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We report a case of non-exposed endoscopic wall-inversion surgery(NEWS)performed by TANKO technique for gastric GIST. A 52-year-old man was diagnosed as having gastric GIST. A 2 cm-sized tumor was found in the lesser curvature of the middle body of the stomach, and an endoscopic biopsy revealed GIST. A 2.5 cm umbilical incision was made and TANKO surgery was performed. After seromyotomy around the tumor, the outer serosal muscularis was sutured closed to invert the tumor into the stomach. The inverted tumor was resected from the stomach wall and recovered using endoscopic techniques. NEWS is an operation developed to resect a tumor without exposing it into the abdominal cavity and is expected to avoid the risk of postoperative abdominal abscess and peritoneal dissemination. On the other hand, the TANKO is a procedure with excellent plastic technique and can be performed in this operation.

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.

Atezolizumab plus bevacizumab combination therapy is the first cancer immunotherapy that has shown efficacy in the treatment of hepatocellular carcinoma(HCC). We report a case of HCC with recurrent peritoneal dissemination for which atezolizumab plus bevacizumab combination therapy was effective. The patient, a 63-year-old man, underwent transarterial embolization(TAE)for ruptured HCC, and a mass with dissemination on the caudal side of liver S3 was observed. Laparoscopic lateral hepatic resection plus resection of the dissemination plus cholecystectomy was thus performed in September 2019. However, in November 2019, multiple peritoneal dissemination recurrence was observed, and lenvatinib therapy was initiated. In May 2020, PD was observed, and we had switched to sorafenib therapy. However, in October 2020, further tumor growth and rapid increase in tumor markers(AFP 25,668 ng/mL, PIVKA-Ⅱ 64,960 mAU/mL)were observed, and the patient was judged to have PD. Atezolizumab plus bevacizumab combination therapy was initiated in the same month. Subsequently, a CT scan in January 2021 showed a marked decrease in tumor size, indicating PR. The tumor markers have since normalized(AFP 5 ng/mL, PIVKA-Ⅱ 28 mAU/mL). The patient has been treated with atezolizumab plus bevacizumab combination therapy again and is maintaining PR as an outpatient.

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.

We present a case of jejunal perforation just below the Treitz ligament treated with primary suture after administration of ramucirumab(RAM). The patient was a 74-year-old male. He was diagnosed with Stage Ⅳ sigmoid colon cancer with liver and lung metastasis. Laparoscopic sigmoid colon cancer resection was performed previously. As adjuvant chemotherapy, the patient received 3 courses of CapeOX plus bevacizumab(BEV)and 20 courses of FOLFOX plus BEV and was in PR. After operation for liver and lung metastases, the patient was observed without any treatment, but pelvic recurrence and lung metastasis were noted, and FOLFIRI plus RAM was started. On the 7th day after the second course, the patient experienced abdominal pain. Since an intestinal perforation was suspected, emergency surgery was performed on the same day. There was a 5-mm-diameter perforation in the jejunum just below the Treitz ligament, and were small ischemic changes near the perforation. The rest of the intestine was clear, the perforation was suspected due to RAM. Since anastomosis was difficult, we performed primary suture and decompression of the location. The postoperative course was uneventful, and the patient was discharged on POD 18. Currently, RAM has been discontinued and chemotherapy is being continued with FOLFIRI.

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 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.

Background For colorectal cancer (CRC) patients, the standard histological lymph node (LN) evaluation has low sensitivity. Our previously developed one-step nucleic acid amplification (OSNA™) assay measures cytokeratin 19 gene expression in whole LNs. We recently showed that 17.6% of pN0 stage II CRC patients were OSNA positive, suggesting a correlation between OSNA results and disease recurrence. This multicenter, prospective study investigateed the prognostic value of the OSNA assay for pStage II CRC patients. Methods We examined 204 CRC patients who were preoperatively diagnosed as cN0 and cN1 and surgically treated at 11 medical institutions across Japan. Nine patients were excluded, and 195 patients (Stage I: n = 50, Stage II: n = 70, Stage III: n = 75) were examined. All LNs, harvested from patients, were examined histopathologically using one-slice hematoxylin–eosin staining. Furthermore, half of the LNs was examined by the OSNA assay. Patients were classified according to the UICC staging criteria and OSNA results, and the 3-year, disease-free survival (DFS) of each cohort was analyzed. Results Average 21.2 LNs/patient were subject to pathological examination. Approximately half of all harvested LNs (average, 9.4 LNs/patient) were suitable for the OSNA assay. Significantly lower 3-year DFS rates were observed in pStage (pathological Stage) II OSNA-positive patients than in OSNA-negative patients (p = 0.005). Among all assessed clinical and pathological parameters, only the OSNA result significantly affected 3-year DFS rates in pStage II CRC patients (p = 0.027). Conclusions This study shows that OSNA positivity is a risk factor for recurrence of the patients with pStage II CRC.

PURPOSE The International Union Against Cancer highlighted tumor budding as a tumor-related prognostic factor. International assessment criteria for tumor budding were recently defined by the 2016 International Tumor Budding Consensus Conference (ITBCC2016). This study aimed to clarify the prognostic and predictive values of tumor budding in a randomized controlled trial evaluating the superiority of adjuvant chemotherapy with oral tegafur-uracil over surgery alone for stage II colon cancer (SACURA trial; ClinicalTrials.gov identifier: NCT00392899 ). PATIENTS AND METHODS Between 2006 and 2010, we enrolled 991 patients from 123 institutions with stage II colon cancer. Tumor budding was diagnosed by central review on the basis of the criteria adopted in the ITBCC2016. We prospectively recorded all clinical and pathologic data, including the budding grade, and performed prognostic analyses after 5 years of completing the patients’ registration. RESULTS Of 991 tumors, 376, 331, and 284 were classified as BD1, BD2, and BD3, respectively; the 5-year relapse-free survival (RFS) rate was 90.9%, 85.1%, and 74.4%, respectively ( P < .001), and ranged widely in T4 tumors (86.6% to 53.3%). The budding grade significantly correlated with recurrence in the liver, lungs, lymph nodes, and peritoneum ( P < .001 to .01). Multivariable analysis revealed that budding and T stage exerted an independent impact on RFS, and on the basis of the Harrell concordance index, these two factors substantially contributed to the improvement of the Cox model for predicting RFS. Both the BD2 and BD3 groups demonstrated greater improvement in the 5-year recurrence rate in the adjuvant chemotherapy group than the surgery-alone group by approximately 5%, but the difference was statistically nonsignificant. CONCLUSION Tumor budding grade on the basis of the ITBCC2016 criteria should be routinely evaluated in pathologic practice and could improve the benefit of adjuvant chemotherapy for stage II colon cancer.

