Interferon-expressing oncolytic adenovirus + chemoradiation inhibited pancreatic cancer growth in a hamster model.

Past clinical trials of adjuvant therapy combined with interferon (IFN) alpha, fluorouracil, cisplatin, and radiation improved the 5-year survival rate of pancreatic ductal adenocarcinoma (PDAC). However, these trials also revealed the disadvantages of the systemic toxicity of IFN and insufficient delivery of IFN. To improve efficacy and tolerability, we have developed an oncolytic adenovirus-expressing IFN (IFN-OAd). Here, we evaluated IFN-OAd in combination with chemotherapy (gemcitabine + nab-paclitaxel) + radiation. Combination index (CI) analysis showed that IFN-OAd + chemotherapy + radiation was synergistic (CI <1). Notably, IFN-OAd + chemotherapy + radiation remarkably suppressed tumor growth and induced a higher number of tumor-infiltrating lymphocytes without severe side toxic effects in an immunocompetent and adenovirus replication-permissive hamster PDAC model. This is the first study to report that gemcitabine + nab-paclitaxel, the current first-line chemotherapy for PDAC, did not hamper virus replication in a replication-permissive immunocompetent model. IFN-OAd has the potential to overcome the barriers to clinical application of IFN-based therapy through its tumor-specific expression of IFN, induction of antitumor immunity, and sensitization with chemoradiation. Combining IFN-OAd with gemcitabine + nab-paclitaxel + radiation might be an effective and clinically beneficial treatment for PDAC patients.

Clinically relevant model of oxaliplatin-induced sinusoidal obstruction syndrome.

AIM: Sinusoidal obstruction syndrome (SOS) induced by oxaliplatin-including chemotherapies (OXCx) is associated with impaired hepatic reserve and higher morbidity after hepatic resection. However, in the absence of an appropriate animal experimental model, little is known about its pathophysiology. This study aimed to establish a clinically relevant reproducible model of FOLFOX-induced SOS and to compare the clinical/histopathological features between the clinical and animal SOS settings. METHODS: We performed clinical/pathological analyses of colorectal liver metastasis (CRLM) patients who underwent hepatectomy with/without preoperative treatment of FOLFOX (n = 22/18). Male micro-minipigs were treated with 50% of the standard human dosage of the FOLFOX regimen. RESULTS: In contrast to the monocrotaline-induced SOS model in rats, hepatomegaly, ascites, congestion, and coagulative necrosis of hepatocytes were absent in patients with CRLM with OXCx pretreatment and OXCx-treated micro-minipigs. In parallel to CRLM cases with OXCx pretreatment, OXCx-challenged micro-minipigs exhibited deteriorated indocyanine green clearance, morphological alteration of liver sinusoidal endothelial cells, and upregulated matrix metalloproteinase-9. Using our novel porcine SOS model, we identified the hepatoprotective influence of recombinant human soluble thrombomodulin in OXCx-SOS. CONCLUSIONS: With distinct differences between monocrotaline-induced rat SOS and human/pig OXCx-SOS, our pig OXCx-SOS model serves as a preclinical platform for future investigations to dissect the pathophysiology of OXCx-SOS and seek preventive strategies.

[A case of acalculous gangrenous cholecystitis due to artery dissection].

A 62-year-old male presented with right intercostal muscle pain. Clinical examination revealed muscular defense in the same area. Abdominal ultrasonography revealed a distended gallbladder and ascites effusion, but no gallstones or polyps were present. Contrast-enhanced computerized tomography was performed, which revealed luminal obstruction due to arterial dissection of the celiac artery and intrinsic hepatic artery. This finding suggested gangrenous cholecystitis; thus, urgent cholecystectomy was performed. Only a few cases of celiac artery dissection and only one case of gangrenous cholecystitis without stones have been reported. We report here an extremely rare case of celiac artery dissection.

nPTD classification: an updated classification of gastric cancer location for function preserving gastrectomy based on physiological lymphatic flow.

