Elevated expression of RAB3B plays important roles in chemoresistance and metastatic potential of hepatoma cells.

BACKGROUND: Cancer stem cells (CSCs) are thought to play important roles in carcinogenesis, recurrence, metastasis, and therapy-resistance. We have successfully induced cancer stem-like sphere cells (CSLCs) which possess enhanced chemoresistance and metastatic potential. To enable the development of targeted therapy against CSLCs, we identified a gene responsible for this phenotype in CSLC. METHODS: Human hepatoma cell line SK-HEP-1 was used for CSLC induction with a unique sphere inducing medium, and HuH-7 cells were used as non-sphere forming cells in the same condition. RNA-sequencing was performed followed by validation with quantitative RT-PCR and western blotting. Knockdown experiments were done by using CRISPR-Cas9 genome-editing, and the rescue experiments were performed using the expressing plasmid vector. Chemoresistance and liver metastasis of the cells, was studied following the splenic injection of cells to severely immune deficient mice and evaluated using the MTS assay. Quantification of exosomes in the medium was done using ELISA. RESULTS: RAB3B was identified as an up-regulated gene in both CSLCs and prognostically poor hepatocellular carcinoma (HCC) by RNA-sequencing. RAB3B-KD cells showed altered CSLC phenotypes such as sphere formation, chemoresistance, and metastatic potentials, and those were rescued by RAB3B complementation. Increased exosome secretion was observed in CSLCs, and it was not observed in the RAB3B-KD cells. In addition, the RAB3B expression correlated with the expression of ABCG2, APOE, LEPR, LXN, and TSPAN13. CONCLUSION: The up regulation of RAB3B may play an important role in the chemoresistance and metastatic potential of CSLCs.

Pancreatic Cancer Stem-Like Cells With High Calreticulin Expression Associated With Immune Surveillance.

OBJECTIVE: Pancreatic cancer stem-like cells (P-CSLCs) are thought to be associated with poor prognosis. Previously, we used proteomic analysis to identify a chaperone pro-phagocytic protein calreticulin (CALR) as a P-CSLC-specific protein. This study aimed to investigate the association between CALR and P-CSLC. METHODS: PANC-1-Lm cells were obtained as P-CSLCs from a human pancreatic cancer cell line, PANC-1, using a sphere induction medium followed by long-term cultivation on laminin. To examine the cancer stem cell properties, subcutaneous injection of the cells into immune-deficient mice and sphere formation assay were performed. Cell surface expression analysis was performed using flow cytometry. RESULTS: PANC-1-Lm showed an increased proportion of cell surface CALR-positive and side-population fractions compared with parental cells. PANC-1-Lm cells also had higher frequency of xenograft tumor growth and sphere formation than PANC-1 cells. Moreover, sorted CALRhigh cells from PANC-1-Lm had the highest sphere formation frequency among tested cells. Interestingly, the number of programmed death-ligand 1-positive cells among CALRhigh cells was increased as well, whereas that of human leukocyte antigen class I-positive cells decreased. CONCLUSION: In addition to the cancer stem cell properties, the P-CSLC, which showed elevated CALR expression on the cell surface, might be associated with evasion of immune surveillance.

Efficacy of intraoperative recurrent laryngeal neuromonitoring during surgery for esophageal cancer.

