Prospective observational study of chemotherapy-induced alopecia after sequential FEC + taxane and the effects of age in breast cancer patients.

BACKGROUND: Chemotherapy-induced alopecia (CIA) is a common and quite distressing adverse effects of chemotherapy. There are few detailed observational studies of CIA or of the impact of age on CIA. We performed a prospective observational study to investigate the prevalence and degree of CIA, including CIA of eyebrows, eyelashes, and body, and we examined patient's recovery from CIA, focusing on age-depending effects. METHODS: We analyzed 68 female Japanese patients with breast cancer (median age 53 years, range 29-76 years) who received perioperative adjuvant chemotherapy with fluorouracil/epirubicin/cyclophosphamide (FEC) and taxane. A questionnaire was administered at the point of chemotherapy completion and 6 and 12 months after chemotherapy completion. RESULTS: CIA occurred in all patients, with severe hair loss irrespective of age. CIA occurred mainly in the scalp but also in the eyebrows, eyelashes, and body for most of the patients. There were significant associations between the patient's age and the onset of hair regrowth in the eyebrows, eyelashes, and body. The onset of eyebrows, eyelash, and body hair growth were significantly shorter in the premenopausal patients. Any hair changes (e.g., thinned diameter, softer texture, curlier structure) were reported by 85.3% of the patients. CONCLUSIONS: Severe CIA occurred in all 68 patients who received FEC and taxane chemotherapy. The present findings provide the first data demonstrating that age was not associated with the degree or incidence of hair loss, but age affected the recovery from CIA. These results contribute more accurate information provision and insights regarding the proper treatment of CIA.

Combination therapy by transarterial injection of miriplatin-iodized oil suspension with radiofrequency ablation (RFA) versus microwave ablation (MWA) for small hepatocellular carcinoma: a comparison of therapeutic efficacy.

PURPOSE: To compare the technical efficacy and complications of the transarterial injection of a miriplatin-iodized oil suspension combined with radiofrequency ablation (RFA) or microwave ablation (MWA) in the treatment of small hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: This retrospective study included 123 HCCs in 101 patients treated with the transarterial injection of a miriplatin-iodized oil suspension and RFA (MPT-RFA) (maximum diameter: 1.5 [Formula: see text] 0.5 cm, range: 0.6-3.0 cm) and 68 HCCs in 49 patients treated with the transarterial injection of a miriplatin-iodized oil suspension and MWA (MPT-MWA) (maximum diameter: 1.6 [Formula: see text] 0.7 cm, range: 0.5-3.0 cm). Technical success was defined as the achievement of an ablative margin of at least 5 mm for each tumor. Technical success, complications, and local tumor progression were compared between the two groups. RESULTS: The initial technical success rate was significantly higher with MPT-MWA (94.1%) than with MPT-RFA (76.4%; P = 0.003). The number of treatment sessions per nodule was significantly lower with MPT-MWA (1.1) than with MPT-RFA (1.3) (P = 0.004). The major complication rates were similar with MPT-RFA (5.8%) and MPT-MWA (2.7%) (P = 0.391). The one-year local tumor progression rate was similar between MPT-RFA (0%) and MPT-MWA (0%) (P = 0.73). CONCLUSION: MPT-MWA may have improved therapeutic efficiency in the treatment of small HCCs.

KPNA2 over-expression is a potential marker of prognosis and therapeutic sensitivity in colorectal cancer patients.

BACKGROUND: Karyopherin α 2 (KPNA2) is a member of the Karyopherin α family and has recently been reported to play an important role in tumor progression. The aim of the current study was to elucidate the clinicopathological significance of KPNA2 over-expression in colorectal cancer (CRC). PATIENTS AND METHODS: KPNA2 expression was evaluated by immunohistochemistry in 122 surgically resected CRC and 13 biopsy specimens obtained at colonoscopy during screening for preoperative hyperthermochemoradiation therapy (HCRT). The association between KPNA2 expression and clinicopathological features and preoperative HCRT efficacy were examined. RESULTS: The high and low KNPA2 expression groups were comprised of 91 (74.6%) and 31 CRC patients, respectively. A significant association was observed between high expression and lymphatic invasion (P = 0.0245). KPNA2 high expression group had decreased overall survival (P = 0.00374). Multivariate analysis demonstrated high KPNA2 expression was independently associated with poor prognosis. Histological examinations revealed 11 (84.6%) and 2 (15.4%) of cases were KPNA2 positive and negative, respectively. Pathological complete response (pCR) was observed in 9.1% of KPNA2-positive cases and 100% of KPNA2-negative cases. CONCLUSION: High KPNA2 expression was found to be associated with poor prognosis and resistance to HCRT.

