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The patient was a 78-year-old man who underwent upper gastrointestinal endoscopy, revealing a sub-circumferential type 2 tumor in the lower body of the stomach. Histopathology revealed poorly differentiated adenocarcinoma. Computed tomography(CT)showed lymph node and liver metastasis(S6, S8), which corresponded to clinical Stage Ⅳ(cT4bcN2cM1 [HEP]). Five courses of XP therapy were administered for Stage Ⅳ disease. The sizes of the primary lesion and metastatic liver tumors were reduced, and a partial response was achieved. Distal gastrectomy and partial hepatectomy were performed. The resected specimen was diagnosed as ypT4b(transverse colon mesenteric), ypN0, ypM1(HEP). Thus, the final Stage was Ⅳ. During adjuvant chemotherapy with S-1, the para-aortic, left common iliac, and external peri-iliac lymph node metastases were detected by CT imaging 6 months after the operation. This prompted XP therapy resumption. The lymph node metastases worsened despite 2 additional XP courses. Progressive disease prompted the change in regimen to PTX plus RAM. After 7 courses, swollen lymph nodes were observed and CPT-11 was initiated. Since the disease continued to progress, nivolumab therapy was administered. The para-aortic, left common iliac, and external peri-iliac lymph nodes shrank after nivolumab initiation. The patient has responded well to nivolumab for more than 3 years without immunological adverse events.

Cholangiolocellular carcinoma(CoCC)was first reported by Steiner et al in 1959. CoCC resembles cholangiocellular carcinoma( CCC)grossly and presents a variety of imaging findings, which often makes preoperative diagnosis difficult. In Japan, CoCC is rare, accounting for only 0.56% of primary liver cancers. We report the results of laparoscopic liver resection (LLR)for CoCC at our institution. Among 845 liver resections(678 LLR and 167 open liver resections)performed at Kansai Rosai Hospital from 2010 to 2020, only 13 were CoCC. Eight patients underwent LLR except for 5 patients who required vascular reconstruction and lymph node dissection. Median age was 71 years (55-77), gender was male/female(7/1), stage was Ⅰ/Ⅱ/Ⅲ/ⅣA(3/3/1/1), liver function was Child-Pugh A/B/C(7/1/0), and liver damage A/B/C(6/2/0). The preoperative diagnosis was 1 CoCC, 3 CCC and 4 HCC. The operative procedure was 3 Hr 0, 3 Hr 1 and 2 Hr 2. The operative time was 342 minutes(168-488), the blood loss was 51.3 g(0-400), and the postoperative hospital stay was 14 days(5- 53). The 5-year disease-free survival rate was 83.3%, and the 5-year overall survival rate was 85.7%. Recurrence was seen in 1 patient. The 5-year survival rate after curative resection of CoCC has been reported to be 73-83%, compared with 28- 36% for CCC. LLR for CoCC at our institution showed good perioperative results. Long-term results were comparable to those reported for liver resection. LLR for CoCC was considered an appropriate technique with good perioperative and long- term results.

A 50s year old woman was referred to former hospital for abdominal pain and melena. Colonoscopy revealed an ascending colon cancer(cT4aN1bM0, cStage Ⅲb, UICC)and gastrointestinal endoscopy revealed an esophagogastric junction cancer(cT1bN0M0, cStage ⅠA, UICC). Preoperative CT showed mild bilateral hydronephrosis. Laparoscopic right hemicolectomy( Lap-RHC, D3)was performed for ascending colon cancer then, and abdominal CT was taken 2 days before the robot-assisted proximal gastrectomy(RAPG, D1+). Right hydronephrosis was observed. No evidence of obvious ureteral damage was found during Lap-RHC. When retrograde pelvic ureterography was performed and a stenosis was found at the right renal pelvis and ureteral junction. It is considered that the ureter stenosis became prominent due to the postoperative inflammatory change of Lap-RHC. RAPG was performed as scheduled. Two months after discharge, a renal fistula was constructed. Pyeloplasty is scheduled to be performed in the future.

Laparoscopic surgery is a safe, minimally invasive, and effective approach in managing abdominal malignancies. Laparoscopic anatomical resection has been covered by insurance in Japan since 2016. Here, we have reported the short-term outcomes of gallbladder cancer in laparoscopic cholecystectomy, gallbladder bed resection, or S4a/S5 liver resection with lymph node dissection.Between May 2012 and December 2020, 28 patients underwent laparoscopic cholecystectomy for gallbladder cancer at Kansai Rosai Hospital. Two patients underwent laparoscopic choledochotomy with lymph node dissection, 6 patients underwent gallbladder bed resection, and 7 patients underwent S4a/S5 liver resection. The control group included 13 patients who received open surgery between July 2010 and November 2019. The patient age was 74.2 and 74.4 years, while the male to female ratio was 19/24 and 8/5 in the laparoscopic and open surgery groups, respectively. According to the Japanese Society of Hepato-Biliary-Pancreatic Surgery, the pathological stage was 0/Ⅰ/Ⅱ/Ⅲ A/ⅢB/ⅣA/ⅣB in 4/17/13/4/2/1/2 and 0/1/2/3/1/1/5 patients(p=0.0100)in the laparoscopic and open surgery groups, respectively. This study was approved by the Human Ethics Review Committee of Kansai Rosai Hospital(Certificate Number: 2101001).The laparoscopic surgery group had an average operation time of 223.3 minutes, an estimated blood loss of 18.7 g, and a hospital stay of 8.5 days. The open surgery group had an average operation time of 514.5 minutes, an estimated blood loss of 1,274.3 g, and a hospital stay of 33.9 days. There was no postoperative bleeding or bile leakage in both groups. After laparoscopic cholecystectomy, the 5-year disease-free survival rate was 100% among Stage 0 or Ⅰ patients, 64.8% among Stage Ⅱ patients, and 0% in Stage Ⅲ or Ⅳ patients. The 5-year overall survival rate was 100% among Stage 0 or Ⅰ patient and 66.7% among Stage Ⅱ patients. The 1-year overall survival rate was 50% among Stage Ⅲ or Ⅳ patients. After laparoscopic liver resection with lymph node dissection, the 5-year disease-free survival rate was 100% among Stage Ⅰ or Ⅱ patients and 66.7% among Stage Ⅲ or Ⅳ patients. The 5-year overall survival rate was 100% among Stage Ⅰ or Ⅱ patients and 62.5% among Stage Ⅲ or Ⅳ patients.Laparoscopic cholecystectomy in Stage 0 or Ⅰ patients and laparoscopic gallbladder bed resection or S4a/S5 liver resection with lymph node dissection were safe and effective approaches to gallbladder cancer management.