AIM: To evaluate the efficacy of intraoperative neuromonitoring in identifying recurrent laryngeal nerves and decreasing the incidence of nerve injury in minimally invasive esophagectomies for esophageal cancers. METHODS: A total of 167 minimally invasive esophagectomy patients were retrospectively reviewed. They were divided into intraoperative neuromonitoring (n = 84) and no intraoperative neuromonitoring (n = 83) groups, based on whether or not intraoperative neuromonitoring was used during surgery. We compared short-term surgical outcomes and incidence of recurrent laryngeal nerve palsy between the two groups before and after propensity score matching. The association between the loss of signal and recurrent laryngeal nerve palsy was also evaluated. RESULTS: The incidence of recurrent laryngeal nerve palsy (grade 2 and higher) was lower in the intraoperative neuromonitoring group than in the no intraoperative neuromonitoring group (6.0% vs 21.2%, P = 0.02). The rate of recurrent laryngeal nerve palsy recovery within 6 months was also significantly higher in the intraoperative neuromonitoring group (87.5% vs 20.0%, P < 0.01). The positive and negative predictive values of intraoperative neuromonitoring for recurrent laryngeal nerve palsy were 60% (9/15) and 86.9% (60/69), respectively. The duration from paralysis to recovery was shorter in recurrent laryngeal nerve palsy cases with negative loss of signal results than in cases with positive loss of signal results (median: 43 days vs 95 days). CONCLUSION: Intraoperative neuromonitoring is useful in identifying recurrent laryngeal nerves and may aid in reducing the incidence of recurrent laryngeal nerve injury during esophageal surgery.

Siglec-7 is a predictive biomarker for the efficacy of cancer vaccination against metastatic colorectal cancer.

Cancer immunotherapy, including vaccination, is considered a major scientific and medical breakthrough. However, cancer immunotherapy does not result in durable objective responses against colorectal cancer (CRC). To improve the efficacy of immunotherapy, the present study investigated several biomarkers for selecting patients who were expected to respond well to immunotherapy. Firstly, a comprehensive proteomic analysis was performed using tumor tissue lysates from patients enrolled in a phase II study, in which five human leukocyte antigen (HLA)-A*24:02-restricted peptides were administered. Sialic acid-binding immunoglobulin type lectin (Siglec)-7 was identified as a potential predictive biomarker. Subsequently, this biomarker was validated using western blot analysis, and immunofluorescence using tissue samples from the patients enrolled in the phase II study. The expression levels of Siglec-7 detected by immunofluorescence were quantified and their association with overall survival (OS) in patients treated with the peptide vaccine was examined. Furthermore, considering the important role of tumor-infiltrating lymphocytes (TILs) for CRC prognosis, the densities of CD3+, CD4+, CD8+ and forkhead box P3 (FOXP3)+ T cells in CRC tissues were examined and compared with Siglec-7 expression. The mean expression levels of Siglec-7 were significantly higher in patients with poor prognosis, with an OS of ≤2 years, as shown in comprehensive proteomic analysis (P=0.016) and western blot analysis (P=0.025). Immunofluorescence analysis demonstrated that Siglec-7 was expressed in intratumoral macrophages. The OS in patients with high Siglec-7 expression was significantly shorter than in that in patients with low Siglec-7 expression (P=0.017) in the HLA-A*24:02-matched patients. However, this difference was not observed in the HLA-unmatched patients. There was no significant difference in OS between patients according to the numbers of TILs, nor significant correlation between TILs and Siglec-7 expression. In conclusion, Siglec-7 expression in macrophages in tumor tissue may be a novel predictive biomarker for the efficacy of immunotherapy against metastatic CRC.

Viral elimination is essential for improving surgical outcomes of hepatitis C virus-related hepatocellular carcinoma: Multicenter retrospective analysis.

AIM: The impact of sustained virologic response (SVR) on surgical outcomes for patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) remains controversial. This study aimed to evaluate the influence of SVR on long-term surgical outcomes after hepatectomy. METHODS: This multicenter study included 504 patients who underwent curative resection for HCV-related HCC. Patients with a history of HCC treatment, HBV infection, poor liver function, and tumor with major vascular invasion were excluded. Long-term surgical outcomes (overall survival [OS] and recurrence-free survival [RFS]) among patients who achieved SVR before hepatectomy (Pre-SVR group: 58 patients), after hepatectomy (Post-SVR group: 54 patients), and without SVR (Non-SVR group: 186 patients) were compared after adjusting for 13 confounding factors. Using the surgically resected specimens, comparison of the pathological changes in liver fibrosis between the first and second hepatectomy were analyzed. RESULTS: Patients with SVR were younger, had better liver function, and less liver fibrosis compared to patients without SVR. Propensity score-matched OS and RFS were significantly better in Pre-SVR group than Non-SVR group (P = .029 and P = .009, respectively). Inverse probability-weighted OS and RFS were also significantly better in the Post-SVR group (P = .001 and P = .021, respectively) than in the Non-SVR group. Histopathological evaluation revealed that only the patients with SVR had regression of liver fibrosis (P < .05). CONCLUSION: Achievement of SVR before or after hepatectomy is essential for improving long-term surgical outcomes in patients with HCV-related HCC.

