Novel candidate factors predicting the effect of S-1 adjuvant chemotherapy of pancreatic cancer.

The collagen gel droplet-embedded drug sensitivity test (CD-DST) was revealed to be useful for predicting the effect of S-1 adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDAC). However, collection of an adequate number of PDAC cells is difficult due to the surrounding fibroblasts. Thus, the aim of this study was to discover novel biomarkers to predict chemosensitivity based on the CD-DST results. Proteomics analysis was performed using liquid chromatography tandem mass spectrometry (LC-MS/MS). Candidate proteins were validated in patients with 5-FU CD-DST results via immunohistochemistry (IHC). The relationships between the candidate proteins and the effect of the adjuvant S-1 were investigated via IHC. Among the 2696 proteins extracted by LC-MS/MS, C1TC and SAHH could accurately predict the CD-DST results. Recurrence-free survival (RFS) was significantly improved in the IHC-positive group compared with the IHC-negative group in both factors. The negative group did not show a significant difference from the group that did not receive S-1. The double-positive group was associated with significantly prolonged RFS compared to the no adjuvant chemotherapy group. C1TC and SAHH have been shown to be useful biomarkers for predicting 5-FU sensitivity as a substitute for the CD-DST in adjuvant chemotherapy for PDAC.

[A Case of Curative Resection after Neoadjuvant Chemotherapy for Locally-Advanced Sigmoid Colon Carcinoma with Urinary Bladder Invasion].

A 56-year-old man was referred to our hospital for multidisciplinary treatment of advanced sigmoid colon carcinoma with a suspected bladder invasion. The patient received 8 courses of modified Leucovorin, fluorouracil, and oxaliplatin (mFOLFOX6)plus panitumumab as neoadjuvant chemotherapy for reliable and safe radical resection after ileostomy construction. There was a significant reduction in the tumor size following chemotherapy; hence, low anterior resection was performed. In addition, since preoperative and intraoperative findings suggested bladder invasion, a total cystectomy with ileal conduit urinary diversion was performed. The pathological diagnosis was ypT4b, N0, M0, and ypStage Ⅱc, with all surgical margins being negative. Subsequently, the patient received adjuvant chemotherapy with 4 courses of mFOLFOX6, and his condition improved with no incidence of cancer recurrence following 8 months after the operation. Neoadjuvant chemotherapy for locally advanced colon cancer is one of the effective treatments for reliable and safe radical resection.

Exploratory study of clinical effectiveness and safety of TJ-116 bukuryoingohangekobokuto for anxiety and postoperative water brash in esophageal cancer patients (TJ116E).

BACKGROUND: Patients with esophageal cancer suffer from anxiety in the perioperative period surrounding esophagectomy; this may increase the risk of postoperative complications. In particular, postoperative aspiration pneumonia carries a high risk of hospital mortality. Bukuryoingohangekobokuto (BRIHK) is a traditional Japanese medicine formula used to treat anxiety, the feeling of a foreign body in the esophagus, and water brash. We hypothesize that BRIHK might be effective for both anxiety and water brash in perioperative patients with esophageal cancer. The aim of this study is to evaluate the efficacy and safety of BRIHK compared to a placebo for anxiety and water brash in perioperative esophageal cancer patients. METHOD/DESIGN: This will be a single-center, single blind, placebo-controlled randomized clinical trial. Twenty-four patients with esophageal cancer undergoing radical resection surgery will be registered to participate, then randomly and blindly assigned to the BRIHK treatment group or control group. Patients will be administered BRIHK or the placebo from 2 weeks before to 6 weeks after surgery. Primary outcome measures will be anxiety and depression (assessed using the Hospital Anxiety and Depression Scale), and water brash (assessed using the 10-item Eating Assessment Tool, Esophagus and Stomach Surgery Symptom Scale, and videofluoroscopy swallowing measurement). Incidences of aspiration pneumonia will be noted and abdominal gas volume, inflammatory markers, and nutrition status will be evaluated. DISCUSSION: This investigative study will provide clinical evidence of BRIHK administration for anxiety and water brash, which might improve mental distress and reduce postoperative mortality. TRIAL REGISTRATION: The protocol and progress are registered on the Japan Registry of Clinical Trials (jRCT s021190001) and University Hospital Medical Information Network (UMIN000031330). The protocol was approved by the Japanese Ministry of Health, Labour and Welfare certified clinical research review board, Tohoku University (CRB2180001).

