Clinical effect of home enteral tube feeding supplementation on nutritional status after esophagectomy with retrosternal gastric tube reconstruction.

Body weight loss and poor nutritional status are frequently observed after esophageal cancer surgery. The aim of this study was to pilot an investigation on the impact of home enteral tube feeding supplementation (HES) for up to 3 months after esophageal cancer surgery. We retrospectively reviewed consecutive 67 esophageal cancer patients who underwent esophagectomy with gastric tube reconstruction. We started HES from April 2017. The patients were divided into 2 groups. Among 67 patients, 40 patients underwent HES between April 2017 and November 2020 (HES group). Other 27 patients who underwent esophagectomy between January 2012 and March 2017 were not administered HES (C group). Thereafter, multiple factors concerning patient nutritional status at long-term follow-up were evaluated. The baseline characteristics were balanced between the two groups. There were no significant differences in nutritional status scores before esophagectomy. The percentage weight loss was less in the HES group compared with the C group both at 3 months and 1 year after surgery: 7.3% (-7.6 to 15.2), 7.7% (-4 to 13.9) in the HES group and 10.6% (-3.6 to 29.1), 10.8% (-5.8 to 20.0) in C group (P < 0.05, P < 0.05). In the patients with anastomotic stenosis, the percentage weight loss was less in the HES group compared with the C group: 7.2% (2.0-14.9) and 14.6% (6.2-29.1), P < 0.05. HES may improve early weight loss in postesophagectomy patients.

Postoperative analgesic effect of ultrasound-guided rectus sheath block and local anesthetic infiltration after laparoscopic cholecystectomy: Results of a prospective randomized controlled trial.

INTRODUCTION: Even if laparoscopic cholecystectomy (LC) has lower invasiveness through small incisions compared with laparotomy, postoperative pain control is important. METHODS: This prospective, randomized, single-blinded, interventional, single-center study was conducted from December 2016 to March 2018 at the Shiga University of Medical Science Hospital in Japan. Enrolled patients were assigned to either a rectus sheath block (RSB) group or an infiltrative local anesthesia (LA) group. After LC, the RSB group received bilateral RSB with 10 mL of 0.375% ropivacaine and the LA group received subcutaneous and fascial injection with 10 mL of 0.75% ropivacaine at the umbilical wound. The primary endpoint was a visual analog scale (VAS) score on postoperative day (POD) 1. RESULTS: This study enrolled 62 patients (RSB group = 31, LA group = 31). On POD1, the mean VAS scores were 36.4 ± 18.9 and 29.4 ± 15.4 in the RSB group and LA groups, respectively, showing that the LA group tended to describe lesser postoperative pain than the RSB group (P = 0.062). CONCLUSIONS: VAS scores on POD1 were not different between the groups. LC patients might obtain postoperative pain control via long-acting local analgesia.

Sorafenib exposure and its correlation with response and safety in advanced hepatocellular carcinoma: results from an observational retrospective study.

PURPOSE: Severe adverse events frequently occur in patients treated with sorafenib, whereas some patients have suboptimal response to sorafenib. We aimed to evaluate the association of sorafenib-induced toxicities and clinical outcomes with the pharmacokinetics of sorafenib in patients with hepatocellular carcinoma (HCC). METHODS: This was a retrospective, observational study in which 26 HCC patients who had been treated with sorafenib were enrolled between September 2010 and March 2015. The association between trough sorafenib concentration and occurrence of grade ≥ 3 toxicities was evaluated. In addition, we estimated the association of trough sorafenib concentration with overall survival (OS). RESULTS: The median sorafenib concentration was 2.91 µg/mL (range 0.74-8.8 µg/mL). Based on the receiver operating characteristic curve, the threshold value of the trough sorafenib concentration for predicting grade ≥ 3 toxicities and responder (complete response or partial response at best response, or stable disease for ≥ 3 months) was 3.45 µg/mL [area under the curve (AUC) 0.74, 95% confidence interval (CI) 0.54-0.93; p <0.05] and 1.40 µg/mL (AUC 0.97, 95% CI 0.97-1.00; p <0.05), respectively. OS of patients with sorafenib 1.40-3.45 µg/mL had a tendency to be longer than those of patients administered < 1.40 µg/mL and ≥ 3.45 µg/mL [median 17.8 months (1.40-3.45 µg/mL) vs. 5.3 months (< 1.40 µg/mL) and 9.5 months (≥ 3.45 µg/mL)]. CONCLUSIONS: From results of this study, we proposed that the target range of sorafenib may be a trough concentration of 1.40-3.45 µg/mL in patients with HCC.

