β-catenin-related genes, activation of the WNT/β-catenin pathway, the presence of Foxp3+ cells, and low numbers of CD8+ TILs may predict recurrence after SR or RFA with adjuvant nivolumab. Clinical trial information: UMIN 000026648.

Background Prospective studies are needed to understand the safety and feasibility of laparoscopic pancreatectomy. The aim of the present study was to describe laparoscopic pancreatectomy currently undertaken in Japan, using a prospective registration system. Methods Patient characteristics and planned operations were registered preoperatively, and then the performed operation and outcomes were reported using an online system. Collected data were also compared between institutions based on their level of experience. This study was registered with UMIN000022836. Results Available data were obtained from 1,429 patients at 100 Japanese institutions, including 1,197 laparoscopic distal pancreatectomies (LDPs) and 232 laparoscopic pancreatoduodenectomies (LPDs). The rates of completion for planned operations were 92% for LDP and 91% for LPD. Postoperative complication rates after LDP and LPD were 17% and 30%, and 90-day mortality rates were 0.3% and 0.4%, respectively. Shorter operation time, less blood loss, and lower incidence of pancreatic fistula were observed in institutions experienced in LDP. A higher rate of pure laparoscopic procedure and shorter operation time were noted in institutions experienced with LPD. Conclusion LDPs and LPDs are performed safely in Japan, especially in experienced institutions. Our data could support the next challenges in the field of laparoscopic pancreatectomy.

Endovascular repair is often difficult in the case of a huge abdominal aortic aneurysm for anatomic reasons. Here, we describe open repair of a huge infrarenal abdominal aortic aneurysm. Open repair was performed through laparotomy with the Cattell-Braasch maneuver, a technique for right-sided medial visceral rotation. Laparotomy with the Cattell-Braasch maneuver is simple and effective in open repair of a huge abdominal aortic aneurysm extending into the right common iliac artery, for which proximal clamping is difficult because of a tortuous proximal neck just below the hepatic region. Keywords: Laparotomy, Cattell-Braasch maneuver, Abdominal aortic aneurysm

The aim of the present study was to compare short‐term outcomes of laparoscopic and open liver resection (LLR and OLR, respectively), and we first analyzed a preoperatively enrolled and prospectively collected database. We carried out a secondary analysis using a preoperative enrolled database that included the details of 786 patients who had been enrolled in a previously carried out randomized controlled trial to assess short‐term outcomes, including morbidities. Statistical analyses included logistic regression, propensity score matching (PSM) with replacement, and inverse probability of treatment weighting (IPTW) analyses. Among 780 liver resections, OLR was carried out in 543 patients and LLR was carried out in 237 patients. LLR was selected in patients with a worse liver function and was related to a smaller resected liver weight and/or partial resection. Logistic regression, PSM, and IPTW analyses revealed that LLR was associated with less blood loss and a lower incidence of morbidities, but a longer operating time. LLR was found to be a preferred factor in biliary leakage by IPTW only. LLR was a preferred factor for blood loss, morbidities and hospital stay, but was associated with a longer operating time. UMIN‐CTR, UMIN000003324.

Background Anatomic variants of the biliary tree present challenges to surgical management during laparoscopic cholecystectomy and affect perioperative outcomes. An aberrant right hepatic duct connecting into the cystic duct is a practically important variation because of the susceptibility to serious postoperative refractory bile leakage. We report a successful case of laparoscopic cholecystectomy in the aberrant right hepatic duct of a patient diagnosed with chronic cystitis. Case presentation A 49-year-old man was referred to our department for treatment of chronic cholecystitis. Magnetic resonance cholangiopancreatography indicated that the cystic duct branched from the common bile duct and an aberrant bile duct connected to the cystic duct. Intraoperative cholangiography revealed that the bile duct was not confluent to the major right branch of the intrahepatic bile duct and drained a narrow area. Preoperative magnetic resonance cholangiopancreatography had diagnostic value. Furthermore, intraoperative cholangiography with the Critical View of Safety method was paramount to achieving safe cholecystectomy based on confirmation of the biliary anatomy and the drainage area of the aberrant right hepatic duct. Conclusion We encountered a rare but clinically significant case of laparoscopic cholecystectomy. This case suggests that precise understanding of the anatomy and drainage area of the aberrant right hepatic duct preoperatively and intraoperatively can lead to safe cholecystectomy. Electronic supplementary material The online version of this article (10.1186/s40792-019-0632-7) contains supplementary material, which is available to authorized users.

