The efficacy of simple oral nutritional supplements versus usual care in postoperative patients with gastric cancer: study protocol for a multicenter, open-label, parallel, randomized controlled trial.

BACKGROUND: Body weight loss (BWL) after gastrectomy impact on the short- and long-term outcomes. Oral nutritional supplement (ONS) has potential to prevent BWL in patients after gastrectomy. However, there is no consistent evidence supporting the beneficial effects of ONS on BWL, muscle strength and health-related quality of life (HRQoL). This study aimed to evaluate the effects of ONS formulated primarily with carbohydrate and protein on BWL, muscle strength, and HRQoL. METHODS: This will be a multicenter, open-label, parallel, randomized controlled trial in patients with gastric cancer who will undergo gastrectomy. A total of 120 patients who will undergo gastrectomy will be randomly assigned to the ONS group or usual care (control) group in a 1:1 ratio. The stratification factors will be the clinical stage (I or ≥ II) and surgical procedures (total gastrectomy or other procedure). In the ONS group, the patients will receive 400 kcal (400 ml)/day of ONS from postoperative day 5 to 7, and the intervention will continue postoperatively for 8 weeks. The control group patients will be given a regular diet. The primary outcome will be the percentage of BWL (%BWL) from baseline to 8 weeks postoperatively. The secondary outcomes will be muscle strength (handgrip strength), HRQoL (EORTC QLQ-C30, QLQ-OG25, EQ-5D-5L), nutritional status (hemoglobin, lymphocyte count, albumin), and dietary intake. All analyses will be performed on an intention-to-treat basis. DISCUSSION: This study will provide evidence showing whether or not ONS with simple nutritional ingredients can improve patient adherence and HRQoL by reducing BWL after gastrectomy. If supported by the study results, nutritional support with simple nutrients will be recommended to patients after gastrectomy for gastric cancer. TRIAL REGISTRATION: jRCTs051230012; Japan Registry of Clinical Trails. Registered on Apr. 13, 2023.

Comparison of Minimally Invasive Surgery with Open Surgery for Remnant Gastric Cancer: A Multi-institutional Cohort Study.

BACKGROUND: Despite growing evidence of the effectiveness of minimally invasive surgery (MIS) for primary gastric cancer, MIS for remnant gastric cancer (RGC) remains controversial due to the rarity of the disease. This study aimed to evaluate the surgical and oncological outcomes of MIS for radical resection of RGC. PATIENTS AND METHODS: Patients with RGC who underwent surgery between 2005 and 2020 at 17 institutions were included, and a propensity score matching analysis was performed to compare the short- and long-term outcomes of MIS with open surgery. RESULTS: A total of 327 patients were included in this study and 186 patients were analyzed after matching. The risk ratios for overall and severe complications were 0.76 [95% confidence interval (CI): 0.45, 1.27] and 0.65 (95% CI: 0.32, 1.29), respectively. The MIS group had significantly less blood loss [mean difference (MD), -409 mL; 95% CI: -538, -281] and a shorter hospital stay (MD, -6.5 days; 95% CI: -13.1, 0.1) than the open surgery group. The median follow-up duration of this cohort was 4.6 years, and the 3-year overall survival were 77.9% and 76.2% in the MIS and open surgery groups, respectively [hazard ratio (HR), 0.78; 95% CI: 0.45, 1.36]. The 3-year relapse-free survival were 71.9% and 62.2% in the MIS and open surgery groups, respectively (HR, 0.71; 95% CI: 0.44, 1.16). CONCLUSIONS: MIS for RGC showed favorable short- and long-term outcomes compared to open surgery. MIS is a promising option for radical surgery for RGC.

Global numerical simulation of fluid-structure-acoustic interaction in a single-reed instrument.