Acceleration of small bowel motility after oral administration of dai-kenchu-to (TJ-100) assessed by cine magnetic resonance imaging.

Dai-kenchu-to (TJ-100) is an herbal medicine used to shorten the duration of intestinal transit by accelerating intestinal movement. However, intestinal movement in itself has not been evaluated in healthy volunteers using radiography, fluoroscopy, and radioisotopes because of exposure to ionizing radiation. The purpose of this study was to evaluate the effect of TJ-100 on intestinal motility using cinematic magnetic resonance imaging (cine MRI) with a steady-state free precession sequence. Ten healthy male volunteers received 5 g of either TJ-100 or lactose without disclosure of the identity of the substance. Each volunteer underwent two MRI examinations after taking the substances (TJ-100 and lactose) on separate days. They drank 1200 mL of tap water and underwent cine MRI after 10 min. A steady-state free precession sequence was used for imaging, which was performed thrice at 0, 10, 20, 30, 40, and 50 min. The bowel contraction frequency and distention score were assessed. Wilcoxon signed-rank test was used, and differences were considered significant at a P-value <0.05. The bowel contraction frequency tended to be greater in the TJ-100 group and was significantly different in the ileum at 20 (TJ-100, 8.95 ± 2.88; lactose, 4.80 ± 2.92; P < 0.05) and 50 min (TJ-100, 9.45 ± 4.49; lactose, 4.45 ± 2.65; P < 0.05) between the groups. No significant differences were observed in the bowel distention scores. Cine MRI demonstrated that TJ-100 activated intestinal motility without dependence on ileum distention.

5-fluorouracil combined with cisplatin and mitomycin C as an optimized regimen for hyperthermic intraperitoneal chemotherapy in gastric cancer.

BACKGROUND AND OBJECTIVES: Optimized drug regimens for hyperthermic intraperitoneal chemotherapy (HIPEC) have not been standardized completely in patients with advanced gastric cancer (GC). We evaluated an optimized anti-tumor protocol comprising 5-fluorouracil (5-FU) combined with cisplatin (CDDP) and mitomycin C (MMC) in vitro for clinical use of HIPEC. METHODS: The sensitivities of 5-FU, CDDP, or MMC, alone or in combination, using different drug concentrations, exposure times, and hyperthermic conditions (42°C) were determined in vitro by the CD-DST method using 3 different differentiated GC cell lines. RESULTS: The tumor cell growth-inhibitory effect of 5-FU was concentration-dependent for all cell lines. In addition, 5-FU showed a hyperthermic sensitization effect at all drug concentrations for all cell lines. The appropriate concentration of each drug was 5-FU, 200 µg/mL; CDDP, 10 µg/mL; MMC, 2 µg/mL. Under hyperthermic conditions, most growth-inhibitory effects for each drug at 30 min was equivalent to 60 min of exposure; use of three drugs combined significantly inhibited growth compared with any of the drugs alone. CONCLUSION: An appropriate in vitro intraperitoneal chemotherapy regimen for GC was combined use of 5-FU, CDDP, and MMC at 42°C for 30 min.

Feasibility and safety of hyperthermic intraperitoneal chemotherapy using 5-fluorouracil combined with cisplatin and mitomycin C in patients undergoing gastrectomy for advanced gastric cancer.