Effect of long interval between hyperthermochemoradiation therapy and surgery for rectal cancer on apoptosis, proliferation and tumor response.

Neoadjuvant chemoradiotherapy is commonly used to improve the local control and resectability of locally advanced rectal cancer, with surgery performed after an interval of a number of weeks. We have been conducting a clinical trial of preoperative chemoradiotherapy in combination with regional hyperthermia (hyperthermo-chemoradiation therapy; HCRT) for locally advanced rectal cancer. In the current study we assessed the effect of a longer (>10 weeks) interval after neoadjuvant HCRT on pathological response, oncological outcome and especially on apoptosis, proliferation and p53 expression in patients with rectal cancer. Forty-eight patients with proven rectal adenocarcinoma who underwent HCRT followed by surgery were identified for inclusion in this study. Patients were divided into two groups according to the interval between HCRT and surgery, ≤ 10 weeks (short-interval group) and >10 weeks (long-interval group). Patients in the long-interval group had a significantly higher rate of pathological complete response (pCR) (43.5% vs. 16.0%) than patients of the short-interval group. Patients of the long-interval group had a significantly higher rate of down-staging of T-stage (78.3% vs. 36.0%) and relatively higher rate of that of N-stage (52.2% vs. 36.0%) than patients of the short-interval group. Furthermore, apoptosis in the long-interval group was relatively higher compared to that of the short-interval group, without a significant difference in the Ki-67 proliferative index and expression of p53 in the primary tumor. In conclusion, we demonstrated that a longer interval after HCRT (>10 weeks) seemed to result in a better chance of a pCR, a result confirmed by the trends in tumor response markers, including apoptosis, proliferation and p53 expression.

Extracapsular lymph node involvement is associated with colorectal liver metastases and impact outcome after hepatectomy for colorectal metastases.

BACKGROUND: Hepatic resection of metastatic colorectal cancer (CRC) has become the treatment of choice for patients after resection of the primary CRC. However, some patients do not benefit from immediate resection because of rapidly progressive disease. The aim of this study was to examine the prognostic value of extracapsular invasion (ECI) of lymph node (LN) metastasis of CRC with liver metastases following liver resection. METHODS: All patients who underwent resection for CRC with liver metastases between 1995 and 2011 were reviewed. All of those with metastasis from primary CRC were included in this study. Preoperative, intraoperative, and postoperative data, including primary tumor pathology results, were retrospectively reviewed. All resected LNs from primary CRC were re-examined to assess ECI. Associations between clinicopathologic factors, survival, and the nodal findings were evaluated. RESULTS: ECI was identified in 47 (48%) patients. ECI was correlated with the number of positive LNs (p = 0.0022), timing of liver metastasis (p = 0.0238), and number of liver metastases (p = 0.0001). Univariate analysis indicated that the number of positive LNs (p = 0.0014), ECI (p = 0.0203), and adjuvant chemotherapy (p = 0.0423) were significant prognostic factors. Patients with ECI had a significantly worse survival (p = 0.0024) after liver resection than patients with LN-negative and ECI-negative groups. CONCLUSIONS: In patients with hepatic CRC metastases, ECI in regional LNs reflects a particularly aggressive behavior, such as a greater number of liver metastases. In CRC patients with liver metastases, ECI in regional LNs might be correlated with poor prognosis following liver resection.

Tumor response and negative distal resection margins of rectal cancer after hyperthermochemoradiation therapy.