Background/Aim: If both distant metastases and the primary tumour of colorectal cancer (CRC) are resectable, resection of the distant metastases is considered. The aim of this retrospective study was to determine the efficacy of curative resection of both primary and metastatic lesions in organs other than liver or lung in CRC patients. Patients and Methods: The medical records of 23 CRC patients who received R0 resection for primary and metastatic regions between 2009 and 2018 were retrospectively analyzed. Results: The 3-year overall survival (OS) in all 23 cases was 80.0%. There was no clinicopathological factor associated with OS on univariate analysis. Conclusion: Curative surgical resection appears to be useful for distant CRC metastases to organs other than liver or lung.

Laparoscopic liver resection (LLR) has been reported as a safe, minimally invasive, and effective surgery for the management of liver tumor. However, the efficacy and safety of laparoscopic repeat liver resection (LRLR) for recurrent liver tumor are unclear. Here, we analyzed the surgical results of LRLR. From June 2010 to May 2019, we performed 575 LLR surgeries in our department, and 454 of them underwent pure LLR for the single tumor. We classified the patients who received pure LLR for the single tumor into three groups: LRLR (n = 80), laparoscopic re-operation after previous abdominal surgery (LReOp; n = 136), and laparoscopic primary liver resection (LPLR; n = 238). We compared patient characteristics and surgical results between patients undergoing LRLR, LReOp and LPLR. We found no significant differences between LRLR and LPLR in the conversion rate to laparotomy (p = 0.8033), intraoperative bleeding (63.0 vs. 152.4 ml; p = 0.0911), or postoperative bile leakage rate (2.50 vs. 3.78%; p = 0.7367). We also found no significant difference in the surgical results between LReOp and LPLR. However, the number of patients undergoing the Pringle maneuver was lower in the LRLR group than the LPLR group (61.3 vs. 81.5%; p = 0.0004). This finding was more pronounced after open liver resection than laparoscopic liver resection (38.9 vs. 67.7%; p = 0.0270). The operative time was significantly longer in patients with proximity to previous cut surface than patients with no proximity to previous cut surface (307.4 vs. 235.7 min; p = 0.0201). LRLR can safely be performed with useful surgical results compared to LPLR.

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.

Pancreatic neuroendocrine tumor(p-NET)is a relatively rare disease, and treatment is multidisciplinary with resection, local therapy, radiotherapy, and chemotherapy. We report on a case in which long-term survival was achieved by multidisciplinary treatment. The case is a 47-year-old male. He was referred to our hospital because of the diagnosis of pancreatic tail tumor and underwent distal pancreatectomy in May 2008. And he was diagnosed as p-NET G1 by the pathological results. After 3 TACE treatments and 1 partial liver resection for recurrent liver metastasis, multiple liver metastases and lymph node metastases were found in August 2014. As a result of the everolimus treatment, the determination of efficacy to lymph nodes was CR and liver lesions were CR with the addition of TACE treatment. In July 2017, he had multiple liver metastases and right humeral metastases, and has been treated with radiotherapy for bone metastases and has maintained CR. After TACE in November 2017, he received 9 rounds of lanreotide treatment. In December 2018, he again had liver metastases and lymph node recurrence. He has been treated with everolimus treatment again and is maintaining SD in outpatient treatment.

Background Although chemotherapy for metastatic colorectal cancer (mCRC) has improved, the standard chemotherapy regimens for patients with RAS wild-type mCRC remain debated. This study aimed to compare S-1 and oxaliplatin (SOX) + bevacizumab (B-mab) with SOX + cetuximab (C-mab) in patients with previously untreated recurrent advanced CRC with wild-type KRAS. Methods This randomized phase II, open-label, multicenter study compared the efficacy and safety of SOX+B-mab with SOX+C-mab in patients with previously untreated advanced CRC with wild-type KRAS. Between February 2012 and October 2016, 45 patients were enrolled. Results Overall response rates were 59.1 and 43.5% (p = 0.29) and disease control rates were 90.9 and 91.3% (p = 0.96) in the SOX+B-mab and SOX+C-mab groups, respectively. Median overall survival (OS) was 25.3 and 15.5 months (HR = 0.607, p = 0.167) and median progression-free survival (PFS) were 11.7 and 5.5 months (HR = 0.558, p = 0.077) in the SOX+B-mab and SOX+C-mab groups, respectively. The OS and PFS of patients with early tumor shrinkage (ETS) were not significantly different in the SOX+B-mab group. However, they were significantly better when ETS was ≥20 in the SOX+C-mab group (p = 0.032 and p = 0.003, respectively). Conclusions The efficacy and safety of SOX+B-mab and SOX+C-mab for wild-type KRAS recurrent advanced CRC as first-line chemotherapy were almost the same. Consideration of the treatment strategy based on ETS may improve patient prognosis, especially in patients receiving the SOX+C-mab regimen. Trial registration UMIN Clinical Trials Registry (UMIN000006706). Date of registration: NOV/11/2011. URL of trial registry record: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000007920

A 80s year old man was referred to our hospital with melena. Colonoscopy revealed an elevated lesion in the sigmoid colon. Laparoscopic sigmoidectomy(D2)was performed in August 2011. Postoperative diagnosis was advanced sigmoid colon cancer(pT2N1M0 and pStage Ⅲa, UICC). In January 2015, He suffered from epigastric discomfort after meals. Gastrointestinal endoscopy revealed advanced gastric cancer and superficial esophageal cancer. For esophageal cancer, endoscopic submucosal dissection was performed with a diagnosis of cStage 0-Ⅱa(UICC). Laparoscopic distal gastrectomy with Billroth Ⅰ reconstruction was performed for gastric cancer with a diagnosis of pT1bN0M0 and pStage ⅠA(UICC). Follow up CT and MRI images in October 2016 showed a liver tumor in S4/S5. Laparoscopic partial liver resection was performed. Postoperative pathological diagnosis was hepatocellular carcinoma pT1N0M0, pStage Ⅰ(UICC). We finished following up period of the sigmoid colon cancer. Gastric cancer and esophageal cancer are followed up by gastrointestinal endoscopy once a year. Hepatocellular carcinoma is followed up every 3 months. He has no recurrence until now.