The effect of the visceral fat area on the predictive accuracy of C-reactive protein for infectious complications after laparoscopy-assisted gastrectomy.

AIM: To investigate the influence of visceral fat area on postoperative C-reactive protein levels and whether it affects its ability to diagnose infectious complications after laparoscopy-assisted gastrectomy. METHODS: A total of 435 consecutive patients who underwent laparoscopy-assisted resection for gastric cancer from 2008 to 2017 were reviewed and divided into four groups according to visceral fat area quartiles. We evaluated the relationship between C-reactive protein and visceral fat area and whether visceral fat area affects the sensitivity and specificity of C-reactive protein in diagnosing postoperative infectious complications. RESULTS: Postoperative C-reactive protein levels increased with increasing visceral fat areas at every postoperative assessment. Multiple linear regression revealed that levels on postoperative day 3 significantly positively correlated with visceral fat area. Postoperative day 3 levels also showed moderate accuracy for diagnosing infectious complications (area under the curve, 0.78; sensitivity, 0.86; specificity, 0.65), with an optimal cut-off of 11.8 mg/dL. The sensitivity for predicting infectious complications was low in the 1st visceral fat area quartile group but high in the 2nd, 3rd, and 4th groups (0.43 vs 1.0 vs 1.0 vs 0.94, respectively). By contrast, the specificity was high in the 1st and 2nd group but low in the 3rd and 4th (0.84 vs 0.70 vs 0.54 vs 0.48, respectively). CONCLUSION: Visceral fat area positively correlated with postoperative C-reactive protein levels and this affected its accuracy in diagnosing infectious complications. A uniform C-reactive protein cut-off may not provide accurate predictions in patients with more extreme visceral fat areas.

Serum LOX-1 is a novel prognostic biomarker of colorectal cancer.

BACKGROUND: Colorectal cancer is the third most common cancer worldwide. If biomarkers can be identified in liquid biopsy, diagnosis and treatment can be optimized even when cancerous tissues are not available. The purpose of this study was to identify proteins from liquid biopsy that would be useful as markers of poor prognosis. METHODS: First, we comprehensively analyzed serum proteins to identify potential biomarkers and focused on serum lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). The relationship between LOX-1 and the prognosis of patients with colorectal cancer has not been reported. Next, we validated this marker using serum samples from 238 patients with colorectal cancer by ELISA and 100 tissue samples by immunohistochemical staining. RESULTS: The optimal cut-off value of serum LOX-1 was 538.7 pg/mL according to time-dependent receiver operating characteristics curve analysis. The overall survival of patients with high levels of serum LOX-1 was significantly poorer than that of individuals with low levels of LOX-1 in the training and test datasets. In multivariate analysis for overall survival, serum LOX-1 was an independent prognostic factor identified in liquid biopsy (hazard ratio = 1.729, p = 0.027). The prognosis of patients with high LOX-1 expression in tumor tissues was significantly poorer than that of individuals with low expression (p =0.047 ). Additionally, inflammatory factors such as white blood cell count, C-reactive protein level, neutrophil/lymphocyte ratio, and monocyte/lymphocyte ratio were significantly higher in the group with high serum LOX-1 levels. CONCLUSIONS: Serum LOX-1 might be a useful biomarker of poor prognosis in colorectal cancer.

