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Anticancer drugs generate excessive reactive oxygen species (ROS), which can cause cell death. Cancer cells can resist this oxidative stress, but the mechanism of resistance and associations with chemoresistance are unclear. Here, we focused on Sirtuin 3 (SIRT3), a deacetylating mitochondrial enzyme, in oxidative stress resistance in colorectal cancer (CRC). To evaluate SIRT3-related changes in mitochondrial function, ROS (mtROS) induction, and apoptosis, we used the human CRC cell lines HT29 and HCT116 transfected with short-hairpin RNA targeting SIRT3 and small interfering RNAs targeting superoxide dismutase 2 mitochondrial (SOD2) and peroxisome proliferator–activated receptor γ coactivator-1 (PGC-1α). In 142 clinical specimens from patients with CRC, we also assessed the association of SIRT3 protein levels (high/low) and prognosis. SIRT3 expression correlated with mtROS generation and apoptosis induction in cells treated with anticancer agents. Suppressing SIRT3 increased mtROS levels and cell sensitivity to anticancer agents. SIRT3 knockdown decreased SOD2 expression and activity, and suppressing SOD2 also improved sensitivity to anticancer drugs. In addition, SIRT3 was recruited with PGC-1α under oxidative stress, and suppressing SIRT3 decreased PGC-1α expression and mitochondrial function. PGC-1α knockdown decreased mitochondrial activity and increased apoptosis in cells treated with anticancer drugs. In resected CRC specimens, high vs low SIRT3 protein levels were associated with significantly reduced cancer-specific survival. SIRT3 expression affected CRC cell chemoresistance through SOD2 and PGC-1α regulation and was an independent prognostic factor in CRC. SIRT3 may be a novel target for CRC therapies and a predictive marker of sensitivity to chemotherapy.

Recently developed molecularly targeted therapies such as EGFR inhibitors have notably improved the prognosis of patients with cancer. However, patients with KRAS and BRAF mutations do not currently benefit from these therapies. Here, we aimed to examine potential effects of crenolanib as a new molecularly targeted therapy in colorectal cancer. We used multiple colorectal cancer cell lines to investigate the growth-inhibitory effect of crenolanib and its effect in combination with other cytotoxic agents. Primary cultures of patient-derived organoids (PDO), a model that reflects the heterogeneity of clinical colorectal cancer, were used to further validate the effects of crenolanib. Unlike cetuximab, crenolanib remarkably suppressed ERK and AKT/mTOR pathways in HT29 cells with BRAF mutation and in HCT116 cells with KRAS mutation with corresponding growth-suppressing effects. Additive or synergistic effects were observed in treatments with combination of crenolanib and other cytotoxic drugs. Moreover, crenolanib suppressed the expression of stem cell markers, such as OCT4, NANOG, and SOX2. These observations were substantiated in seven PDOs with KRAS mutation and two PDOs without KRAS/BRAF mutations, with crenolanib suppressing the growth of all PDOs regardless of their KRAS mutation status. Furthermore, crenolanib abrogated PDGF- and TGFβ-induced increase of OCT4-positive cells in PDOs. Together, these findings suggest that crenolanib may have clinical utility for patients with colorectal cancer, especially patients with KRAS/BRAF mutations. Implications: These findings indicate that crenolanib can be a useful target agent for patients with colorectal cancer, especially patients with KRAS/BRAF mutations.

Chromosome instability is one of the hallmarks of cancer. Stromal antigen (STAG) 3 is a core component of the meiosis-specific cohesin complex, which regulates sister chromatid cohesion. Although aberrantly activated genes encoding the cohesin complex have been identified in cancers, little is known about the role of STAG3 in colorectal cancer (CRC). Here, we evaluated the prognostic impact and role of STAG3 in CRC. Analysis of 172 CRC surgical specimens revealed that high STAG3 expression was associated with poor prognosis. STAG3 knockdown inhibited cell migration and increased drug sensitivity to oxaliplatin, 5-fluorouracil, irinotecan hydrochloride hydrate, and BRAF inhibitor in CRC cell lines. The enhanced drug sensitivity was also confirmed in a human organoid established from a CRC specimen. Moreover, suppression of STAG3 increased γH2AX foci. Particularly, in BRAF-mutant CRC cells, STAG3 silencing suppressed the expression of snail family transcriptional repressor 1 and phosphorylation of extracellular signal-regulated kinase via upregulation of dual-specificity phosphatase 6. Our findings suggest that STAG3 is related to poor clinical outcomes and promotes metastasis and chemotherapeutic resistance in CRC. STAG3 may be a novel prognostic marker and potential therapeutic target for CRC.

A 70-year-old woman underwent treatment for cecal cancer(pT4bN1M0, Stage Ⅲb)in 2010. Four years and 2 months after the first surgery, she underwent ileum resection for stenosis due to perineal dissemination(P3). Two years after this recurrence, during which time she had completed 26 courses of FOLFIRI plus bevacizumab(Bmab), 9 courses of capecitabine plus oxaliplatin(CapeOX)plus Bmab, and 3 courses of Cape, no peritoneal dissemination was detected by computed tomography( CT). Thereafter, an additional 19 courses of Cape plus Bmab were introduced, but CEA continued to increase. Right ovarian metastasis was suspected based on CT and FDG-PET/CT examination. Four years and 1 month after the initial recurrence of perineal dissemination, the patient underwent bilateral ovarian resection, during which the lack of peritoneal dissemination was confirmed. Pathologically, right ovarian metastasis was diagnosed. The patient is still alive 4 years and 6 months after the first operation.

A 77-year-old woman was referred to our hospital for detailed examination of a cystic liver tumor. Contrast-enhanced CT and MRIshowed a cystic liver tumor with an enhanced mural nodule in S6 of the liver. Under a preoperative diagnosis of hemorrhagic hepatic cyst and mucinous cystic neoplasm(MCN)of the liver, extended posterior segmentectomy was performed. Histological examination of the tumor revealed no neoplastic cells, and the tumor was finally diagnosed as a hemorrhagic hepatic cyst of the liver.Similar to previous reports of hemorrhagic hepatic cysts, preoperative differential diagnosis from MCN of the liver was difficult in this case. Hemorrhagic hepatic cysts are rare and are sometimes confused with MCN of the liver, especially when an enhanced mural nodule is found in the cyst. The possibility of hemorrhagic hepatic cysts should be considered during diagnosis of liver cystic tumors.

We describe a case of residual stomach preserving surgery performed under evaluation of residual gastric blood flow with indocyanine green(ICG)fluorography, for gastric cancer with recurrence of splenic lymph node metastasis after distal gastrectomy( DG)in a 65-year-old man. After 4 courses of S-1 plus CDDP(SP)therapy for advanced gastric cancer with ascites, DG, D2 dissection, and Billroth Ⅰ reconstruction were performed and radical resection was obtained(L, Type 3, pap/tub, ypT3N1H0P0CY0M0, ypStage ⅡB). Three years and 6 months after the surgery, a mass 4 cm in diameter was found in the splenic hilum, and a pancreatosplenial resection was performed to remove the tumor for diagnosis and treatment purposes. We confirmed that there was no problem with blood flow, and we were able to preserve the stomach. Intraoperative ICG fluorescence imaging was considered a promising method for evaluating residual gastric blood flow.