[A Case of Radically Resected Sigmoid Colon Cancer with Bladder Invasion after Chemotherapy and Weight Loss in an Extremely Obese Patient].

A 30's extremely obese patient(body mass index: BMI 45 kg/m2)was referred to our hospital with a chief complaint of bloody urine and stool. Colonoscopy revealed a sigmoid colon tumor. Barium enema examination revealed stenosis of the sigmoid colon. CT scan showed a tumor in the sigmoid colon, with bladder invasion. The para-aortic lymph node was partially swollen. We considered surgery to be high risk because of the patient's severe obesity. Therefore, we decided to examine the possibility of radical surgery followed by chemotherapy(mFOLFOX6/cetuximab)with weight reduction. Following this, the tumor had shrunk remarkably, and the patient's BMI decreased from 45 kg/m2 to 39 kg/m2. The visceral fat area was reduced from 298 cm2 to 199 cm2 at the umbilical level. We then performed a sigmoid colectomy with partial resection of the bladder. Thus, chemotherapy combined with weight loss enabled us to perform radical surgery safely for a locally advanced sigmoid colon cancer in a patient with severe obesity.

The Influence of the Perioperative Nutritional Status on the Survival Outcomes for Esophageal Cancer Patients with Neoadjuvant Chemotherapy.

BACKGROUND: Studies have shown a variety of nutritional indices to be prognostic predictors for esophageal cancer patients. However, which nutritional index should be used and when it should be measured during the perioperative period remain unclear. This study attempted to clarify the details surrounding predictive nutritional evaluation by assessing the longitudinal data of serologic indices in perioperative esophageal cancer patients. METHODS: The study included 141 esophageal cancer patients who underwent neoadjuvant chemotherapy after radical esophagectomy at Tohoku University Hospital from April 2008 to December 2017. The nutritional status was retrospectively assessed during the perioperative period, and the prognostic factors related to survival were analyzed. RESULTS: Use of the controlling nutritional status (CONUT) score showed that malnutrition occurred only from 14 days after surgery in most cases. Use of the prognostic nutritional index (PNI) showed that the ratio of malnutrition increased gradually from presurgery to 14 days after surgery. The timing of malnutrition that affected survival was 14 days after surgery with the CONUT score and presurgery and 4 months after surgery with the PNI. A multivariable analysis of independent prognostic factors predicting survival identified malnutrition 14 days after surgery with the CONUT score and a low PNI before surgery, invasion depth of the primary lesion, and node metastasis. CONCLUSIONS: Malnutrition occurring during the perioperative state of esophageal cancer was shown to be a survival prognostic factor. Development of an optimal nutritional intervention is recommended for esophageal cancer patients to prevent malnutrition both before and after surgery.

Collagen gel droplet-embedded culture drug sensitivity test (CD-DST) predicts the effect of adjuvant chemotherapy on pancreatic cancer.