BACKGROUND: The correlation between tumor location and lymphatic flow distribution in gastric cancer has been previously reported, and PTD (Proximal - Transitional - Distal) classification was proposed. Our group updated and developed the nPTD classification. METHOD: We retrospectively studied gastric cancer patients who underwent the dye method sentinel node biopsy from 1993 to 2020. The inclusion criteria were a single lesion type 0 cancer of ≤5 cm in the long axis, clinically node-negative, and invasion within the proper muscle layer pathologically. In this study, the distribution of dyed lymphatic flow was evaluated for each occupied area of the tumor. RESULTS: We included 416 patients in this study. The tumors located in the watershed of the right and left gastroepiploic arteries near greater curvature had extensive lymphatic flow; therefore, a newly circular region with a diameter of 5 cm is set on the watershed of the greater curvature between P and T zone as the 'n' zone. In addition, for cancers located in the lesser P curvature, lymphatic flow to the greater curvature was not observed. Therefore, the P zone was divided into two: the lesser curvature side (PL) and the greater curvature side (PG). CONCLUSIONS: The advantage of the nPTD classification is that it provides not only proper nodal dissection but also adequate function-preserving gastrectomy. If the tumor is localized within the PL, the proximal gastrectomy resection area can be further reduced. In contrast, for cancers located in the 'n' zone, near-total gastrectomy is required because of the extensive lymphatic flow.

Relationship between fatty liver change and nutritional status after total gastrectomy in gastric cancer patients: a retrospective study.

BACKGROUND: The relationship between chronological nutritional changes and development of fatty liver after total gastrectomy (TG) in gastric cancer (GC) patients is still unclear. This study aimed to evaluate relationship between development of fatty liver and chronological changes of nutritional parameters during 12 months after TG. METHODS: We retrospectively analyzed medical records of 59 patients with GC who underwent TG at the Kanazawa Medical University Hospital between January 2009 and December 2017. We defined fatty liver change as a mean liver-to-spleen attenuation ratio (L/S ratio) of less than 1.2 in the computed tomography images at 12 months after TG and divided the patients into fatty liver (FL) and non-FL groups from the L/S ratio. We analyzed serum levels of total protein and albumin, and psoas muscle index (PMI) before TG and at 6 and 12 months after TG in the non-FL and FL groups. RESULTS: Six patients showed an L/S ratio of less than 1.2 at 12 months after TG and were included into FL group. There was no significant difference between the groups in serum parameters, L/S ratio, and PMI before TG. In the FL group, the mean levels of total protein and albumin decreased after TG and were significant lower at 6 months, compared with the non-FL group. And then, these levels in the FL group recovered at 12 months. In contrast, the mean levels of total protein and albumin in the non-FL group did not decrease below the preoperative levels throughout the year after surgery. As with laboratory parameters, all patients in the FL group showed decrease of PMI at 6 months after TG. This proportion was significantly higher than that in the non-FL group (100% vs. 40.8%, P = 0.006). CONCLUSIONS: We evaluated that the patients with fatty liver occurring after TG had significantly lower levels of serum nutritional parameters and skeletal muscle index at 6 months, not but 12 months, after TG.

[Role of Surgical Resection after Chemoradiotherapy in Locally Advanced Pancreatic Cancer].

We investigated 34 cases of preoperative chemoradiotherapy(CRT)for locally advanced pancreatic cancer including resectable pancreatic cancer in our department during the past 11 years. For resectable(R)or borderline resectable(BR)pancreatic cancer, survival curves were generally higher in the CRT plus S-1 group treated after CRT than in the CRT group treated with post-CRT chemotherapy, but there was no statistically significant difference. In non-resected cases, local exacerbation was observed, which was one of the causes of a decline in terminal QOL. From the above, at present, it is desirable to remove R or BR pancreatic cancer after CRT, but the significance of surgery may change in the future due to the improvement of multidisciplinary treatment.