A92 -year-old man was diagnosed with pancreatic cancer 14 years after undergoing distal gastrectomy for gastric cancer. His remnant stomach was fed by the cardiac branch of the left inferior phrenic artery, short gastric artery, and posterior gastric artery. We planned distal pancreatectomy(DP). Intraoperative indocyanine green(ICG)fluorography showed that the remnant stomach was perfused under the clamp of the splenic artery. We also confirmed that regional oxygen saturation (rSO2)of the remnant stomach was not decreased by the clamp. Based on the findings, we judged that blood flow in the remnant stomach was preserved at the clamp. We then performed DP with preservation of the remnant stomach. Postoperative complications associated with the remnant stomach were not observed. The patient is alive without any postoperative recurrences of pancreatic cancer or trouble associated with the remnant stomach 22 months after the surgery. This case suggested that ICG fluorography and rSO2 monitoring are useful to evaluate blood flow in the remnant stomach.

A 68-year-old man underwent a subtotal stomach-preserving pancreatoduodenectomy(SSPPD)for a distal bile duct carcinoma(BDC)pT3aN1M0, pStage ⅡB and adjuvant chemotherapy with gemcitabine. One year 7 months after the initial surgery, CT revealed a nodule with an increasing tendency in the left lung. As it was difficult to distinguish primary lung cancer from BDC lung metastasis, we performed a thoracoscopic left wedge resection. The histopathology of the resected specimen was BDC lung metastasis. In the follow-up with adjuvant chemotherapy with S-1 for 10 months, 2 nodules were found in the right lung, and we performed thoracoscopic right S6 segmentectomy. Eight months later, another nodule was found in the left lung, and we performed thoracoscopic left wedge resection. The histopathology was BDC lung metastasis for all the resected specimens. The patient is alive with no evidence of recurrence after 9 months of the latest surgery(4 years 11 months after the initial surgery). Although the standard treatment for metastatic recurrence of BDC is systemic chemotherapy, some cases treated with surgical resection had relatively good prognosis, such as the present case. Surgical resection might be feasible as a treatment option for metastatic recurrence of BDC.

A 65-year-old man visited our hospital for hepatocellular carcinoma(HCC)and underwent extended posterior sectionectomy. Eight months after the hepatic resection, follow-up computed tomography(CT)revealed a solitary, recurrent tumor in S4 of the liver, and transcatheter arterial chemoembolization and radiofrequency ablation were performed for the intrahepatic recurrence. After 12 postoperative months, follow-up CT demonstrated pulmonary metastases in S5 of the right lung and S10 of the left lung. Since there were no other metastases, the 2 metastatic lesions were resected using video-assisted thoracoscopic surgery(VATS). The resected tumors were histologically diagnosed as pulmonary metastases of HCC. Three years after the pulmonary resection, 3 additional pulmonary metastases were detected on CT in S3 and S10 of the right lung and S4 of the left lung. No other metastases were found. Bilateral VATSmetastasectomy was performed for the metastases. The tumors were diagnosed as pulmonary metastases of HCC on histological examination. One year and 8 months after the surgery, he was alive in a good condition, with no recurrences. The present case suggested that some patients with pulmonary metastasis of HCC can have long-term survival with surgical resection of the metastasis. Therefore, while systemic chemotherapy is generally considered the standard treatment for extrahepatic metastasis of HCC, surgical resection might be an option.

A 70s man presented with a solitary liver tumor measuring 4.5 cm on CT. On contrast-enhanced CT, the tumor appeared partly well-enhanced in the late phase, and the remaining part was enhanced in the early phase and washed out in the late phase. Contrast-enhanced MRIshowed fused multiple nodules, and the enhancement/washout pattern was clearer than that of the contrast-enhanced CT. The tumor showed a defective image in the hepatobiliary phase and a high signal on diffusionweighted imaging. Then, the tumor was diagnosed as hepatocellular carcinoma, and thus, left liver lobectomy was performed. On histological examination of the resected specimen, the tumor was found to be composed of uniform and small tumor cells with solid or trabecular growth fashion. On immunohistochemical staining, synaptophysin and chromogranin A positivity was noted, and the Ki-67 index was 14%. Finally, the tumor was diagnosed as a NET G2. Postoperatively, somatostatin receptor scintigraphy was performed to identify the primary site; however, no obvious primary site could not be identified, and thus a diagnosis of primary hepatic NET was made. Eighteen months postoperatively, the patient is alive without relapse. Preoperative diagnosis of primary hepatic NETs is difficult because NETs present various imaging findings and are rare. Moreover, no accurate preoperative diagnosis was reached in our case, suggesting the difficulty in the preoperative diagnosis of NETs.

A 60s man underwent upper gastrointestinal endoscopy at a regular medical check-up without symptoms, which showed an ulcerative region in the duodenal ampulla, measuring 3 cm in diameter. He was diagnosed with poorly differentiated adenocarcinoma on biopsy and referred to our hospital. Abdominal contrast-enhanced CT scan revealed an enhanced-ulcerative tumor, measuring 3 cm, at the duodenal ampulla. After the preoperative diagnosis of adenocarcinoma of the duodenal ampulla, subtotal stomach-preserving pancreatoduodenectomy with regional lymph node dissection was performed. The final diagnosis was neuroendocrine carcinoma(NEC)of the duodenal ampulla. He has been alive for 9 years with no recurrences. NEC of the duodenal ampulla is rare, and its prognosis is poor. We report a case of long-term survival after resection of NEC of the duodenal ampulla.

Laparoscopic hepatectomy has gained popularity owing to its merits, such as low invasiveness and reduced bleeding. However, the efficacy of laparoscopic repeat hepatectomy(LRH)has not been confirmed. The aim of this study was to evaluate the feasibility and efficacy of LRH compared to that of open repeat hepatectomy(ORH). We performed 60 repeat hepatectomies from January 2011 to March 2019, of which 19 were LRH(Lap group)and 41 were ORH(Open group). This study retrospectively compared the patient characteristics and short-term outcomes of repeat hepatectomy between the Lap and Open groups. There were no significant differences in patient characteristics, except for the type of approach in the previous hepatectomy(p0.01). The Lap group had lesser blood loss(median: 150 mL vs 355 mL, p0.01)and shorter postoperative hospital stays(median: 8 days vs 11 days, p0.01). There were no differences in operation time or severe postoperative complications. LRH is feasible and useful, providing good short-term outcomes.

In recent years, systemic chemotherapy has significantly improved the prognosis of metastatic colorectal cancer (CRC); however, different patients have different responses to chemotherapeutics. Dipeptidyl peptidase 9 (DPP9) is an enzyme in the dipeptidyl peptidase IV family that has been reported to increase drug sensitivity in acute myeloid leukemia. In this study, we examined the relationship between DPP9 expression and the prognosis of patients with CRC, as well as the role of DPP9 in anticancer drug resistance. Moreover, the effects of the DPP9 inhibitors talabostat and vildagliptin in CRC cell lines and primary cultured cells were assessed. High expression of DPP9 was associated with worse prognosis in 196 patients with CRC. Cell viability was markedly inhibited in CRC cell lines transfected with DPP9 small interfering RNA or small hairpin RNA. Talabostat suppressed proliferation in CRC cell lines and primary cultured cells, and increased their sensitivity to chemotherapy. Vildagliptin, a DPP family inhibitor currently administered for diabetes, also increased the sensitivity of CRC cells to anticancer drugs. DPP9 was a poor prognostic factor for CRC and could be a new therapeutic target, while vildagliptin could be used as a repositioned drug for CRC treatment.

