ypN0 in Patients With Definitive cN-positive Status After Preoperative Treatment Is a Prognostic Factor in Esophageal Cancer.

BACKGROUND: Histopathological tumor regression grade is applied not to lymph nodes but primary tumors modified by preoperative treatments. This study focused on patients whose pathological examination at the time of surgery showed no residual tumor after chemo(radio)therapy in the primary lesion (ypT0) or lymph nodes (ypN0). PATIENTS AND METHODS: A total of 87 patients with clinical stage II/III thoracic esophageal cancer underwent esophagectomy following preoperative treatments to evaluate significances between pathological response and clinical outcomes; 51 patients with clinically definitive lymph node metastasis (cN+) were analyzed as a subgroup. RESULTS: ypT0 rates were 20.7% and 23.5%, and ypN0 rates were 47.1% and 27.5% in the whole cohort and in the cN+ subgroup, respectively. Disease-free survival, from surgery to relapse or death, was significantly influenced by ypN status (p=0.035) but not by ypT status in the 51 patients with definitive cN+ disease. Preoperative chemoradiation was an independent favorable factor for achievement of ypN0 in the 51 patients (odds ratio=0.09; p=0.007). CONCLUSION: ypN status was a predictive factor for DFS in patients treated with docetaxel plus low-dose 5-fluorouracil and cisplatin combined chemotherapy, superior to ypT status, especially in patients with definitive cN+ disease.

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.

Hyperglycemia and subsequent torsades de pointes with marked QT prolongation during refeeding.

OBJECTIVE: A fatal cardiac complication can occasionally present in malnourished patients during refeeding; this is known as refeeding syndrome. However, to our knowledge, hyperglycemia preceding torsades de pointes with QT prolongation during refeeding has not been reported. In the present study, we present a case in which hyperglycemia preceded torsades de pointes with QT prolongation during refeeding. The aim of this study was to determine the possible mechanism underlying QT prolongation during refeeding and indicate how to prevent it. METHODS: A 32-y-old severely malnourished woman (body mass index 14.57 kg/m2) was admitted to the intensive care unit of our institution after resuscitation from cardiopulmonary arrest due to ventricular fibrillation. She was diagnosed with anorexia nervosa. Although no obvious electrolyte abnormalities were observed, her blood glucose level was 11 mg/dL. A 12-lead electrocardiogram at admission showed sinus rhythm with normal QT interval (QTc 0.448). RESULTS: Forty mL of 50% glucose (containing 20 g of glucose) was intravenously injected, followed by a drip infusion of glucose to maintain blood glucose level within normal range. After 9 h, the patient's blood glucose level increased to 569 mg/dL. However, after 38 h, an episode of marked QT prolongation (QTc 0.931) followed by torsades de pointes developed. CONCLUSIONS: Hyperglycemia during refeeding can present with QT prolongation; consequently, monitoring blood glucose levels may be useful in avoiding hyperglycemia, which can result in QT prolongation. Furthermore, additional monitoring of QT intervals using a 12-lead electrocardiogram should allow the early detection of QT prolongation when glucose solution is administered to a malnourished patient with (severe) hypoglycemia.

Sternoclavicular joint septic arthritis with chest wall abscess in a healthy adult: a case report.

BACKGROUND: Septic arthritis of the sternoclavicular joint is rare. It can be associated with serious complications such as osteomyelitis, chest wall abscess, and mediastinitis. In this report, we describe a case of an otherwise healthy adult with septic arthritis of the sternoclavicular joint with chest wall abscess. CASE PRESENTATION: A 68-year-old Japanese man presented to our hospital complaining of pain and erythema near the right sternoclavicular joint. Despite 1 week of oral antibiotics, his symptoms did not improve. Computed tomography revealed an abscess with air around the right pectoralis major muscle. After being transferred to a tertiary hospital, emergency surgery was performed. Operative findings included necrotic tissue around the right sternoclavicular joint and sternoclavicular joint destruction, which was debrided and packed open. Methicillin-susceptible Staphylococcus aureus was identified in blood and wound cultures. Negative pressure wound therapy and hyperbaric oxygen therapy were performed for infection control and wound healing. The patient's general condition improved, and good granulation tissue developed. The wound was closed using a V-Y flap on hospital day 48. The patient has been free of relapse for 3 years. CONCLUSIONS: Septic arthritis of the sternoclavicular joint is an unusual infection, especially in otherwise healthy adults. Because it is associated with serious complications such as chest wall abscess, prompt diagnosis and appropriate treatment are required.

