Study on prediction of early adverse events by CapeOX therapy in patients with colorectal cancer.

CapeOX is a regimen used as postoperative adjuvant chemotherapy for the treatment of advanced recurrent colorectal cancer. If early adverse events occur, treatment may not progress as planned and further dose reduction may be necessary. In this study, we investigated whether pre-treatment medical records could be used to predict adverse events in order to prevent adverse events caused by CapeOX treatment. The 178 patients were classified into two groups (97 in the adverse event positive group and 81 in the adverse event-negative group) based on withdrawal or postponement of four or fewer courses. In univariate analysis, age, height, weight, body surface area (BSA), creatinine clearance, muscle mass, and lean body mass were associated with early adverse events (P<0.05). The area under the receiver operating characteristic curve obtained by Stepwise logistic regression analysis using the Akaike information criterion method was 0.832. For nested k-fold cross validation, the accuracy rates of the support vector machine, random forest, and logistic regression algorithms were 0.71, 0.70, and 0.75, respectively. The results of the present study suggest that a logistic regression prediction model may be useful in predicting early adverse events caused by CapeOX therapy in patients with colorectal cancer. J. Med. Invest. 71 : 141-147, February, 2024.

Baseline ctDNA gene alterations as a biomarker of survival after panitumumab and chemotherapy in metastatic colorectal cancer.

Certain genetic alterations and right-sided primary tumor location are associated with resistance to anti-epidermal growth factor (EGFR) treatment in metastatic colorectal cancer (mCRC). The phase 3 PARADIGM trial (n = 802) demonstrated longer overall survival with first-line anti-EGFR (panitumumab) versus antivascular endothelial growth factor (bevacizumab) plus modified FOLFOX6 in patients with RAS wild-type mCRC with left-sided primary tumors. This prespecified exploratory biomarker analysis of PARADIGM (n = 733) evaluated the association between circulating tumor DNA (ctDNA) gene alterations and efficacy outcomes, focusing on a broad panel of gene alterations associated with resistance to EGFR inhibition, including KRAS, NRAS, PTEN and extracellular domain EGFR mutations, HER2 and MET amplifications, and ALK, RET and NTRK1 fusions. Overall survival was prolonged with panitumumab plus modified FOLFOX6 versus bevacizumab plus modified FOLFOX6 in patients with ctDNA that lacked gene alterations in the panel (that is, negative hyperselected; median in the overall population: 40.7 versus 34.4 months; hazard ratio, 0.76; 95% confidence interval, 0.62-0.92) but was similar or inferior with panitumumab in patients with ctDNA that contained any gene alteration in the panel (19.2 versus 22.2 months; hazard ratio, 1.13; 95% confidence interval, 0.83-1.53), regardless of tumor sidedness. Negative hyperselection using ctDNA may guide optimal treatment selection in patients with mCRC. ClinicalTrials.gov registrations: NCT02394834 and NCT02394795 .

Panitumumab vs Bevacizumab Added to Standard First-line Chemotherapy and Overall Survival Among Patients With RAS Wild-type, Left-Sided Metastatic Colorectal Cancer: A Randomized Clinical Trial.