Objective : Surgical treatment is an important option for inducing remission in Crohn's disease (CD); indeed, the longer the disease duration, the higher the cumulative surgical rate. Previous studies have shown that the pathogenesis of Crohn's disease was associated with sarcopenia, a condition of reduced skeletal muscle mass. Here, we investigated the effect of preoperative sarcopenia on postoperative disease activity. Methods : This retrospective study included 56 patients with CD with medical records that met our inclusion criteria. Sarcopenia was diagnosed, based on the psoas muscle mass index (PMI) derived from computed tomography (CT) images, with predetermined PMI cut-off values of Results : Of the 56 included subjects, nine (16%) had sarcopenia. The rate of preoperative treatment with biological drugs was significantly lower in the sarcopenia group than in the normal group. In addition, the operation time was significantly longer, and hemorrhage occurred more often in the sarcopenia group than in the normal group. Postoperatively, the CD activity index at six months had significantly decreased in the normal group (p = 0.01), but not in the sarcopenia group (p = 0.20). Univariate and multivariate analyses showed that a low total serum protein level was significantly associated with sarcopenia. Conclusion : Our results suggested that, to maximize the effect of surgical treatment for CD, an appropriate nutritional intervention should be performed before surgery, or surgery should be postponed until the patient recovers from sarcopenia.

Crohn’s disease causes chronic inflammation in the gastrointestinal tract and its pathogenesis remains unclear. In the intestine of Crohn’s disease patients, CD14+CD11+CD163low macrophages contribute to inflammation through the induction of Th17 cells and production of inflammatory cytokines; the CD14+CD11c+163high fraction is anti-inflammatory through the production of IL-10 in normal cases. In this report, the 16S rRNA gene amplicon sequencing method was used to identify bacteria that are specifically present in intestinal CD14+CD11c+ macrophages of Crohn’s disease patients. Bacteria present in intestinal CD14+CD11c+ macrophages and mucus of Crohn’s disease patients were separated into different clusters in principal coordinates analysis. There was a statistically significant increase in the relative composition of CD14+CD11c+ macrophages from mucus in two phyla (Proteobacteria [p = 0.01] and Actinobacteria [p = 0.02]) and two families (Moraxellaceae [p

Background: Human intestinal innate myeloid cells can be divided into 3 subsets: HLA-DRCD14 cells, HLA-DRCD103 dendritic cells (DCs), and HLA-DRCD14CD103 cells. CD103 DCs generate Treg cells and Th17 cells in the ileum, but their function in the colon remains largely unknown. This study characterized CD103 DCs in the colon and investigated whether these cells are implicated in the pathogenesis of ulcerative colitis (UC). Methods: Normal intestinal mucosa was obtained from intact sites of patients with colorectal cancer (n = 24). Noninflamed and inflamed colonic tissues were obtained from surgically resected specimens of patients with UC (n = 13). Among LinCD45HLA-DR intestinal lamina propria cells, CD14 cells and CD103 DCs were sorted and analyzed for microRNA expression of cytokines and toll-like receptors by quantitative real-time polymerase chain reaction. In addition, IL-4/IL-5/IL-13/IL-17/IFN-γ production and Foxp3 expression by naive T cells cultured with CD14 cells and CD103 DCs were analyzed. Results: CD103 DCs in the normal colon showed lower expression of toll-like receptors and proinflammatory cytokines than CD14 cells. Coculture with naive T cells revealed that CD103 DCs generated Treg cells. CD103 DCs from patients with UC did not generate Treg cells, but they induced IFN-γ-, IL-13-, and IL-17-producing CD4 T cells and showed higher expression of IL6 (P < 0.0001), IL23A (P < 0.05), IL12p35 (P < 0.05), and TNF (P < 0.05). Conclusions: In patients with UC, CD103 DCs show the impaired ability to generate Treg cells, but exhibit a colitogenic function inducing Th1/Th2/Th17 responses. These findings show how human CD103 DCs could contribute to the pathogenesis of UC.

Innate lymphoid cells (ILC) are responsible for mucosal tissue homeostasis and are involved in the progression and suppression of several types of cancer. However, the effects of ILCs on colorectal cancer are poorly understood. We characterized human ILCs in normal colon and colorectal cancer tissue, investigating their role in the tumor immune microenvironment. Normal mucosa and tumor tissues were obtained from patients with colorectal cancer, and the cells were isolated by enzymatic digestion. NKp44

This report describes a case of primary adenosquamous carcinoma of the liver with hepatolithiasis. A 70's man was followed up at a clinic for hepatolithiasis, gallbladder stone, and dilatation of the intrahepatic duct. He visited our hospital for computed tomography(CT)examination. CT showed a 30mm diameter low-density mass in the S2 liver and dilatation of the intrahe- patic duct filled with hepatolithiasis. Blood examination showed elevated levels of tumor markers(CEA 8.0 ng/mL, CA19-9 19,196 U/mL). We diagnosed the tumor as cholangiocellular carcinoma(cT2N1M0, cStage ⅣA)with hepatolithiasis and performed left hepatectomy and lymphadenectomy. In the specimen, a 39×22mm diameter solid tumor was detected and the intrahepatic duct was filled with haptolithiasis. Pathologically, a mixture of adenocarcinoma and squamous cell carcinoma was observed adjacent to the bile duct. Accordingly, a diagnosis of adenosquamous carcinoma was made(pT3N0M0, pStage Ⅲ). Multiple liver metastases were detected 8 months after the operation, and chemotherapy was started. He remains alive 11 months after the operation. We experienced a rare case of adenosquamous carcinoma in the liver with hepatolithiasis.

Background Inadequate blood flow is an important risk factor for anastomotic leakage. Indocyanine green (ICG) fluorescence imaging allows intraoperative assessment of intestinal blood flow. This study determined the risk factor of anastomotic hypoperfusion in colorectal surgery using ICG fluorescence imaging. Methods This study included 74 consecutive patients who underwent colorectal surgery between April 2017 and March 2018. ICG was injected intravenously after dividing the mesentery and central vessels along the planned transection line, but before completing the anastomosis. Intraoperative blood flow was evaluated using ICG fluorescence imaging. With regard to the patient-, tumor-, and surgery-related factors, anastomotic perfusion was evaluated based on the changed transection line and prolonged (more than 60 s) perfusion time. Results Intraoperative ICG fluorescence imaging was performed in all patients, and no adverse events were associated with ICG injection. Based on the perfusion assessment, we changed the transection line in six patients (8.1%). The prolonged perfusion time was observed in nine patients (12.2%). The postoperative course was uneventful in 63 (85.1%) patients, but one patient (1.4%) had postoperative anastomotic leakage. The changed transection line was significantly associated with anticoagulation therapy ( P = 0.029). Well-known risk factors, including surgical site, sex, smoking, blood loss, operative time, and preoperative chemoradiotherapy, were not related to the changed transection line. Prolonged ICG perfusion time was not associated with any patient-, tumor-, or surgery-related factors. Conclusions The evaluation of intraoperative blood flow using ICG fluorescence imaging may be able to detect anastomotic hypoperfusion, and anticoagulation therapy is a risk factor of anastomotic hypoperfusion in colorectal surgery.