A numerical simulation of a single-reed instrument with a pressure chamber is conducted to examine the interaction among the flow, reed oscillation, and acoustic propagation. The flow and acoustic fields are predicted using the three-dimensional compressible Navier-Stokes equations, whereas the one-dimensional dynamic beam equation is solved for reed oscillation. The deforming geometry in the aeroacoustic field is expressed by the volume penalization method as an immersed boundary technique. The results showed that the waveforms of the tip opening and far-field acoustic spectra agreed well with those measured experimentally. The three-dimensional flow configuration near the tip opening was visualized, and the measurement of the instantaneous volume flow rate at the tip opening revealed that 30%-40% of the total flow rate passed through the side opening. The spectral tendencies of the time derivatives of the flow rate for different tip openings were consistent with that of the far-field sound, indicating that the slope of the flow rate waveform significantly affects the generated sound's harmonics.

Primary results of a randomized two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with two and four courses of cisplatin/S-1 and docetaxel/cisplatin/S-1 as neoadjuvant chemotherapy for advanced gastric cancer.

AIM: Neoadjuvant chemotherapy (NAC) is promising to improve the survival of resectable gastric cancer. However, suitable regimen and treatment duration for NAC have not yet been established. METHODS: We conducted a randomized phase II trial to compare two and four courses of neoadjuvant S-1/cisplatin (SC) and S-1/cisplatin/docetaxel(DCS) using a two-by-two factorial design for locally resectable advanced gastric cancer. Patients with M0 and either T4 or T3 in case of junctional cancer or scirrhous-type cancer received two or four courses of SC or DCS. Then, patients underwent D2 gastrectomy and adjuvant S-1 chemotherapy for 1 year. The primary endpoint was 3-year overall survival. The planned sample size was 120 eligible patients. RESULTS: Between October 2011 and September 2014, 132 patients were assigned to CS (n = 66; 33 in 2-courses and 33 in 4-courses) and DCS (n = 66; 33 in 2-courses and 33 in 4-courses). The 3-year OS was 58.1% in CS and 60.0% in DCS with hazard ratio of 0.80 (95% CI, 0.48-1.34), while it was 53.1% in the two courses and 65.0% in the four courses with hazard ratio of 0.72 (95% CI, 0.43-1.22). In the survival analysis by duration in each regimen, the 3-year OS was 58.1% for both two and four courses in CS, while it was 48.5% for two courses of DCS and 71.9% for four courses of DCS. CONCLUSIONS: Considering high 3-year OS, four courses DCS has a value to be tested in a future phase III study to confirm superiority of neoadjuvant chemotherapy for locally advanced gastric cancer.

Long-term outcomes of incidental gallbladder carcinoma without additional resection: A single institution experiment.

Incidental gallbladder carcinoma (IGC), defined as unexpected malignancy identified in the surgical gallbladder specimen of a cholecystectomy performed for a benign diagnosis, can be difficult to suspect preoperatively. Furthermore, there are valid clinical reasons to defer reoperation for additional resection, particularly in elderly patients. The present study aimed to determine the long-term outcomes and prognostic factors associated with recurrence in patients with IGC. The medical records of 678 patients who underwent cholecystectomy at Toyooka Hospital between September 2011 and November 2017 were reviewed. The cases identified to be IGC were retrospectively analyzed to determine patient and histopathological characteristics, surgical details, long-term outcomes and factors associated with cancer recurrence. A total of 22 patients were diagnosed with gallbladder carcinoma following cholecystectomy by histopathological examination, and 12 of these were identified to be IGC. The median age was 80 years (range 70-89 years). Although 6 of the 12 patients with IGC had stage pT2 or pT3 tumors, only 1 patient underwent additional resection. Recurrence occurred in 3 of the 8 patients who did not undergo additional resection and were available for long-term follow-up. Recurrence was not associated with the extent of tumor invasion but may be associated with other histopathological findings, preoperative treatment history and risk factors for recurrence. Furthermore, long-term survival was observed in patients with pT2 and pT3 tumors who did not undergo additional resection. Recurrence was not associated with the extent of tumor invasion but may be associated with other histopathological findings, preoperative treatment history, and risk factors for recurrence. Furthermore, long-term survival was observed in patients with pT2 and pT3 tumors who did not undergo additional resection. Even if it is a progressive IGC case, appropriate preoperative treatment or cholecystectomy without persistence of the carcinoma cell, based on a preoperative image evaluation and a postoperative histopathological examination, may greatly influence the long-term prognosis of IGC.