BACKGROUND AND OBJECTIVES: We conducted a dose-finding study for 5-fluorouracil (5-FU) administered with cisplatin (CDDP) and mitomycin C (MMC) to find an improved regimen for hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer (GC). METHODS: The appropriate HIPEC regimen previously determined in vitro was 5-FU (200 µg/mL), MMC (2 µg/mL), and CDDP (10 µg/mL) at hyperthermic conditions (42°C) for 30 min. This was a clinical study to determine the recommended dose of 5-FU in combination with MMC and CDDP at 42°C for 30 min and to evaluate HIPEC safety in patients at high risk of developing peritoneal metastases following GC surgery. RESULTS: Twelve patients were treated with surgery plus HIPEC using 5-FU at 0, 500, 750, and 1000 mg combined with MMC (10 mg) and CDDP (50 mg) in the perfusate (5 L). Dose-limiting toxicities did not develop until 1000 mg 5-FU was reached. Four patients experienced grade 1 or 2 adverse events. The recommended dose was 1000 mg 5-FU/5 L perfusate. Eight (66.7%) patients demonstrated no recurrence of peritoneal metastases; 5-year overall survival rate was 83.3%. CONCLUSION: Gastrectomy and HIPEC with MMC, CDDP, and 5-FU is feasible, safe, and may protect against peritoneal metastasis following surgery for advanced GC.

[Clinical Evaluation of Hyperthermic Intraperitoneal Chemotherapy(HIPEC)in Colorectal Cancer Patients at High Risk of Peritoneal Recurrence].

PURPOSE: We herein report the clinical outcomes of hyperthermic intraperitoneal chemotherapy(HIPEC)in patients at high risk of colorectal peritoneal metastasis. PATIENTS AND METHODS: We enrolled 21 patients with advanced colorectal cancer who were received HIPEC between 2009 and 2014. Retrospectively, we evaluated the short-term and long-term outcomes of these cases. RESULTS: We performed HIPEC for 12 patients with primary cancer and 9 with recurrent cancer. Perioperative complications characteristic of HIPEC did not occur. Seventeen patients(81%)had postoperative recurrence, 5 of whom had a peritoneal recurrence, and all of them already had synchronous peritoneal metastasis at the time of HIPEC. Patients with a higher peritoneal cancer index(PCI)had a tendency towards a higher rate of peritoneal recurrence than those with a lower PCI(11[median]vs 4; p=0.08).

[Stage IV Gastric Cancer with Positive Peritoneal Washing Cytology or Peritoneal Dissemination Was Successfully Treated with Gastrectomy and Hyperthermic Intraperitoneal Chemotherapy(HIPEC)Followed by Systemic Chemotherapy - A Report of Two Cases].

Survival of Stage IV gastric cancer is poor. We report 2 cases of Stage IV gastric cancer with positive peritoneal washing cytology or peritoneal dissemination that were successfully treated with gastrectomy and hyperthermic intraperitoneal chemotherapy( HIPEC)followed by systemic chemotherapy. Case 1: A 59-year-old woman. She was diagnosed with advanced gastric cancer and underwent gastrectomy with HIPEC. Her peritoneal washing cytology was positive during the gastrectomy. After the surgery, she underwent chemotherapy consisting of 8 courses of combination S-1 plus CPT-11 and 19 courses of PTX. It has been 5 years and 7 months since she had the surgery and she survives without recurrence of the cancer. Case 2: A 60-year-old woman. She was diagnosed with advanced gastric cancer and peritoneal dissemination(peritoneal cancer index: 3 points). She underwent gastrectomy, hemi-colectomy, and HIPEC. After the surgery, she underwent chemotherapy, 35 courses of combination S-1 plus PSK/DOC, and 13 courses of S-1 plus PSK. It has been 5 years since her surgery and she survives without exacerbation of the cancer. These cases suggest a gastrectomy and HIPEC followed by systemic chemotherapy may represent an effective treatment for advanced gastric cancer with a small amount of peritoneal metastasis.