Introduction: Recently, “low-grade appendiceal mucinous neoplasms” (LAMNs) have been proposed as one subtype of appendiceal mucinous neoplasms, characterized by a villous or flat proliferation of mucinous epithelium with low-grade cytologic atypia. The aim of this study was to clarify the clinicopathological characteristics of LAMN. Methods: In this multi-institutional cohort study, we retrospectively analyzed the clinicopathological characteristics in appendiceal neoplasms patients who underwent treatment from 2000 to 2017. Results: In total, 922 patients were enrolled, with 279 (30.3%) cases of LAMN, and 93 (10.1%) cases of non-LAMN disease. In comparison with patients with non-LAMN disease, those with LAMN had significantly lower levels of CA19-9 (p = 0.045), a lower frequency of T4 tumors (p < 0.0001), a lower frequency of lymph node metastasis (p < 0.0001), and a lower frequency of distant metastasis (p < 0.0001). Survival analysis revealed that patients with LAMN had a significantly better prognosis than did those with non-LAMN disease (p < 0.001). Among the patients with distant metastasis, those with LAMN had a significantly better prognosis than did those with non-LAMN disease (p = 0.0020), but among the patients without distant metastasis, the difference between the 2 groups was not significant (p = 0.26). However, among patients who underwent complete resection, the difference in prognosis between the 2 groups was not significant (p = 0.10). Conclusions: A multicenter retrospective study revealed that the clinicopathological characteristics of LAMN was different from those of non-LAMN.

BACKGROUND Appendiceal tumor has recently been treated differently from colorectal cancer. However, obtaining knowledge of this disease is difficult because of its rareness. OBJECTIVE This study aimed to investigate the clinicopathological characteristics of appendiceal tumors in a Japanese cohort. DESIGN This was a nationwide multi-institution retrospective observational study. SETTING This study was conducted at the participating tertiary referral hospitals. PATIENTS Patients with appendiceal tumor who were diagnosed between 2000 and 2017 were included. MAIN OUTCOME MEASURES The primary outcome measured was the total survivability. RESULTS A total of 922 patients from the 43 facilities that participated were identified. Of these, 114 patients were diagnosed with cancer other than adenocarcinomas. The remaining 760 patients, with the exception of 48 patients with unknown survival data, were eligible for the final cohort analysis. Of these 760 patients, 515 (67.8%) had mucinous adenocarcinomas and 245 (32.2%) had nonmucinous adenocarcinomas. Within the mucinous adenocarcinoma group, 267 patients (35.1%) were diagnosed as having low-grade appendiceal mucinous neoplasm. The 5-year survival rate of mucinous adenocarcinoma (83.1%) was superior to that of nonmucinous adenocarcinoma (62.0%; p < 0.01). Regarding mucinous adenocarcinoma, multivariate analysis revealed that high differentiation grade (American Joint Committee on Cancer grade 2/3), distant metastases, and R2 operation were significantly associated with a higher 5-year mortality rate. The 5-year survival rate was significantly better for low-grade appendiceal mucinous neoplasms (93.3%) than for other mucinous adenocarcinomas (72.1%; p < 0.01). LIMITATIONS This study was limited by its retrospective study design. CONCLUSIONS We cumulatively investigated appendiceal tumors in a multicenter retrospective study; this is the first such report from Asia. Grouping the grades as per the American Joint Committee on Cancer was useful as a prognostic indicator of appendiceal mucinous adenocarcinomas, including low-grade appendiceal mucinous neoplasm. See Video Abstract at http://links.lww.com/DCR/B282. ANALISIS DE LAS CARACTERISTICAS CLINICOPATOLOGICAS DE LOS TUMORES APENDICULARES EN JAPON: UN ESTUDIO CLINICO RETROSPECTIVO COLABORATIVO MULTICENTRICO: UNA ENCUESTA NACIONAL JAPONESA: El tumor apendicular recientemente se ha tratado de manera diferente al cancer colorrectal. Sin embargo, obtener conocimiento de esta enfermedad es dificil debido a su rareza.Este estudio tuvo como objetivo investigar las caracteristicas clinicopatologicas de los tumores apendiculares en una cohorte Japonesa.Este fue un estudio observacional retrospectivo de multiples instituciones a nivel nacional.Este estudio se realizo en los hospitales de referencia terciarios participantes.se incluyeron pacientes con tumor apendicular que fueron diagnosticados entre el 2000 y 2017.El resultado primario medido fue la supervivencia total.Se identificaron un total de 922 pacientes de las 43 instalaciones que participaron. De estos, 114 pacientes fueron diagnosticados con cancer distinto de adenocarcinomas. Los 760 pacientes restantes, excepto 48 pacientes con datos de supervivencia desconocidos, fueron elegibles para el analisis de cohorte final. De estos 760 pacientes, 515 (67,8%) tenian adenocarcinomas mucinosos y 245 (32,2%) tenian adenocarcinomas no mucinosos. Dentro del grupo de adenocarcinoma mucinoso, 267 pacientes (35,1%) fueron diagnosticados con neoplasia mucinica apendicular de bajo grado (LAMN). La tasa de supervivencia a 5 anos del adenocarcinoma mucinoso (83.1%) fue superior a la del adenocarcinoma no mucinoso (62,0%) (p

A man in his 60s who had epigastric pain was referred to our hospital and diagnosed with advanced type 3 gastric cancer with multiple liver metastases, cT4acN2cN1(H1), cStage Ⅳ(HER2 3+). He underwent chemotherapy using capecitabine, cisplatin(CDDP), and trastuzumab(T-mab)(XPT). After 7 courses of XPT and 23 courses of XT, liver metastases disappeared, and we decided to perform open distal gastrectomy, D2+ #18 lymphadenectomy, and Billroth Ⅰ reconstruction as a conversion surgery. Despite adjuvant chemotherapy with S-1 plus T-mab, multiple lymph nodes recurrence occurred 3 months after the surgery. He was found to be in complete remission as assessed by CT after 5 courses of second-line CPT-11 treatment, which was discontinued after 17 courses. The patient is alive without recurrence at 57 months after the initial treatment and 22 months after the last treatment.

Although accessory spleens are often found in clinical practice, it is rare to identify cystic disease in an intrapancreatic accessory spleen. Here, we report a case of an epithelial cyst that occurred in the intrapancreatic accessory spleen. The patient was a 54-year-old male. Liver dysfunction was identified by the primary care doctor, and abdominal CT showed a tumorous lesion in the pancreatic tail. The patient was then referred to our hospital. Contrast-enhanced CT revealed a multilocular cystic lesion in the pancreatic tail. In endoscopic ultrasound, there was no obvious solid tumor in the cyst. A cystic disease such as serous cystic neoplasm(SCN)or mucinous cystic neoplasm(MCN)was suspected, and we performed a laparoscopic distal pancreatectomy. Postoperative pathological examination revealed an accessory spleen in the tail of the pancreas. The identified epithelial cyst was present in this accessory spleen. An epithelial cyst that occurs in the intrasplenic accessory spleen is a rare disease, but it is necessary to keep in mind as a possible differential diagnosis.