Repeat liver resection is an effective treatment approach for patients with recurrent hepatocellular cell carcinoma (HCC). However, the surgical feasibility and oncological significance of repeat laparoscopic liver resection (r-LLR) remain unproven. This study evaluates and compares the clinical outcomes of non-anatomic r-LLR applied towards recurrent HCC, with those of primary LLR (p-LLR) for primary HCC. This retrospective study reports 104 patients with HCC, treated with LLR between 2014 and 2018. Twenty eight of these patients underwent r-LLR for recurrent HCC. The clinical and surgical variables were reviewed for all cases. The analysis was limited to non-anatomic resection across both groups (r-LLR: 89% (25/28) vs. p-LLR: 80% (61/76)). There were no statistically significant differences about patient background between the two groups, with the exception of Child–Pugh classification. r-LLR surgical techniques included single-site laparoscopic adhesiolysis (32%, 8/25), Pringle maneuver (8%, 2/25), and crush–clamp method using BiClamp for hepatic parenchymal transection (72%, 18/25). No severe postoperative complications were observed in the r-LLR group. Postoperative hospital stays and procedure-related postoperative survival were similar for both groups. Non-anatomical r-LLR renders comparable surgical and oncological outcomes. Our data suggest that non-anatomical r-LLR is a safe and feasible therapeutic approach to recurrent HCC.

A 57-year-old female underwent abdominoperineal resection for rectal cancer. Although she received postoperative adjuvant chemotherapy, she had presacral recurrence with pain 26 months postoperatively. We provided palliative care in parallel with systemic chemotherapy, but she had difficulty controlling pain despite using high-dose opioids at 43 months after surgery. Multimodal therapy contributed to a reduction in opioid use for a brief time. Nevertheless, she required high-dose opioid therapy again at 50 months after the procedure. Since she used a rescue dose for relieving anticipatory anxiety for pain, we estimated that she developed chemical coping. After we tried analgesic adjuvant therapy and psychotherapy, her opioid use was reduced. For 10 months afterward, her disease worsened with time, but her pain was well-controlled. In cases where it is difficult to control pain, protection against exacerbation or opioid dose escalation should be considered. Furthermore, psychological contexts, including chemical coping, should also be considered. It may lead to the use of a proper dose of opioids and improve quality of life for patients.

4070 Background: The NIVOLVE trial was designed to assess the efficacy and safety of nivolumab as an adjuvant therapy for HCC, and to identify biomarkers predictive of recurrence in patients after SR or RFA (Registration # UMIN 000026648). Methods: The trial involved 11 sites and was conducted in patients with HCC who showed a complete response after SR (n = 33) or RFA (n = 22) (ITT). Overall, 53 of 55 patients with Child-Pugh A received nivolumab (240 mg/body every 2 weeks (8 cycles)), followed by nivolumab (480 mg/body every 4 weeks (8 cycles)) within 6 weeks after SR or RFA. The primary endpoint was the 1 year recurrence-free survival rate (RFSR). The key secondary endpoint was RFS. Exploratory biomarker analysis included mutations, copy number alterations, and tumor mutation burden in tumor tissues. Techniques included next generation sequencing, immunohistochemical staining (IHC) of formalin-fixed paraffin-embedded tissues (n = 31, 13 with recurrence and 18 without) for CD8, PD-1, PD-L1, Foxp3, and β-catenin, and ctDNA analysis using pre-nivolumab whole blood by deep sequencing (CAPP-seq; Avenio). Results: The 1-year RFSR and median RFS were 76.7% and 26.0 months (95% confidence interval (CI), 23.9–28.1), respectively, with no difference between SR and RFA. Copy number gains (CNGs) in WNT/β-catenin related genes ( APC, CTNNB1, TCF7L1, TCF7L2) (n = 8) correlated with shorter RFS (positive: 11.8 months vs. negative: not reached [NR]; p = 0.0003). IHC revealed that negative staining for PD-1 (p < 0.0001), a low combined positive score for PD-L1 (p = 0.0113), a low number of CD8+ tumor infiltrating lymphocytes (TILs) (p = 0.0130), and positivity for Foxp3+ cells (p = 0.0076) correlated with recurrence. Treatment-related adverse events (AEs) (n = 53) were as follows: all grades, 68%; grades 3–4 (18.9%); and immune related AEs, 25%. HCC cases with low numbers of CD8+ TILs or cases positive for Foxp3+ cells (n = 16) showed a significantly shorter RFS (16.8 months [95% CI, 8.7–25.1]) than those with high numbers of CD8+ TILs and those positive for PD-1/PD-L1 expression (n = 15) (NR [95% CI,26.2months–NR]) (p < 0.0001). HCC cases with activation of the WNT/β-catenin pathway assessed by IHC (n = 9) showed shorter RFS (17.0 months [95% CI,1.1–26.2]) than those without activation (n = 22) (NR [95% CI,24.7 months–NR]) (p = 0.0191). Patients positive for ctDNA (n = 10) before nivolumab tended to have shorter RFS than those without ctDNA (n = 30) (26.2 vs. NR). There was no correlation between TMB and RFS. Conclusions: The 1 year RFSR and RFS in the NIVOLVE trial were 76.6% and 26.0 months, respectively. No new safety signal was observed. CNG in WNT/β-catenin-related genes, activation of the WNT/β-catenin pathway, the presence of Foxp3+ cells, and low numbers of CD8+ TILs may predict recurrence after SR or RFA with adjuvant nivolumab. Clinical trial information: 000026648.