BACKGROUND: The safety of regional hyperthermia has been tested in locally advanced rectal cancer. The aim of this study was to assess the effects of shorter distal margins on local control and survival in rectal cancer patients who were treated with preoperative hyperthermochemoradiation therapy (HCRT) and underwent rectal resection by using the total mesorectal excision (TME) method. PATIENTS AND METHODS: Ninety-three patients with rectal adenocarcinoma who received neoadjuvant HCRT (total radiation: 50 Gy) were included in this study. Surgery was performed 8 weeks after HCRT, and each resected specimen was evaluated histologically. Length of distal surgical margins, status of circumferential margins, pathological response, and tumor node metastasis stage were examined for their effects on recurrence and survival. RESULTS: Fifty-eight (62.4%) patients had tumor regression, and 20 (21.5%) had a pathological complete response. Distal margin length ranged from 1 to 55 mm (median, 21 mm) and did not correlate with local recurrence (p=0.57) or survival (p=0.75) by univariate analysis. Kaplan-Meier estimates of recurrence-free survival and local recurrence for the <10 mm versus ≥10 mm groups were not significantly different. Positive circumferential margins and failure of tumors to respond were unfavorable factors in survival. CONCLUSION: Distal resection margins that are shorter than 10 mm but are not positive appear to be equivalent to longer margins in patients who undergo HCRT followed by rectal resection with TME. To improve the down-staging rate, additional studies are needed.

Cell to cell interaction in clusters enhances thermosensitivity in HT29 human colon cancer cells.

BACKGROUND/AIMS: Tumor cells at high density are considered to be resistant to hyperthermia. Our objective in this study was to investigate hyperthermia sensitivity of clusters, cancer cell aggregation, compared with that of monolayer cells. METHODOLOGY: Colon carcinoma cells HT29 were cultured on poly 2-hydroxyethyl methacrylate-coated dishes for 7 days and the clusters were selected by a 40µm pore filter. To detect the cell reproductive potential, a colony formation assay was performed in HT29 cells from a monolayer and from clusters after exposure to cis-diamino-dichloroplatinum, fluorouracil and/or hyperthermia. Western blotting was used to analyze the induction of heat shock protein expression by hyperthermia. RESULTS: Histological findings of the clusters less than 400µm in diameter showed dividing cells and no secondary central necrosis. Cluster cells were more sensitive to hyperthermia than monolayer cells (p<0.0001). However, cluster formation induced cis-diamino-dichloroplatinum resistance (p<0.0001). The enhancement of hyperthermia sensitivity in clusters was not observed when the cells were heated after dispersion to single cells (p<0.0001). No difference of heat-induced HSP70/72 and HSP27 expression between cluster cells and monolayer cells was found. CONCLUSIONS: Cluster formation induced hyperthermia sensitivity, and cell-to-cell interaction in the clusters might enhance hyperthermia sensitivity.

Effectiveness of intraperitoneal hyperthermo-chemotherapy for malignant peritoneal mesothelioma and estimation of its effect by repeated FDG-PET: a case report.

Malignant peritoneal mesothelioma is a rare neoplasm derived from the peritoneum of the abdominal cavity. Here, we report on a case of malignant peritoneal mesothelioma that expanded aggressively after initial surgery, followed by successful treatment with cytoreductive surgery, intra-abdominal hyperthermo-chemotherapy, to allow the patient to perform daily activities with reduced symptoms. The therapeutic effects were monitored by FDG-PET/CT. The patient, a 55-year-old female, was referred to our hospital with a diagnosis of pelvic tumor. Laparotomy and cytoreductive surgery revealed the diagnosis of malignant mesothelioma. The tumor progressed rapidly in the abdominal cavity, so cytoreduction and intra-abdominal hyperthermo-chemotherapy were performed as strong local therapies. In addition, monthly hyperthermo-chemotherapy was performed. The patient lived for 21 months after the first surgery. Severe bowel obstruction and malignant ascites did not appear. Cancerous pain was controllable throughout this portion of her life. In conclusion, we experienced a case of malignant peritoneal mesothelioma and treated it with hyperthermo-chemotherapy. This treatment helped the patient to maintain daily activities throughout the remainder of her life. Thus, hyperthermo-chemotherapy can be considered an option in the treatment of malignant peritoneal mesothelioma.

Statins restore ischemic limb blood flow in diabetic microangiopathy via eNOS/NO upregulation but not via PDGF-BB expression.