A 62-year-old man was referred to our hospital with complaints of upper abdominal pain and weight loss while being treated for diabetes mellitus at his family doctor. He was diagnosed as locally advanced unresectable pancreatic adenocarcinoma that involved superior mesenteric artery(SMA). Gemcitabine(GEM)and S-1 combined chemoradiotherapy(CRT) was administered. After CRT, CT test showed improved involvement of SMA, and radical resection was possible. We performed the radical pancreaticoduodenectomy and adjuvant chemotherapy, and he has been followed up for more than 5 years after the operation without recurrence. For locally advanced unresectable pancreatic adenocarcinoma, CRT or chemotherapy is recommended in the Pancreatic Cancer Practice Guidelines(2019 edition). However, the prognosis is extremely poor. We report a case of locally advanced unresectable pancreatic adenocarcinoma that was successfully curatively resected due to the good response of CRT.

We report a case of cholangiocellular carcinoma(CCC)with high-frequency microsatellite instability(MSI-H)in Lynch syndrome that was managed using a multimodal treatment approach including an immune checkpoint inhibitor. The patient was a 74-year-old man who presented with fever as the chief complaint. He had a history of Vater's papilla cancer and colorectal cancer in Lynch syndrome. A diagnosis of CCC in the left lobe of the liver was made, and left hepatectomy and left caudate lobectomy were performed. From about 2 years and 5 months after the operation, the patient developed several episodes of cholangitis, and recurrence of CCC was diagnosed based on the results of biliary cytology. Gemcitabine and cisplatin therapy was started, but exacerbation of bile duct stenosis associated with cancer progression was observed, and pembrolizumab, an immune checkpoint inhibitor, was started as the solid cancer had an MSI-H status. The tumor markers then improved and the cholangitis subsided. We experienced a case of recurrence of CCC with MSI-H in Lynch syndrome managed by multimodal treatment including an immune checkpoint inhibitor.

Advances and improvements in cancer diagnosis and treatment have made it possible to find multiple primary cancers. We report here a rare case of metachronous quintuple cancer involving the stomach, rectum, colon, liver and prostate. An 80s‒ year‒old male was referred to our hospital with abnormality on upper GI series. He had undergone a distal gastrectomy in May 2005. Postoperative diagnosis was advanced gastric cancer (pT2N1M0, pStage ⅡA). In August 2006, anterior resection was performed with a diagnosis of advanced rectal cancer(pT3N0M0, pStage Ⅱa). For ascending colon polyps, endoscopic submucosal dissection was performed with a diagnosis of adenocarcinoma in adenoma(pTisN0M0, pStage 0)in September 2007. In June 2016, laparoscopic ileocecal resection was performed with a diagnosis of advanced cecum cancer(pT3N0M0, pStage Ⅱa). Follow up CT images showed a liver tumor in S4. Partial liver resection was performed in October 2010. Postoperative pathological diagnosis was hepatocellular carcinoma(pT2N0M0, pStage Ⅱ). Prostate cancer(cT2aN0M0)was treated by androgen deprivation therapy from February 2018. Although he had high‒frequency microsatellite instability, germline mutations in hMLH1 and hMSH2 genes were not detected. Histopathological examination showed that each tumor was an independent tumor and had not metastasized from any others. The patient had a good clinical course after these treatment until now.

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.

Conditioned place preference (CPP) is widely used to investigate the rewarding properties of cocaine. Various brain regions and neurotransmitters are involved in developing cocaine CPP. However, the contribution of cholinergic transmission in the ventral tegmental area (VTA) to cocaine CPP remains largely unexplored. Here, we examined the role of cholinergic input arising from the laterodorsal tegmental nucleus (LDT) to the VTA in the acquisition and expression of cocaine CPP in rats. Intra-LDT injection of carbachol, which hyperpolarizes LDT neurons, and of NMDA and AMPA receptor antagonists before cocaine conditioning blocked and attenuated cocaine CPP, respectively, indicating the necessity of LDT activity for acquiring the CPP. Additionally, intra-VTA injection of scopolamine or mecamylamine before cocaine conditioning also attenuated cocaine CPP, demonstrating the contribution of cholinergic transmission via muscarinic and nicotinic acetylcholine receptors in CPP acquisition. Furthermore, intra-VTA injection of scopolamine or mecamylamine immediately before the test attenuated cocaine CPP, indicating that cholinergic signaling is also associated with the expression of CPP. These results suggest that cholinergic transmission from the LDT to the VTA is critically involved in both acquiring and retrieving cocaine-associated memories in cocaine CPP.