Importance: For patients with RAS wild-type metastatic colorectal cancer, adding anti-epidermal growth factor receptor (anti-EGFR) or anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibodies to first-line doublet chemotherapy is routine, but the optimal targeted therapy has not been defined. Objective: To evaluate the effect of adding panitumumab (an anti-EGFR monoclonal antibody) vs bevacizumab (an anti-VEGF monoclonal antibody) to standard first-line chemotherapy for treatment of RAS wild-type, left-sided, metastatic colorectal cancer. Design, Setting, and Participants: Randomized, open-label, phase 3 clinical trial at 197 sites in Japan in May 2015-January 2022 among 823 patients with chemotherapy-naive RAS wild-type, unresectable metastatic colorectal cancer (final follow-up, January 14, 2022). Interventions: Panitumumab (n = 411) or bevacizumab (n = 412) plus modified fluorouracil, l-leucovorin, and oxaliplatin (mFOLFOX6) every 14 days. Main Outcomes and Measures: The primary end point, overall survival, was tested first in participants with left-sided tumors, then in the overall population. Secondary end points were progression-free survival, response rate, duration of response, and curative (defined as R0 status) resection rate. Results: In the as-treated population (n = 802; median age, 66 years; 282 [35.2%] women), 604 (75.3%) had left-sided tumors. Median follow-up was 61 months. Median overall survival was 37.9 months with panitumumab vs 34.3 months with bevacizumab in participants with left-sided tumors (hazard ratio [HR] for death, 0.82; 95.798% CI, 0.68-0.99; P = .03) and 36.2 vs 31.3 months, respectively, in the overall population (HR, 0.84; 95% CI, 0.72-0.98; P = .03). Median progression-free survival for panitumumab vs bevacizumab was 13.1 vs 11.9 months, respectively, for those with left-sided tumors (HR, 1.00; 95% CI, 0.83-1.20) and 12.2 vs 11.4 months overall (HR, 1.05; 95% CI, 0.90-1.24). Response rates with panitumumab vs bevacizumab were 80.2% vs 68.6%, respectively, for left-sided tumors (difference, 11.2%; 95% CI, 4.4%-17.9%) and 74.9% vs 67.3% overall (difference, 7.7%; 95% CI, 1.5%-13.8%). Median duration of response with panitumumab vs bevacizumab was 13.1 vs 11.2 months for left-sided tumors (HR, 0.86; 95% CI, 0.70-1.10) and 11.9 vs 10.7 months overall (HR, 0.89; 95% CI, 0.74-1.06). Curative resection rates with panitumumab vs bevacizumab were 18.3% vs 11.6% for left-sided tumors; (difference, 6.6%; 95% CI, 1.0%-12.3%) and 16.5% vs 10.9% overall (difference, 5.6%; 95% CI, 1.0%-10.3%). Common treatment-emergent adverse events were acneiform rash (panitumumab: 74.8%; bevacizumab: 3.2%), peripheral sensory neuropathy (panitumumab: 70.8%; bevacizumab: 73.7%), and stomatitis (panitumumab: 61.6%; bevacizumab: 40.5%). Conclusions and Relevance: Among patients with RAS wild-type metastatic colorectal cancer, adding panitumumab, compared with bevacizumab, to standard first-line chemotherapy significantly improved overall survival in those with left-sided tumors and in the overall population. Trial Registration: ClinicalTrials.gov Identifier: NCT02394795.

A case of aortoduodenal fistula presenting with postoperative lymphatic leakage.

INTRODUCTION AND IMPORTANCE: Secondary aortoduodenal fistula (sADF) is a complication of prosthetic graft replacement of the abdominal aorta which often follows a fatal course. This report details our experience with a case of lymphatic fistula that developed after sADF repair. The fistula was refractory to conservative treatment but ultimately responded to lipiodol lymphangiography. CASE PRESENTATION: A 75-year-old man had undergone prosthetic graft replacement to treat an abdominal aortic aneurysm in 2012 and a thoracic aortic aneurysm in 2015. Upper gastrointestinal endoscopy was performed in 2020, and examination for worsening anemia revealed that the abdominal aortic graft had eroded into the horizontal duodenum. The patient was treated with prosthetic graft replacement and duodenectomy. A refractory lymphatic fistula was noted after surgery, which made ascites accumulation difficult to control, but the patient's condition rapidly improved following therapeutic lymphangiography. CLINICAL DISCUSSION: Surgery is the first-line therapy for sADF, but clinicians must stay vigilant for infection recurrence and aortoenteric fistulae after a repair, and this requires patient-specific postoperative management. Our modifications, intended to minimize contamination of the operative field in the present case, also facilitated our ability to subsequently treat a refractory lymphatic fistula, which is a rare postoperative complication of the procedure. CONCLUSION: Procedural modifications to sADF repair aimed at minimizing perioperative contamination are crucial for preventing infection recurrence. Given the extent of invasion, the surgery can cause various postoperative complications, requiring individualized strategies for management and treatment. Therapeutic lymphangiography is one such approach, which holds promise as a first-line treatment for refractory lymphatic fistula.

A phase II study of FOLFOXIRI plus bevacizumab as initial chemotherapy for patients with untreated metastatic colorectal cancer: TRICC1414 (BeTRI).