There have been few reports discussing treatments for primary duodenal cancer. In this study, 15 cases of primary duodenal cancer that were treated by curative resection in our hospital between April 2005 and December 2017 were analyzed to study appropriate operative procedures. Prognostic analysis revealed that the median of relapse-free survival and overall survival were 49 months and 74 months, respectively. The 5-year survival rate was 47%. On univariate analysis of relapse-free survival, lymph node metastasis(p0.01)and post-operative adjuvant therapy(p=0.02)were significant independent prognostic factors. Analysis of the relationship between lymph node metastasis and the depth or location of tumors suggested that pancreaticoduodenectomy with lymph node dissection should be performed to achieve radical resection, since there were some cases that involved lymph node metastasis around the pancreatic head or hepatoduodenal ligament.

We report a case of recurrent gastric cancer that was successfully treated by S-1 chemotherapy.An 81-year-old woman with advanced gastric cancer[L Less, Type 2, cT4a(SE), cN0H0P0M0, cStageⅡB]underwent distal gastrectomy.Abdominal CT performed 6 months after surgery revealed a low-density area in the liver.She was diagnosed with liver metastasis and started receiving S-1 chemotherapy.The liver metastasis achieved complete response, so S-1 chemotherapy was discontinued 12 months after recurrence.Abdominal CT performed 9 months after the discontinuation of S-1 chemotherapy revealed multiple low-density areas in the liver.She started receiving S-1 chemotherapy again, but S-1 chemotherapy was discontinued because of side effects after 2 courses.The patient died 24 months after receiving S-1 chemotherapy.

A60s woman was followed-up regularly for primary biliary cholangitis and a solitary enlarging hepatic mass in the S6 segment of her liver was discovered by ultrasonography. We diagnosed the mass as hepatocellular carcinoma by contrast ultrasonography, contrast computed tomography, and ethoxbenzyl magnetic resonance imaging and laparoscopic partial hepatectomy of S6 segment was performed. The resected specimen was histopathologicaly diagnosed as liver-reactive lymphoid hyperplasia(RLH). The patient is alive without recurrence 17 months after the surgery. Although liver RLH is a rare disease, it should be considered in the differential diagnosis of small liver tumors.

A 55 -year-old woman presented at our hospital in 2017. In 2014, a large cyst had been detected in her liver by ultrasonography, and she was followed up at a clinic. Abdominal computed tomography(CT)revealed a large multilocular cystic tumor measuring 12 cm in diameter in the left lobe of the liver. Although no solid component was identified in the tumor, the cystic tumor was increasing in size, and the serum level of CA19-9 was elevated. Under a preoperative diagnosis of mucinous cystic neoplasm(MCN)of the liver, we performed extended left liver lobectomy. There were no postoperative complications. Histopathological examination of the resected specimen revealed low-grade intraepithelial neoplasia, and the epithelium covered an ovarian-type stroma. The ovarian-type stromal cells were immunoreactive for estrogen receptor and progesterone receptor. The definitive diagnosis of the tumor was MCN of the liver with low-grade intraepithelial neoplasia. Eight months after the surgery, the patient remains alive without any recurrence.

A 72-year-old man received chemoradiotherapy for lung squamous cell carcinoma(T4N2M0, Stage Ⅲb). Nine months after the start of chemoradiotherapy, a 60 mm sized mass was identified in the spleen on abdominal CT. FDG-PET/CT examination revealed abnormal FDG accumulation in the tumor, and no obvious accumulation was observed in other sites. By endoscopic ultrasound-guided fine needle aspiration cytology, the tumor was diagnosed as splenic metastasis from lung cancer. Since the primary lung tumor was well controlled by the chemoradiotherapy and no metastatic lesions were found except in the spleen, laparoscopic excision of the splenic metastasis was planned. Since the tumor was suspected to have infiltrated the tail of the pancreas, laparoscopic distal pancreatectomy and splenectomy were performed. There were no severe postoperative complications. The resected tumor was histopathologically diagnosed as not splenic metastasis, but lymph node metastasis at the splenic hilum from lung cancer invading the pancreas and spleen. Brain metastasis and bone metastasis were observed 3 months postoperatively. He did not undergo any treatments for the metastatic lesions, and he died because of the cancer 11 months after the operation. This case suggests the clinical significance of surgical treatment for distant metastatic lesions from lung cancer.

A 63-year-old man was referred to our hospital for detailed examinations and treatment of a hepatic tumor. Abdominal contrast-enhanced CT examination showed a huge mass measuring 12 cm in diameter with ring enhancement in the left liver lobe. The liver tumor was accompanied by a macroscopic tumor thrombus in the left portal branch. Under preoperative diagnosis of intrahepatic cholangiocarcinoma with portal vein tumor thrombus, left liver lobectomy, removal of the tumor thrombus, extrahepatic bile duct excision, and lymph node dissection were performed. Histopathological examination of the resected specimens revealed moderately differentiated adenocarcinoma concomitant with tumor thrombus in the left portal branch. Adjuvant chemotherapy with S-1 was administered. However, 3 months after the surgery, CT examination revealed postoperative recurrences in the liver, lung, and bone. Systemic chemotherapy with gemcitabine and cisplatin was administered with radiotherapy for the bone metastasis. However, the chemotherapy was not effective, and 6 months after surgery, he died of the cancer. There have been few reports of cases with ICC accompanied by a macroscopic portal vein tumor thrombus. Based on the reported cases and the present case, prognosis of the disease seems very poor.

Inappropriate activation of T helper (Th) cells, such as Th1 and Th17 cells, is implicated in the pathogenesis of chronic inflammatory disorders including ulcerative colitis (UC). CX3CR1high macrophages contribute to intestinal homeostasis through various mechanisms in mice. However, whether mononuclear phagocytes with regulatory functions are present in the human colon is not clearly defined. We investigated whether innate myeloid cells that suppress activation of effector T cells exist in the human intestinal mucosa. Among intestinal lamina propria cells, Lin− HLA-DRhigh CD14+ CD163high cells were subdivided into CD160low and CD160high cells. Both subsets produced high levels of IL-10. CD163high CD160high cells suppressed effector T cell proliferation, whereas CD163high CD160low cells induced Th17 differentiation. Patients with UC exhibited increased numbers of CD163high CD160low cells, while showing profoundly decreased numbers of CD163high CD160high cells. In this context, CD163high CD160high cells had higher CD80/CD86 expression and lower IL10RB expression, and these cells did not suppress effector T cell proliferation. The CD163high CD160high subset in normal intestinal mucosa inhibits inappropriate Th1/Th17 responses through suppression of their proliferation, and its number and suppressive activity are impaired in patients with UC. These findings indicate how human innate immune cells might prevent UC development.