Extra-adrenal paraganglioma is a rare form of neuroendocrine neoplasm capable of catecholamine secretion. The surgical risks associated with the tumor location are compounded in this case of a kyphotic patient. This report presents the successful application of laparoscopy on extra-adrenal paraganglioma located behind the Spiegel lobe in a kyphotic patient. The operation was performed after 1 week of α-blocker administration. The laparoscopic approach, with the patient in the left hemilateral decubitus position on a rotating table, provided optimal access for safe tumor resection after complete hepatic right lobe mobilization. The patient's postoperative course was uneventful. Based on the results, the laparoscopic approach can be a safe and effective method for resecting extra-adrenal paraganglioma in the challenging case of a kyphotic patient.

The incidence of pancreatic fistula after distal pancreatectomy (DP) remains high at 16% to 35% of cases, and it is associated with a higher incidence of life-threatening complications such as intraabdominal abscess, intraabdominal hemorrhage, or sepsis.1–4 A strategy to decrease pancreatic fistula after DP is urgently required. Stapler closure has recently become a standard technique for pancreatic stump closure; however, the multicenter randomized DISPACT trial found that stapler closure did not significantly reduce the incidence of pancreatic fistula after DP in comparison to hand-sewn closure.5 In addition, we previously reported that stapler closure for transection of a thick pancreas (>12 mm) significantly increased the incidence of pancreatic fistula after DP.6,7 The most appropriate closure technique for the pancreatic stump during DP remains controversial. Several studies have demonstrated that pancreatic fistula in a pancreaticojejunostomy (PJ) of the pancreatic stump does not occur in patients who have undergone DP.8–10 Furthermore, our previous study reported that PJ of the pancreatic stump in DP with en bloc celiac axis resection prevents an extremely high amylase level (>4000 IU/L) in the drainage fluid.11 Several studies have evaluated the association between high drain amylase level and pancreatic fistula.12,13 However, no randomized controlled trials (RCTs) have confirmed the efficacy of PJ of the pancreatic stump during DP. Therefore, a randomized controlled multicenter trial was designed to evaluate whether PJ of the pancreatic stump decreases the incidence of pancreatic fistula after DP compared with stapler closure.

An 80-year-old man was admitted to our hospital with appetite loss in December 2014. Gastroduodenal scope, abdominal computed tomography(CT), and laparoscopy revealed type 4 advanced gastric cancer(poorly differentiated adenocarcinoma) with multiple lymph node(LN)involvement and multiple peritoneal metastasis. S-1(80mg/body)was administrated between January 2015 and September 2015 in the outpatient clinic. A partial response was obtained, but a gastric tumor, ascites, and LN re-growth were observed. Since October 2015, paclitaxel(PTX)(70mg/m2; day 1, 8, and 15)and ramucir- umab(RAM)(8mg/kg; day 1 and 15)have been administered. After 2 courses, bi-weekly PTX plus RAM were continued for grade 3 neutropenia and grade 2 anorexia. The tumor and LNs partially responded, and the ascites disappeared. With this dosage and administration schedule, the partial response(PR)was maintained for approximately 8 months without any severe adverse reactions. This successful case might indicate that it is important for elderly patients with gastric cancer that progressed with prior chemotherapy regimens to consider appropriate reduction of the PTX dosage, schedule, and continuation of RAM.