Intraductally administered pegylated liposomal doxorubicin reduces mammary stem cell function in the mammary gland but in the long term, induces malignant tumors.

Previously, we have shown that the intraductal (i.duc) administration of pegylated liposomal doxorubicin (PLD) to Her2/neu transgenic mice is associated with mammary tumor regression and prevention. Exploring the mechanism underlying the protection afforded by PLD, we studied: the effects of i.duc PLD-treatment with a subsequent pregnancy on outgrowth of tumors in Her2/neu mice; whether the i.duc PLD antitumor effect was mediated partially through changes in normal mammary stem cells (MaSCs); and the long-term safety of i.duc PLD into the normal mouse mammary gland. Her2/neu mice were treated with two i.duc injections of PLD given four weeks apart; pregnancy was induced and mice were followed up for changes in physiology, and tumor formation. We found that all pups born to i.duc PLD-treated Her2/neu mice died without weight gain within 7 days after birth. Despite an additional pregnancy, compared to vehicle control PLD-treated Her2/neu mice had a significantly longer latency and lower frequency of tumor development. Mammary epithelial cells isolated from untreated and i.duc PLD-treated 6-8 months-old multiparous FVB/N mice were analyzed for their repopulating ability in mammary fat pads of naïve recipients. Mice were also monitored for abnormalities in mammary gland morphology and function, including tumor formation. PLD-treated FVB/N mice displayed histomorphologic changes and a significant reduction in the outgrowth potential of cells from the mammary glands. Thus, i.duc PLD administration altered the mammary gland structurally and functionally by reducing the MaSC population, which could compromise milk production. Followed long term, i.duc PLD-treated FVB/N mice developed malignant mammary tumors, confirming similar published findings on doxorubicin injected into the mammary gland of rats. Unless there are fundamental species differences in PLD metabolism in rodents and humans, this finding seriously limits the consideration of i.duc PLD use in the clinic for treatment or prevention of breast cancer.

Triterpenes augment the inhibitory effects of anticancer drugs on growth of human esophageal carcinoma cells in vitro and suppress experimental metastasis in vivo.

The antineoplastic effects of combinations of anticancer drugs (5-fluorouracil, irinotecan and cisplatin) and triterpenes (ursolic acid, betulinic acid, oleanolic acid and a Japanese apricot extract (JAE) containing triterpenes) on esophageal squamous carcinoma cells were examined by the WST-8 (2-(2-methoxy- 4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt) assay in vitro and by an animal model in vivo. Triterpenes and JAE showed additive and synergistic cytotoxic effects, respectively, on esophageal squamous carcinoma cells (YES-2 cells) by combinational use of 5-fluorouracil. JAE and 5-fluorouracil induced cell cycle arrest at G2/M phase and at S phase, respectively, and caused apoptosis in YES-2 cells. A new animal model of esophageal cancer causing tumor colonization of the peritoneal cavity and producing bloody ascites was made by injecting YES-2 cells into the peritoneal cavity of a severe combined immunodeficiency mouse. In this model, 5-fluorouracil inhibited colonization of tumor cells in the peritoneum. The addition of JAE to 5-fluorouracil augmented the suppression of experimental metastasis of the peritoneum. The numbers of peritoneal nodules of more than 2 mm in diameter in mice treated with 5-fluorouracil and JAE were less than those in mice treated with 5-fluorouracil alone or JAE alone. These results suggest that triterpenes, especially JAE, are effective supplements for enhancing the chemotherapeutic effect of 5-fluorouracil on esophageal cancer.

Hyperbaric oxygen therapy for radiation-induced hemorrhagic cystitis.

Hyperbaric oxygen (HBO) therapy has recently emerged as a potential primary option for the management of hemorrhagic cystitis. We review our experience treating hemorrhagic cystitis with HBO. Between January 2001 and May 2007, eight patients with radiation-induced hemorrhagic cystitis underwent HBO therapy. There were five men and three women with a mean age of 64.3 years (47-73). Radiation was given for local disease, and the mean dosage delivered was 56.6 Gy (42-70). The mean duration between the onset of hematuria and the beginning of HBO therapy was 8.9 months (3-34). Mean follow-up period was 15.5 months (2-31). Hematuria resolved completely in six of the eight patients, one of whom suffered recurrence of hematuria and was treated with HBO until the hematuria resolved again. The response rate was 75%, compatible with the previous reports, and no side-effects of HBO were noted. HBO treatment should be attempted for radiation-induced hemorrhagic cystitis.