Rapid weight gain during infancy and early childhood is related to higher anthropometric measurements in preadolescence.

BACKGROUND: This study examined the relationship between rapid weight gain during infancy and/or early childhood and anthropometric measurements [body mass index (BMI), percent body fat (%BF), waist circumference (WC) and waist-to-height ratio (WHtR)] in preadolescence by sex. METHODS: Subjects were fourth-grade school children (aged 9 to 10 years) from elementary schools in Ina-town, Japan, in 2010. Measurements of height, weight, %BF and WC were conducted for each subject. We obtained data on height and weight of subjects at birth, age 1.5 years and age 3 years from the Maternal and Child Health handbook. Rapid weight gain was defined as a change in weight-for-age standard deviation score greater than 0.67 from birth to age 1.5 years (infancy) or from age 1.5 to 3 years (early childhood). RESULTS: All anthropometric variables (BMI, %BF, WC and WHtR) at age 9 to 10 years were significantly higher in the rapid weight gain during both infancy and early childhood period group than in the no rapid weight gain group, regardless of sex. When compared with the no rapid weight gain group, rapid weight gain during early childhood period had significantly higher BMI and WC in boys and BMI, %BF and WC in girls. Compared with the no rapid weight gain group, the rapid weight gain during infancy group had a significantly higher WC in boys and significantly higher BMI and WC in girls. CONCLUSION: Rapid weight gain during both infancy and early childhood was related to higher anthropometric measurements, including WHtR, among Japanese preadolescents, regardless of sex. This study suggests that rapid weight gain during infancy and early childhood may be a risk factor for general/abdominal obesity later in life.

Salvage pharyngolaryngectomy with total esophagectomy following definitive chemoradiotherapy.

Historically, total pharyngolaryngectomy with total esophagectomy has been the standard radical surgical treatment for synchronous cancer of the thoracoabdominal esophagus and pharyngolaryngeal region, and for cancer of the cervical esophagus that has invaded as far as the thoracic esophagus. Although definitive chemoradiotherapy that enables preservation of the larynx has often been the first choice of treatment for cancers involving the cervical esophagus, total pharyngolaryngectomy with total esophagectomy is required as a salvage therapy for cases involving failure of complete remission or locoregional recurrence after chemoradiotherapy. However, salvage esophageal surgery after definitive high-dose chemoradiotherapy is generally associated with high morbidity and mortality. The aim of this study was to examine the short-term outcome of salvage total pharyngolaryngectomy with total esophagectomy. From 2001 to 2014, nine patients underwent salvage total pharyngolaryngectomy with total esophagectomy at the Department of Gastroenterological Surgery, Nagoya University. The mortality and morbidity rates were high at 22% and 89%, respectively. Four patients (44%) developed tracheal necrosis, which in two patients eventually led to lethal hemorrhage. Salvage total pharyngolaryngectomy with total esophagectomy is an uncommon and highly demanding surgical procedure that should be carefully planned and conducted in selected centers of excellence. Measures must be taken to preserve the tracheal blood supply, thus avoiding fatal complications.

Detection of serum melanoma-associated antigen D4 in patients with squamous cell carcinoma of the esophagus.

Despite improvements in surgical techniques, perioperative management, and multidisciplinary therapy, treatment outcomes of patients with esophageal squamous cell carcinoma (ESCC) remain poor. Therefore, development of novel molecular biomarkers, which either predict patient survival or become therapeutic targets, is urgently required. In the present study, to facilitate early detection of ESCC and predict its clinical course, we investigated the relationship of the serum level of melanoma-associated antigen (MAGE)-D4 to patients' clinicopathological characteristics. Using quantitative real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assays, we determined the levels of MAGE-D4 mRNA and protein in cell lysates and conditioned medium of cultures, respectively, of nine ESCC cell lines. Further, we determined MAGE-D4 levels in serum samples collected from 44 patients with ESCC who underwent radical esophagectomy without neoadjuvant therapy as well as from 40 healthy volunteers. Samples of conditioned medium and cell lysates contained comparable levels of MAGE-D4 that correlated closely with the levels of MAGE-D4 mRNA. Preoperative MAGE-D4 levels in the sera of 44 patients with ESCC, which varied from 0 to 2,354 pg/mL (314 ± 505 pg/mL, mean ± standard deviation), were significantly higher compared with those of healthy volunteers. By setting the cutoff at the highest value for healthy volunteers (50 pg/mL), the MAGE-D4-positive group of patients was more likely to have shorter disease-specific and disease-free survival compared with those of the MAGE-D4-negative group, although the differences were not statistically significant. Our results indicate that the elevation of preoperative serum MAGE-D4 levels in some patients with ESCC was possibly caused by excess production of MAGE-D4 by tumor cells followed by its release into the circulation. Clinical implications of serum MAGE-D4 levels should be validated in a large population of patients with ESCC.