Most solitary fibrous tumors(SFT)occur in the thoracic cavity and reports on liver SFT are very rare. We encountered a case of SFT of the liver, and thus, decided to report it with a review of literature. A 70-year-old man was informed of a liver tumor by his previous doctor and referred to us for further examination and treatment. Contrast-enhanced CT revealed a 3.5 cm cyst in the S2/3 of the liver and a 3.2 cm tumor with an early staining within the cyst. Laparoscopic lateral segmentectomy was performed and a diagnosis of hepatic cystic adenocarcinoma was made. Macroscopically, the tumor was white and welldefined. Histopathological examination revealed round chromatin-enriched tumor cells proliferated with round fibrillar cells or intercalated structures consisting of round or short spindle-shaped cells. Immunohistochemistry yielded negative results for CAM5.2, HepPar1, CD31, CD99, SMA, and HMB45 but positive results for CD34, Factor Ⅷ, Bcl-2, and STAT6; therefore, the patient was further diagnosed with liver SFT. Although liver SFT is rare, it was considered a differential diagnosis when multiple bloody liver tumors were detected. In addition, since there were reports of recurrence, careful follow-up in future, was deemed necessary.

Hepatocellular carcinoma with bile duct invasion is rare, with a reported incidence of 3.4%. A 71-year-old man with hepatocellular carcinoma underwent radiofrequency ablation(RFA)(S6, S7, S8)and required readmission 22 months after the RFA for hepatocellular carcinoma recurrence detected by gadoxetic acid-enhanced magnetic resonance imaging. Enhanced abdominal computed tomography and magnetic resonance cholangiopancreatography revealed a tumor thrombus in a biliary branch and left adrenal gland metastases. We performed a right lobectomy and left adrenalectomy. The biliary thrombus was easily removed. Postoperative histopathological examination of the resected specimen showed a moderately differentiated hepatocellular carcinoma invading the biliary tract and the absence of viable cells in the liver tumor. The patient has shown no recurrence 6 months after the hepatectomy.

Trifluridine/tipiracil (FTD/TPI) improves the overall survival (OS) of metastatic colorectal cancer (mCRC) patients. Additionally, FTD/TPI plus bevacizumab (BEV) has demonstrated promising efficacy for mCRC patients who are refractory to standard chemotherapy. Chemotherapy-induced neutropenia (CIN) has been reported to be an indicator of efficacy for FTD/TPI. This study investigated whether CIN was an indicator of efficacy for FTD/TPI plus BEV. We reviewed chemo-refractory mCRC patients who were treated with FTD/TPI alone (monotherapy) or FTD/TPI plus BEV (combination) at our institution and compared the safety and efficacy of the two. Progression-free survival (PFS) and OS were analyzed using Kaplan–Meier curves. We also investigated correlations between CIN and outcomes. In total, 56 patients received FTD/TPI, among whom 24 and 32 were treated with monotherapy and combination therapy, respectively. The median PFS was 1.8 and 4.7 months for the monotherapy and combination arms, respectively (hazard ratio [HR]: 0.28; 95% confidence interval [CI]: 0.15–0.51; P

The efficacy of lenvatinib was evaluated in 7 patients with advanced hepatocellular carcinoma(HCC), between March 2018 and February 2019. Their mean age was 74.3 years, and 6 of them were men. All patients had an Eastern Cooperative Oncology Group(ECOG)performance status(PS)of 0. The median number of treatment days was 185. The relative dose intensity was 87.5%. The major Grade was 3, and the overall toxicity events were AST elevation(14.3%)and hypertension (14.3%). The 6-month progression-free and overall survival rates were 71.4% and 100%, respectively. The overall response rate was 57.1%, and the disease control rate was 71.4%. Lenvatinib can be used as a standard treatment for patients with advanced HCC.

We report a case of liver metastases of ampullary carcinoma that achieved clinical complete response after gemcitabine plus cisplatin(GC)combination chemotherapy. A 69-year-old man with obstructive jaundice was diagnosed with ampullary carcinoma and underwent laparoscopic pancreaticoduodenectomy. Postoperative histopathological examination revealed pT3aN0M0, Stage ⅡA adenocarcinoma of the papilla of Vater. Five months after surgery, multiple liver metastases were identified by CT and MRI. The patient received GC chemotherapy intravenously at doses of 1,000 and 25mg/m2 on days 1 and 8, respectively, every 3 weeks. After 3 courses of GC chemotherapy, a CT scan revealed that the liver metastases reduced in size, and PR was achieved based on the RECIST standard. However, Grade 3 neutropenia appeared. After 7 courses, the liver metastases disappeared, and the patient had achieved CR. After 9 courses, the clinical CR continued. Approximately 14 months have passed since the recurrence, and the patient is currently alive.

A 67-year-old man without a history of surgery presented with bloody stool and anal pain. Colonoscopy and abdominal CT revealed locally advanced rectal cancer with right lateral lymph node metastasis. We administered 6courses of neoadjuvant therapy with capecitabine, oxaliplatin, and irinotecan(XELOXIRI)to the patient. After neoadjuvant chemotherapy, remarkable tumor shrinkage was observed. The patient underwent safety intrasphincteric resection(ISR)and lateral lymph node dissection with anal preservation. The postoperative course was uneventful, and he was discharged 17 days postoperatively. Pathologically, no residual cancer cells were observed in the rectum and lymph nodes(pathological CR). This case of locally advanced rectal cancer was successfully treated with laparoscopic ISR after XELOXIRI chemotherapy, and showed pathological CR. ISR after neoadjuvant XELOXIRI chemotherapy was safely performed and might be a good option for locally advanced rectal cancer.

Aflibercept beta and FOLFIRI combination therapy were approved for metastatic colorectal cancer as secondline treatment in 2017. Aflibercept beta is a recombinant fusion protein that traps vascular endothelial growth factor(VEGF)- A, VEGF-B, and placental growth factor(PlGF).We retrospectively evaluated the efficacy and safety of aflibercept beta and FOLFIRI in metastatic colorectal cancer patients(pts)between June 2017 and April 2018 at our institution. Afliber- cept beta(4mg/kg)was administered with FOLFIRI every 2weeks.Twenty pts received aflibercept beta and FOLFIRI. There were 11 males and 9 females, with a median age of 69.5(53-81)years. Performance status(PS)was 0 in 12 pts and 1 in the remaining 8 pts. Aflibercept beta and FOLFIRI were prescribed as second-line treatment in 8 pts and the others in 12 pts. The median number of aflibercept beta and FOLFIRI cycles was 5(1-11)cycles. Progression -free survival and overall survival have not yet been estimated. In terms of adverse events, serious adverse events of Grade 3 or higher, including Grade 5 neutropenia, were seen among all pts.Aflibercept beta and FOLFIRI demonstrated acceptable toxicity in heavily pretreated metastatic colorectal cancer patients.

