Pentalogy of Cantrell with a double-outlet right ventricle: 3.5-year follow-up in a prenatally diagnosed patient

Pentalogy of Cantrell is a rare congenital defect associated with five ventral midline anomalies and high mortality. An obstetric sonogram revealed a fetus with a body wall defect suggesting a diagnosis of this condition. Soon after birth, the infant underwent a closure of the upper abdominal wall defect followed by the successful repair of double-outlet right ventricle and pulmonary valve stenosis at the age of 5 months. The patient is currently alive and well 3.5 years after surgery. It is concluded that a deliberate therapeutic strategy based on the intrauterine diagnosis may alter the natural history of this devastating disorder.     

Evaluating the WHO Assessment Instrument for Mental Health Systems by comparing mental health policies in four countries

Mental health is a low priority in most countries around the world. Minimal research and resources have been invested in mental health at the national level. As a result, WHO has developed the Assessment Instrument for Mental Health Systems (WHO-AIMS) to encourage countries to gather data and to re-evaluate their national mental health policy. This paper demonstrates the utility and limitations of WHO-AIMS by applying the model to four countries with different cultures, political histories and public health policies: Iraq, Japan, the Philippines and The former Yugoslav Republic of Macedonia. WHO-AIMS provides a useful model for analysing six domains: policy and legislative framework; mental health services; mental health in primary care; human resources; education of the public at large; and monitoring and research. This is especially important since most countries do not have experts in mental health policy or resources to design their own evaluation tools for mental health systems. Furthermore, WHO-AIMS provides a standardized database for cross-country comparisons. However, limitations of the instrument include the neglect of the politics of mental health policy development, underestimation of the role of culture in mental health care utilization, and questionable measurement validity.     

Zonula Occludens-1 alterations and enhanced intestinal permeability in methotrexate-treated rats

Purpose

The molecular mechanisms that underlie the methotrexate (MTX)-mediated disruption of intestinal barrier function have not been fully characterized. Epithelial barrier function is determined in large part by a multiprotein complex located at the most apical part of the lateral membrane, which is referred to as a tight junction (TJ). In the present study, we examined the alteration of zonula occludens-1 (ZO-1), which is a scaffolding protein that plays a pivotal role in the formation of TJs, to identify an additional molecular mechanism for epithelial barrier dysfunction.

Methods

Male Wistar rats were administered MTX (15 mg kg^?1) orally once daily for 3–5 days. Intestinal mucosal permeability was determined using the in vitro everted intestinal sac technique. Mucosal inflammation was assessed by myeloperoxidase activity and production of reactive oxygen species. Altered expression, tyrosine phosphorylation, and localization of ZO-1 were evaluated by RT–PCR, Western blotting, immunoprecipitation, and immunohistochemistry.

Results

A barrier function study revealed increased intestinal permeability in rats treated with MTX for 4 days, as indicated by enhanced fluorescein isothiocyanate-dextran flux. In addition, mucosal inflammation was linked to enhanced intestinal permeability. Quantitative analysis of ZO-1 expression showed the absence of significant differences in MTX-treated rats, whereas tyrosine dephosphorylation of ZO-1 was observed. Moreover, we also detected an obvious reduction of ZO-1 immunostaining along the apical membrane of intestinal villi.

Conclusions

These results indicate that, in MTX-treated rats, ZO-1 alterations may contribute to disturbance of the TJ barrier, which leads to enhanced intestinal permeability.     

A long-term survival case of local recurrence of breast cancer treated with combined modality therapy

The case was a 70-year-old woman. In 1997, the patient underwent pectoral muscle-preserving mastectomy and axillary/subclavicular lymph node dissection for the treatment of right breast cancer. Histological diagnosis was invasive ductal carcinoma (T2, N2, M0, Stage IIIA). She received a combination therapy with TAM and UFT for 5 years postoperatively. Because tumor recurrence occurred in right axillary lymph nodes in the 9th postoperative year, the patient underwent resection of these lymph nodes followed by 6 cycles of AC-based chemotherapy. Multiple lung metastases occurred in the 10th postoperative year, and then, the patient received 8 cycles of DOC-based chemotherapy. In the 11th postoperative year, a mass appeared again in the right axilla, and 6 cycles of capecitabine-based chemotherapy was administered. In the 12th postoperative year, pulmonary metastasis was in progression and an increased right axillary mass were noted. Thus, the specimen extirpated in 2006 was examined again, revealing negative ER, negative PgR and positive HER2. Six cycles of combined trastuzumab+PTX therapy were administered. Lung metastasis decreased in size, allowing a judgment of partial response. Because the right axillary mass had grown to 10 cm, and the patient's QOL was reduced, it was extirpated. The patient is scheduled to receive a postoperative radiotherapy, followed by resumption of chemotherapy.     