Management for obstructive cancer of the colon diverges into many ways. The aim of this study was to evaluate the treatment course of patients with malignant obstruction after ileo/coleostomy. Thirty-six patients with malignant obstruction who underwent ileo/coleostomy in our hospital from May 2012 to January 2016were enrolled in the study. Clinical outcomes were the period before treatment initiation, chemotherapy, radiotherapy, primary lesion resection, and death, and these were retrospectively analyzed. Although 9 stomal complications occurred, no case experienced a delayed treatment start. However, patients with perioperative complications, sepsis due to the tumor, pneumonia, cerebral infractions, and ileus needed a long recovery period before treatment initiation. Patients who need ileo/coleostomy must be considered for performance status and ways to decrease perioperative complications to prevent stomal complications from chemo/radiotherapy.

A66 -year-old woman presented with abdominal pain and nausea. She was diagnosed with wall thickening of the gastric antrum and bowel obstruction caused by tumors of the splenic flexure on computed tomography. Aself -expandable metallic stent(SEMS)was placed in the splenic flexure of the colon 4 days after transanal ileus tube replacement. No complication was observed, and she could ingest a normal diet, permitting her discharge from the hospital 12 days after SEMS placement. She was diagnosed with gastric cancer(Type 4, cT4a[SE], N2, H0, P1, M1[LYM], cStage IV )on upper gastrointestinal endoscopy and computed tomography, and administration of S-1 plus oxaliplatin(SOX)was started. Nab-paclitaxel as the second-line chemotherapy was administered after 8 courses of SOX therapy because of an increase in the amount of ascites. No late complication associated with stent placement was recognized. SEMS placement was suggested to be effective for treating colon obstruction due to metastatic gastric cancer.

Laparoscopic surgery is less invasive and has better cosmetic results. Laparoscopic liver resection(LLR)was covered by health insurance in April 2010, and has increasingly been performed in many hospitals, and also in cases of elderly patients. We report the results of laparoscopic liver resection for hepatocellular carcinoma(HCC)in patients ≥80 years old. From June 2010 through March 2016, 237 cases of laparoscopic hepatectomy for HCC were performed in our hospital, and 35 of 237 cases were patients ≥80 years old(the elderly group). The operation time in the elderly vs the non-elderly group was 321 minutes vs 340.9 minutes(p=0.4676), the blood loss was 447.2mL vs 331.5mL(p=0.6691), and the hospital stay after the operation was 18 days vs 16 days(p=0.6347). The 3 year disease free survival rate for stage I was 66.7% vs 58.6%(p= 0.1849), for stage II was 35.6% vs 31.8%(p=0.7538), for stage III was 33.3% vs 49.5%(p=0.8683), and for stage IV was 100% vs 32.4%(p=0.3452). Laparoscopic hepatectomy for HCC can be performed safely, even for patients ≥80 years old. Further studies are necessary to confirm the benefits of laparoscopic liver resection for elderly patients compared with the non-elderly.

Background: Colon cancer rarely invades the retroperitoneum and surrounding organs, such as the iliopsoas muscle, resulting in retroperitoneal abscesses. We present three cases of colon cancer with retroperitoneal abscesses (CRA, treated using different initial conservative therapies (ICTs, followed by laparoscopic surgery. We also reviewed 18 cases of CRA reported in Japanese literature from 2000 to 2016. Case presentation: In Case 1 and 2, patients underwent abscess drainage as ICT. In Case 3, the patient diagnosed with cecum cancer underwent initial treatment with separation surgery, which isolated the right side of the colon from the left side and created a mucus fistula of the right-side colon to prevent stool from running through the lesion. In all cases, ICT combined with antibiotic therapy improved the general condition of the patients and reduced the volume of the abscess cavity, enabling a laparoscopic surgery to be performed. All cases underwent en bloc resection of the main tumor and invaded organ with adequate lymph node dissection. Rather than attempting complete resection of the entire abscess cavity, the debridement of the abscess cavity was performed. Although one patient complained of mild neuropathic pain of the left thigh after surgery, the postoperative clinical courses of the three patients were almost uneventful. The follow-up periods of Case 1, 2, and 3 were 24, 6, and 2 months respectively, and they have shown no signs of recurrence after surgery. Conclusion: Following a review of 18 CRA cases, ICT for CRA didn’t make any significant differences in postoperative complication and length of hospital stay compared with surgery alone. However, based on our cases, ICT before surgery clearly provided benefit to the patients and made the use of laparoscopic surgery possible. ICT can be a useful strategy for the treatment of CRA.