Background The randomized phase III study (WJOG4407G) showed equivalent efficacy between FOLFOX and FOLFIRI in combination with bevacizumab as the first-line treatment for metastatic colorectal cancer (mCRC). We studied whole genome copy number profiles using array-based comparative genomic hybridization (aCGH) analysis of tumor tissue samples obtained in this study. The aim of this study was to identify gene copy number alterations that could aid in selecting either FOLFOX or FOLFIRI in combination with bevacizumab for patients with mCRC. Materials and Methods DNA was purified from 154 pretreatment formalin-fixed paraffin-embedded tissue samples (75 from the FOLFOX arm and 79 from the FOLFIRI arm) of 395 patients enrolled in the WJOG4407G trial and analyzed by aCGH. Genomic regions greater than 1.2-fold were regarded as copy number gain (CNG). Results Patient characteristics between the treatment arms were well balanced except for tumor laterality (left side; 64% in FOLFOX arm and 80% in FOLFIRI arm, p = .07). FOLFIRI showed a trend toward better response rate (RR), progression-free survival (PFS) and overall survival (OS) than FOLFOX in the patients with CNG of chromosome 8q24.1 (Fisher's exact test, p = .134 for RR; interaction test, p = .102 for PFS and p = .003 for OS) and 8q24.2 (Fisher's exact test, p = .179 for RR; interaction test, p = .144 for PFS and p = .002 for OS). Conclusion Chromosome 8q24.1–q24.2 may contain genes that could potentially serve as predictive markers for selecting either FOLFOX or FOLFIRI in combination with bevacizumab for treatment of patients with mCRC. Implications for Practice Bevacizumab has been used as a standard first-line treatment for patients with metastatic colorectal cancer (mCRC) in combination with either oxaliplatin-based or irinotecan-based chemotherapy. Until now, there has been no predictive marker to choose between the two combination chemotherapies. This array-based comparative genomic hybridization analysis revealed that the difference in therapeutic effect between the two combination chemotherapies is prominent in patients with mCRC with gene copy number gain in chromosome 8p24.1–p24.2. Such patients showed more favorable response and survival when treated with irinotecan-based combination chemotherapy. Overlapping genes commonly found in this region may be predictive biomarkers of the efficacy of the combination chemotherapy with bevacizumab.

Pre-operative chemotherapy is an option for patients with local advanced rectal cancer, but the response rate to pre-operative chemotherapy with oxaliplatin is still low. If the therapeutic effect of pre-operative chemotherapy could be assessed, we may be able to convert to surgery early. The purpose of the present study was to validate the correlation between the maximum standardized uptake value (SUVmax) in 18F-fluorodeoxyglucose positron emission tomography–computed tomography (PET–CT) of the primary tumor and the therapeutic effect of pre-operative chemotherapy in advanced colorectal cancer. Retrospective cohort study from January 2011 to October 2015. We examined 28 patients with pathologically confirmed sigmoid or rectal cancer that underwent pre-operative chemotherapy and surgery. The correlation between Response Index (RI), calculated as (SUVmax after chemotherapy)/(SUVmax before chemotherapy), and the therapeutic effect on the primary tumor in advanced colorectal cancer. The degree of differentiation (p = 0.04), SUVmax in the primary tumor after chemotherapy (p = 0.02), and RI (p = 0.008) were significant predictors of the therapeutic effect in univariate analysis. The areas under the ROC curve constructed with RI and therapeutic effect was 0.77. The optimal cut-off values for the RI in the responder group was

We aimed to determine the recommended dose for bi-weekly XELIRI plus bevacizumab for second-line chemotherapy and examined its safety and efficacy in patients with metastatic colorectal cancer resistant to oxaliplatin-based first-line chemotherapy. Irinotecan and bevacizumab were administered as a continuous intravenous infusion on Day 1 at 150 mg/mm2 and 5 mg/kg, respectively. Capecitabine was orally administered in two divided doses on Days 2–8. Each 2-week treatment cycle was defined as a single course of treatment. During Phase I, we determined the recommended dose for capecitabine. In Phase II trials, efficacy and treatment safety was verified (UMIN000003934). The recommended dose of capecitabine was determined to be 2000 mg/m2. Median progression-free survival was 7.8 months [95% confidence interval (CI) 6.1–10.9 months], and median overall survival was 18.9 months (95% CI 11.6–28.4 months). Response rate was 17.4% (95% CI 6.4–28.3%). The most common Grade ≥3 hematotoxic adverse events were anemia (10.9%), neutropenia (10.9%), and leukopenia (8.7%), while the occurrence rate of Grade ≥3 non-hematotoxic adverse events was relatively low (

BACKGROUND Small bowel adenocarcinoma (SBA) is rare. For unresectable or recurrent SBA, systemic treatment is the only potentially promising option. PATIENTS AND METHODS This retrospective study included 13 patients with SBA treated at our Institute. All patients received fluorouracil- or fluoropyrimidine-based regimens. We analyzed associations between the progression-free interval (PFI) and therapeutic regimen (n=17) and patient characteristics. RESULTS The 5-year overall survival of patients with SBA was 23.5%. The 5-year relapse-free survival of patients with curatively resected (R0 or R1) SBA (n=6) was 45%. Patients with unresectable or recurrent SBA (n=10) had a median overall survival time of 28.0 months. No factor was significantly associated with PFI, except the number of treatment regimens required: patients that received only one line of treatment survived significantly longer than those receiving multiple lines. CONCLUSION Fluorouracil- or fluoropyrimidine-based regimens might effectively treat unresectable or recurrent SBA. We did not investigate any additive agents that might have increased efficacy of these regimens.

Background Venous thromboembolism is the most common preventable cause of hospital death. The objective of this study was to clarify risk factors for postoperative bleeding related to thromboprophylaxis after laparoscopic colorectal cancer surgery. Methods The study was conducted at 23 Japanese institutions and included patients with colorectal cancer who underwent laparoscopic or open surgery followed by fondaparinux treatment. We performed a retrospective analysis from a prospectively maintained database. We used multivariate analyses to evaluate clinical risk factors for prophylaxis-related bleeding events. Results After multivariate analysis, male gender, intraoperative blood loss of less than 25 mL, and a preoperative platelet count below 15 × 104/μL were found to be independent risk factors in the laparoscopic surgery group. Only the preoperative platelet count was an independent risk factor in the open surgery group. Conclusions Different prophylactic treatments for postoperative venous thromboembolism may be necessary in laparoscopic vs open surgery for colorectal cancer.