In patients with Crohn's disease (CD) and intestinal failure, home parenteral nutrition (HPN) is a necessary lifesaving treatment. The aim of this study was to investigate the long-term outcomes of patients with CD after initiation of HPN.This study included patients with CD receiving HPN for intestinal failure. The patients were treated at Osaka University Hospital between January 2000 and December 2019. Patients' demographic characteristics, HPN dependence and complications, and mortality were analyzed. HPN dependence was estimated using the Kaplan-Meier method. Cox regression analysis was used for between-group comparisons.Twenty-one patients with CD received HPN. HPN dependence rates were 85%, 75%, 75%, and 64%, respectively, at 2, 5, 10, and 15 y after HPN initiation. Patients who weaned off HPN exhibited lower rates of immunomodulator therapy and additional intensive CD treatment (P0.05). Multivariate analysis revealed that not requiring additional intensive CD treatment was a significant factor in weaning off HPN. Two patients (9%) died, at a median of 14.9 y after HPN initiation, due to HPN-related liver disease and CD-associated carcinoma. Among all patients, 61% experienced catheter-related bloodstream infections (CRBSIs), with an incidence of 0.32/1000 catheter-days. Methicillin-resistant bacteria and Candida spp. each accounted for 27% of all pathogens detected in CRBSI.Patients with CD receiving HPN had a good prognosis, despite frequent CRBSIs in which methicillin-resistant bacteria and fungi were common pathogens. Some patients with CD can wean off HPN, even after a long period of HPN treatment. A stable disease condition during HPN might be an important factor for weaning off HPN.

Background: The gene POU5F1, encoding the POU domain, class 5, is a transcription factor. and the expression is found in embryonic stem cells. In these pluripotent stem cells, POU5F1 gene controls self-renewal and differentiation, regulating the pluripotency and proliferation. Regarding the tumor heterogeneity and microenvironment, primary culture of cancer cells derived from the patient's tumor can provide important information of the “individual tumor,” representing the tumor heterogeneity. We focused on the gene expression and the relationship between colorectal cancer stem cells and the tumor heterogeneity, in the primary culture model. Methods: Using POU5F1 promoter-containing sequence, POU5F1-EGFP-positive cells were established by the construct with lentiviral vector, and we examined their sub-populations. The capacity to form distant metastasis in vivo was examined using the primary culture models. Results: We obtained clinical samples from surgically resected gastrointestinal cancers. They were mechanically and enzymatically digested and collected using customized filters. Obtained cells were cultured on a matrix-coated plate with chemically defined stem-cell culture medium. All these primary cultured cells grew and about 90% of them were successfully passaged. The morphology and gene expressions were similar to each parental clinical tumor. Using these primary tumors, POU5F1 expressing cells were examined. The POU5F1-EGFP-positive cells highly expressed stem cell-associated markers and they had self-renewal and differentiation abilities. POU5F1-high cells actively formed liver metastasis. Conclusion: POU5F1-positive cells have the self-renewal and differentiation abilities as cancer stem cells. The positive cells produce tumor heterogeneity. POU5F1 contributes to the ability forming liver metastasis in CRC. Keywords: colorectal cancer, tumor heterogeneity, metastasis, POU5F1. Citation Format: Norikatsu Miyoshi, Shiki Fujino, Masaru Sasaki, Takayuki Ogino, Hidekazu Takahashi, Mamoru Uemura, Chu Matsuda, Tsunekazu Mizushima, Hidetoshi Eguchi, Yuichiro Doki. Tumor heterogeneity driven by cancer stem cell expressing POU5F1 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4962.

Backgrounds: Although radiation therapy is effective for many cancers, tumor regrowth and recurrence can occur after irradiation. Various mechanisms have been reported regarding the resistance, including the involvement of cancer stem cells and radioresistance genes. However, acquisition of resistance and recurrence are still crucial problems in clinical field. Tumor heterogeneity is thought to play an important role and greatly involve in the acquisition of therapeutic resistance. It is difficult to examine heterogeneous population using cancer cell lines consisted of homogenous cells. Therefore, we have developed primary cultured cells, named 2D organoid (2DO) which maintained clinical tumor heterogeneity. The purpose of this study is to reveal a novel mechanism of radiation resistance by focusing on changes in various populations and persister cells after irradiation using 2DO. Materials and Methods: Colorectal cancer cell lines and 2DOs established from surgery resected specimens were irradiated with various doses (2-10Gy once, 1-4Gy for 5 days consecutive, etc.). Cancer stem cell markers were evaluated before and after irradiation using flow cytometry. Results: In the cell lines, CD44+ cells remained after irradiation, and no significant change was observed in stem cell population before and after irradiation. In the 2DOs, CD44+ cells remained after irradiation, and in addition CD44− cells also newly emerged. The CD44− cells were sorted by cell sorter and cultured. The CD44− cells reproduced CD44+ cells and reconstructed the heterogenous population similar to the parent 2DOs. However, CD44− cells sorted from the parent cells not irradiated did not reconstructed the heterogenous population. Furthermore, the cells reproduced from the survived CD44− cells had more resistance to anti-tumor drugs than cells from the survived CD44+ cells. Other stem cell markers such as CD24 and CD133 were also examined, but no significant changes were observed before and after irradiation. Conclusions: In addition to CD44+ cells, CD44− cells also survived after irradiation. The survived CD44− cells after irradiation had more resistance to anti-tumor drugs compared with the survived CD44+ cells. These newly emerged CD44− cells may be important persister cells in tumor regrowth and recurrence. We report on the functional analysis of these cells. Citation Format: Masaru Sasaki, Norikatsu Miyoshi, Shiki Fujino, Takayuki Ogino, Hidekazu Takahashi, Mamoru Uemura, Chu Matsuda, Hirofumi Yamamoto, Tsunekazu Mizushima, Masaki Mori, Yuichiro Doki. Newly emerging CD44 negative cells after irradiation reproduce CD44 positive cells and promote radioresistance [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6170.

Purpose. Cancer tissues contain a substantial amount of stromal tissues, and transcriptome derived from bulk samples originates from a mixture of the cancer epithelium and stroma. Gene signature of epithelial-mesenchymal transition (EMT) cells is similar to that of stromal cells; therefore, gene signature that we considered to be related EMT might be only contamination of stroma. Here, we identify novel EMT inducers by analysis of independent gene expression profiles in the colorectal cancer epithelium and stroma. Materials and Methods. Gene expression data of pure epithelial tissue was obtained using laser microdissection technique from 13 colorectal cancer tissues. Next, the ratio of each gene expression in the stroma to in the epithelium and correlation of each gene expression with a target gene derived from The Cancer Genome Atlas (TCGA) is plotted in two dimensions, and correlation coefficients are calculated. We regard genes with high correlation coefficients but highly expressed in the epithelium as candidates of EMT inducers. We manipulate the expression of some candidate genes in colorectal cancer cell lines to investigate the alterations of EMT markers and migration ability in vitro. Results. We extract 91 new putative EMT-related genes in silico. They are highly expressed in similar cell lines to known EMT markers in a public database. Furthermore, some candidates have reported having a relation to EMT, and that indicates the validity of this procedure. The knockdown of three candidate genes upregulates epithelial gene expression and downregulates mesenchymal gene expression. The knockdown of one of the three genes reduces cell migration. In contrast, overexpression of the gene downregulates epithelial gene expression and leads to cell migration. Conclusion. We identify novel EMT inducers successfully using purified gene expression data. They could be new prognostic markers and therapeutic targets of colorectal cancer. Citation Format: Satoshi Ishikawa, Naohiro Nishida, Shiki Fujino, Takayuki Ogino, Hidekazu Takahashi, Norikatsu Miyoshi, Mamoru Uemura, Chu Matsuda, Tsunekazu Mizusima, Hirofumi Yamamoto, Koshi Mimori, Masaki Mori, Yuichiro Doki, Hidedoshi Eguchi. Identification of novel epithelial-mesenchymal transition inducers and their clinical significance in colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1535.