Primary colon carcinoma within an inguinal hernia sac is very rare and most reported cases were found at emergency open surgery for an incarcerated hernia. We report a case of incarcerated sigmoid colon carcinoma diagnosed preoperatively and treated with elective laparoscopic surgery. A 67-year-old man with a 2-year history of swelling of the scrotum and a breast lump was referred to us for surgical treatment of an irreducible left inguinal hernia and a right breast tumor. Blood examination results showed severe anemia. Computed tomography scan and endoscopic biopsy confirmed sigmoid colon carcinoma incarcerated in the left inguinal hernia. Thus, we performed definitive laparoscopic sigmoidectomy and conventional hernia repair for preoperatively diagnosed sigmoid colon carcinoma within an inguinal hernia.

Surgical site infection (SSI) surveillance in Japan is based on the National Nosocomial Infection Surveillance system, which categorizes all hepato-biliary-pancreatic surgeries, except for cholecystectomy, into “BILI.” We evaluated differences among BILI procedures to determine the optimal subdivision for SSI surveillance. We conducted multicenter SSI surveillance at 20 hospitals. BILI was subdivided into choledochectomy, pancreatoduodenectomy, hepatectomy, hepatectomy with biliary reconstruction, pancreatoduodenectomy with hepatectomy, distal pancreatectomy and total pancreatectomy to determine the optimal subdivision. The outcome of interest was SSI. Univariate and multivariate analyses were performed to determine the predictive significance of variables in each type of surgery. 1,926 BILI cases were included in this study. SSI rates were 23.2 % for all BILI; for choledochectomy 23.6 %, pancreatoduodenectomy 39.3 %, hepatectomy 12.8 %, hepatectomy with biliary reconstruction 41.9 %, pancreatoduodenectomy with hepatectomy 27.3 %, distal pancreatectomy 31.8 %, and total pancreatectomy 20.0 %. SSI rates for hepatectomy were significantly lower than those for non-hepatectomy BILI. Risk factors for developing SSI with hepatectomy were drain placement and long operative duration, while for non-hepatectomy BILI, risk factors were use of intra-abdominal silk sutures, SSI risk index and long operative duration. Hepatectomy and non-hepatectomy BILI differ with regard to the incidence of and risk factors for developing SSI. These surgeries should be assessed separately when conducting SSI surveillance.

The REGARD and RAINBOW trials showed that ramucirumab(RAM)alone and RAM plus paclitaxel(PTX) were effective therapies for advanced gastric cancer patients previously treated with chemotherapy. In this retrospective study, we evaluated the safety and efficacy of RAM alone and PTX plus RAM in such patients.Patients who were received RAM at 8mg/kg or RAM plus PTX at 80mg/m2(on days 1, 8, and 15 of a 28-day cycle)between June 2015 and March 2016 were enrolled in this study. We compared the clinical outcome of RAM alone(RAM group, n=10)with that of RAM plus PTX(PTX+RAM group, n=13).The RAM group contained many more patients with poor performance status or prior chemotherapy of 2 or more regimens than the PTX+RAM group. All patients in both groups received chemotherapy on an outpatient basis. One case of grade 3 or 4 hematological adverse events was found in the RAM group and 6 cases were found in the PTX+RAM group. The overall response rate was 10% in the RAM group and 30% in the PTX+RAM group. Progression-free survival was 54 days in the RAM group and 187 days in the PTX+RAM group(p=0.0374). Overall survival was 158 days in the RAM group and was not reached in the PTX+RAM group(p=0.1091).RAM alone and RAM plus PTX can be administered safely on an outpatient basis and are beneficial for advanced gastric cancer patients previously treated with chemotherapy.

We report a case of small intestinal adenocarcinoma treated with laparoscopic surgery. A 70-year-old woman had abdominal pain and epigastralgia. There were no abnormal findings on upper and lower endoscopy. The symptoms continued for 4 months after endoscopy, so she presented to our hospital. After CT examination, small bowel cancer with ileus was suspected. An ileus tube was inserted to relieve the bowel pressure and she was diagnosed with ileum cancer by enteroscopy. Laparoscopic surgery was performed and the pathological stage was determined as pStage Ⅲa. She was treated with oral chemotherapy (UFT plus LV) and had no recurrence 6 months after surgery.