Overexpression of melanoma-associated antigen D4 is an independent prognostic factor in squamous cell carcinoma of the esophagus.

To pursue an urgently needed treatment target for esophageal cancer (EC), we investigated the function of the recently discovered melanoma-associated antigen (MAGE)-D4 in squamous cell EC. MAGE-D4 messenger RNA (mRNA) expression was analyzed in nine EC cell lines using quantitative reverse transcription polymerase chain reaction. In 65 surgical specimens of squamous cell EC with no prior neoadjuvant therapy, MAGE-D4 mRNA expression in EC tissues and corresponding normal tissues was analyzed and compared, and evaluated in terms of clinicopathological factors. In representative cases, MAGE-D4 protein distribution was analyzed immunohistochemically. The heterogeneity of MAGE-D4 mRNA expression was confirmed in EC cell lines by quantitative reverse transcription polymerase chain reaction. In surgical specimens, MAGE-D4 mRNA expression was significantly higher in EC tissues than in corresponding normal tissues (P < 0.001). Patients with the highest MAGE-D4 mRNA expression in EC tissues (top quartile, n = 17) had significantly shorter overall survival than patients with low expression (2-year survival: 44% and 73%, respectively, P = 0.006). Univariate analysis identified age (≥65 years), lymphatic involvement, and high MAGE-D4 mRNA expression as significant prognostic factors; high MAGE-D4 mRNA expression was also an independent prognostic factor in multivariable analysis (hazard ratio: 2.194; P = 0.039) and was significantly associated with Brinkman index (P = 0.008) and preoperative carcinoembryonic antigen level (P = 0.002). Immunohistochemical MAGE-D4b expression was consistent with MAGE-D4 mRNA profiling. Our results suggest that MAGE-D4 overexpression influences tumor progression, and MADE-D4 can be a prognostic marker and a potential molecular target in squamous cell EC.

Value of peritoneal cytology in potentially resectable pancreatic cancer.

BACKGROUND: Peritoneal lavage cytology (CY) is used in the diagnosis and staging of various cancers. The clinical significance of positive cytology results in patients with pancreatic cancer is yet to be determined. METHODS: Peritoneal washing samples were collected from consecutive patients with pancreatic cancer between July 1991 and December 2012. The correlations between cytology results, clinicopathological parameters and recurrence patterns were evaluated. The prognostic impact of CY status, regarding resectability and the effectiveness of adjuvant chemotherapy, were analysed. RESULTS: Of 523 included patients, 390 underwent resection. Patients with tumours at least 2 cm in diameter were more likely to have CY+ status than patients with tumours smaller than 2 cm (48 of 312 versus 3 of 78 respectively; P = 0·005) and there was a significant correlation between CY+ status and tumour invasion of the anterior pancreatic capsule (43 of 276 versus 8 of 113 with no invasion of the capsule; P = 0·030). Although the overall survival of patients with resected CY+ tumours was worse than that of patients with resected CY- tumours, it was significantly better than the survival of unresected patients regardless of CY status. Multivariable analysis of all patients who had pancreatectomy did not identify CY+ as an independent prognostic factor. Patients with CY+ tumours tended to develop peritoneal metastasis more often than those with CY- tumours, although not significantly so. The median survival time of 34 patients with resected CY+ tumours who received adjuvant chemotherapy was better than that of 17 patients who had surgery alone, although this was not statistically significant (15·3 versus 10·0 months; P = 0·057). CONCLUSION: CY+ status is not clinically equivalent to gross peritoneal metastasis in patients with pancreatic cancer. Curative resection is still recommended regardless of CY status.