[Significance of Preoperative Chemoradiotherapy for Resectable Pancreatic Cancer].

We investigated the effect of chemoradiotherapy(CRT)on pancreatic cancer and the significance of preoperative chemoradiotherapy( NACRT)on resectable pancreatic cancer. The subjects were 36 patients who underwent CRT for locally advanced pancreatic cancer experienced in our department in the past 12 years(. 1)Regarding the antitumor effect of CRT, tumor diameter, tumor marker, and FDG for PET examination were reduced in 72%, 81%, and 96% of cases, respectively. In addition, the effect of Grade 1b plus 2 was observed in 10 of 16 patients who were resected after CRT(response rate 63%). In these successful cases, irradiation of 40 Gy or more and oral administration of S-1 1,500 mg or more were performed during this period. In addition, the survival rate of the NACRT plus S group(16 cases)was the same as that of the SF group (20 cases)of cStage ⅡA or lower at the same time, 50% survival was longer, and local recurrence was less. Based on the above, preoperative chemoradiotherapy combined with S-1 for resectable pancreatic cancer may be a promising preoperative treatment in the future.

The neutrophil/lymphocyte ratio as a predictor of successful conversion surgery for stage IV gastric cancer: a retrospective study.

BACKGROUND: Conversion surgery (CS) following a response to chemotherapy occasionally leads to prolonged survival in patients with stage IV gastric cancer (GC). This study aimed to evaluate the predictive value of the neutrophil/lymphocyte ratio (NLR) for the success of CS in patients with stage IV GC. METHODS: We retrospectively analyzed data of 50 patients with stage IV GC who received systemic chemotherapy between January 2009 and December 2017 at the Kanazawa Medical University Hospital. The successful CS group included the patients who underwent R0 or R1 resection with CS, and the failed CS group included the patients who did not undergo CS after chemotherapy or those who, despite undergoing CS, had to additionally undergo R2 resection. Clinicopathological characteristics were examined in both groups. Univariate and multivariate analyses were performed to identify pretherapeutic parameters that were independently associated with the achievement of successful CS. RESULTS: The number of patients in the successful and failed CS groups were 12 and 38, respectively. On univariate analysis, gender (P = 0.01), NLR (P = 0.003), albumin levels (P = 0.004), and absence of peritoneal metastasis (P = 0.004) were found to be significantly correlated with a successful CS. On multivariate analysis, NLR < 4 and absence of peritoneal metastasis were independently correlated with a successful CS (P = 0.02 and P = 0.002, respectively). In patients without peritoneal metastasis, successful CS rates in patients with NLR < 4 were significantly higher than those in patients with NLR ≥ 4 (61.1% vs. 10.0%, P = 0.005). CONCLUSIONS: The NLR was a significant independent predictor of the achievement of successful CS in stage IV GC patients, especially among the patients without peritoneal metastasis. Patients with a low NLR could have higher possibility of achieving successful CS.

[A Case of Effective Disease Control of Advanced Gastric Cancer with Distant Lymph Node Metastases Following Nivolumab Treatment].

A 66-year-old man was diagnosed with advanced gastric cancer(L, Less, Type 2, T4a[SE], N2, M1[LYM], H0, P0, cStage Ⅳ)and received treatment with S-1/cisplatin as first-line chemotherapy. This treatment resulted in partial response(PR) after 3 months, with reduction in the sizes of metastatic lymph nodes surrounding the pancreatic head and paraaortic lesion. However, the sizes of metastatic lymph nodes increased after 7 months of chemotherapy. Ramucirumab/nab-paclitaxel was then administered as second-line chemotherapy, and the diameter of the metastatic lymph nodes subsequently decreased after 4 months of the regimen. However, progressive disease was observed at 7 months, and blood transfusion was required because of bleeding from the primary gastric tumor. Therefore, nivolumab was initiated as third-line chemotherapy 14 months after the first treatment. After nivolumab administration, a 28% reduction in metastatic lymph nodes was achieved within 3 months, together with the regression of the primary gastric tumor and improvement in anemia within 6 months. PR was achieved after 12 months of nivolumab administration, and effective disease control was maintained for 16 months without any adverse reaction to nivolumab.