[Two Cases of Long-Term Use of TAS-102 for Unresectable Colorectal Cancer].

TAS-102 has been administered to patients with unresectable colorectal cancer. We initiated TAS-102 administration in 2014 and gradually increased the number of indications. In a global, multicenter, randomized, double-blind, phase III study (RECOURSE study), TAS-102 administration improved overall survival by 1.8 months and progression-free survival by 0.3 months compared with those in the placebo group. However, there are limited clinical reports of long-term administration of TAS-102. We encountered 2 cases of continuous long-term use of the TAS-102 for over 2 years. In our cases, although the cancer had been recognized early as exhibiting slow growth during follow-up, the physical symptoms did not appear for an extended period. Although grade 3 neutropenia was pointed out several times during the follow-up term, severe digestive symptoms had not occurred. Therefore, the patients could remain motivated to receive the drug. In our cases, the adequate treatment for neutropenia enabled long-term administration of TAS-102; therefore, TAS-102 would be tolerable for patients of colorectal cancer after receiving chemotherapy for an extended period.

Phase I study of neoadjuvant chemotherapy with S-1 and oxaliplatin for locally advanced gastric cancer (Neo G-SOX PI).

BACKGROUND: The prognosis of locally advanced gastric cancer, such as clinical T4 disease, bulky nodal involvement, type 4 and large type 3 gastric cancer, remains unsatisfactory, even with D2 gastrectomy followed by adjuvant chemotherapy. One promising approach is neoadjuvant chemotherapy. Combination chemotherapy with S-1 and oxaliplatin (SOX) is recognised as a potentially promising regimen for gastric cancer. However, the use of neoadjuvant chemotherapy consisting of SOX for locally advanced gastric cancer has not been reported. The aim of this study was to determine the maximum tolerated dose (MTD) and recommended dose of preoperative chemotherapy combined with SOX for locally advanced gastric cancer. METHODS: Patients received two cycles of neoadjuvant chemotherapy with oxaliplatin on day 1, as well as S-1 (80 mg/m2/day, twice daily) for 14 days, repeated every 3 weeks. They then underwent gastrectomy with curative D2/3 lymph node dissection followed by adjuvant S-1 (80 mg/m2/day, twice daily) for 1 year. Escalation of oxaliplatin dose was planned (starting at level 0, oxaliplatin 100 mg/m2; level 1, 130 mg/m2). RESULTS: Six patients were enrolled. MTD was not reached at level 1. Oxaliplatin 130 mg/m2 in combination with S-1 80 mg/m2/day twice daily could be administered with acceptable toxicity. Peripheral neuropathy was observed in all patients but with no functional disorders. No treatment-related death was observed and the incidence of operative morbidity was tolerable. Resection with curative intent was undertaken in all patients with R0 resection performed in five (83%) and R1 in one. Two of the six patients had a pathological complete response (33%). CONCLUSION: Neoadjuvant chemotherapy with an SOX regimen was feasible in patients with locally advanced gastric cancer. The recommended phase II dose was determined to be oxaliplatin 130 mg/m2 in combination with S-1 80 mg/m2/day, twice daily.

Predictive factors for body weight loss and its impact on quality of life following gastrectomy.