PURPOSE: FOLFOXIRI plus bevacizumab is regarded as a first-line therapeutic option for selected patients with metastatic colorectal cancer (mCRC). Our aim was to assess the efficacy and safety of induction treatment with FOLFOXIRI plus bevacizumab in patients with untreated mCRC harboring UGT1A1 wild (*1/*1), or single-hetero (*1/*6 or *1/*28) genotypes. METHODS: Twelve cycles of FOLFOXIRI plus bevacizumab were administered to patients with untreated mCRC. The primary endpoint was the overall response rate (ORR) assessed by central independent reviewers. Secondary endpoints included time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), relative dose intensity (RDI), R0 resection rate, and safety. The exploratory objectives were early tumor shrinkage (ETS) and depth of response (DoR). RESULTS: Of the 47 patients enrolled, 46 and 44 patients were eligible for the safety and efficacy analysis, respectively. The primary endpoint was met. The ORR was 63.6% (95% CI 47.8-77.6). At a median follow-up of 25.4 months, median TTF, PFS, and OS was 8.1, 15.5, and 34.4 months, respectively. The median RDI of 5-fluorouracil, irinotecan, oxaliplatin, and bevacizumab was 72, 69, 62, and 71%, respectively. R0 resection rate was 22.7%. Grade 3 or higher adverse events (≥ 10%) included neutropenia (65.2%), febrile neutropenia (26.1%), leukopenia (23.9%), anorexia (10.9%), nausea (10.9%), and diarrhoea (10.9%). No treatment-related deaths were observed. ETS and DoR were 70.5 and 45.4%, respectively. CONCLUSIONS: FOLFOXIRI plus bevacizumab induction treatment of Japanese patients was shown to be beneficial and manageable, although caution is required since the treatment causes febrile neutropenia.

Impact of preoperative chemotherapy as initial treatment for advanced gastric cancer with peritoneal metastasis limited to positive peritoneal lavage cytology (CY1) or localized peritoneal metastasis (P1a): a multi-institutional retrospective study.

BACKGROUND: Gastric cancer (GC) patients with peritoneal metastasis are defined as stage IV in the Japanese classification of GC. For patients with peritoneal metastasis limited to positive peritoneal lavage cytology (CY1) and/or localized peritoneal metastasis (P1a), gastrectomy followed by S1 monotherapy is one of the most widely accepted therapeutic strategy in Japan. This study investigated the efficacy of preoperative chemotherapy as initial treatment in GC patients with CY1 and/or P1a. METHODS: We retrospectively reviewed GC patients diagnosed with CY1 and/or P1a at 34 institutions in Japan between 2008 and 2012. Selection criteria were: adenocarcinoma, no distant metastasis except CY1 or P1a, and no prior treatment. The subjects were divided into an Initial-Chemotherapy group and an Initial-Surgery group, according to the initial treatment. RESULTS: A total of 824 patients were collected and 713 eligible patients were identified for this study. As the initial treatment, 150 patients received chemotherapy (Initial-Cx), and 563 patients underwent surgery (Initial-Sx). Initial-Cx regimens were cisplatin plus S1/docetaxel plus cisplatin plus S1/others (n = 90/37/23). Both overall survival (OS) and progression-free survival (PFS) were similar between the Initial-Cx and Initial-Sx groups (median OS 24.8 and 24.0 months, HR 1.07, 95% CI 0.87-1.3; median PFS 14.9 and 13.9 months, HR 1.04, 95% CI 0.85-1.27). The 5-year OS rates were 22.3% in the Initial-Cx group and 21.5% in the Initial-Sx group. CONCLUSIONS: Although, the preoperative chemotherapy did not show a survival benefit for GC patients with CY1 and/or P1a, initial-Cx showed favorable survival in patients who converted to P0 and CY0.

Pancreaticoduodenectomy after distal gastrectomy: A case series.

INTRODUCTION: Pancreatoduodenectomy (PD) after gastrectomy requires more attention during surgery than ordinary PD due to anatomical variation with different types of gastrointestinal anastomoses, the complication of anatomical dissection, and the extent of adhesions present. Herein, we describe the PD strategies we used in three patients who strategy for three patients who had previously undergone distal gastrectomy for gastric cancer treatment. DISCUSSION: Generally, reconstruction following PD in patients who have undergone a prior Billroth I reconstruction is simple, as there is no previous afferent loop. By comparison, reconstruction after a Billroth II or R-Y reconstruction requires special consideration of the point of circulation and length of the remnant intestine used for pancreaticojejunostomy, choledochojejunostomy or gastrojejunostomy. CONCLUSION: There is no consensus regarding the best method for performing PD and reconstruction in patients with a prior history of gastrectomy. The appropriateness of using the existing afferent loop for reconstruction depends on whether the jejunum is of sufficient length for bile duct and pancreatic anastomosis. Regardless of the approach used, it is necessary to avoid excessive tension during reconstruction. Based on our experience and previous studies published in the English literature, we propose that reconstruction needs to be considered on a case-by-case basis.