Elevated levels of circulating ITIH4 are associated with hepatocellular carcinoma with nonalcoholic fatty liver disease: from pig model to human study.

BACKGROUND: Noninvasive biomarkers are urgently needed for optimal management of nonalcoholic fatty liver disease (NAFLD) for the prevention of disease progression into nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). In order to identify the biomarkers, we generated the swine hepatocellular carcinoma (HCC) model associated with NAFLD and performed serum proteomics on the model. METHODS: Microminipigs were fed a high-fat diet to induce NAFLD and a normal diet as the control. To induce HCC, diethylnitrosamine was intraperitoneally administered. Biopsied liver samples were histopathologically analyzed every 12 weeks. Serum proteins were separated by blue native two-dimensional gel electrophoresis and proteins of interest were subsequently identified by MALDI-TOF MS/MS. Human serum samples were analyzed to validate the candidate protein using antibody-mediated characterization. RESULTS: In the NAFLD pigs, hepatic histology of nonalcoholic steatohepatitis (NASH) was observed at 36 weeks, and HCC developed at 60 weeks. Among serum proteins identified with MALDI-TOF MS/MS, serum inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4), an acute response protein which is secreted primarily by liver, was identified as the most characteristic protein corresponding with NAFLD progression and HCC development in the NAFLD pigs. With immunoassay, serum ITIH4 levels in the NAFLD pigs were chronologically increased in comparison with those in control animal. Furthermore, immunohistochemistry showed ITIH4 expression in hepatocytes also increased in both the cancer lesions and parenchyma as NAFLD progressed. Human study is also consistent with this observation because serum ITIH4 levels were significantly higher in HCC-NAFLD patients than in the simple steatosis, NASH, and virus-related HCC patients. Of note, HCC-NAFLD patients who had higher serum ITIH4 levels exhibited poorer prognosis after hepatectomy. CONCLUSIONS: We established an HCC pig model associated with NAFLD. Serum proteomics on the swine HCC with NAFLD model implicated ITIH4 as a non-invasive biomarker reflecting NAFLD progression as well as subsequent HCC development. Most importantly, the results in the swine study have been validated in human cohort studies. Dissecting speciation of serum ITIH4 promises to have clinical utility in monitoring the disease.

The neutrophil/lymphocyte ratio as a predictor of peritoneal metastasis during staging laparoscopy for advanced gastric cancer: a retrospective cohort analysis.

BACKGROUND: The use of staging laparoscopy (SL) has become widespread in patients with advanced gastric cancer (GC). This study aimed to evaluate the predictive value of the neutrophil/lymphocyte ratio (NLR) for the presence of peritoneal metastasis during staging laparoscopy in patients with advanced GC. METHODS: This retrospective analysis was performed in 35 patients with advanced GC who underwent SL at Kanazawa Medical University Hospital between January 2009 and December 2017. Clinicopathological characteristics were examined and multivariate analyses were performed to identify preoperative laboratory parameters that were independently associated with the presence of peritoneal metastasis or cytological malignancy (P/CY positive) during SL. RESULTS: A P/CY-positive result was confirmed during SL in 16 patients (45.7%). Patients with type 4 or diffuse type 3 tumors showed a significantly higher P/CY-positive rate than those with other tumor types (58.3% vs. 18.2%, P = 0.02). In the univariate analysis for preoperative laboratory parameters, NLR (P < 0.0001) and total protein (P = 0.03) and albumin (P = 0.04) levels were significantly correlated with a P/CY-positive result. On multivariate analysis, NLR was significantly correlated with a P/CY-positive result (P = 0.0002). In patients with type 4 or diffuse type 3 tumors, a high NLR (> 3.5) was associated with a significantly higher P/CY-positive rate than a low NLR (≤ 3.5) (83.3% vs. 33.3%, P = 0.01). Moreover, in patients without type 4 or diffuse type 3 tumors, the P/CY-positive rates were 100% and 0% in patients with NLR > 3.5 and NLR ≤ 3.5, respectively. CONCLUSIONS: The preoperative NLR was a significant independent predictor of the presence of peritoneal metastasis during SL. Regardless of tumor type, patients with a high NLR could be reasonable candidates for SL. On the other hand, non-diffuse type tumor accompanied by a low NLR may not need to undergo SL.