A phase I study of multi-HLA-binding peptides derived from heat shock protein 70/glypican-3 and a novel combination adjuvant of hLAG-3Ig and Poly-ICLC for patients with metastatic gastrointestinal cancers: YNP01 trial.

BACKGROUND: This phase I study aimed to evaluate the safety, peptide-specific immune responses, and anti-tumor effects of a novel vaccination therapy comprising multi-HLA-binding heat shock protein (HSP) 70/glypican-3 (GPC3) peptides and a novel adjuvant combination of hLAG-3Ig and Poly-ICLC against metastatic gastrointestinal cancers. METHODS: HSP70/GPC3 peptides with high binding affinities for three HLA types (A*24:02, A*02:01, and A*02:06) were identified with our peptide prediction system. The peptides were intradermally administered with combined adjuvants on a weekly basis. This study was a phase I dose escalation clinical trial, which was carried out in a three patients' cohort; in total, 11 patients were enrolled for the recommended dose. RESULTS: Seventeen patients received this vaccination therapy without dose-limiting toxicity. All treatment-related adverse events were of grades 1 to 2. Peptide-specific CTL induction by HSP70 and GPC3 proteins was observed in 11 (64.7%) and 13 (76.5%) cases, respectively, regardless of the HLA type. Serum tumor marker levels were decreased in 10 cases (58.8%). Immunological analysis using PBMCs indicated that patients receiving dose level 3 presented with significantly reduced T cell immunoglobulin and mucin-domain containing-3 (TIM3)-expressing CD4 + T cells after one course of treatment. PD-1 or TIM3-expressing CD4 + T cells and T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT)-expressing CD8 + T cells in PBMCs before vaccination were negative predictive factors for survival. CONCLUSIONS: This novel peptide vaccination therapy was safe for patients with metastatic gastrointestinal cancers.

[Recurrent Esophageal Cancer with Metastatic Lymph Node Penetrating in the Reconstructed Gastric Tube-A Case Report].

A 60-year-old man underwent thoracoscopic subtotal esophagectomy and posterior mediastinal gastric tube reconstruction after neoadjuvant chemotherapy. One year and 8 months postoperatively, recurrence was observed in the abdominal lymph nodes around the celiac artery and abdominal aorta. Chemoradiotherapy was initiated, followed by chemotherapy. Two months after the completion of chemoradiotherapy, the patient developed epigastric pain and anorexia because of the necrotic lymph node penetrating the gastric tube with cavity formation. Upper gastrointestinal endoscopy revealed a 25- mm-sized ulcer with central necrotic slough on the posterior wall of the stomach. Abdominal symptoms alleviated after conservative treatment with fasting and administration of antibiotics, and the inflammatory reaction improved. Oral nutritional supplements were started on hospitalization day 7, and abdominal symptoms or inflammatory reactions did not recur after resuming diet. The patient was discharged on hospitalization day 39 when the general condition stabilized. Subsequently, chemotherapy was restarted, and no regrowth of metastatic lesions was observed on endoscopy or CT examination 4 months later. Three years and 8 months after the recurrence, the recurrent disease has been controlled.

[Two Cases of Unresectable Gastric Cancer Where Bleeding Was Controlled by Radiation].

Case 1: The patient was a 74-year-old man with a performance status(PS)of 0. He was referred to our department for pyloric gastric cancer with multiple liver, lung, and lymph node metastases. We started chemotherapy after making the diagnosis of an unresectable gastric cancer. During chemotherapy, the hemoglobin level dropped due to bleeding from the tumor. We attempted endoscopic hemostasis, which was not successful; therefore, we attempted a palliative radiotherapy. The total dose was 30 Gy in 10 Fr and hemostasis was achieved on the 10th day from the start of the radiotherapy. There were no adverse events due to the radiation, and the chemotherapy could be restarted 5 days after the end of the radiotherapy. Case 2: The patient was a 78-year-old man with a PS of 2. He was referred to our department because of vomiting and anemia. As a result of a close inspection, we made the diagnosis of an unresectable gastric body cancer with para-aortic lymph node metastasis and peritoneal dissemination, for which chemotherapy was initiated. Anemia was observed at the first visit, and we started radiotherapy to stop the tumor bleeding. The total dose was 30 Gy in 10 Fr, and hemostasis was achieved on the 12th day. There were no adverse events during the radiotherapy, and chemotherapy could be continued. Palliative radiotherapy is an available method of hemostasis that is less invasive than surgery or transcatheter arterial embolization and can be expected to have a certain effect for gastric cancer bleeding, although it takes several days to obtain a therapeutic effect.