Secondary aorto-duodenal fistula successfully treated with a novel surgical method: A case report.

INTRODUCTION: Secondary aorto-duodenal fistula (sADF) is a complication of abdominal aorta artificial blood vessel replacement that often leads to death. However, an optimal operative method has not yet been established. We describe a patient who underwent artificial blood vessel reimplantation and duodenectomy after endovascular aneurysmal repair (EVAR) with positive outcomes. PRESENTATION OF CASE: An 84-year-old man underwent artificial blood vessel replacement in 2015. In September 2016, he visited our emergency department and was diagnosed with sADF based on computed tomography. Urgent EVAR was performed, followed by duodenal segmental resection on the next day without opening the syringeal part to minimize the pollution of the operative field. Artificial blood vessel reimplantation and omental flap transposition were performed. As of 2020, about 3 years after surgery, there has been no relapse of the infection. DISCUSSION: Using our novel operative method, we can minimize exposure of the artificial blood vessel and surrounding tissue to intestinal juice and pus. We believe that this reduces the risk of postoperative artificial blood vessel reinfection. CONCLUSION: Controlling bleeding by EVAR and resection of the duodenum and artificial blood vessels as a group without opening the syringeal part can contribute to positive long-term results as this method minimizes the pollution of the duodenectomy surgical field.

Repair of a perforated duodenal diverticulum using intraduodenal suture in 94 year old woman: A case report.

INTRODUCTION: In case of gastrointestinal diverticula, the duodenal type is quite frequent; duodenum is the second most common site for diverticula following the colon (Glener et al., 2016). However, duodenal diverticular perforation is rare, so the appropriate surgical treatment for this condition is yet unclear (Simoes et al., 2014). This literature has been written in line with the SCARE criteria (Agha et al., 2018). PRESENTATION OF CASE: A 94-year-old woman emergently presented to our department with diffuse abdominal tenderness and guarding, indicating pan-peritonitis. Computed tomography revealed pneumoretroperitoneum; Therefore, gastrointestinal perforation was suspected. Emergency surgery was performed; we detected the perforated diverticulum located at the posterior wall of the duodenum with accompanying inflammation. Considering the location, postoperative leakage, and the patient's advanced age, we placed trans-section on duodenal wall against the lesion and resected the diverticulum, The lumen was then manually sutured from within. The anterior wall was closed using linear staplers. The patient recovered uneventfully and was discharged 24 days after surgery. DISCUSSSIONS: As perforated duodenal diverticulum is rare, the ideal management is unclear. Several studies mention various surgical procedures. However, actual treatment varies based on the patient's situation and surgeon's assessment. Almost all cases that require surgery present emergently; therefore, simpler and more effective treatment methods are required (Simoes et al., 2014; Philip et al., 2019; Fujisaki et al., 2014). CONCLUSION: We used a unique surgical technique; intraduodenal suture for perforated diverticulum. This technique can be a feasible alternative for managing this condition.

The sterno-tracheal distance is an important factor of anastomotic leakage of retrosternal gastric tube reconstruction after esophagectomy.

BACKGROUND: Anastomotic leakage (AL) is a serious complication after esophagectomy. The retrosternal (RS) route has been selected majorly to reduce reflux and related pneumonia and considering mediastinal recurrences. AL has been developed more in RS than posterior mediastinal (PM) route reconstruction. Therefore, we suspected the sterno-tracheal distance (STD) might be related to AL and started the selection according to the STD from 2009. METHODS: A total of 221 patients who underwent a subtotal esophagectomy with gastric tube reconstruction during January 2004-April 2017 were investigated. The patients were classified into the 'after STD selection' (A; n = 144) group and the 'before STD selection' (B, n = 77) group. The incidences of and the risk factors for AL between the two groups were compared. RESULTS: The incidence of AL was high in the B group (18.2%), and 78.6% of the patients who developed AL were treated with RS route reconstruction. The median STDs of the patients with AL and no AL were 10.3 mm and 14.5 mm, respectively (p = 0.001). These results demonstrated that the STD was a risk factor for AL in the RS route. Based on these results, 13 mm was set as the cutoff value. After STD selection, the median STD increased from 14.0 to 17.3 mm (p = 0.001), and the incidence of AL decreased significantly from 26.2 to 11.1% in the RS route (p = 0.037). CONCLUSION: The STD was the independent risk factor for AL in the RS route. RS route reconstruction should be avoided for the patients with STD < 13 mm.