Antitumor efficacy of oncolytic herpes simplex virus adsorbed onto antigen-specific lymphocytes.

Although several studies have reported that locally administering oncolytic viruses effectively targets malignancies, the efficacy of systemically administered oncolytic viruses is restricted. Recently, however, it was reported that systemic administration of oncolytic vesicular stomatitis virus adsorbed onto antigen-specific lymphocytes was effective against malignancies. We hypothesized that intravenously administering such virus might have significant potential in treatment of the malignant tumors. We adsorbed oncolytic herpes simplex virus-1 mutant R3616 onto lymphocytes harvested from mice with acquired antitumor immunity. We administered adsorbed R3616 to peritoneally disseminated tumors and analyzed the efficacy of this treatment. Mice administered adsorbed R3616 survived significantly longer than mice administered R3616 adsorbed onto non-specific lymphocytes, or mice administered either virus or tumor antigen-specific lymphocytes alone. In this context, herpes oncolytic virus is a promising treatment not only for primary lesions, but also for multiple metastasizing lesions. This treatment strategy may become one of the most effective methods for systemic virus delivery.

Impact of novel oncolytic virus HF10 on cellular components of the tumor microenviroment in patients with recurrent breast cancer.

Oncolytic viruses are a promising method of cancer therapy, even for advanced malignancies. HF10, a spontaneously mutated herpes simplex type 1, is a potent oncolytic agent. The interaction of oncolytic herpes viruses with the tumor microenvironment has not been well characterized. We injected HF10 into tumors of patients with recurrent breast carcinoma, and sought to determine its effects on the tumor microenvironment. Six patients with recurrent breast cancer were recruited to the study. Tumors were divided into two groups: saline-injected (control) and HF10-injected (treatment). We investigated several parameters including neovascularization (CD31) and tumor lymphocyte infiltration (CD8, CD4), determined by immunohistochemistry, and apoptosis, determined by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Median apoptotic cell count was lower in the treatment group (P=0.016). Angiogenesis was significantly higher in treatment group (P=0.032). Count of CD8-positive lymphocytes infiltrating the tumors was higher in the treatment group (P=0.008). We were unable to determine CD4-positive lymphocyte infiltration. An effective oncolytic viral agent must replicate efficiently in tumor cells, leading to higher viral counts, in order to aid viral penetration. HF10 seems to meet this criterion; furthermore, it induces potent antitumor immunity. The increase in angiogenesis may be due to either viral replication or the inflammatory response.

Identification of the A kinase anchor protein 12 (AKAP12) gene as a candidate tumor suppressor of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major health problem, and identification of new tumor-related genes is an urgent task. METHODS: To detect tumor-related genes effectively, we performed double-combination array analysis, which consisted of an expression array and a single nucleotide polymorphism (SNP) array of a single surgical HCC specimen. RESULTS: Expression array analysis identified AKAP12 as one of the genes with reduced expression in HCC tissues when compared with non-cancerous adjacent hepatic tissues. In addition, AKAP12 expression levels in tumor tissues from 48 HCC samples were significantly lower (P < 0.001) than those in normal tissues, and the downregulation was significantly correlated with poor overall survival rate (P = 0.003). However, SNP array analysis revealed that locus 6q24-q25 where AKAP12 was located did not show chromosomal deletion. In contrast, hypermethylation in the AKAP12 promoter regions was observed in 41 of 48 HCC samples. We then confirmed that AKAP12 gene re-expression occurs after 5-aza-2'-deoxycytidine (5-aza-dC) treatment through direct sequence analysis of the AKAP12 promoter region in HCC cell lines. CONCLUSIONS: The current data suggest that AKAP12 is downregulated in cancer tissues through promoter hypermethylation, and may have a role as a candidate tumor suppressor gene for HCC.