CAAT/enhancer binding protein-homologous protein deficiency attenuates liver ischemia/reperfusion injury in mice.

Ischemia/reperfusion injury (IRI) is one of the main causes of liver dysfunction after liver surgery. Involvement of endoplasmic reticulum (ER) stress in various diseases has been demonstrated, and CAAT/enhancer binding protein-homologous protein (CHOP) is a transcriptional regulator that is induced by ER stress. It is also a key regulator of ER stress-mediated apoptosis. The aim of this study was to investigate the role of CHOP in liver IRI. Wild type (WT) and CAAT/enhancer binding protein-homologous protein knockout (CHOP-/-) mice were subjected to 70% liver warm ischemia/reperfusion for 60 minutes. At different times after reperfusion, liver tissues and blood samples were collected for evaluation. Induction of ER stress including CHOP expression was ascertained. Liver damage was evaluated based on serum liver enzymes, liver histology, and neutrophil infiltration. Hepatocyte death including apoptosis was assessed. Liver warm IRI induced ER stress in both WT and CHOP-/- mice. In addition, CHOP expression was up-regulated in WT mice. At 6 hours after reperfusion, liver damage was attenuated in CHOP-/- mice. On the basis of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining, apoptotic and necrotic cells were significantly reduced in CHOP-/- mice. CHOP deficiency also reduced the cleavage of caspase 3 and expression of the proapoptotic protein B cell lymphoma 2-associated X protein. Liver IRI induces CHOP expression, and CHOP deficiency attenuates liver IRI by inhibiting apoptosis. Elucidation of the function of CHOP in liver IRI may contribute to further investigation for a therapy against liver IRI associated with the ER stress pathway. Liver Transplantation 24 645-654 2018 AASLD.

Posthepatectomy Liver Failure Affects Long-Term Function After Resection for Hepatocellular Carcinoma.

BACKGROUND: This study examined whether the severity of posthepatectomy liver failure (PLF) affected the long-term postoperative liver recovery of patients with hepatocellular carcinoma (HCC). METHODS: We performed a retrospective cohort study of 395 HCC patients who underwent hepatectomy from 2004 to 2012 at the Kyoto University Hospital. The severity of PLF between postoperative days 5 and 10 was categorized according to the International Study Group of Liver Surgery criteria. We compared the Child-Pugh (C-P) score, platelet count (PLT), and the ratio of future remnant liver volume (FRLV) to the total liver volume (%RLV) at 3, 6, and 12 months after hepatectomy in the non-PLF, grade A, and grade B groups. RESULTS: The non-PLF, grade A, and grade B groups contained 272, 63, and 56 patients, respectively. The C-P score in the grade A group recovered from 5.37 points before hepatectomy to 5.38 points at 12 months after hepatectomy. The C-P score in the grade B group increased from 5.51 to 6.81 points at 3 months and was significantly higher (6.00 points) at 12 months than in the non-PLF group (5.47 points). The PLT significantly decreased at 12 months in the grade B group compared with the non-PLF group. The %RLV at 12 months in the non-PLF, grade A, and grade B groups were 84, 83, and 78 %, respectively. The remnant liver hypertrophy in the grade B group was significantly slower than that in the non-PLF group. CONCLUSIONS: PLF severity affects long-term liver function recovery and remnant liver hypertrophy after hepatectomy.

Prognostic factors in T4b gastric cancer after surgery: A more balanced and sequential therapy for patients?