AIM: To determine the predictive factors and impact of body weight loss on postgastrectomy quality of life (QOL). METHODS: We applied the newly developed integrated questionnaire postgastrectomy syndrome assessment scale-45, which consists of 45 items including those from the Short Form-8 and Gastrointestinal Symptom Rating Scale instruments, in addition to 22 newly selected items. Between July 2009 and December 2010, completed questionnaires were received from 2520 patients with curative resection at 1 year or more after having undergone one of six types of gastrectomy for Stage I gastric cancer at one of 52 participating institutions. Of those, we analyzed 1777 eligible questionnaires from patients who underwent total gastrectomy with Roux-en-Y procedure (TGRY) or distal gastrectomy with Billroth-I (DGBI) or Roux-en-Y (DGRY) procedures. RESULTS: A total of 393, 475 and 909 patients underwent TGRY, DGRY, and DGBI, respectively. The mean age of patients was 62.1 ± 9.2 years. The mean time interval between surgery and retrieval of the questionnaires was 37.0 ± 26.8 mo. On multiple regression analysis, higher preoperative body mass index, total gastrectomy, and female sex, in that order, were independent predictors of greater body weight loss after gastrectomy. There was a significant difference in the degree of weight loss (P < 0.001) among groups stratified according to preoperative body mass index (< 18.5, 18.5-25 and > 25 kg/m2). Multiple linear regression analysis identified lower postoperative body mass index, rather than greater body weight loss postoperatively, as a certain factor for worse QOL (P < 0.0001) after gastrectomy, but the influence of both such factors on QOL was relatively small (R2, 0.028-0.080). CONCLUSION: While it is certainly important to maintain adequate body weight after gastrectomy, the impact of body weight loss on QOL is unexpectedly small.

Phase I Study of Neoadjuvant Chemotherapy with Capecitabine and Oxaliplatin for Locally Advanced Gastric Cancer.

AIM: To determine the recommended dose of neoadjuvant chemotherapy of combined capecitabine and oxalipatin (G-XELOX) for locally advanced gastric cancer. PATIENTS AND METHODS: Patients received two cycles of neoadjuvant chemotherapy with oxaliplatin on day 1 and capecitabine (2,000 mg/m2/day, b.i.d.) on days 1-14, repeated every 3 weeks. They then underwent gastrectomy with curative D2/3 lymph-node dissection followed by adjuvant therapy with S-1 for 1 year. De-escalation of oxaliplatin dose was planned (starting at level 1, oxalipatin 130 mg/m2). RESULTS: Six patients were enrolled. The maximum tolerated dose was not reached at level 1. Oxaliplatin at 130 mg/m2 combined with capecitabine at 2,000 mg/m2/day, b.i.d. had acceptable toxicity. No treatment-related death occurred. Most frequent drug-related adverse events during neoadjuvant G-XELOX were nausea and peripheral sensory neuropathy. One patient declined surgical resection, leaving five undergoing resection with curative intent, of whom four achieved pathological down-staging after neoadjuvant G-XELOX. CONCLUSION: Neoadjuvant G-XELOX was feasible in patients with locally advanced gastric cancer.

Phase II study of the effectiveness and safety of trastuzumab and paclitaxel for taxane- and trastuzumab-naïve patients with HER2-positive, previously treated, advanced, or recurrent gastric cancer (JFMC45-1102).

Paclitaxel is a standard second-line gastric cancer treatment in Japan. Trastuzumab could be active as second-line chemotherapy for taxane/trastuzumab-naïve patients with epidermal growth factor 2 (HER2)-positive advanced gastric cancer. Patients aged ≥20 years with HER2-positive, previously treated (except for trastuzumab and taxane), unresectable or recurrent gastric adenocarcinoma underwent combined trastuzumab (first and subsequent doses of 8 and 6 mg kg-1 , respectively, every 3 weeks) and paclitaxel (days 1, 8, 15, every 4 weeks) treatment. Study endpoints were best overall response, progression-free survival, overall survival, and safety. From September 2011 to March 2012, 47 Japanese patients were enrolled. Forty patients discontinued treatment after a median of 128.5 (range 4-486) days. Complete and partial responses were obtained in one and 16 patients (response rate of 37% [95% CI 23-52]), respectively. Median progression-free survival and overall survival were 5.1 (95% CI 3.8-6.5) and 17.1 (95% CI 13.5-18.6) months, respectively. Grade 3/4 adverse events were neutropenia (32.6%), leukopenia (17.4%), anemia (15.2%) and hypoalbuminemia (8.7%). There was no clinically significant cardiotoxicity or cumulative toxicity. Three (disturbed consciousness, pulmonary fibrosis, and rapid disease progression) grade 5 events occurred. In conclusion, trastuzumab combined with paclitaxel was well tolerated and was a promising regimen for patients with HER2-positive, previously treated, advanced or recurrent gastric cancer.