A 69-year-old man was administered S-1/oxaliplatin/trastuzumab as induction chemotherapy for advanced gastric cancer (cT4b[liver, pancreas], N2M1(H1P0CYX), cStage IV). After 4 courses, because contrast-enhanced computed tomography showed remarkable reduction of the tumor, distal gastrectomy, partial hepatectomy, and radiofrequency ablation for the liver metastasis were performed. The patient was histopathologically diagnosed with gastric neuroendocrine carcinoma(NEC). S- 1/oxaliplatin/trastuzumab was continued after surgery; however, recurrence in the remnant liver was observed after 4 cours- es. For recurrence, cisplatin/irinotecan as first-line and paclitaxel/ramucirumab as second-line treatment were administered, but progression of liver metastasis and ascites due to peritoneal dissemination were observed. As third-line treatment, nivolumab was initiated. Ascites decreased after 3 courses, but after 2 more courses, progression of ascites, liver recurrence, and multiple metastasis in the lumbar vertebra were observed.

Malnutrition is a frequently observed phenomenon in patients with esophageal cancer after esophagectomy. Nutritional support and the enhanced recovery after surgery(ERAS)protocol may prevent malnutrition.Nine patients who underwent esophagectomy for esophageal cancer received perioperative management according to the ERAS protocol and enteral nutrition support(ELENTAL®or ENEVO®). We retrospectively evaluated the efficacy and safety of our perioperative management.The median day of first oral intake(water)was the second postoperative day. The median day of first oral intake(food)was the seventh postoperative day. The patients could consume more than one and a half bottle of enteral nutrition for a year after surgery. The prognostic nutritional index(PNI)was higher than 40, and the neutrophil-to-lymphocyte ratio(NLR)was lower than 3 for a year after surgery.Perioperative management according to the ERAS protocol and enteral nutrition support(ELENTAL®or ENEVO®)might be feasible and prevent malnutrition in patients after esophagectomy.

Background Intraductal papillary-mucinous neoplasms (IPMNs) are potentially malignant intraductal epithelial neoplasms that sometimes penetrate into other organs. To the best of our knowledge, no report has yet described a case with penetration into the spleen. We recently encountered a case of IPMN with penetration of the stomach and spleen that was successfully treated by total pancreatectomy. Case presentation A 70-year-old female visited our hospital with a complaint of fever and abdominal pain. Contrast-enhanced computed tomography (CT) revealed dilatation of the main pancreatic duct in the entire pancreas and penetration into the stomach and spleen. Upper gastrointestinal endoscopy revealed mucin extruding from four openings of the fistula in the stomach. No malignancy was detected based on cytology of the mucin. Inflammation markers and tumor markers (CEA, CA19–9) were elevated in the blood. The pre-operative diagnosis was IPMN of main pancreatic duct type penetrating into the stomach and spleen. A total pancreatectomy and splenectomy were performed, combined with distal gastrectomy including resection of the fistulas between the pancreas and stomach. No postoperative complications were noted. Histopathological examination of the resected specimen revealed atrophy of the pancreatic parenchyma, and the main duct of the pancreas was filled with mucin. Mucin-producing malignant tumor cells were detected in the epithelium of the main pancreatic duct with no signs of invasion. No malignancy was found at the fistulas between the pancreas and stomach or spleen. The patient was finally diagnosed with non-invasive intraductal papillary-mucinous carcinoma (IPMC) of main pancreatic duct type. Mechanical penetration was suspected as a mechanism of the penetration. The patient remained disease-free without evidence of recurrence more than 15 months after the operation. Conclusion Though IPMNs sometimes penetrate into other adjacent organs, penetration into two organs, including the spleen, is rare. The rare case of IPMC penetrating into the stomach and spleen presented here was treated successfully by total pancreatectomy.

Adequate blood flow in anastomosis is of paramount importance to prevent anastomotic leakage. However, it is sometimes difficult to predict the viability of the intestine during surgery. During left-sided colectomy, blood flow on the remnant distal bowel is supplied only from the middle and inferior rectal arteries. The blood backflow after the root ligation of the inferior mesenteric artery is often said to be kept up to promontorium levels; however, this premise is actually based on experience, without reliable evidence. Here, we introduce the intraoperative evaluation of blood flow on the remnant distal bowel during left-sided colectomy using an indocyanine green fluorescence technique.

Currently, we lack tools that can reliably guide laparoscopic surgeons to a target anatomical destination for dissection. We aimed to develop and evaluate a fluorescent destination marker (FDM), composed of a resected omental appendix injected with indocyanine green (ICG), for real-time navigation in laparoscopic surgery for colorectal cancer in this pilot study. This study included ten patients diagnosed with colorectal cancer. To prepare FDMs, we laparoscopically harvested omental appendices attached to the colon we planned to resect. The harvested appendices were injected with diluted ICG, and a gauze tag was attached. The FDMs were placed at target intra-abdominal sites with a ligation clip. Patient diagnoses included 1 cecal, 2 ascending colon, 3 transverse colon, 2 sigmoid colon, and 2 rectal cancers. No conversion to open surgery was required and no intraoperative complications occurred. We created 12 sets of FDMs, which were placed at a total of 13 sites in abdominal cavities. FDM fluorescence was successfully detected in all cases. Furthermore, FDMs could be detected earlier than the gauze tags at 12 points, and they were detected at the same time at 1 point. All FDMs facilitated laparoscopic surgery by allowing the surgeon to find the tissue to be dissected, particularly in procedures that required the dissection of lymph nodes around middle colic vessels and mobilization of the splenic flexure. FDMs showed potential for guiding the laparoscopic surgeon to a target anatomical destination. This marker represents a contribution to the evolution of real-time navigation surgery.

A 50-year-old woman with abdominal fullness, lower abdominal pain, elevated serum CA125, and ascites, underwent neoadjuvant chemotherapy with 6 courses of PTX/CBDCA followed by total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and intrapelvic peritoneal stripping based on a diagnosis of serous surface papillary carcinoma(SSPC) of the peritoneum. Complete response(CR)was shown after adjuvant chemotherapy with 3 courses of the same regimen. After 6 months, serum CA125 level re-increased and abdominal CT showed small low density areas in the patient's spleen and the perisplenic fat tissue. After the additional chemotherapy with 3 courses of PTX/CBDCA were performed based on a diagnosis of metastatic lesion from SSPC, anaphylactic shock occurred as the severe adverse event. The patient was given 9 more courses of the chemotherapy changed the regimen to PTX/CDDP. The splenic metastatic lesion had grown rapidly in the followed CT and then, laparoscopic splenectomy with peritoneal resection was performed based on a diagnosis of splenic metastasis from SSPC. The pathological examinations showed the tumor to be a splenic metastasis and peritoneal dissemination from SSPC. No recurrent lesion has been detected in the 9 months since removal of the splenic metastasis without adjuvant chemotherapy and the patient has survived for 4 years and 6 months since initial treatment.