[Salvage Surgery after CRT for Advanced Esophageal Cancer Resulting in a Pathological Complete Response and More Than Five Years' Survival].

A 62-year-old woman visited our hospital because of dysphagia. She was diagnosed with upper-middle esophageal type 4 cancer, which was 9 cm in length, according to the results of endoscopy. Squamous cell carcinoma was demonstrated using endoscopic biopsy. A CT scan revealed that the tumor had directly invaded into the trachea(cT4). Chemoradiotherapy(CRT) (5-FU and CDDP with 50 Gy of radiation)was administered. Although CT after CRT resulted in shrinkage of the tumor and no further tracheal invasion, esophageal stenosis remained. Therefore, salvage surgery(subtotal esophagectomy with 3-field lymph node dissection)was performed. Pathologically, no carcinoma cells were found in the resected specimen and a com- plete response(grade 3)was diagnosed. The patient received adjuvant chemotherapy(tegafur/uracil at 300mg/day per os) for 1 year. The patient is alive with no relapse of carcinoma more than 5 years after the first treatment.

Proposed preoperative risk factors for early recurrence in patients with resectable pancreatic ductal adenocarcinoma after surgical resection: A multi-center retrospective study.

BACKGROUND/OBJECTIVE: Although surgical resection remains the only chance for cure in patients with pancreatic ductal adenocarcinoma (PDAC), postoperative early recurrence (ER) is frequently encountered. The purpose of this study is to determine the preoperative predictive factors for ER after upfront surgical resection. METHODS: Between 2001 and 2012, 968 patients who underwent upfront surgery with R0 or R1 resection for PDAC at seven high-volume centers in Japan were retrospectively reviewed. ER was defined as relapse within 6 months after surgery. Study analysis stratified by resectable (R) and borderline resectable (BR) PDACs was conducted according to the National Comprehensive Cancer Network guidelines. RESULTS: ER occurred in 239 patients (25%) with a median survival time (MST) of 8.8 months. Modified Glasgow prognostic score = 2 (odds ratio (OR) 2.06, 95% confidence interval (CI) 1.05-3.95; P = 0.044), preoperative CA19-9 ≥300 U/ml (OR 1.94, 1.29-2.90; P = 0.003), and tumor size ≥30 mm (OR 1.72, 1.16-2.56; P = 0.006), were identified as preoperative independent predictive risk factors for ER in patients with R-PDAC. In the R-PDAC patients, MST was 35.5, 26.3, and 15.9 months in patients with 0, 1 and ≥2 risk factors, respectively. There were significant differences in overall survival between the three groups (P < 0.001). No preoperative risk factors were identified in BR-PDAC patients with a high rate of ER (39%). CONCLUSIONS: There is a high-risk subset for ER even in patients with R-PDAC and a simple risk scoring system is useful for prediction of ER.

Successful surgical approach for a patient with encapsulating peritoneal sclerosis after hyperthermic intraperitoneal chemotherapy: a case report and literature review.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a rare surgical complication that can occur after intraperitoneal treatment. It is also a serious and potentially fatal complication of continuous ambulatory peritoneal dialysis. The present report describes a case of surgically treated EPS that probably occurred as a complication of hyperthermic intraperitonal chemotherapy (HIPEC). CASE PRESENTATION: A 39-year-old man required sigmoidectomy for serosal invasive advanced sigmoid colon cancer. HIPEC with oxaliplatin, 5-fluorouracil and mitomycin C were given as adjuvant therapy. Subsequently, intestinal obstruction developed at 15 months postoperatively, and the patient was hospitalized. Abdominal computed tomography showed a dilated small intestine enveloped by a thickened membrane. We found no evidence of peritoneal recurrence, but exploratory surgery revealed EPS, probably caused by HIPEC. We peeled the capsule off of the intestine. The patient's postoperative course was uneventful, and sufficient nutritional intake after surgery was noted. Seven months after surgery, he is well with no recurrence. CONCLUSION: The surgical treatment via peritonectomy and enterolysis for postoperative EPS appears safe and effective. A diagnosis of EPS should be considered when intestinal obstruction does not show improvement with conservative treatment in patients who have undergone HIPEC, provided the possibility of peritoneal cancer recurrence is excluded.