Clinicopathological factors associated with HER2 status in gastric cancer: results from a prospective multicenter observational cohort study in a Japanese population (JFMC44-1101).

BACKGROUND: Human epidermal growth factor (HER) 2 positivity and its association with clinicopathological factors remain unclear in Japanese gastric cancer (GC) patients. We performed a prospective, multicenter, observational cohort study to evaluate HER2 protein expression and gene amplification in Japanese metastatic and recurrent GC patients, and explored its correlations with clinicopathological features. METHODS: HER2 protein expression and gene amplification were centrally assessed in formalin-fixed, paraffin-embedded GC tissue by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Patient information was collected, and associations between clinicopathological factors and HER2 positivity (IHC score 3+ and/or FISH positive) and low HER2 expression (IHC score 0/FISH positive or IHC score 1+/FISH positive) were examined. RESULTS: From September 2011 to June 2012, 1461 patients were registered across 157 sites, and the HER2 status of 1427 patients was evaluated. The rate of HER2 positivity was 21.2 %, whereas the rate of high HER2 expression (IHC score 2+/FISH positive or IHC score 3+) was 15.6 % and that of low HER2 expression was 7.0 %. Multiple logistic regression analysis identified intestinal type, absence of peritoneal metastasis, and hepatic metastasis as significant independent factors related to HER2 positivity. The intestinal type was confirmed to be the GC subtype predominantly associated with lower HER2 expression. Sampling conditions including number of biopsy samples, formalin concentration, and formalin-fixation time did not significantly affect HER2 positivity. CONCLUSIONS: HER2 expression in Japanese patients was comparable to that in other populations examined. Intestinal type was an independent factor related to HER2 positivity and low HER2 expression.

The preventive surgical site infection bundle in patients with colorectal perforation.

BACKGROUND: Incisional surgical site infection (SSI) is one of the most frequent complications that occur after colorectal surgery. Surgery for colorectal perforation carries an especially high risk of incisional SSI because fecal ascites contaminates the incision intraoperatively, and in patients who underwent stoma creation, the incision is located near the infective origin and is subject to infection postoperatively. Although effectiveness of the preventive SSI bundle of elective colorectal surgery has been reported, no study has focused exclusively on emergency surgery for colorectal perforation. METHODS: Patients with colorectal perforation who underwent emergency surgery and stoma creation from 2010 to 2015 at our center were consecutively enrolled in the study. In March 2013, we developed the preventive incisional SSI bundle for patients with colorectal perforation undergoing stoma creation. The effectiveness of the bundle in these patients was determined and the rates of incisional SSI between before and after March 2013 were compared. RESULTS: We enrolled 108 patients with colorectal perforation who underwent emergency operation during the study period. Thirteen patients were excluded because they died within 30 days after surgery, and 23 patients without stoma were excluded; thus, 72 patients were analyzed. There were 47 patients in the pre-implementation group and 25 patients in the post-implementation group. The rate of incisional SSI was significantly lower after implementation of preventive incisional SSI bundle (43% vs. 20%, p = 0.049). Postoperative hospital stay was significantly shorter after implementation of the bundle (27 vs. 18 days respectively; p = 0.008). CONCLUSIONS: The preventive incisional SSI bundle was effective in preventing incisional SSI in patients with colorectal perforation undergoing emergency surgery with stoma creation.

Direct numerical simulation of fluid-acoustic interactions in a recorder with tone holes.