Unresectable Advanced Gastric Cancer with Skin Invasion followed by Total Gastrectomy after Second-Line Chemotherapy.

Conversion surgery has been reported but few cases have undergone surgical R0 resection after second-line chemotherapy. We report a case of an unresectable locally advanced gastric cancer in a patient who finally underwent the operation (R0) after second-line chemotherapy. The 77-year-old male was diagnosed with gastric cancer (cT4 [SI; Skin, Liver] N0M0 c Stage IIIA) with invasion to the skin of the abdominal wall, and chemotherapy was initially performed because of his poor performance status and due to the large defect in the abdominal wall that might occur if an operation was performed. Partial response (PR) was observed after S-1+CDDP (SP) therapy, which was then stopped after which progressive disease (PD) was observed. Ramucirumab+Paclitaxel (RAM/PTX) therapy was chosen as second-line therapy, and PR was obtained again, following which total gastrectomy was performed (D2 dissection of lymph nodes, Roux-en-Y reconstruction, and combined resection of the partial skin and the affected region of the liver). At 30 months postoperatively, no recurrence has occurred and the patient is alive after the operation without chemotherapy.

[Effectiveness of Ramucirumab Therapy for Advanced Gastric Cancer after Stent Placement for Esophagogastric Junction Carcinoma Obstruction-A Case Report].

According to the REGARD and RAINBOW trials, ramucirumab(RAM)was introduced as second-line therapy for advanced or metastatic gastric cancer. Endoscopic metallic stent placement and angiogenesis inhibitor administration carry the risk of gastrointestinal perforation. The outcomes of patients who undergo endoscopic placement of metallic stents during RAM treatment have not yet been fully assessed. A 60's man was diagnosed with advanced esophagogastric junction cancer(por) with Virchow's lymph node metastases. His tumor was classified as cT4a(SE), N1(#1), M1, stage Ⅳ. He received chemotherapy, but the size of the primary tumor and metastases increased. After stenting for gastric outlet obstruction, he received a paclitaxel(PTX)plus RAM regimen as third-line treatment. Because of CTCAE Grade 2 peripheral neuropathy, PTX was discontinued after 10 courses. For 11 months, tumor control without adverse events was maintained. The patient was then switched to CPT-11 as fourth-line treatment.

Thoracoscopic Oesophagectomy Using Prone Positioning for Oesophageal Cancer With Right Aortic Arch: A Case Report.

BACKGROUND/AIM: Right aortic arch (RAA) is a rare abnormality of the aortic arch that forms a vascular ring. Oesophageal cancer (EC) accompanied with RAA is even rarer, and in such cases, it is very important to understand the anatomical structure in the upper mediastinum in order to perform a safe and curative operation. PATIENTS AND METHODS: A 67-year-old man who presented with pharyngeal discomfort was admitted to our hospital. Further examinations revealed advanced thoracic EC accompanied with RAA and aortic diverticulum. RESULTS: After neoadjuvant chemotherapy, we successfully and safely performed thoracoscopic oesophagectomy and lymphadenectomy using the prone positioning. CONCLUSION: There exist only a few reports of thoracoscopic oesophagectomy for EC with RAA. Sufficient preoperative preparation and sharing an adequate strategy for the surgical approach with the surgical team are definitely necessary. Although the thoracoscopic approach for EC with RAA is useful, more considerations are needed for some issues.

Relationship Between Toe Muscular Strength and the Ability to Change Direction in Athletes.