PURPOSE: We evaluated the clinical effectiveness of collagen gel droplet-embedded culture drug sensitivity tests (CD-DSTs) in predicting the efficacy of adjuvant chemo-therapeutic treatments for pancreatic cancer (PC). METHODS: The clinicopathological characteristics and prognoses of 22 PC patients who underwent CD-DST after pancreatectomy at Tohoku University between 2012 and 2016 were analyzed retrospectively. Eligibility criteria were resectable or borderline resectable PC, successful evaluation for 5-fluorouracil sensitivity by CD-DST, treatment with S-1 adjuvant chemotherapy, and no preoperative chemotherapy. RESULTS: The rate of successful evaluation by CD-DST was 52.3% in PC. The optimal T/C ratio, defined as the ratio of the number of cancer cells in the treatment group (T) to that in the control group (C), for 5-fluorouracil was 85% using receiver operating characteristic curve analysis. The sensitive group (T/C ratio < 85%; n = 11) had a better recurrence-free survival rate than the resistant group (T/C ratio ≥ 85%; n = 11; P = 0.029). A Cox proportional hazards regression model demonstrated that sensitivity to 5-fluorouracil was an independent predictor of recurrence on multivariate analysis (hazard ratio 3.28; 95.0% CI 1.20-9.84; P = 0.020). CONCLUSIONS: CD-DSTs helped to predict PC recurrence after S-1 adjuvant chemotherapy.

Evaluation of the impact of psoas muscle index, a parameter of sarcopenia, in patients with esophageal squamous cell carcinoma receiving neoadjuvant therapy.

BACKGROUND: The impact of sarcopenia on digestive cancer is widely known. Muscle mass, defined as the psoas muscle index (PMI), is an important parameter of sarcopenia. However, the relationship between esophageal cancer and PMI has not been fully investigated, especially in patients receiving neoadjuvant therapy. METHODS: To elucidate the influence of the PMI on patients with esophageal squamous cell carcinoma receiving neoadjuvant therapy, the progression of sarcopenia defined by the PMI, the relationship between pretherapeutic/preoperative sarcopenia and patient characteristics, and patient survival were retrospectively investigated in 82 patients with esophageal squamous cell carcinoma who underwent neoadjuvant therapy. RESULTS: The PMI decreased by more than 20 mm2/m2 between the pretherapeutic and preoperative periods in 75.6% of the patients. Pretherapeutic sarcopenia (low PMI) correlated with the pathological therapeutic response, postoperative recurrence, and pretherapeutic body mass index. Neoadjuvant chemoradiotherapy was associated with the progression of sarcopenia. The pretherapeutic sarcopenia group (low PMI) had worse disease-free survival (DFS) than the non-sarcopenia group. Furthermore, pretherapeutic sarcopenia (low PMI) was an independent prognostic risk factor of DFS according to univariate and multivariate analyses. CONCLUSIONS: The PMI may decrease during neoadjuvant therapy, especially during neoadjuvant chemoradiotherapy. Pretherapeutic sarcopenic (low PMI) patients should be followed-up more carefully postoperatively because higher risks of recurrence and poorer rates of disease-free survival are associated with these patients.

Roles of bile acid conjugates and phospholipids in in vitro activation of pancreatic lipase by bear bile and cattle bile.

ETHNOPHARMACOLOGICAL RELEVANCE: Bear bile (BB) originally used as a traditional Chinese medicine has also been adopted in Japan as a traditional home remedy mainly for gastrointestinal problems due to impaired digestion. However, recently, efforts have been made to find alternatives to BB for ecological and ethical reasons. AIMS OF THE STUDY: To find alternatives to BB for facilitating fat digestion, we compared the potency of cattle bile (CB) or synthetic mixtures of major bile components to activate pancreatic lipase with that of BB. MATERIALS AND METHODS: The compositions of bile acid conjugates and phospholipids in BB and CB were determined by high-performance liquid chromatography and thin layer chromatography, respectively. The effects of BB and CB as well synthetic mixtures of bile acid conjugates and phospholipids on pancreatic lipase activity in vitro were examined. RESULTS: BB and CB contained markedly different types and quantities of bile acid conjugates and phospholipids, although the potencies of BB and CB to activate pancreatic lipase were not significantly different. The potency of BB to activate pancreatic lipase was reconstituted by the major bile acid conjugates and phospholipids found in BB. In contrast, only bile acid conjugates found in CB could reconstitute its potency to activate pancreatic lipase. CONCLUSIONS: Our observations indicate that CB or the synthetic mixture of bile components can be used as an alternative to BB for facilitating fat digestion.