A phase I dose-escalation clinical trial of intraoperative direct intratumoral injection of HF10 oncolytic virus in non-resectable patients with advanced pancreatic cancer.

In 2005, we initiated a clinical trial that examined the efficacy of the oncolytic virus HF10 to treat pancreatic cancer. Pancreatic cancer continues to have a high mortality rate, despite multimodal treatments for patients, and new therapeutic methods are greatly needed. The current mainstream methods for cancer treatment include biological therapeutics such as trastuzumab (Herceptin) for breast cancer or erlotinib (Tarceva) for non-small cell lung cancer. Oncolytic virus therapy is a new and promising treatment strategy for cancer. Oncolytic viruses are novel biological therapeutics for advanced cancer that appear to have a wide spectrum of anticancer activity with minimal human toxicity. To examine the efficacy of oncolytic virus therapy for pancreatic cancer, we initiated pilot studies by injecting six patients with non-resectable pancreatic cancer with three doses of HF10. All patients were monitored for 30 days for local and systemic adverse effects and were not administered any other therapeutics during this period. There were no adverse side-effects, and we observed some therapeutic potential based on tumor marker levels, survival, pathological findings and diagnostic radiography. The tumors were classified as stable disease in three patients, partial response in one patient and progressive disease in two patients.

Computerized method for estimation of the location of a lung tumor on EPID cine images without implanted markers in stereotactic body radiotherapy.

The purpose of this study was to develop a computerized method for estimation of the location of a lung tumor in cine images on an electronic portal imaging device (EPID) without implanted markers during stereotactic body radiotherapy (SBRT). Each tumor region was segmented in the first EPID cine image, i.e., reference portal image, based on a multiple-gray level thresholding technique and a region growing technique, and then the image including the tumor region was cropped as a 'tumor template' image. The tumor location was determined as the position in which the tumor template image took the maximum cross-correlation value within each consecutive portal image, which was acquired in cine mode on the EPID in treatment. EPID images with 512 x 384 pixels (pixel size: 0.56 mm) were acquired at a sampling rate of 0.5 frame s(-1) by using energies of 4, 6 or 10 MV on linear accelerators. We applied our proposed method to EPID cine images (226 frames) of 12 clinical cases (ages: 51-83, mean: 72) with a non-small cell lung cancer. As a result, the average location error between tumor points obtained by our method and the manual method was 1.47 +/- 0.60 mm. This preliminary study suggests that our method based on the tumor template matching technique might be feasible for tracking the location of a lung tumor without implanted markers in SBRT.

Adverse prognosis of epigenetic inactivation in RUNX3 gene at 1p36 in human pancreatic cancer.

Alteration in transforming growth factor-beta signalling pathway is one of the main causes of pancreatic cancer. The human runt-related transcription factor 3 gene (RUNX3) is an important component of this pathway. RUNX3 locus 1p36 is commonly deleted in a variety of human cancers, including pancreatic cancer. Therefore, we examined genetic and epigenetic alterations of RUNX3 in human pancreatic cancer. Thirty-two patients with pancreatic cancer were investigated in this study. We examined the methylation status of RUNX3 promoter region, loss of heterozygosity (LOH) at 1p36, and conducted a mutation analysis. The results were compared with clinicopathological data. Promoter hypermethylation was detected in 20 (62.5%) of 32 pancreatic cancer tissues, confirmed by sequence of bisulphite-treated DNA. Loss of heterozygosity was detected in 11 (34.3%) of 32 pancreatic cancers. In comparison with clinicopathological data, hypermethylation showed a relation with a worse prognosis (P=0.0143). Hypermethylation and LOH appear to be common mechanisms for inactivation of RUNX3 in pancreatic cancer. Therefore, RUNX3 may be an important tumour suppressor gene related to pancreatic cancer.