Non-surgical care for locally advanced breast cancer: radiologically assessed therapeutic outcome of a new enzyme-targeting radiosensitization treatment, Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas, Type II (KORTUC II) with systemic chemotherapy

We have previously developed a new enzyme-targeting radiosensitization treatment named Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas, Type II (KORTUC II), which markedly enhances radiotherapeutic effects on various types of locally advanced malignant neoplasms. KORTUC II was approved by our local ethics committee for use against various types of malignant neoplasms. A maximum of 6 ml of radiosensitizer was injected into tumor tissue under ultrasonographic guidance just before each administration of radiotherapy. Seventeen patients with locally advanced breast cancer were enrolled to receive KORTUC II with systemic chemotherapy without surgical care. Patients were eligible if they had declined surgical treatment. Median observation period was 13.4 months (range, 1-26 months). This therapy was well tolerated. Contrast-enhanced magnetic resonance imaging revealed complete response in all primary breast tumors, and no patients displayed local recurrence during the follow-up period. Ultrasonography depicted tumor-like findings in 9 of 17 cases after therapy. The existence rate of posterior shadow artifacts behind the tumor was 2/17 before therapy, increasing to 8/17 after therapy. Intratumoral flow signals on color Doppler sonography were seen in 16/17 cases before therapy, but had disappeared from all cases after therapy. The increased rate of posterior shadow artifacts and absence of flow signals after therapy suggest that the tumor-like finding on ultrasonography represents scar tissue. Computed tomography revealed positive axillary nodes metastases in 16/17 and 2/17 cases before and after therapy, respectively. Nodal metastatic failure affected only 1 patient, who refused adjuvant systemic chemotherapy at the end of the observation period. Abnormal lymph node findings on computed tomography remained stable in the other patient. Excellent locoregional control based on accurate radiological evaluation implies that KORTUC II with chemotherapy has the potential to replace surgery in therapy for locally advanced breast cancer.     

Osteo-odonto-keratoprosthesis in Japan

Osteo-odonto-keratoprosthesis (OOKP) is a keratoprosthesis technique in which the patient's own tooth root is used to support an optical cylinder. It was invented by Strampelli in 1963 and modified and established by Falcinelli about 10 years later. This method is particularly useful for restoring sight in end-stage Stevens-Johnson syndrome (SJS) and ocular cicatricial pemphigoid (OCP). We started performing OOKP surgery in June 2003 supported by Dr Christopher Liu of Sussex Eye Hospital, Brighton, UK. Till now, we have performed 4 OOKP surgeries for end-stage SJS and OCP. We modified the original method by using artificial buccal mucous membranes to the bone and buccal mucous membrane defects for better wound healing. Case 1 was a 49-year-old woman (SJS), and the corrected visual acuity was 0.5 in 4 years 8 months. Case 2 was a 68-year-old woman (SJS), and the corrected visual acuity was 0.04 in 3 years 10 months. Case 3 was a 63-year-old man (SJS), and the corrected visual acuity was 0.1 in 3 years 2 months. Case 4 was a 71-year-old woman (OCP), and the corrected visual acuity was 0.04 in 1 year 3 months. Despite some minor optical cylinder troubles such as MRSA colonization, tilting, and buccal mucous coverage, their visual acuities were stable without any serious complications. It was demonstrated that OOKP is useful for visual rehabilitation and durable with minimum eye care for severe ocular surface diseases.     

Demonstration of mother-to-child transmission of Streptococcus mutans using multilocus sequence typing

A new reliable genotyping method, multilocus sequence typing (MLST), was used to evaluate vertical transmission of the cariogenic pathogen Streptococcus mutans. A total of 136 S. mutans strains were isolated from saliva samples of 20 Japanese mother-child pairs, including 5 girls and 5 boys with primary dentition, and 5 girls and 5 boys with mixed dentition. The nucleotide sequences of 8 partial housekeeping genes, aroE, murI, gltA, glnA, glk, tkt, lepC, and gyrA, were analyzed and a similarity for all of those sequences between strains from a mother-child pair was regarded as indicating transmission, which was shown in 70% of the pairs. Interestingly, the rate of transmitted strains from mothers was significantly higher in the girls (90%) than in the boys (p = 0.001). Furthermore, the S. mutans sequence type (ST) with the highest distribution percentage in each maternal saliva sample was found to be transferred to their children. In addition, variations in two large conjugative-transfer associated regions, TnSmu1 and TnSmu2, were determined and compared with the STs defined by MLST. No variations in those two regions shown by PCR patterns were present in any of the strains isolated from the same families with the same STs, though isolates of some STs from different families showed distinct patterns for TnSmu2. Our results indicate that mothers are the main source for transmission of S. mutans to their children, while the present MLST method was also shown to be useful for investigating bacterial transmission.     

Preplanned safety analysis of the JFMC37-0801 trial: a randomized phase III study of six months versus twelve months of capecitabine as adjuvant chemotherapy for stage III colon cancer

Background

Six months of adjuvant chemotherapy is regarded as the standard of care for patients with stage III colon cancer. However, whether longer treatment can improve prognosis has not been fully investigated. We conducted a phase III study comparing 6 and 12 months of adjuvant capecitabine chemotherapy for stage III colon cancer, and report here the results of our preplanned safety analysis.

Methods

Patients aged 20–79 years with curatively resected stage III colon cancer were randomly assigned to receive 8 cycles (6 months) or 16 cycles (12 months) of capecitabine (2500 mg/m²/day on days 1–14 of each 21-day cycle). Treatment exposure and adverse events (AEs) were evaluated.

Results

A total of 1304 patients (642 and 636 in the 6-month and 12-month groups, respectively) were analyzed. The most common AE was hand-foot syndrome (HFS). HFS, leukocytopenia, neutropenia, and hyperbilirubinemia (any grade) occurred more frequently in the 12-month group than in the 6-month group. HFS was the only grade ≥3 AE to have a significantly higher incidence in the 12-month group (23 vs 17%, p = 0.011). The completion rate for 8 cycles was 72% in both groups, while that for 16 cycles was 46% in the 12-month group. HFS was the most common AE requiring dose reduction and treatment discontinuation.

Conclusions

Twelve months of adjuvant capecitabine demonstrated a higher cumulative incidence of HFS compared to the standard 6-month treatment period, while toxicities after 12 months of capecitabine were clinically acceptable.

Trial registration

UMIN-CTR, UMIN000001367.