This study aimed to investigate the relationship between toe muscular strength and the ability to change direction in athletes. Seventeen collegiate American-football players participated in the study (age 19.9 ± 0.9 years, competition experience 7.3 ± 1.7 years). Two types of measurements were performed to evaluate toe muscular strength: toe flexor strength with the metatarsophalangeal joint in the planter flexed position and toe-pushing force with the metatarsophalangeal joint in the dorsiflexed position. The ability to change direction was evaluated using the pro-agility and 3-cone tests and change of direction deficits, calculated by subtracting the sprint times from the pro-agility and 3-cone times. There were significant correlations between toe-pushing force and the results of the pro-agility and 3-cone tests, but no significant correlations between toe flexor strength and the pro-agility and 3-cone tests. Neither toe-pushing force nor toe flexor strength was significantly correlated with the sprint test results. Furthermore, toe-pushing force was significantly correlated with the 3-cone test deficit, but toe flexor strength was not. The ability to change direction is more strongly affected by toe muscular strength (measured as toe-pushing force) with the metatarsophalangeal joint in the dorsiflexed angle than by toe muscular strength (measured as toe flexor strength) with the metatarsophalangeal joint in the plantar flexed angle. Our results suggest that athletes can improve their ability to change direction with toe muscular strength training with the metatarsophalangeal joint in the dorsiflexed position.

The effects of the herbal medicine Daikenchuto (TJ-100) after esophageal cancer resection, open-label, randomized controlled trial.

BACKGROUND: Daikenchuto (TJ-100), a traditional Japanese herbal medicine, is widely used in Japan. Its effects on gastrointestinal motility and microcirculation and its anti-inflammatory effect are known. The purpose of this prospective randomized controlled trial was to investigate the effect of TJ-100 after esophagectomy in esophageal cancer patients. METHODS: Forty patients for whom subtotal esophageal resection for esophageal cancer was planned at our institute from March 2011 to August 2013 were enrolled and divided into two groups at the point of determination of the operation schedule after informed consent was obtained: a TJ-100 (15 g/day)-treated group (n = 20) and a control group (n = 20). The primary efficacy end-points were maintenance of the nutrition condition and the recovery of gastrointestinal function. The secondary efficacy end-points were the serum C-reactive protein (CRP) level and adrenomedullin level during the postoperative course, the incidence of postoperative complications, and the length of hospital stay after surgery. RESULTS: We examined 39 patients because one patient in the TJ-100 group was judged as having unresectable cancer after surgery. The mean age of the TJ-100 group patients was significantly older than that of the control group patients.The rate of body weight decrease at postoperative day 21 was significantly suppressed in the TJ-100 group (3.6% vs. the control group: 7.0%, p = 0.014), but the serum albumin level was not significantly different between the groups. The recovery of gastrointestinal function regarding flatus, defecation, and oral intake showed no significant between-group differences, but postoperative bowel symptoms tended to be rare in the TJ-100 group. There was no significant between-group difference in the length of hospital stay after surgery. The serum CRP level at postoperative day 3 was 4.9 mg/dl in the TJ-100 group and 6.9 mg/dl in the control group, showing a tendency of a suppressed serum CRP level in the TJ-100 group (p = 0.126). The rate of increase in adrenomedullin tended to be high postoperatively, but there was no significant difference between the two groups. CONCLUSIONS: TJ-100 treatment after esophageal cancer resection has the effects of prompting the recovery of gastrointestinal motility and minimizing body weight loss, and it might suppress the excess inflammatory reaction related to surgery.

Multicenter phase II study of trastuzumab plus S-1 alone in elderly patients with HER2-positive advanced gastric cancer (JACCRO GC-06).

BACKGROUND: S-1 plus cisplatin is a standard regimen for advanced gastric cancer (AGC) in Asia. The ToGA trial established a fluoropyrimidine plus cisplatin and trastuzumab as a standard treatment for human epidermal growth factor receptor 2 (HER2)-positive AGC. In the HERBIS-1 trial, trastuzumab combined with S-1 plus cisplatin showed promising antitumor activity in patients with HER2-positive AGC. However, cisplatin has several important drawbacks, including vomiting and renal toxicity. These disadvantages of cisplatin are prominent in elderly patients. Therefore, we conducted a prospective phase II study of trastuzumab plus S-1 without cisplatin in elderly patients with HER2-positive AGC. METHODS: Patients 65 years or older who had HER2-positive AGC received S-1 orally on days 1-28 of a 42-day cycle and trastuzumab intravenously on day 1 of a 21-day cycle. RESULTS: A total of 51 patients were enrolled. Two patients were ineligible. The full analysis set thus comprised 49 patients. The median age was 71 years (range 65-85). The confirmed response rate was 40.8% (95% CI 27.1-54.6%), and the null hypothesis was rejected. The median follow-up period was 10.6 months. Median overall survival was 15.8 months. Median progression-free survival was 5.1 months, and time to treatment failure was 4.0 months. Major grade 3 or 4 adverse events included neutropenia (12.0%), anemia (24.0%), diarrhea (10.0%), and anorexia (12.0%). There was one treatment-related death. CONCLUSIONS: Trastuzumab in combination with S-1 alone demonstrated promising antitumor activity and manageable toxic effects as well as promising survival results in elderly patients with HER2-positive AGC. CLINICAL TRIALS REGISTRATION: UMIN000007368.