Recent trends in hepatectomy for elderly patients with hepatocellular carcinoma.

PURPOSE: The incidence of hepatocellular carcinoma (HCC) in the elderly population has recently been increasing. In this study, we focused on a recent 10-year survey, and compared the clinicopathological features and postoperative outcomes of HCC in elderly (≥75 years of age) and younger patients (<75 years of age). METHODS: A total of 255 patients who underwent hepatectomy for HCC from 2001 to 2010 at Wakayama Medical University Hospital were reviewed. The clinical characteristics were compared between the elderly and younger patients. The risk factors for postoperative complications and prognostic factors were identified using the multivariate analyses. RESULTS: A total of 66 patients were classified as elderly patients. The incidence of HCC without viral liver disorders was significantly high in the elderly group than in the younger group. The independent risk factors [odds (95% confidence intervals)] for postoperative complications were an ASA score of 3 [2.57 (1.20-5.49)] and the length of the operation [1.41 (1.09-1.81)]. The survival was similar between the two groups, and the only independent prognostic factor for survival in the elderly patients was vessel invasion. CONCLUSIONS: HCC derived from non-viral liver disorders was dominant in the elderly patients. Aging itself was not a risk factor for postoperative complications or the survival outcome.

[Multidisciplinary therapy for pancreatic cancer - clinical impact for preoperative therapy and peptide vaccine therapy].

Pancreatic cancer survival is poor for those with high-grade malignancy, so multidisciplinary therapy is required for pancreatic cancer patients. Borderline resectable pancreatic cancer patients, according to the National Comprehensive Cancer Net- work(NCCN), have a high incidence of R1/2 resection, which demonstrates poor survival. It is thought that not only postoperative therapy but also preoperative therapy is essential to improve the survival of advanced pancreatic cancer patients. Preoperative chemoradiotherapy leads to R0 resection, resulting in improved survival of borderline resectable pancreatic cancer patients. Metastatic disease survival might be improved by intensive chemotherapy, and super-responder chemotherapy might be performed for resection, which means the new concept of adjuvant chemotherapy. On the other hand, antigenspecific CD8-positive CTL is generated by stimulation of peptide. Three clinical trials are on-going using OCV-101, OCV-105, and OTS-102, respectively. The development of a peptide vaccine used as a medicine is anticipated.

Adjuvant chemolipiodolization reduces early recurrence derived from intrahepatic metastasis of hepatocellular carcinoma after hepatectomy.

BACKGROUND: The recurrence of hepatocellular carcinoma is still high even after surgery. Two general recurrence patterns occur: intrahepatic metastasis (IM) and multicentric carcinogenesis (MC). The aim of this study was to investigate the effectiveness of adjuvant chemolipiodolization for reducing IM or MC recurrences after surgery. METHODS: A retrospective case-control study was carried out. From April 2005, adjuvant chemolipiodolization was performed in 63 initial hepatocellular carcinoma patients 3 months after surgery. Sixty-four patients who underwent surgery between April 2001 and March 2005 were analyzed as the control group. Recurrence-free and overall survival as well as prognostic factors were analyzed univariately and multivariately. RESULTS: The 2-year recurrence-free survival was 57% in the chemolipiodolization group and 37% in the control group (P = 0.02). However, there was no significant difference at 5 years after surgery (P = 0.09). The 5-year overall survival rates in the chemolipiodolization and the control groups were 82.4 and 55.7%, respectively (P = 0.04). Cox proportional multivariate analysis revealed that adjuvant chemolipiodolization was an independent favorable prognostic factor for 2-year recurrence-free survival, and the odds ratio [95% confidential interval] was 0.55 [0.34-0.90] (P = 0.02). However, adjuvant chemolipiodolization was not an independent favorable prognostic factor for 5-year overall survival. CONCLUSIONS: Adjuvant chemolipiodolization can reduce the risk of early recurrences, which would be mainly IM derived. However, chemolipiodolization did not reduce late phase recurrences after surgery, which would be mainly MC derived. To prevent late phase recurrences, another novel strategy would be needed.