Refractory ascites associated with cancerous peritonitis causes abdominal tension and reduced oral intake. Frequent ascites drainage can cause rapid worsening ofa patient's general condition. Cell-free and concentrated ascites reinfusion therapy (CART)for refractory ascites was first covered in 1981, and the general conditions ofpatients and their symptoms could be improved after undergoing CART. Herein, we report a case of effective palliative care with CART for refractory ascites associated with cancerous peritonitis. A 66-year-old man was admitted to our hospital because ofabdominal distension. Computed tomography revealed the presence ofascites and gastric wall thickness; upper gastrointestinal endoscopy revealed an ulcerated lesion with raised margins on the body ofthe stomach. Biopsy ofthis lesion confirmed the diagnosis ofadenocarcinoma, and he was diagnosed with gastric cancer(M, Type 3, cT4a[SE], cN0, cH0, cP1, cM1, cStage IV). He underwent palliative care for ascites, followed by FLTAX regimen chemotherapy(5-fluorouracil[5-FU]and Leucovorin[LV]combined with weekly paclitaxel[PTX]). He received CART for 8 courses without complications, and his symptoms improved after receiving CART. He survived for about 18 months, and could ingest a normal diet for a long time. CART may be favorable in palliative care for massive ascites associated with cancerous peritonitis.

Background/Aims: There is a heterogeneous subset innate myeloid cells, such as macrophages and dendritic cells, in the human intestinal lamina propria. Several studies have demonstrated that these cells contribute to the maintenance of gut homeostasis through the induction of inflammatory responses and tolerance via cell type-specific mechanisms; whereas, disrupted innate immune responses are implicated in the pathogenesis of Crohn’s disease (CD). However, the detailed mechanisms by which each innate myeloid subset regulates gut homeostasis and inflammation largely remain unknown. We aimed to clarify the comprehensive gene expression profiles of innate myeloid cell ­subsets in the lamina propria from normal human colons (NC) and the inflamed colon sites from patients with Crohn’s disease (CDi). Methods: We performed RNA-sequencing analysis and precise bioinformatics analysis on 3 innate myeloid cell subsets, CD14–CD11c–, CD14–CD11c+, and CD14+CD11c+CD163low cells from NC and CDi. Results: Transcriptional analysis of the 3 subsets from the NC showed distinct gene expression patterns and gene ontology (GO) enrichment analysis revealed the associated innate myeloid subset-specific biological process (BP) terms. In addition, changes in gene expression patterns were observed in innate myeloid subsets from CDi. Furthermore, the core GO-BP terms for the genes upregulated in the innate myeloid cells from CDi were distinct from those found in NC. Conclusion: Our data identified the innate myeloid cell subset-specific transcriptomes and the associated enriched GO-BP terms in the NC and found these patterns were altered in CDi.

A 74-year-old femalewas admitted to our hospital dueto thebulky abdominal tumor pointed out by ultrasonography of medical screening. Abdominal CT revealed the tumor, in a diameter 20 cm, replaced the total pancreas and compressed the surrounding organs and portal vein. We diagnosed as a pancreatic serous cystic neoplasm with a possibility of malignancy. The operative findings showed the tumor tightly adhered to stomach, duodenum, liver, transverse colon mesenterium, retroperitoneum and the surrounding main vessels. Total pancreatectomy, cholecystectomy, splenectomy and distal gastrectomy were performed. As a histopathological finding, thetumor surfacewas smooth and theinsidewas sponge-likeappe arancemixe d with microcystic and solid components. No malignant finding was observed. The patient was discharged without major complications on postoperative day 42, and remains alive with no recurrence for 9 months after surgery.

The patient was a 50-year-old man who complained of bloody stool and proctal discomfort. After hospitalization, he was diagnosed bearing advanced lower rectal cancer with lateral lymph nodes and bilateral pulmonary metastases(cT3N3M1a, Stage IV ). He was treated with irinotecan, Leucovorin and 5-fluorouracil(FOLFIRI)plus cetuximab because of RAS wild type. After 11 courses of the chemotherapy, all pulmonary metastases were disappeared(CR). Six months after the initialtreatment, laparoscopic abdominoperineal resection with lateral lymph node resection was performed with curative intent. After the operation, additional1 2 courses of the same chemotherapy were carried out. One year after operation, there is no sign of recurrence. Though used to be considered non-curative, advanced rectal cancer with distant metastases could be potentially cured by multidisciplinary treatments.

This study evaluated the venous variations of the right colon using preoperative three-dimensional computed tomography (3D-CT), and to investigate its usefulness in laparoscopic complete mesocolic excision (CME) for right colon cancer. 3D-CT was performed prior to surgery in 81 consecutive patients with right colon cancer. Laparoscopic right hemicolectomy was performed without conversion to open surgery in all cases (100 %). All 81 patients had a single ileocolic vein (ICV). The ICV flowed into the superior mesenteric vein (SMV) in 98 % of patients and the gastrocolic trunk (GCT) in 2 % of patients. The right colic vein (RCV) was absent in 6 % of patients. One RCV was present in 88 % of patients and two were present in 6 % of patients. The main RCV flowed into the GCT in 84 % of patients and the SMV in 10 % of patients. The superior RCV was present in 21 % of patients, and all cases flowed into the GCT. One middle colic vein (MCV) was present in 49 % of patients, two in 46 %, and three in 5 % of patients. The main MCV flowed into the SMV in 68 % of patients, GCT in 20 %, jejunal vein in 6 %, inferior mesenteric vein in 5 %, and the splenic vein in 1 % of patients. The GCT was present in 88 % of patients. Although the venous tributaries of the right colon are variable, preoperative 3D-CT is informative and helpful for surgeons performing laparoscopic CME for right colon cancer.

Background Generally, cancer cell lines are established from the patients of which cancer cells are dissected, cultured and maintained in vitro. These cell lines have been traditionally used in cancer research; however, they have changed better to survive in culture condition in vitro, and not restored the original characters when they grew in vivo, meaning the lack of tumor heterogeneity. Primary culture of cancer cells derived from patients’ tumors can provide crucial information as each “individual tumor”. The primary culture method of clinical cancer and the evaluation for the treatment have not been clearly optimized in gastrointestinal cancers. Methods We have developed a simple 2D/3D-culture method for primary cancer. We obtained 40 clinical samples from surgically resected colorectal cancers (CRCs). They were mechanically and enzymatically digested and are filtered by customized preparation tools, followed by in vitro culture system. The gene expression profiles and the sensitivity for the drugs were analyzed. Results Culture cells were analyzed These cultured cancer cells were named “isolated-tumor derived Cancer Cells (iCCs).” All iCCs grew and about 90 % of iCCs were successfully passaged. These iCCs were transplanted into the subcutaneous tissue of nonobese diabetic (NOD) - severely compromised immune deficient (SCID) mice, and the tumor growth and pathological examination were evaluated. The morphology was similar to each parental clinical tumor. Microarray analyses showed that RNA expression of iCCs was similar to each parental tumor. Surface markers regarding cancer stem cells expressed in iCCs. Furthermore, multi-drug sensitivity assay by our bespoke plates including commonly used as anti-cancer/molecular target drugs was performed. Conclusions The iCCs are very similar to each parental tumor, leading to the personalized medicine, and the analyses of the tumor characteristics seem to reflect the clinical presentation. Legal entity responsible for the study The authors. Funding Japanese Agency for Medical Research and Development. Disclosure All authors have declared no conflicts of interest.