INTRODUCTION: This study aimed to evaluate the prognostic factors in T4b gastric cancer (GC) in order to improve future therapeutic strategies. METHODS: We retrospectively analyzed the medical records of 43 patients with advanced GC who underwent surgery and were surgically or pathologically diagnosed with T4b GC. The overall survival (OS) rate of patients with T4b GC was analyzed, and univariate and multivariate analyses were performed to identify clinicopathological factors that were independently associated with OS. In addition, we assessed the relationship between postoperative chemotherapy and laboratory parameters 4 weeks post-surgery. RESULTS: The proportion of patients with invasion of cancer in organs, including the pancreas, transverse colon, and liver, were 58.1%, 18.6%, and 14.0%, respectively. The proportion of patients who exhibited distant metastases was 44.2%, and R0 resection was achieved in 30.2% of patients. A total of 69.8% of patients underwent postoperative chemotherapy. The median survival rate was 12.3 months. Upon multivariate analysis, the presence of distant metastases (P = 0.01, HR; 3.48), the use of postoperative chemotherapy (P = 0.0004, HR; 0.12), and R0 resection (P < 0.0001, HR; 0.14) were significantly correlated with OS. Patients who did not undergo postoperative chemotherapy showed significantly higher levels of inflammatory parameters and lower levels of nutritional parameters 4 weeks after surgery than those who did. CONCLUSIONS: We evaluated that the presence of distant metastases was significantly associated with a poor prognosis, and the use of postoperative chemotherapy and R0 resection was significantly associated with a better prognosis in patients with T4b GC. It would be more important for a T4b GC treatment to balance between therapeutic tolerance for postoperative chemotherapy and surgical therapeutic effect.

Infectivity-Enhanced, Conditionally Replicative Adenovirus for COX-2-Expressing Castration-Resistant Prostate Cancer.

BACKGROUND: The development of conditionally replicative adenoviruses (CRAds) for castration-resistant prostate cancer (CRPC), particularly neuroendocrine prostate cancer (NEPC), has two major obstacles: choice of control element and poor infectivity. We applied fiber-modification-based infectivity enhancement and an androgen-independent promoter (cyclooxynegase-2, COX-2) to overcome these issues. METHODS: The properties of the COX-2 promoter and the effect of fiber modification were tested in two CRPC cell lines (Du-145 and PC3). Fiber-modified COX-2 CRAds were tested in vitro for cytocidal effect as well as in vivo for antitumor effect with subcutaneous CRPC xenografts. RESULTS: In both CRPC cell lines, the COX-2 promoter showed high activity, and Ad5/Ad3 fiber modification significantly enhanced adenoviral infectivity. COX-2 CRAds showed a potent cytocidal effect in CRPC cells with remarkable augmentation by fiber modification. In vivo, COX-2 CRAds showed an antitumor effect in Du-145 while only Ad5/Ad3 CRAd showed the strongest antitumor effect in PC3. CONCLUSION: COX-2 promoter-based, infectivity-enhanced CRAds showed a potent antitumor effect in CRPC/NEPC cells.

Recurrent malignant peritoneal mesothelioma treated by a second resection: A case report.

Key Clinical Message: Malignant peritoneal mesothelioma, a rare and poor prognosis disease, is seldom treated surgically, especially for recurrence. However, early diagnosis and aggressive treatment of primary and recurrent tumors can achieve long-term patient survival. Abstract: Malignant peritoneal mesothelioma (MPM) is a rare and aggressive tumor, and rarely indicated for surgery, especially for recurrence. In the present case, we report a rare case who could survive long-term after two surgeries in 4 years for MPM.

Obesity and Pancreatic Cancer: Recent Progress in Epidemiology, Mechanisms and Bariatric Surgery.