Pancreatic ductal carcinoma is one of the leading causes of cancer deaths in Japan. However, with remarkable progress in chemotherapy, studies have reported successful resection of initially unresectable pancreatic adenocarcinoma after chemotherapy. We report a case of curative surgery of pancreatic ductal adenocarcinoma with liver metastasis after chemotherapy. A 66-year-old man presenting with jaundice and weight loss was admitted to our hospital for an evaluation of pancreatic lesions. Computed tomography revealed a hypoattenuating mass in the head of the pancreas. We diagnosed this cancer as cT4(SMA1/2)N1M0, cStage Ⅲand performed chemoradiotherapy for this locally advanced pancreatic cancer. Because of the appearance of liver metastasis, we treated this patient with GEM plus nab-PTX chemotherapy. There were no serious adverse events. After 3 therapy courses, the existing liver metastasis disappeared, and no new metastases were noted. Therefore, radical subtotal stomach-preserving pancreatoduodenectomy was performed. The tumor was diagnosed as moderately differentiated adenocarcinoma, ypT1a ypN0 ypM0, ypStage ⅠA, R0.

A 70s man was admitted to another hospital with a complaint of abdominal pain, and was diagnosed with a gastrointestinal perforation based on the presence of free air in the abdominal cavity on computed tomography. The patient was transferred to our hospital in shock and underwent emergency surgery. Operative findings showed a perforation of the rectosigmoid colon and rectal cancer at the anal side of the perforation site. As his general condition was unstable due to septic shock, only the segments of the colon including the perforation site and rectal cancer were resected for source control. The abdominal wall was kept open, and intraperitoneal contamination was managed with an open management method using negative pressure wound therapy. Systemictreatments for septicshoc k were performed in the intensive care unit with a vasopressor and polymyxin-B hemoperfusion. The general condition became stable with intensive care by postoperative day 3. We performed additional lymph node dissection and one-step rectal sigmoidoscopic anastomosis on postoperative day 4. The pathological results confirmed pT4aN1M0, pStage Ⅲa disease. Although the course was complicated by postoperative pneumonia, the patient was discharged on postoperative day 28. We experienced a case in which curative resection with radical lymph node dissection and one-step anastomosis were performed after infection and source control with open abdomen management.

Sorafenib is an oral multi-targeted tyrosine kinase inhibitor used in cases of unresectable advanced HCC that significantly improves progression-free and overall survival. Complete response(CR)is uncommon; however, if major or complete radiological response are obtained, the issue of the discontinuation of sorafenib remains unresolved. The present study reported a case of a 75-year-old man with non-hepatitis B and C virus-related cirrhosis and multiple recurrent HCCs followingresection. In December 2010, a CT scan revealed multiple intrahepatic recurrence after TACE. Laboratory testingshowed Child-Pugh class A cirrhosis and an alpha-fetoprotein level of over 20,000 ng/mL. Sorafenib(800mg/day)was started in December 2010. The subsequent dynamic CT performed at the 6th month of therapy showed a partial response accordingto RECIST criteria and a complete response accordingto mRECIST. The AFP had decreased to within normal levels. In May 2012, the sorafenib dose was reduced(200 mgtwice daily)due to side effects(skin reaction). In December 2013, treatment was stopped after confirmation of a CR associated with shrinkage of the HCC. The patient maintained this remission until June 2018, more than 54 months after the discontinuation of sorafenib therapy. The adverse events of sorafenib were reversible. Further reportingof similar cases should help in the design of treatment strategies after CR to sorafenib therapy.

A 51-year-old man with a gallstone was found to have a tumor in the tail of the pancreas during preoperative examination. We performed EUS-FNA and a pancreatic neuroendocrine tumor was suspected.Therefore, laparoscopic distal pancreatectomy and cholecystectomy were performed.Pathological examination and immunohistochemistry showed that the pancreatic endocrine cells were uniformly increased and were composed of normal Langerhans islets.Therefore, the patient was diagnosed with pancreatic endocrine cell hyperplasia.Typical pancreatic endocrine cell hyperplasia does not form a tumor and is asymptomatic.However, some cases are symptomatic; therefore, when hypoglycemia or pancreatic hormone elevation are found without a clear cause, it should be distinguished.Because pancreatic tumors are difficult to diagnose definitely by imaging inspection alone, needle biopsy is necessary.However, neuroendocrine tumor and neuroendocrine cell hyperplasia are difficult to differentiate by biopsy.

Gemcitabine and cisplatin combination therapy(GC therapy)is now considered a highly effective regimen for patients with unresectable and metastatic biliary tract cancer. We performed GC therapy for 18 patients between January 2014 and April 2018. The median age of the patients was 67.5 years, and 13 patients were men. Fifteen patients had a performance status (PS)score of 0, and 3 patients had a PS score of 1. Nine patients had distal cholangiocarcinoma, 3 had intrahepatic cholangiocarcinoma, 3 had duodenum papilla cancer, and 3 had gallbladder cancer. Fourteen patients showed recurrence after the radical resection, and 9 had liver metastasis. Sixteen patients had over Grade 3 hematological or non-hematological toxicities. The most-common adverse event was neutropenia. None of the patients had Grade 5 adverse events. The response rate was 11.1%, and the disease-control ratio was 66.7%. GC therapy was effective for patients with unresectable and recurrent biliary tract cancer. However, it is necessary to examine the eligibility of patients before treatment.

An 82-year-old man was diagnosed with advanced gastric cancer(tub2, HER2-positive), and the clinical findings were T3N3M1(LYM), Stage Ⅳ. We started chemotherapy with capecitabine, cisplatin, and trastuzumab. After the first course, the dose of capecitabine was reduced and cisplatin was discontinued due to Grade 3 neutropenia. After 4 courses, the remarkable shrinking of the primary tumor and metastatic lymph nodes enabled us to assess the possibility of radical resection, but the patient and his family declined it because of his advanced age. Thereafter, we continued the chemotherapy with capecitabine and trastuzumab for 75 courses. Until multiple lung, liver, and lymph node metastasis occurred after 77 courses, he was adequately managed and maintained good performance status(PS)over a long period of about 53 months.

Schwannomas are rarely observed in the gastrointestinal tract. A 63-year-old man was referred to our hospital with gastric submucosal tumor with central ulceration by upper gastrointestinal endoscopy. Biopsy was performed, but pathological diagnosis was not obtained. A contrast-enhanced computed tomography scan of the abdomen revealed a round mass in the lower part of the stomach and regional lymphadenopathies. A distal gastrectomy with dissection of the regional lymph nodes (D2)was performed. The submucosal tumor measuring 67×49mm was resected. Histopathological examination revealed spindle-shaped cells arranged in palisades. The specimen was positive for S-100 protein, but negative for desmin, SMA, c-kit, and CD34. No tumor cells were found in the resected enlarged lymph nodes, indicating reactive lymphadenopathies. Based on these findings, the tumor was identified as a benign gastric schwannoma. Our patient shows no recurrence at 6 month follow-up.