Correction: Intratumoural-infiltrating CD4 + and FOXP3 + T cells as strong positive predictive markers for the prognosis of resectable colorectal cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Intratumoural-infiltrating CD4 + and FOXP3 + T cells as strong positive predictive markers for the prognosis of resectable colorectal cancer.

BACKGROUND: CD3 + and CD8 + T-cell infiltration were reported as positive predictive markers of survival in colorectal cancer (CRC) patients. Here, we demonstrate the prognostic significance of CD4 + and FOXP3 + T-cell densities in CRC. METHODS: We quantified the intratumoural densities of CD3 + , CD8 + , CD4 + and FOXP3 + T cells by immunohistochemistry and digital pathology in 342 CRC patients who underwent curative resection. Microsatellite instability was also assessed in 322 specimens. Patient demographics, clinicopathological features and survival rates were analysed. RESULTS: High CD3 + , CD4 + and FOXP3 + T-cell densities were associated with improved relapse-free survival (RFS); high CD8 + , CD4 + and FOXP3 + T-cell densities were associated with improved disease-specific survival (DSS). Patients with low CD4 + and low FOXP3 + T-cell densities exhibited extremely poor prognoses. T stage, vascular/lymphatic invasion and CD4 + T-cell density were independent prognostic indicators for DSS. The distributions of CD4 + and FOXP3 + T-cell densities were not significantly different between the high microsatellite instability group and other groups, in contrast to those of CD3 + and CD8 + T-cell densities. CONCLUSIONS: Intratumoural CD4 + T-cell density and combined CD4 + and FOXP3 + T-cell densities were stronger prognostic indicators than other clinicopathological features. These results may facilitate the establishment of novel prognostic factors and therapeutic strategies for CRC.

Identification of a Promiscuous Epitope Peptide Derived From HSP70.

We previously found that heat-shock protein 70 (HSP70) is expressed on hepatocellular carcinoma cells and developed an HSP70 mRNA-transfected dendritic cell therapy for treating unresectable or recurrent hepatocellular carcinoma. The phase I trial was completed successfully. The purpose of this study is to identify a promiscuous epitope peptide derived from HSP70 for the purpose of developing a novel cancer peptide vaccine. Using a computational algorithm to analyze the specificity of previously reported major histocompatibility complex class I-binding peptides, we selected candidates that bound to >2 of the 3 HLA types. Twenty-nine HSP70-derived peptides (9-mers) that bound to HLA-class I was selected. The peptides were prioritized based on the results of peptide binding experiments. Using dendritic cells stimulated with the candidate peptide described previously as stimulators and CD8 T cells as effectors, an ELISPOT assay was performed. Cytotoxicity of CD8 lymphocytes stimulated with the candidate peptides toward HSP70-expressing cancer cells was analyzed using an xCELLigence System. Peptides were administered to HLA-A 24 transgenic mice as vaccines, and peptide-specific T-cell induction was measured in vivo. We identified a multi-HLA-class I-binding epitope peptide that bound to HLA-A*02:01, *02:06, and *24:02 in vitro using an interferon-γ ELISPOT immune response induction assay. Cytotoxicity was confirmed in vitro, and safety and immune response induction were confirmed in vivo using HLA-A 24 transgenic mice. Our study demonstrated that the promiscuous HSP70-derived peptide is applicable to cancer immunotherapy in patients with HLA-A*24:02-positive, *02:01-positive, and *02:06-positive HSP70-expressing cancers.