Correction to: Multicenter phase II study of trastuzumab plus S-1 alone in elderly patients with HER2-positive advanced gastric cancer (JACCRO GC­06).

The correct name of the twelfth author should be ''Yasuhiro Yuasa", and not ''Yasuhiko Yuasa'' as given in the original publication of the article.

CXCR4 Expression is Associated with Poor Prognosis in Patients with Esophageal Squamous Cell Carcinoma.

BACKGROUND: Chemokines and their receptors are known to play important roles in the tumorigenesis of many malignancies. The chemokine CXCL12 and its receptors CXCR4 and CXCR7 were suggested to be involved in cancer invasion and metastasis. The aim of this retrospective study was to evaluate the prognostic impact of the expressions of CXCL12, CXCR4 and CXCR7 in patients with esophageal squamous cell carcinoma (ESCC). METHODS: We used immunohistochemistry (IHC) and reverse transcriptase-polymerase chain reaction (RT-PCR) to evaluate the expressions of CXCL12, CXCR4, and CXCR7 in ESCC patients' tumor biopsy specimens obtained during preoperative endoscopy or surgery. These results were compared with the patients' clinicopathological parameters and survival. RESULTS: IHC was conducted for 172 patients. High expression of CXCR4 in the cytoplasm and nuclei and that of CXCR7 were associated with poor cause-specific survival (CSS) (P= .002 and .010, respectively). The specimens from 52 of the 172 patients were examined by RT-PCR and quantitative real-time PCR. The expression levels of messenger RNA (mRNA) of CXCR4 and CXCR7 were significantly increased in the tumors compared with normal esophageal mucosae (P < .0001). The expression level of mRNA of CXCR4 was associated with poor recurrence-free survival and CSS (P = .012 and .038, respectively). CONCLUSIONS: CXCR4 expression is associated with poor prognosis in patients with ESCC.

Risk Factors for Injury Among Japanese Collegiate Players of American Football Based on Performance Test Results.

Iguchi, J, Watanabe, Y, Kimura, M, Fujisawa, Y, Hojo, T, Yuasa, Y, Higashi, S, and Kuzuhara, K. Risk factors for injury among Japanese collegiate players of American football based on performance test results. J Strength Cond Res 30(12): 3405-3411, 2016-The purpose of this study was to identify how risk factors for injury during American football are related to players' physical strength as determined using typical performance tests. One hundred 53 Japanese collegiate players of American football were recruited for this study. Eight potential risk factors were evaluated: position (skill vs. lineman), body mass index, back squat one-repetition maximum, vertical jump height, power, height, body weight, and previous injury. Using multivariate Cox regression, we examined how these factors were associated with knee sprain, ankle sprain, and hamstring strain. We recorded 63 injuries (17 knee sprains, 23 ankle sprains, and 23 hamstring strains). Players with higher power were at significantly greater risk for knee sprains (p = 0.04), those with low power had a significantly higher incidence of ankle sprain (p = 0.01), and vertical jump height was a significant predictor of hamstring strain (p = 0.02). We identified several independent predictors of injuries associated with American football. Our findings may contribute to the development of effective screening tests and prevention exercises.

Mesh-Airtight-Preperitoneum: a simple method for confirming mesh placement in transabdominal preperitoneal repair of inguinal hernia.

We devised a method for confirming the position of mesh placed during transabdominal preperitoneal repair (TAPP) of an inguinal hernia. The preperitoneum is sufficiently detached, and the mesh is fixed in place as usual. Before completely closing the peritoneum, pressure is applied from outside the body and inside the abdominal cavity to remove as much air as possible from the detached preperitoneum; the peritoneum is then sutured using a V-Loc(TM) closure device so that it does not constrict. By releasing the pressure all at once, the airtightness of the preperitoneum is maintained, and the position of the mesh can be observed through the translucent peritoneum. This method, called Mesh-Airtight-Preperitoneum (MAPP), could become widely used as a simple technique for confirming mesh position in TAPP. J. Med. Invest. 63: 270-273, August, 2016.