More than 30% of people in the United States (US) are classified as obese, and over 50% are considered significantly overweight. Importantly, obesity is a risk factor not only for the development of metabolic syndrome but also for many cancers, including pancreatic ductal adenocarcinoma (PDAC). PDAC is the third leading cause of cancer-related death, and 5-year survival of PDAC remains around 9% in the U.S. Obesity is a known risk factor for PDAC. Metabolic control and bariatric surgery, which is an effective treatment for severe obesity and allows massive weight loss, have been shown to reduce the risk of PDAC. It is therefore clear that elucidating the connection between obesity and PDAC is important for the identification of a novel marker and/or intervention point for obesity-related PDAC risk. In this review, we discussed recent progress in obesity-related PDAC in epidemiology, mechanisms, and potential cancer prevention effects of interventions, including bariatric surgery with preclinical and clinical studies.

Intra-tumoral FGFR2 Expression Predicts Prognosis and Chemotherapy Response in Advanced HER2-positive Gastric Cancer Patients.

BACKGROUND/AIM: This study aimed to evaluate the relationship between clinical outcomes and intra-tumoral fibroblast growth factor receptor 2 (FGFR2) expression in human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) patients who had undergone HER2-targeted chemotherapy. PATIENTS AND METHODS: A retrospective analysis was performed in 22 patients with HER2-positive GC, who had undergone systemic chemotherapy. We performed immunohistochemistry staining of FGFR2 expression using surgically resected specimens or biopsied samples and evaluated clinicopathological characteristic and overall survival (OS) in the FGFR2-negative and -positive GC groups. RESULTS: A total of 8 and 14 patients were placed in the FGFR2-negative and -positive group, respectively. The median OS rates were 56.2 and 16.0 months in the FGFR2-negative and -positive groups, respectively. The FGFR2-negative group had a significantly better prognosis after HER2-targeted chemotherapy [p=0.027 (log-rank test)]. The univariate analysis revealed that performing gastrectomy, response to combination chemotherapy with trastuzumab, and FGFR2 positivity were significantly correlated with OS. In a multivariate analysis, the response to combination chemotherapy with trastuzumab (p=0.008) was significantly correlated with OS. In addition, the proportions of patients who showed CR or PR in response to chemotherapy were 87.5 and 42.9% in the FGFR2-negative and -positive groups, respectively (p=0.031). CONCLUSION: HER2-positive GC patients, without overexpression of FGFR2, exhibited an improved prognosis and response rate to trastuzumab combination chemotherapy. Assessment of intra-tumoral FGFR2 expression could be helpful in predicting the prognosis and response to trastuzumab in HER2-positive GC patients.

Preoperative diagnosis of gallbladder torsion by magnetic resonance cholangiopancreatography: A case report.

Gallbladder torsion is a rare and potentially fatal condition presenting with acute abdominal pain. Gallbladder torsion requires early diagnosis and treatment; however, preoperative diagnosis is difficult. In the present case, magnetic resonance cholangiopancreatography provided definitive imaging findings and was very useful in making the preoperative diagnosis.

Hyaluronic Acid May Be a Predictive Biomarker for Thrombocytopenia and Liver Dysfunction After Oxaliplatin-based Chemotherapy.

Background/Aim: Following oxaliplatin-based chemotherapy, approximately half of all colorectal cancer patients develop sinusoidal obstruction syndrome (SOS). SOS can be monitored by measuring splenic volume; however, obtaining this measurement is not a simple process. In this study, we evaluated changes in hyaluronic acid (HA) concentrations as a simpler marker of SOS. Patients and Methods: We measured splenic volume and laboratory data, including hyaluronic acid concentration, liver enzymes, and platelet counts, in 34 patients with colorectal cancer who underwent radical resection and who received capecitabine plus oxaliplatin (CapeOx) chemotherapy. Results: A strong correlation was identified between ≥30% increase in splenic volume and significantly elevated HA concentrations. Affected patients also had persistent thrombocytopenia and liver dysfunction compared to patients without elevated HA concentration. Conclusion: HA concentration may predict SOS in patients who receive CapeOx adjuvant chemotherapy.