[Questionnaire Survey of Secondary Chemotherapy for Gastric Cancer in the Yamaguchi Prefecture].

A questionnaire survey was conducted on the administration of secondary chemotherapy for unresectable or recurrent gastric cancer by 43 doctors involved in gastric cancer treatment in the Yamaguchi prefecture. Seventy-one percent of doctors replied that the secondary chemotherapy transfer rate was more than 60%, and 29% of doctors replied that the secondary chemotherapy transfer rate was less than 60%. The reasons why patients could not be transferred to secondary chemotherapy included inferior performance status, poor general condition, and elderly age, among others. Weekly paclitaxel plus ramucirumab therapy was used as the major regimen of secondary chemotherapy by 95% of doctors. In addition, 93% of doctors indicated that weekly nab-paclitaxel would be an option for gastric cancer secondary chemotherapy. Secondary chemotherapy for gastric cancer in the Yamaguchi prefecture has a standard regimen selection according to guidelines.

[Two Cases of Rupture of Elevated Jejunal Varices after Operation for Hilar Cholangiocarcinoma].

Case 1: A 64-year-old man with a chiefcomplaint ofbloody stools was seen in our hospital. He underwent an extended right lobe resection for hilar cholangiocarcinoma 3 years ago and was in the middle of chemotherapy for multiple metastases. Case 2: A 69-year-old man with a chiefcomplaint ofbloody emesis and stools was seen. He underwent left hepatic trisegmentectomy for hilar cholangiocarcinoma and ligation of the right portal vein for postoperative portal venous thrombus 6 months ago. After careful examination, the patients in both cases were diagnosed with bleeding of the jejunal varices formed at the site ofhepaticojejunostomy. The patient in Case 1 underwent percutaneous transhepatic obliteration ofvarices and the patient in Case 2 underwent transileocolic vein obliteration ofvarices. After hepatobiliary pancreatic surgery with biliary tract reconstruction, we should be aware of ectopic varices during differential diagnosis of gastrointestinal bleeding.

[A Case of Locally Re-Recurrent Colon Cancer Involving the Iliac Bone That Underwent Curative Resection].

A 65-year-old woman with cecum cancer underwent laparoscopic right colectomy.After 3 years, she was diagnosed with a local recurrence with small bowel invasion and underwent tumor resection.One year later, she had a re-recurrent lesion involving her right iliac bone.After one year of chemotherapy, a PET-CT showed no other abdominal lesions suggestive of malignancy.She underwent resection of the re-recurrent tumor involving the right iliac bone and R0 resection was achieved. She was able to ambulate postoperatively and returned home.In selected cases, extended surgery including bone resection can be an option for the local recurrence of advanced colon cancer.

[A Case of Distal Pancreatectomy with En Bloc Celiac Axis Resection after Distal Gastrectomy].

A 77-year-old man underwent a follow-up examination after distal gastrectomy. Contrast-enhanced computed tomography revealed a tumor of the pancreatic body and tail that contacted the common hepatic artery/celiac artery. Subsequently, the tumor was diagnosed as a borderline resectable pancreatic cancer. After chemoradiation therapy, the tumor was considered resectable. Preoperative angiography with intraoperative contrast-enhanced ultrasonography and indocyanine green fluorescence imaging confirmed blood flow in the residual stomach. Postoperatively, ischemic necrosis of the residual stomach was not observed. After distal gastrectomy, distal pancreatectomy with en bloc celiac axis resection was performed to safely and curatively address the cancer of the pancreatic body and tail.

Efficacy of perioperative immunonutrition in esophageal cancer patients undergoing esophagectomy.