Laparoscopic surgery is less invasive and provides better cosmetic outcomes than conventional surgery. Laparoscopic liver resection has been covered by insurance since April 2010 and is increasingly performed in many hospitals. However, laparoscopic hepatectomy is sometimes difficult to perform safely in the case of HCC recurrence because adhesions restrict vision and manipulation of forceps. We report the results of laparoscopic hepatectomy for cases of HCC recurrence. From June 2010 through December 2014, 180 laparoscopic hepatectomy procedures for HCC were performed in our hospital; 33 were in patients with HCC recurrence. Of the 33 patients, 26 underwent pure laparoscopic partial hepatectomy. The median operative time was 242 min, the median bleeding amount was less than 5 g, and the median hospital stay after surgery was 12.0 days. In the group that underwent laparoscopic hepatectomy after open liver resection (12 patients), the median operative time was 303.5 min, the median bleeding amount was less than 5 g, and the median hospital stay after surgery was 9.0 days. Among the 21 patients that underwent laparoscopic hepatectomy after laparoscopic liver resection, the median operative time was 248 min (p=0.382), the median bleeding amount was less than 5 g (p=0.112), and the median hospital stay after surgery was 11.0 days (p=0.236). We could perform laparoscopic hepatectomy for cases of HCC recurrence. This procedure can be suitable for HCC recurrence, which sometimes requires poly-surgery.

The aim of this study was to compare the efficacy of self-expandable metallic stent (SEMS) and transanal tube as preoperative treatments for left-sided obstructive colon cancer. Forty-three patients (the SEMS group: 28 cases, the tube group: 15 cases) were included in this study. Clinicopathological data (age, sex, tumor location, depth, histological type, stage) were comparable between the 2 groups. In addition, there was no difference in intestinal decompression rate between the SEMS group and the tube group (technical success rate: 100% vs 86.7%, clinical success rate: 92.8% vs 73.3%, complication rate: 7.1% vs 0%). A significantly higher number of patients in the SEMS group underwent laparoscopic surgery because of difference of historical background. However, no significant difference was observed between the 2 groups in postoperative outcome(complication rate, hospital stay duration). SEMS insertion had several benefits compared to transanal tube placement, such as the resumption of oral intake because of rapid resolution of obstruction and easier management because SEMSs do not require washing. SEMS insertion could be a safe and effective bridge to subsequent surgery in patients with left-sided obstructive colon cancer.

症例は53歳, 男性. 口渇および体重減少 (-10kg/1カ月) にて精査したところ, 耐糖能異常 (HbA1C12.2%), 腫瘍マーカー上昇 (CEA4.9ng/ml, CA19-9 325U/ml) を指摘された. 腹部CTにて膵頭部腫大および周囲のリンパ節腫大を認めたため, 膵癌を疑いERCPを行ったが, 主膵管の壁不整像認めず, 細胞診陰性であった. 良悪性鑑別のためFDG-PET施行したところ, 膵頭部の腫大部位に一致してFDGの異常集積 (standardized uptake value ; SUV=3.62) を認めた. 膵癌が強く疑われ, 膵頭十二指腸切除術を施行した. 術中, 膵は全体的に硬化し腫瘤は不明瞭で, 切除標本でも明らかな腫瘤を認めなかった. 病理組織検査では膵実質の萎縮と炎症細胞浸潤, 間質には線維化を認め, 慢性および急性膵炎に相当する像を示し, 悪性所見は認めなかった. FDG-PET高集積にて膵癌との鑑別が困難であった腫瘤形成性膵炎の1例を経験したので報告する.

膵癌に対する第1選択化学療法剤として広く使用されているgemcitabine（GEM）の作用機序解析に基づいた治療効果増強のための基礎的・臨床的検討を行った．ヒト膵癌細胞株およびヌードマウス移植ヒト膵癌モデルにおいて行い，5-fluorouracil（5-FU）によるGEM取込み増強効果および5-FU系薬剤によるGEMとの至適併用スケジュールを検討した．その結果，5-FU剤先行投与によってGEM取込みが増強し，先行投与後GEM施行が最も抗腫瘍効果が高いことが明らかになった．さらに，切除不能進行・再発膵癌に対して，至適併用スケジュール（UFT先行GEM投与：UFT250 mg/m2：day1～6，day8～13，GEM 800 mg/m2：day7，14，休薬：day15～21）による第II相試験を行い，重篤な有害事象は認めず，奏功率25％，50％生存期間7ヶ月，1年生存率25％と言う成績を得た．また，GEM耐性ヒト膵癌細胞株の網羅的遺伝子発現解析から，GEM代謝に関連するRibonucleotide reductase M1 subunit（RRM1）発現昂進がGEM耐性に最も関連することを明らかにし，RRM1 RNAiを用いたRRM1発現抑制によってGEM感受性が向上することを検証した．さらに，臨床例の検討から，RRM1がGEM感受性にも関与している可能性を示した．