A 78-year-old man complained of dysphagia. Gastrointestinal endoscopy showed a Type 2 tumor in the lower esophagus and a Type 0-Ⅱa lesion in the posterior wall of the upper gastric body. An enhanced CT scan showed several swollen abdominal and cervical lymph nodes as well as bilateral lung multiple nodules, suggesting distant metastasis. We diagnosed the patient with double cancers consisting of an unresectable advanced esophageal squamous cell carcinoma with multiple lymph nodes and lung metastases(Lt, cT3N4M1, cStage Ⅳb)and early gastric cancer(U, post, cType 0-Ⅱa, cT1N0M0, cStageⅠ). On day 4 of the first course of chemotherapy(docetaxel plus cisplatin plus 5-FU: DCF), a high fever was observed. A chest CT scan revealed suspected mediastinitis and right pyothorax due to perforation by the esophageal cancer. Thoracoscopic mediastinal drainage was immediately performed. CT-guided abscess drainage was added for a residual abscess in the right thoracic cavity on day 10 after drainage surgery. The patient's general condition improved, and he was discharged on 24th postoperative day. The patient was able to reinstitute and continue DCF therapy until disease progression.

Hypoxia is an essential feature of cancer malignancy, but there are no methods for the routine detection of hypoxia-inducible prognostic factors and potential therapeutic targets. We reported previously that the hypoxic tumor cells of metastatic liver tissue from patients with colorectal cancer (CRC) could be used as an 'in vivo' hypoxia culture model. Several potential hypoxia-inducible genes were identified using this model. Among them, one glycolytic enzyme was of special interest. There is currently increasing attention on glycolytic enzymes as potential therapeutic targets due to their association with cancer-specific metabolism. To better understand the molecular mechanisms of cancer malignancy, we investigated the expression of fructose-bisphosphate aldolase A (ALDOA) and its relationship with cancer metabolism. We found that ALDOA was induced by hypoxia in CRC-derived cell lines, and univariate and multivariate analyses of microarray data from the resected CRC samples of 222 patients revealed that ALDOA was an independent prognostic factor for CRC. We also analyzed the malignant potential of ALDOA in vitro using overexpression and knockdown assays. We found that ALDOA was negatively related to chemosensitivity and radiosensitivity and positively associated with proliferation, sphere formation and invasion in both normoxia and hypoxia. These associations were due to the roles of ALDOA in regulating glycolysis, the epithelial-mesenchymal transition and the cell cycle. These findings demonstrate that ALDOA is a hypoxia-inducible prognostic factor that is closely related to CRC malignancy, and also provide new insights into the importance of ALDOA and glycolysis in cancer and suggest new targets for anticancer therapies.

The impact of anti-tumor necrosis factor alpha (TNFα) treatment for Crohn’s disease (CD) on surgical outcomes is still controversial. The aim of this study was to assess the feasibility of laparoscopic surgery for CD patients treated preoperatively with anti-TNFα agents. We investigated, retrospectively, the clinical features and surgical outcomes of 35 consecutive CD patients who underwent laparoscopic surgery after receiving scheduled anti-TNFα treatment preoperatively. We compared the surgical outcomes of an “early surgery group”, comprised of patients who underwent surgery less than 3 years after the initiation of anti-TNFα treatment, with those of a “late surgery group”, comprised of patients who underwent surgery more than 3 years after the initiation of anti-TNFα treatment. The mean operating time and blood loss were 203 min and 259 mL, respectively. The rates of conversion to open surgery and postoperative complications were 8.6 and 11.4 %, respectively. Operating time and blood loss were correlated with the interval between the initiation of anti-TNFα agent treatment and the time of surgery. The proportion of patients with acquired resistance to anti-TNFα agents and the rate of conversion to open surgery were higher and operating times were longer in the late surgery group than in the early surgery group. Laparoscopic surgery can be performed safely for CD patients treated preoperatively with anti-TNFα agents, although operating times may be longer and estimated blood loss (EBL) greater for those who have been on prolonged anti-TNFα treatment.

Background Given the role of microRNA in colorectal cancer (CRC) progression, we explored the association between microRNA (miRNA) expression and CRC-related prognosis. Methods Three types of tissue samples (primary CRC lesions without liver metastasis, primary lesions with liver metastasis, and liver metastatic tissues) were used for miRNA profiling to identify differentially expressed miRNA. Quantitative real-time PCR was used to examine miRNA expression in CRC cells and in tumor tissues. Results MiR-132 was significantly down-regulated in primary CRC tissues with liver metastasis and liver metastatic lesions compared to primary lesions without liver metastasis. Multivariate analysis for overall survival indicated that low miR-132 expression was an independent prognostic factor for CRC patients (overall survival P = 0.040, disease-free survival P = 0.015). Ectopic expression of miR-132 significantly inhibited cell proliferation and cell invasion. The luciferase reporter assay revealed that anoctamin 1 (ANO1) was a direct target of miR-132. Kaplan–Meier survival curves showed that high ANO1 expression was a significant prognostic factor for overall survival of patients with CRC (P = 0.0344). Conclusions Down-regulation of miR-132 is associated with poor prognosis in CRC. ANO1 could be one of the crucial targets of miR-132 in CRC. Electronic supplementary material The online version of this article (doi:10.1245/s10434-016-5133-3) contains supplementary material, which is available to authorized users.

(Aim) Bacterial infection underlies the pathogenesis of many human diseases, including acute and chronic inflammation. Here, we investigated a possible role for bacterial infection in the progression of chronic pancreatitis. (Materials and Methods) Pancreatic juice was obtained from patients with pancreatic cancer (n = 20) or duodenal cancer/bile duct cancer (n = 16) and subjected to PCR using universal primers for the bacterial 16S ribosomal RNA gene. Bacterial species were identified by PCR using bile samples from four pancreatic cancer patients. PCR products were subcloned into T-vectors, and the sequences were then analyzed. Immunohistochemical and serologic analyses for Enterococcus faecalis infection were performed on a large cohort of healthy volunteers and patients with chronic pancreatitis or pancreatic cancer and on mice with caerulein-induced chronic pancreatitis. The effect of E. faecalis antigens on cytokine secretion by pancreatic cancer cells was also investigated. (Results) We found that 29 of 36 pancreatic juice samples were positive for bacterial DNA. Enterococcus and Enterobacter species were detected primarily in bile, which is thought to be a pathway for bacterial infection of the pancreas. Enterococcus faecalis was also detected in pancreatic tissue from chronic pancreatitis and pancreatic cancer patients; antibodies to E. faecalis capsular polysaccharide were elevated in serum from chronic pancreatitis patients. Enterococcus-specific antibodies and pancreatic tissue–associated E. faecalis were detected in mice with caerulein-induced chronic pancreatitis. Addition of Enterococcus lipoteichoic acid and heat-killed bacteria induced expression of pro-fibrotic cytokines by pancreatic cancer cells in vitro. (Conclusion) Infection with E. faecalis may be involved in chronic pancreatitis progression, ultimately leading to development of pancreatic cancer.