症例は40歳代の男性で，25歳頃より腸閉塞の診断で入退院を繰り返し，保存的療法で改善していた．2008年6月にS状結腸過長症と診断され，他院で腹腔鏡下S状結腸切除術を施行された．しかし同年7月に再び腸閉塞症状のため当院に入院した．入院3日目に腹膜炎症状が出現し，緊急手術を施行した．上行結腸が捻転しており同部位より口側結腸が拡張していたため，結腸右半切除術を施行した．術後も腸閉塞状態が改善せず，腹部膨満症状を改善するため，回腸人工肛門造設を施行した．その後，慢性偽性大腸閉塞症を考え，同年12月に結腸全摘術を施行した．症状の改善は認めたが，術後も腹部単純X線検査で小腸は著明に拡張した状態であったため，慢性偽性小腸閉塞症と最終診断した．術後1年経過した現在，蠕動促進薬を内服して日常生活を送っている状態である．

症例1は44歳の男性で, 肛門縁より7cmにわたる4型腫瘍で生検の結果がsignet-ring cell carcinomaであり, 術前CRT後に腹会陰式直腸切断術, 側方郭清を施行. 術後20日目に右下肢の浮腫, 疼痛が出現しCTにて骨盤内リンパ嚢腫および右外腸骨静脈～大腿静脈に血栓を認めた. 抗凝固療法およびリンパ嚢腫のドレナージを施行後, 症状は改善した. 症例2は54歳の女性で, 術前CTで側方リンパ節転移を認め, CRT後に腹会陰式直腸切断術, 側方郭清, 膣後壁合併切除を施行. 術後42日目より労作時呼吸困難が出現し, CT, USにて肺塞栓, 両側外腸骨静脈の血栓および骨盤内リンパ嚢腫を認めた. 永久型下大静脈フィルターを留置し, 抗凝固療法, 血栓溶解療法およびリンパ嚢腫のドレナージを施行後, 症状は改善した. 2症例とも骨盤内リンパ嚢腫による外腸骨静脈圧排像を認めており, リンパ嚢腫と静脈血栓塞栓症との関連が示唆された.

Solitary fibrous tumor (SFT) are relatively rare neoplasms that usually arise in the thoracic cavity in adults. Although many cases of extrathoracic SFT have been recently reported, SFT from the omentum is rare. A 32-year-old woman consulted a gynecologist complaining of irregular vaginal bleeding. Magnetic resonance imaging (MRI) revealed a tumor in the omentum, and the patient was admitted to our department. The patient underwent laparoscopic tumorectomy. The tumor size was 48 × 35 × 30 mm, and grayish-white nodules were observed. Histological examination showed hyperplastic spindle-shaped tumor cells with a pattern-less arrangement. Immunohistochemical staining showed the tumor was positive for CD34 and bcl-2, slightly positive for alpha smooth muscle actin(a-SMA), and negative for S-100 and c-kit. Accordingly, a diagnosis of SFT was made. The patient has not shown any recurrence 12 months after surgery. Most SFTs are benign, although there are some reports of recurring tumors. There are no clear guidelines for the treatment of SFT because of its rarity. Therefore, close long-term follow-up should be performed.

Although simultaneous resection of primary colorectal cancer and synchronous liver metastases is reported to be safe and effective, the feasibility of a laparoscopic approach remains controversial. This study evaluated the safety, feasibility, and short-term outcomes of simultaneous laparoscopic surgery for primary colorectal cancer with synchronous liver metastases. From September 2008 to December 2013, 10 patients underwent simultaneous laparoscopic resection of primary colorectal cancer and synchronous liver metastases with curative intent at our institute. The median operative time was 452 minutes, and the median estimated blood loss was 245 mL. Median times to discharge from the hospital and adjuvant chemotherapy were 13.5 and 44 postoperative days, respectively. Negative resection margins were achieved in all cases, with no postoperative mortality or major morbidity. Simultaneous laparoscopic colectomy and hepatectomy for primary colorectal cancer with synchronous liver metastases appears feasible with low morbidity and favorable outcomes.

Background & Aims Abnormal activity of innate immune cells and T-helper (Th) 17 cells has been implicated in the pathogenesis of autoimmune and inflammatory diseases, including Crohn's disease (CD). Intestinal innate immune (myeloid) cells have been found to induce development of Th17 cells in mice, but it is not clear if this occurs in humans or in patients with CD. We investigated whether human intestinal lamina propria cells (LPCs) induce development of Th17 cells and whether these have a role in the pathogenesis of CD. Methods Normal intestinal mucosa samples were collected from patients with colorectal cancer and noninflamed and inflamed regions of mucosa were collected from patients with CD. LPCs were isolated by enzymatic digestion and analyzed for expression of HLA-DR, lineage markers CD14 and CD163 using flow cytometry. Results Among HLA-DR high Lin − cells, we identified a subset of CD14 + CD163 low cells in intestinal LPCs; this subset expressed Toll-like receptor ( TLR ) 2 , TLR4 , and TLR5 mRNAs and produced interleukin (IL)-6, IL-1β, and tumor necrosis factor in response to lipopolysaccharide. In vitro co-culture with naive T cells revealed that CD14 + CD163 low cells induced development of Th17 cells. CD14 + CD163 low cells from inflamed regions of mucosa of patients with CD expressed high levels of IL-6 , IL-23p19 , and tumor necrosis factor mRNAs, and strongly induced Th17 cells. CD14 + CD163 low cells from the noninflamed mucosa of patients with CD also had increased abilities to induce Th17 cells compared with those from normal intestinal mucosa. Conclusions CD14 + CD163 low cells in intestinal LPCs from normal intestinal mucosa induce differentiation of naive T cells into Th17 cells; this activity is increased in mucosal samples from patients with CD. These findings show how intestinal myeloid cell types could contribute to pathogenesis of CD and possibly other Th17-associated diseases.

The spacer placement is a prevalent procedure to separate the surrounding normal tissues from locally recurrent rectal tumor before the application of radiotherapy. However, complications could occur due to the foreign nature of the spacer. This report describes a case of 60-year-old man who had undergone radiotherapy two years earlier for a recurrent rectal tumor and presented with small bowel obstruction. A spacer was used before radiotherapy. Radiological assessment and laparotomy revealed the presence of the spacer inside the small bowel lumen. It is possible that the spacer established contact with the intestine, elicited local inflammatory reaction that facilitated the complete penetration of the intestinal wall without causing any clinical symptoms.