OBJECTIVE: Malnutrition is common in patients with esophageal cancer, resulting in increased postoperative complications and mortality. Although preoperative immunonutrition can significantly reduce the incidence of postoperative infectious complications, its effect in patietns with esophageal cancer undergoing esophagectomy remains unclear. The aim of this study was to investigate the effects of perioperative immunonutritional support on the postoperative course and long-term survival of this group of patients. METHODS: This prospective, randomized study enrolled 40 patients with thoracic esophageal carcinoma undergoing esophagectomy. The patients were divided into two groups and received either immunomodulating enteral nutrition (IMPACT group; IG) or standard enteral nutrition (Ensure group; EG) continuously for 7 d before and 7 d after surgery. Nutritional status, such as rapid turnover protein, postoperative intensive care unit (ICU) length of stay (LOS), postoperative hospital LOS, morbidity, and mortality were investigated prospectively. RESULTS: There were no significant differences in patient demographic characteristics between the two groups. Levels of retinol-binding protein, as a rapid-turnover protein, were significantly higher on postoperative day (POD) -1, 7, and 14 in the IG compared with the EG group (P = 0.009, P = 0.004, and P = 0.024, respectively). The incidence of postoperative infectious complications and changes to therapeutic antibiotics were significantly lower in the IG group than in the EG group (P = 0.048 and P = 0.012, respectively). There was no significant difference in postoperative ICU or postoperative hospital LOS between the two groups. The 5-y progression-free survival rates in the IG and EG groups were 75% and 64%, respectively (P = 0.188), and the overall survival rates were 68% and 55%, respectively (P = 0.187). CONCLUSIONS: Perioperative immunonutrition may improve early postoperative nutritional status and reduce postoperative infectious complications in patients with esophageal cancer undergoing esophagectomy.

[A Case of Surgical Resection of an Esophageal Gastrointestinal Stromal Tumor after Neoadjuvant Therapy with Imatinib].

A 64-year-old man presented with dysphagia. Esophagogastroduodenoscopy revealed a submucosal tumor of 52mm in size at the lower thoracic esophagus. Biopsy yielded a pathological diagnosis of c-kit-positive esophageal gastrointestinal stromal tumor(GIST). We started neoadjuvant therapy with imatinib to avoid excessive surgical invasion. After 6 months of treatment, CT revealed a reduction in tumor size to 27 mm. We performed laparoscopic lower esophagectomy, proximal gastrectomy, double-tract reconstruction, and complete tumor resection. Neoadjuvant imatinib therapy was effective for the esophageal GIST.

Outcomes following liver resection for multinodular Barcelona Clinic Liver Cancer-B hepatocellular carcinoma.

Management of multinodular hepatocellular carcinoma (HCC) in the intermediate Barcelona Clinic Liver Cancer (BCLC)-B stage is controversial. The aim of the present study as to identify the subgroup of patients with BCLC-B HCC who could benefit from liver resection. The present study retrospectively analyzed the outcomes of 65 patients (training cohort) who underwent liver resection for multinodular BCLC-B HCC. Cox's regression analysis was conducted to identify the independent prognostic factors for overall survival and to develop the prognostic score. As some authors have reported that maximum tumor size (cm) plus tumor number (N+S) is a prognostic factor in patients with BCLC-B HCC who undergo chemoembolization, the usefulness of this factor in patients who underwent liver resection was also evaluated. Subsequently, the validity of the prognostic score was assessed in an independent validation cohort (n=132). Multivariate analysis revealed that positivity for hepatitis C virus antibody (HCV-ab), platelet count ≤1010/l, N+S >8, and des-γ-carboxy prothrombin (DCP) >400 mAU/ml were independent prognostic factors for overall survival. The prognostic score differentiated two groups (≤2, ≥3) with distinct outcomes (median survival time 68.3 months vs. 29.1 months; P<0.0001). This result was confirmed in an external validation cohort. Therefore, surgery can promote long-term survival in patients with multinodular HCC although the indications for surgery are limited. HCV-Ab status, preoperative platelet count, DCP level and N+S may be useful for patient selection.