Hypermethylation of multiple genes as clonal markers in multicentric hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is highly malignant and prone to multicentric occurrence. Differentiation between a true relapse of HCC and a second primary tumour appearing is of clinical importance. At this point, no convenient method is available to determine the origin of these HCCs. Tissue samples were obtained from 19 patients and analysed for the promoter hypermethylation status of multiple tumour suppressor genes (p16, DAP-Kinase, MGMT, GSTP1, APC, RIZ1, SFRP1, SFRP2, SFRP5, RUNX3, and SOCS1) using methylation-specific PCR (MSP). Methylation status was used to determine tumour clonality. In each of the 19 cases, at least one tumour was recognised as having an aberrantly methylated gene. The frequency of the methylation in tumour tissue was 57.1% in p16, 2.4% in DAP-kinase, 23.8% in GSTP1, 90.5% in APC, 45.2% in RIZ1, 64.3% in SFRP1, 59.5% in SFRP2, 28.6% in SFRP5, 47.6% in RUNX3, and 54.8% in SOCS1, while in MGMT, no aberrant methylation was detected. The methylation status of these genes was assessed using MSP as being either positive or negative, and was used to determine the tumour clonality. The clonality of every tumour could be decided even with lesions that could not be judged by clinical diagnosis or by another molecular method (mt DNA mutation). Determining the methylation status of multiple genes in multicentric HCC was useful as a clonal marker and provided useful information for characterising the tumour. From our findings, multicentric HCCs tend to occur more independently than metastatically from the original tumour. Expanded study should be pursued further for a better understanding of the molecular mechanism of hepatocarcinogenesis.

Suitability of a US3-inactivated HSV mutant (L1BR1) as an oncolytic virus for pancreatic cancer therapy.

Recently, the use of oncolytic viruses against cancer has attracted considerable attention. We studied the potential of the US3 locus-deficient herpes simplex virus (HSV), L1BR1, for oncolytic virus therapy. Its high specificity and potency indicate that L1BR1 is a promising candidate as a new oncolytic virus against pancreatic cancer. Moreover, the virus exhibited the unique characteristic of increasing apoptosis when used in combination with anticancer drugs. We assessed the feasibility of using the US3 locus-deficient HSV named L1BR1 as a new replication-competent oncolytic virus for the treatment of pancreatic cancer. The US3 locus of HSV has been shown to be a key gene in producing a multifunctional protein kinase that inhibits apoptosis induced by viral infections, chemicals and ultraviolet (UV) light. L1BR1 has been reported to be more than 10 000-fold less virulent than the parental virus in mice. In this study, we examined the tumor specificity and oncolytic effect of this attenuated replication-competent virus, L1BR1, in pancreatic cancers derived from SW1990, Capan2 and Bxpc-3cells compared with the parent virus and other well-known oncolytic herpes viruses (R3616 and hrR3). We also studied the efficacy of L1BR1 for the induction of apoptosis as an attribute of this virus in combination with the anticancer drugs 5FU and cisplatin. The combined treatment of the pancreatic cancer cells with L1BR1 and these anticancer drugs enhanced apoptosis significantly. More importantly, L1BR1 showed the lowest replication capacity in normal human hepatocytes, but the highest tumor-reducing effect in vivo among the oncolytic herpes viruses tested. In addition, L1BR1 significantly increased the induction of apoptosis of cancer cells when treated in combination with anticancer drugs although the parental virus inhibited the induction of apoptosis. These results suggest that L1BR1 is promising as a new anticancer oncolytic virus.

Oncolytic virus therapy--foreword.

We are very pleased and proud to be able to publish this special issue of Current Cancer Drug Targets devoted to oncolytic virus therapy covering basic and clinical research on adenovirus, vaccinia virus, herpes virus, and Newcastle disease virus. In these papers, we welcome the world's top authorities in the field who have generously contributed their latest review articles for exclusive publication in this special issue. Moreover, this issue also includes a range of opinion from government drug organizations. Here we simply wish to bring together the newest knowledge and experience in the field of cutting-edge oncolytic virus therapy for researchers and every kind of cancer therapist. The Foreword presents a historical perspective on the development of oncolytic virus together with the encouraging results of recent clinical trials (e.g., H101 has been tested in clinical trial of nearly 250 patients and approved for human use by the Chinese FDA, while PV701 has been tried in over 110 patients, as described in our special issue).