3-Hydroxy-3-methyl-glutaryl CoA reductase inhibitors, or statins, have pleiotropic effects and can protect the vasculature in a manner independent of their lipid-lowering effect. The effectiveness of statins in reducing the risk of coronary events has been shown even in patients with diabetes, and their effects on diabetic complications have been reported. Using a model of severe hindlimb ischemia in streptozotocin-induced diabetic mice (STZ-DM), we investigated the effects and mechanisms of statin therapy in diabetic angiopathy in ischemic hindlimbs. As a result, STZ-DM mice frequently lost their hindlimbs after induced ischemia, whereas non-DM mice did not. Supplementation with statins significantly prevented autoamputation. We previously showed that diabetic vascular complications are caused by impaired expression of PDGF-BB, but statin therapy did not enhance PDGF-BB expression. Statins helped enhance endogenous endothelial nitric oxide (NO) synthase (eNOS) expression. Furthermore, the inhibition of NO synthesis by the administration of N(omega)-nitro-l-arginine methyl ester impaired the ability of statins to prevent STZ-DM mouse limb autoamputation, indicating that the therapeutic effect of statins in hindlimb ischemia in STZ-DM mice occurs via the eNOS/NO pathway. A combination therapy of statins and PDGF-BB gene supplementation was more effective for diabetic angiopathy than either therapy alone. In conclusion, these findings indicate that statin therapy might be useful for preventing intractable diabetic foot disease in patients with diabetic angiopathy.

A Delayed Recrudescent Case of Sigmoidocutaneous Fistula due to Diverticulitis.

Colocutaneous fistula caused by diverticulitis is relatively rare, and a delayed recrudescent case of colocutaneous fistula is very uncommon. We herein report a rare case of a Japanese 56-year-old male with delayed recrudescent sigmoidocutaneous fistula due to diverticulitis. A colocutaneous fistula was formed after a drainage operation against a perforation of the sigmoid colon diverticulum. After 5 years from treatment, he was admitted to our hospital because of lower abdominal pain. We diagnosed the recrudescent sigmoidocutaneous fistula by abdominal computed tomography and gastrografin enema, and managed the patient with total parenteral nutrition and antibiotics. As the fistula formation did not improve, a low anterior resection with fistulectomy was performed. The postoperative course was uneventful and the patient was discharged. It has been reported that, in fistulas of the skin caused by diverticular disease, complete closure of the fistula by conservative therapy may not be possible. This case also implies the possibility of a recurrence of the fistula even if the conservative treatment was effective. In cases of colocutaneous fistulas due to diverticulitis, radical surgery is considered necessary because of possibility of recurrence of the fistula.

Diabetic microangiopathy in ischemic limb is a disease of disturbance of the platelet-derived growth factor-BB/protein kinase C axis but not of impaired expression of angiogenic factors.

Diabetic foot is caused by microangiopathy and is suggested to be a result of impaired angiogenesis. Using a severe hindlimb ischemia model of streptozotocin-induced diabetic mice (STZ-DM), we show that diabetic foot is a disease solely of the disturbance of platelet-derived growth factor B-chain homodimer (PDGF-BB) expression but not responses of angiogenic factors. STZ-DM mice frequently lost their hindlimbs after induced ischemia, whereas non-DM mice did not. Screening of angiogenesis-related factors revealed that only the expression of PDGF-BB was impaired in the STZ-DM mice on baseline, as well as over a time course after limb ischemia. Supplementation of the PDGF-B gene resulted in the prevention of autoamputation, and, furthermore, a protein kinase C (PKC) inhibitor restored the PDGF-BB expression and also resulted in complete rescue of the limbs of the STZ-DM mice. Inhibition of overproduction of advanced-glycation end product resulted in dephosphorylation of PKC-alpha and restored expression of PDGF-BB irrespective of blood sugar and HbA1c, indicating that advanced-glycation end product is an essential regulator for PKC/PDGF-BB in diabetic state. These findings are clear evidence indicating that diabetic vascular complications are caused by impairment of the PKC/PDGF-B axis, but not by the impaired expression of angiogenic factors, and possibly imply the molecular target of diabetic foot.

Inducible production of alcohol oxidase and catalase in a pectin medium by Thermoascus aurantiacus IFO 31693.

Thermoascus aurantiacus showed the best growth on medium containing pectin as a carbon source. The enzyme involved in the production of catalase in the fungus was alcohol oxidase. Formaldehyde dehydrogenase and formate dehydrogenase, in addition to alcohol oxidase and catalase, were detected in the cells grown on pectin. Alcohol oxidase was alkali resistant (pH 7 to 11), and was comparatively heat stable (55 degrees C).