A 69-year-old man was admitted for the growing anal tumor and referred to our hospital. The tumor was about 40mm in size, and by biopsy, he was diagnosed the adenocarcinoma. Based on this diagnosis, abdominoperinealresection and edge resection were performed. Histopathologicalfindings showed mucinous carcinoma originating from analgl and with pagetoid spread. Postoperative chemotherapy was not performed, but 1 year 6 months after the surgery, inguinall ymph node recurrence was found, and lymph node dissection was performed. One year after the operation, recurrence was not found.

The standard strategy for locally advanced lower rectal cancer is chemoradiotherapy followed by total mesorectal excision (TME) in Western countries and TME followed by adjuvant chemotherapy without preoperative treatment in Japan. This phase II trial evaluated the efficacy of a preoperative CAPOX chemotherapy regimen without radiation therapy for patients with locally advanced rectal cancer. The primary endpoint was 2-year disease-free survival. The trial enrolled 45 patients from 9 institutions between 2012 and 2014. The mean age was 63.5 (29–74) years; 31 patients were male. Most patients (n = 41) received preoperative chemotherapy (CTx), and the preoperative CTx completion rate was 95.2%. R0 resection after CTx was performed in 41 patients. The pathological complete response rate was 7.3% (3/41). After surgery, 35 patients (85.3%) received adjuvant CTx, and 22 of 35 completed the protocol treatment. The follow-up period ranged from 0.71 to 4.68 years (median 2.86 years). There was recurrence in 13 of 40 patients who underwent R0 resection, and the 2-year disease-free survival rate and overall survival rate were 71.6 and 92.7%, respectively. Here we report the completion rates for neoadjuvant CTx and adjuvant CTx, the pathological complete response rate, and the mid-term prognosis. The results indicate that CAPOX followed by TME may be a safe treatment strategy for locally advanced rectal cancer.

A 66-year-old man reporting chest stenosis was examined. Upper gastrointestinal endoscopy showed type 2 esophageal cancer. An enhanced CT scan showed several swollen lymph nodes in the lesser curvature of the esophagus. We diagnosed the patient as having advanced esophageal cancer with multiple lymph node metastases(cT3N2M0, Stage III ). After 2 courses of chemotherapy(DCF), a significant reduction was observed in the esophageal tumor; however, the tumor at the lesser curvature was almost unchanged. MIBG scintigraphy showed high uptake in the left adrenal gland. In addition, urinary adrenaline was elevated. Therefore, we diagnosed the patient with pheochromocytoma. Metachronous surgery was performed. First, left adrenalectomy was performed. After we confirmed stability of blood pressure, esophagectomy was performed. The patient is alive without recurrence for 7 months after these operations.

The aim of this study was to evaluate the rate of surgical site infection(SSI)after hepatectomy in elderly patients with hepatocellular carcinoma(HCC). From June 2010 through December 2016, 276 cases of hepatectomy for HCC were performed in our hospital, and 39 cases included patients aged80 years. The rate of SSI in the elderly group compared to the non-elderly group was 15.38%(6/39 cases)vs 7.73%(p=0.0855). The Child-Pugh classification(A/B/C)in the SSI group (n=6)vs in the non-SSI group(n=33)was 6/0/0 vs 32/1/0(p=0.5605), the liver damage classification(A/B/C)was 4/ 2/0 vs 25/8/0(p=0.6467), BMI was 23.3 kg/m / 2 vs 22.8 kg/m2(p=0.6544), PNI was 43.1 vs 46.2(p=0.3804), the operation time was 348.5 minutes vs 315.1 minutes(p=0.4478), blood loss was a small amount vs 401.5mL(p=0.0143), and the hospital stay after the operation was 27.5 days vs 10.0 days(p=0.0401), respectively. Hepatectomy for elderly patients was safe and feasible, and the only significant risk factor for SSI in elderly HCC patients was intraoperative blood loss.

A 60-year-oldman was diagnosedwith ascending colon cancer with multiple bilobar metastases. He then received7 courses of tegafur-gimeracil-oteracil andoxaliplatin (SOX)plus panitumumab as downstaging chemotherapy. This treatment significantly reducedthe size of the metastatic tumor, andwe subsequently triedto perform a curative resection. A twostage hepatectomy was plannedto avoidthe risk of hepatic failure from small future liver remnant. First, the anterior segmentectomy andthe left portal vein ligation were performed. Then, a curative resection consisting of a left lobectomy andextend - edright hemicolectomy were performed2 0 days after the first surgery. No recurrence was observed1 5 months after the operation. Two-stage hepatectomy as well as a combination of induction chemotherapy and portal vein ligation may have contributedto the improvedprognosis of the initially unresectable multiple bilobar liver metastases.

Pancreatic neuroendocrine tumor(P-NET)is relatively rare and often has less aggressive biological behavior. P-NET was re-designated by the WHO in 2010 and 2017. Laparoscopic surgery is minimally invasive but has technical difficulties such as limitation of movement and laparoscopic view. The purpose of this study is to evaluate the efficacy of laparoscopic pancreatectomy(LPT)for P-NET.Between January 2012 and June 2017, 6 patients underwent LPT for P-NET at Kansai Rosai Hospital. Five patients who received open pancreatectomy(OPT)for P-NET and 41 patients who received laparoscopic distal pancreatectomy(LDP)for cystic tumor(CyT)or invasive ductal carcinoma(IDC)were included for comparison.All patients who underwent LPT for P-NET were NET G1 in WHO Classification 2017 and Stage I in UICC TNM 2016. No significant differences were noted between LPT and OPT groups with respect to patient age or gender. Operation time was 421.5 versus 423.5 minutes(ns), blood loss was 121.7 versus 1,918.3mL(ns), hospital stay was 20.5 versus 58.0 days(ns)for LPT and OPT respectively. In LDP, there were no significant differences between PNEN, CyT, and IDC groups with respect to patient age, gender, operation time, blood loss and hospital stay. All patients who underwent LPT for P-NET alive without recurrence. The average observation period was 58.4 months.Laparoscopic pancreatectomy is safe and effective approach to the management of pancreatic neuroendocrine neoplasm.