Normal hepatic hemodynamics during early postoperative period in recipients with adult live donor liver transplantation.

To recognize "normal" hepatic hemodynamics after live donor liver transplantation (LDLT), we analyzed Doppler parameters on recipients with a right liver graft and donors after extended left hepatectomy. Theoretically these values should be the same. From April 2000 to October 2004, 20 LDLTs were performed using a right liver graft. The 10 recipients without postoperative complications and their donors were included in this study. Portal venous velocity (PVV; cm/s), hepatic arterial peak systolic velocity (cm/s), and hepatic venous peak velocity (HVPV; cm/s) were measured during the first 2 weeks. In donors PVV and HVPV after LDLT were significantly higher after than before left hepatectomy: 19.2 +/- 4.2 vs. 31.5 +/- 13.0 cm/s (P = .013) and 23.0 +/- 7.2 vs. 41.8 +/- 10.3 cm/s respectively (P = .010). However, there were mild degrees of increased PVV and HVPV. In recipients, a markedly increased PVV (106.3 +/- 45.2 cm/s on day 1) was significantly higher than that in donors on each postoperative day. The hepatic arterial resistive index in recipients was also significantly higher than that in donors on each postoperative day, for example, 0.72 +/- 0.11 vs 0.62 +/- 0.04 on day 1 (P = .0326). In conclusion, we have shown "abnormal" hepatic hemodynamics in even those recipients without complications during the early postoperative period after LDLT.

Influence of ascorbic acid on bonding of peroxide-affected dentin and 4-META/MMA-TBB resin.

The purpose of this study was to evaluate the tensile bond strength (TBS) to peroxide-exposed dentin. Furthermore, the effect of ascorbic acid (AA) on the bond strength of peroxide-exposed dentin was investigated. Extracted bovine dentin was exposed to 10% carbamide peroxide, 30% hydrogen peroxide, or distilled water for 30 min, then treated with 10% AA (0, 30, 90, and 180 min), and conditioned with 10% citric acid/3% ferric chloride. The polymethyl-methacrylate (PMMA) rod was bonded to the treated bovine dentin with 4-META/MMA-TBB resin. A minidumbbell-shaped bonded specimen was prepared from these bonded assemblies and the TBS was tested. The fractured surfaces were also observed with a scanning electron microscope. Exposure to peroxide before bonding significantly reduced bond strength. The application of AA to the peroxide-exposed dentin increased bond strength. On the other hand, an adverse effect of AA was found in distilled water-affected dentin. Extended resin fibers were partially seen in the peroxide-exposed dentin. In conclusion, peroxide reduced the bond strength, and the stronger the oxidation, the weaker the obtained bond. Antioxidation with AA recovered the bond strength, and this effect increased the longer the AA was applied.

[Drug-eluting stents restenosis 2 months after the procedure and necessitating semi-emergency off-pump coronary artery bypass].

Drug-eluting stents (sirolimus-eluting stent: Cypher stent) have showed a reducing the frequency of in-stent restenosis and a good safety profile. One case involving edge dissection with Cypher stent restenosis for 2 lesions was diagnosed in 2 months after the procedure. This case occurred in a hypertensive 63-year-old woman with complex coronary lesions. The coronary angiography showed uncovered proximal dissection with 90% restenosis in left anterior descending coronary artery to left main trunk and 75% restenosis in right coronary artery. We were able to perform semi-emergency off-pump coronary artery bypass (OPCAB). There is the relationship between coronary dissection and restenosis. Cypher stent delayed dissected arterial healing and promote some inflammation at the lesion. Patients implanted Cypher stent with uncovered coronary dissection need more frequent follow-up.

Correlation between copy number of mitochondrial DNA and clinico-pathologic parameters of hepatocellular carcinoma.