Pancreatic cancer is the most lethal of all solid tumors partially because of its chemoresistance. Although gemcitabine is widely used as a first selected agent for the treatment of this disease despite low response rate, molecular mechanisms of gemcitabine resistance in pancreatic cancer still remain obscure. The aim of this study is to elucidate the mechanisms of gemcitabine resistance. The 81-fold gemcitabine resistant variant MiaPaCa2-RG was selected from pancreatic cancer cell line MiaPaCa2. By microarray analysis between MiaPaCa2 and MiaPaCa2-RG, 43 genes (0.04%) were altered expression of more than 2-fold. The most upregulated gene in MiaPaCa2-RG was ribonucleotide reductase M1 subunit (RRM1) with 4.5-fold up-regulation. Transfection with RRM1-specific RNAi suppressed more than 90% of RRM1 mRNA and protein expression. After RRM1-specific RNAi transfection, gemcitabine chemoresistance of MiaPaCa2-RG was reduced to the same level of MiaPaCa2. The 18 recurrent pancreatic cancer patients treated by gemcitabine were divided into 2 groups by RRM1 levels. There was a significant association between gemcitabine response and RRM1 expression (p = 0.018). Patients with high RRM1 levels had poor survival after gemcitabine treatment than those with low RRM1 levels (p = 0.016). RRM1 should be a key molecule in gemcitabine resistance in human pancreatic cancer through both in vitro and clinical models. RRM1 may have the potential as predictor and modulator of gemcitabine treatment.

We report a case of radical resection of rectal cancer with multiple liver and lung metastases after preoperative chemotherapy. A 54-year-old woman presented with abdominal pain and loss of body weight due to rectal cancer with multiple liver and lung metastases. Therefore, the patient received 14 courses of bevacizumab+mFOLFOX6, and 7 courses of panitumumab+FOLFIRI. After the chemotherapy, the size of the distant metastases reduced by 62% on computed tomography, according to RECIST. Due to the reduction in size, a conversion surgery was attempted. First, an abdominal operation with laparoscopy was performed, and 2 months later an operation to resect the lung metastases via thoracoscopy was performed. Currently, 3 months after surgery, the patient is alive, without recurrence.

Background The incidence of postoperative biliary leakage and hemorrhage is low, but these factors remain important in liver surgery, and this study's objective was to explore the efficacy of fibrin sealant (FS) with polyglycolic acid (PGA) vs fibrinogen-based collagen fleece (CF) at the liver cut surface. Fibrinogen-based collagen fleece is generally used for hemostasis; PGA-FS has reduced biliary leakage in several retrospective studies. Study design We designed a multicenter, randomized, controlled trial. The primary outcome was the rate of biliary leakage and hemorrhage. Secondary outcomes included morbidities and effusion at the liver cut surface at 3 months post-surgery. Biliary leakage was diagnosed when the drain/serum bilirubin ratio was >5. Hemorrhage was diagnosed when relaparotomy or transfusion was needed. Results Of 786 patients from 11 institutions enrolled from 2009 to 2014, a total of 391 were randomly assigned to PGA-FS and 395 to CF. Regarding primary outcomes, rates of biliary leakage were 4.1% with PGA-FS and 5.1% with CF, and rates of hemorrhage were 1.0% in each group; groups did not differ significantly. For secondary outcomes, morbidity rates were 18.7% in the PGA-FS group and 24.6% in the CF group (p = 0.0450). Effusion at the cut liver surface was less with PGA-FS (22.2%) than with CF (32.9%) (p = 0.0142). Regarding morbidity, infection around the liver, jaundice, and abdominal paracentesis were less in the PGA-FS group. Conclusions Compared with CF, PGA-FS did not reduce biliary leakage and hemorrhage. Surgical site infection around the liver, effusion at the liver cut surface, and abdominal paracentesis were less in the PGA-FS group.