To clarify fluid-acoustic interactions in an actual recorder with opened and closed tone holes, flow and acoustic fields were directly numerically simulated on the basis of the compressible Navier-Stokes equations. To validate the simulation accuracy, the flow field around the windway and sound pressure above the window were measured. The predicted acoustic fields clarify changes of the positions of pressure nodes and anti-nodes in accordance with the state of the tone holes and the Mach number of the jet velocity. The fundamental mechanism of the self-sustained oscillations in a three-dimensional actual recorder is visualized by the predicted acoustic and flow fields. This result is also consistent with the relationship between the jet behaviors and pressure fluctuations based on the jet-drive model. Moreover, the effects of the fine vortices in the jet, which appear at the high Mach number of jet velocity of 0.099, on the sound are discussed. The time difference between the generation of the disturbances and the most intense deflection of the jet is identified and compared with the time delay of acoustic reflection around the window.

Prediction of mortality in patients with colorectal perforation based on routinely available parameters: a retrospective study.

INTRODUCTION: Even after surgery and intensive postoperative management, the mortality rate associated with colorectal perforation is high. Identification of mortality markers using routinely available preoperative parameters is important. METHODS: We enrolled consecutive patients with colorectal perforation who underwent operations from January 2010 to January 2015. We divided them into a mortality and survivor group and compared clinical characteristics between the two groups. Additionally, we compared the mortality rate between different etiologies: malignant versus benign and diverticular versus nondiverticular. We used the χ (2) and Mann-Whitney U tests and a logistic regression model to identify factors associated with mortality. RESULTS: We enrolled 108 patients, and 52 (48 %) were male. The mean age at surgery was 71 ± 13 years. The postoperative mortality rate was 12 % (13 patients). Multivariate logistic regression analysis showed that a high patient age (odds ratio [OR], 1.09; 95 % confidence interval [CI], 1.020-1.181) and low preoperative systolic blood pressure (OR, 0.98; 95 % CI, 0.953-0.999) were independent risk factors for mortality in patients with colorectal perforation. In the subgroup analysis, there was no significant difference between the malignant and benign group (11.8 % vs. 23.9 %, respectively; p = 0.970), while the diverticular group had a significantly lower mortality rate than the nondiverticular group (2.6 % vs. 17.1 %, respectively; p = 0.027). CONCLUSIONS: Older patients and patients with low preoperative blood pressure had a high risk of mortality associated with colorectal perforation. For such patients, operations and postoperative management should be performed carefully.

Comparison between anatomical subsegmentectomy and nonanatomical partial resection for hepatocellular carcinoma located within a single subsegment: a single-center retrospective analysis.

BACKGROUND/AIMS: For hepatocellular carcinoma (HCC) within a single subsegment, the superiority of anatomical subsegmentectomy over non-anatomical partial resection is still controversial. In this study, we assessed the potential benefit of subsegmentectomy. METHODOLOGY: We selected 44 patients with a single HCC lesion within one subsegment who had undergone anatomical subsegmentectomy or non-anatomical partial resection from among 173 patients who underwent hepatectomy in our hospital from August 2003 to May 2013. We compared the results following anatomical subsegmentectomy (Group A; n = 16) and non-anatomical partial resection (Group N; n = 28). RESULTS: One- and two-year survival rates were 92.5% and 89.3%, respectively; 1- and 2-year recurrence-free survival (RFS) rates were 88.9% and 69.1%, respectively. There was no significant difference in overall survival or RFS between the groups. However, among HBV-positive patients, RFS was significantly better for Group A than Group N (p = 0.008). CONCLUSIONS: For HBV-positive HCC within a single subsegment, we recommend subsegmentectomy.

[A case of jejunal ectopic pancreatic cancer: the diagnostic usefulness of MRI].