AIMS: In the current study, we investigated possible correlations of the mtDNA copy number in hepatocellular carcinoma (HCC) with the pathological findings and prognosis. METHODS: We studied 31 HCC specimens using quantitative real-time polymerase chain reaction analysis, and the correlation between the mtDNA copy number and the clinicopathologic parameters and mutations in the D-loop region of the mitochondrial genome. RESULTS: The mtDNA copy number was reduced in HCCs compared with the corresponding non-cancerous liver tissues (p=0.002), and significantly correlated with tumour size (p=0.014) and cirrhosis (p=0.048). Patients with a low mtDNA copy number tended to show shorter 5-year survival rates than patients with a high mtDNA copy number when assessed by Kaplan-Meier curves, but not a significant (overall survival rate, 63 vs 83%; p=0.19). The copy number of HCC with mtDNA D-loop mutation or deletion was lower, but not significantly so (p=0.656, p=0.590, respectively). CONCLUSIONS: Our results indicated that a reduced copy number of mtDNA is correlated with HCC and associated with malignant potential.

Effect of 8-MHz radiofrequency-capacitive regional hyperthermia with strong superficial cooling for unresectable or recurrent colorectal cancer.

A well-known disadvantage of a radiofrequency-capacitive device for deep-seated tumours is preferential heating of the subcutaneous fat tissue. The authors previously developed the hyperthermia with their own external cooling unit and achieved strong superficial cooling, and reported its usefulness for the reduction of the preferential heating. The purpose of the present study was to evaluate the effect of hyperthermia with strong superficial cooling on the treatment results for unresectable or recurrent colorectal cancers. From 1986 to 2002, 44 patients with primary unresectable or locally recurrent colorectal cancer treated with thermoradiotherapy were analysed retrospectively. The patients with obesity as a subcutaneous fat thickness more than 3 cm, a high age or other serious complications did not undergo therapy. The results were compared between 17 cases with strong superficial cooling treated after 1997 (Group A) and 27 cases without strong superficial cooling treated before 1996 (Group B). Significant differences in thermometry data of T(max), T(ave) and T(min) were noted between Groups A (45.3, 44.4 and 43.6 degrees C, respectively) and B (42.9, 42.0 and 41.1 degrees C, respectively) (p<0.01). Complete response plus partial response rates were better for Group A than for Group B (59 versus 26%, p = 0.05). Multivariate analysis by logistic regression to evaluate the effects of certain factors on complete response plus partial response was strongly correlated with strong superficial cooling (p<0.05). The median survival times for overall survival were 24.3 months for Group A and 17.1 months for Group B (p<0.05). Eight-megahertz radiofrequency-capacitive regional hyperthermia with strong superficial cooling is potentially useful for improving treatment results in unresectable or recurrent colorectal cancers.

[Assessment of blood flow of the internal thoracic artery in patients with aortic stenosis].

The number of patients undergoing combined aortic valve replacement (AVR) for aortic stenosis (AS) and coronary artery bypass grafting (CABG) has been increasing. In CABG, the internal thoracic artery (ITA) is the preferred conduit for its long-term patency. Although Doppler studies on ITA have been widely used, flow characteristics of the vessel in patients with AS have not been reported. To evaluate blood flow pattern of the ITA in AS, duplex scanning was performed in 10 patients before and after AVR. Peak systolic velocity was measured, and blood flow was calculated from mean velocity and cross-sectional area. The mean diameters of the vessels were approximately 1.8 mm on both sides. AVR caused an increase in systolic velocities from 61.2 cm/sec to 85.5 cm/sec in right ITA and from 58.4 cm/sec to 84.7 cm/sec in left ITA. The flow volumes increased from 32.2 ml/min to 46.7 ml/min in right and increased from 31.6 ml/min to 46.3 ml/min in left after AVR. In simultaneous AVR for AS and CABG, suitability of the ITA should be assessed before its use, and concomitant AVR may be quite important to provide adequate flow of the ITA as a conduit.