Laparoscopic hepatectomy has been reported as a safe and effective approach for the treatment of hepatocellular carcinoma ( HCC). However, few studies have reported survival outcomes after laparoscopic hepatectomy in HCC patients with cirrhosis. In the present study, we evaluated the surgical outcomes and disease-free survival in these cases. Between June 2010 and March 2013, 35 HCC patients with cirrhosis underwent laparoscopic hepatectomy. Operative variables for laparoscopic vs open hepatectomy were as follows: operative times, 268.3 vs 183.3 minutes (p=0.0043); blood loss volume, 151.0 vs 1,106.1 g (p.001); 1-year disease-free survival rate, 73.1 vs 71.6%; and 2-year disease-free survival rate, 39.9% vs 28.6% (p=0.568), respectively. Laparoscopic hepatectomy is feasible and safe in selected patients with liver cirrhosis, with similar outcomes in disease-free survival when compared with open hepatectomy.

A 63-year-old woman underwent breast-conserving resection and axillary lymph node dissection for bilateral breast cancer in December 2008. Histopathological diagnosis for the right breast cancer was t=1.3 cm, n=1/29, estrogen receptor (ER) (+), progesterone receptor (PgR) (+), human epidermal growth factor receptor 2(HER2) (-), and that for the left breast cancer was t=1.8 cm, n=9/28, ER (+), PgR (+), and HER2 (-). She was administered adjuvant chemotherapy (4 courses of fluorouracil, epirubicin, and cyclophosphamide [FEC 100] and 4 courses of docetaxel[DTX], 75 mg/m²), letrozole, and bilateral radiation therapy for the remaining breast tissue. She noticed a mass in the left breast in December 2013. Fine-needle aspiration cytology and core-needle biopsy indicated a malignant phyllodes tumor or stromal sarcoma. Positron emission tomography-computed tomography (PET-CT) revealed the accumulation of fluorodeoxyglucose (FDG) only in the mass. The tumor enlarged rapidly to more than 5 cm during the pre-operative period. In January 2014, the patient underwent left mastectomy. The histopathological diagnosis was malignant phyllodes tumor in the left breast, with a tumor diameter of 7 cm, and negative margins. Presently, 6 months after the operation, the patient is alive without recurrence.

A 26-year-old man was admitted to hospital because of lower quadrant pain. Colonoscopy showed a polypoid lesion (0- Ip: protruded, pedunculated)in the cecum. Endoscopic biopsy revealed a tubular adenoma with severe atypia. Laparoscopy- assisted ileocecal resection was performed, as the diameter of the tumor made colonoscopic treatment difficult. Appendiceal intussusceptions were found in the excised specimen. The tumor was mucosal in origin. The patient remained cancer-free after the surgery.

A 94-year-old woman with a distended abdomen was transferred to our hospital.Based on the enhanced abdominal computed tomographic (CT) finding, she was diagnosed with colonic obstruction due to sigmoid cancer. Colonoscopy was performed to make definitive and qualitative diagnoses, and to release the stenosis using a self-expanding metallic stent (SEMS). The SEMS was inserted without complication.On the fifth day after the decompression, the patient underwent laparoscope-assisted sigmoidectomy with lymph node resection.Despite the colon obstruction, a primary anastomosis was performed.The operation time was 163 min, and 3 mL of blood was lost.The patient was discharged without complications. We describe the case of a bridge to surgery in a very elderly patient. A bridge to surgery can be an effective option for the treatment of colon obstruction in non-elderly and very elderly patients.

A 69-year-old woman had undergone breast conserving surgery and axillary lymph node dissection for left breast cancer 10 years previously. The tumor was positive for estrogen receptor (ER) and progesterone receptor (PgR), and negative for human epidermal growth factor receptor-2 (HER2). Adjuvant tamoxifen and radiation therapy were administered to the conserved breast for 5 years. The patient detected a painless neck mass 1 year previously. Computed tomography (CT) revealed a hyoid bone mass, and fine needle aspiration cytology indicated a diagnosis of adenocarcinoma. Positron emission tomography combined with CT (PET-CT) revealed masses in the pelvis, spine, hyoid bone, and cervical lymph node. For definitive diagnosis, excisional biopsy of the hyoid bone was performed. Immunohistostaining revealed that the cells were CK7 (+), CK20(-), mammaglobin (+), GCDFP-15 (+), ER (+), PgR (+), and HER2 (-). The final diagnosis was multiple bone metastasis(hyoid, pelvis, spine)as well as cervical lymph node metastasis from breast cancer. After diagnosis, the patient was treated with anastrozole and denosumab, and she achieved a partial response. She has experienced progression free survival for 12 months. Metastasis to the hyoid bone is uncommon for breast cancer. We report a case in which hormone therapy was effective after it was selected based on the results of excisional biopsy.