A 70-year-old man was referred to our hospital because of elevated CA19-9. Magnetic resonance imaging revealed a jejunal tumor having duct and retention cyst-like structures, which suggested ectopic pancreatic cancer. We resected that part of the jejunum and the lymph nodes around the tumor. Pathological examination revealed an adenocarcinoma originating from a Heinrich type I ectopic pancreas in the jejunum. Adjuvant chemotherapy with gemcitabine was performed for half a year. After 8 months, CA19-9 remained elevated, and liver metastasis occurred. We began treatment with tegafur/gimeracil/oteracil potassium (S-1) and particle beam therapy. After 7 months, CA19-9 was normal, and the patient has remained in partial remission with S-1 treatment. Ectopic pancreas tissues typically occur in the stomach and duodenum and rarely become cancerous. Here, we report the features of a rare and illustrative case of jejunal ectopic pancreatic cancer.

Mutational diversity of NS5A and NS3 during triple therapy (telaprevir, pegylated-interferon-α 2b and ribavirin) for genotype 1b chronic hepatitis C: The Kobe Hepatitis Therapeutic Group.

Telaprevir, a non-structural (NS)3/4A protease inhibitor, is a direct-acting antiviral drug that inhibits viral replication. Triple therapy with telaprevir, pegylated interferon, and ribavirin is a standard therapeutic regimen for patients with genotype 1b chronic hepatitis C virus (HCV) infection and a high viral load. Several factors, including mutations in the NS5A gene, are important predictors of the efficacy of interferon therapy. In this study, we examined the mutational diversity of NS5A and its impact on the efficacy of triple therapy. We enrolled patients with genotype 1b chronic HCV infection and a high viral load (31 males/17 females; mean age, 57.6 years), who were treated with triple therapy. This study was conducted at Kobe University Hospital and at three affiliated hospitals in Hyogo prefecture, Japan, between November 2011 and June 2013. A sustained viral response after 12 weeks (SVR12) was achieved in 37/48 patients (77%). Based on intent-to-treat analysis, SVR12 was significantly greater in patients with the major allele than in those with the minor allele for the IL28B single nucleotide polymorphism (SNP; 88 vs. 56%; P<0.05). The prevalence of the V2334I mutation in NS5A was significantly higher in patients who achieved SVR12, while that of G2356E was significantly higher in patients who did not achieve SVR12 (P<0.05). Mutations in the NS3 region that are thought to confer resistance to telaprevir were detected in 3/27 patients who achieved SVR12 (Val36, n=3) and in 5/10 patients who did not achieve SVR12 (Val36, n=4; Thr54, n=1). In conclusion, the IL28B SNP and mutations in the NS5A region were associated with the therapeutic response to triple therapy. Half of the patients who did not achieve SVR12 had mutations conferring resistance to telaprevir. However, pre-existing mutations in NS3 did not affect the efficacy of triple therapy.

[A case of mixed adenoneuroendocrine carcinoma of the transverse colon].

A 7 1-year-old man presented to our hospital with constipation and abdominal pain. Computed tomography of the abdomen and colonoscopy revealed advanced cancer of the transverse colon. The biopsy specimen indicated a highly differentiated adenocarcinoma. The patient underwent extended right hemicolectomy with regional lymph node dissection. Pathological examination showed a neuroendocrine carcinoma (NEC) with concurrent adenocarcinoma of the transverse colon and regional lymph node metastases of the NEC and adenocarcinoma. The histopathological examination confirmed a diagnosis of mixed adenoneuroendocrine carcinoma (MANEC) in accordance with the 2010 WHO Classification of Tumors of the Digestive System. Liver and lung metastases were identified 8 months after the surgery. We administered chemotherapy including 5-fluorouracil, Leucovorin, and oxaliplatin (mFOLFOX) plus bevacizumab, with limited therapeutic effect, as the disease progressed despite treatment. The patient chose best supportive care 13 months after the surgery. Several studies have reported that most patients with adenoendocrine cell carcinoma, including MANEC, experience relapse within 1 year after surgery, and few patients remain disease-free for long periods after surgery. The optimal strategy for the management of MANEC is variable owing to its rarity; only 2 cases of MANEC in the colon, including the present case, have been reported in Japan. It is thus important to gather more evidence on this disease and its management.