Liver metastasis as an initial recurrence has no impact on the survival of patients with resectable pancreatic adenocarcinoma.

BACKGROUND: Prognosis of the patients with pancreatic adenocarcinoma is still poor due to a recurrence, and liver metastasis is a distant metastasis that is foreboded the short survival period. METHODS: Between 1999 and 2005, 68 patients for pancreatic adenocarcinoma underwent a pancreaticoduodenectomy (n = 17), a pylorus-preserving pancreaticoduodenectomy (n = 27), distal pancreatectomy (n = 22), or total pancreatectomy (n = 2) with an extensive lymph node dissection. RESULTS: A tumor recurrence occurred to 55 patients (13 of the liver, 21 of the local recurrence, 16 of peritoneal dissemination, three of the lymph node, and two of lung). The low tumor grade and female demonstrated a risk factor for a liver metastasis (P = 0.043, P = 0.031). A logistic regression analysis demonstrated female (P = 0.02) and low tumor grade (P = 0.04) as independent risk factors for recurrence with liver metastasis. The median survival time (MST) was 13.6 months, and MST of patients with a liver metastasis as an initial recurrent site was 13.7 months; the liver metastasis as an initial recurrent site has no impact on the MST after pancreatic resection. CONCLUSIONS: We concluded potentially supporting the hypothesis that even patients thought to be at higher risk of liver metastasis may still be given the chance of resection, considering the satisfying survival.

Clinical efficacy of doxifluridine and correlation to in vitro sensitivity of anticancer drugs in patients with colorectal cancer.

UNLABELLED: We examined thymidine phosphorylase (TP) expression and sensitivity to anticancer drugs and compared the findings with the efficacy of 5'-deoxy-5-fluorouridine (5'-DFUR), an intermediate metabolite of capecitabine. PATIENTS AND METHODS: Patients were enrolled in this study from January 1995 to June 1998 for stages II-III colorectal cancer with curative resection. We conducted sensitivity tests of tumor tissue to 5'-DFUR and 5-fluorouracil (5-FU) using the MTT method, and measured tumor tissue TP levels using enzyme-linked immunosorbent assay (ELISA). From 2 weeks postoperatively, the patients were given oral 5'-DFUR 800 mg/m2/day (5 days administration followed by 2 days discontinuation) for one year and they were followed for 3 years postoperatively. RESULTS: Of 139 patients registered, 124 were analyzed for the present study. The median 5'-DFUR administration was 362 days and the median total dose was 245.0 g. We compared prognoses in patients with positive and negative 5-FU sensitivity test results. There was a significantly better prognosis in 5-FU sensitivity-positive patients with stage III than that in the sensitivity-negative patients (p = 0.041). We also compared prognoses in patients with positive and negative 5'-DFUR sensitivity test results. There was no significant difference in cases with a cut-off value of 50% (p = 0.055), although patients with 5'-DFUR-positive-sensitivity tended to show longer survival. Patients with stage II and higher TP levels tended to have longer survival than those with lower TP expression, but there was no significant difference between groups (p = 0.087). The prognosis of patients with 5-FU-positive sensitivity and higher TP levels, the positive group, tended to have longer survival than in the negative group, but there was no significant difference between groups (p = 0.083). CONCLUSION: 5'-DFUR sensitivity test results and TP values may predict the clinical effects of this drug in colorectal cancer.