Yuko Tsunoda

Quality of Life after Low Anterior Resection and Temporary Loop Ileostomy

PurposeLow anterior resection has become the operation of choice for mid rectal or low rectal cancer. A defunctioning stoma is routinely created at some centers to decrease the risk of leakage requiring surgical intervention. This study was designed to evaluate the quality of life in patients undergoing low anterior resection with a temporary ileostomy.MethodsA prospective longitudinal study was conducted in 22 patients with rectal cancer who underwent low anterior resection with a loop ileostomy. Quality of life was assessed by using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR38 questionnaires. Twenty-five patients who underwent high anterior resection for rectosigmoid cancer were studied concurrently to evaluate the impact of major colorectal resection without a stoma.ResultsPatients’ scores on the quality of life questionnaires generally improved after high anterior resection; however, for patients who underwent low anterior resection, the scores for physical and role functioning before ileostomy closure were worse than the preoperative values. The scores on the quality of life questionnaires generally improved after ileostomy closure. Ileostomy closure required a short hospital stay and was rarely associated with complications.ConclusionPatients who underwent low anterior resection with ileostomy had significant reductions in physical and role functioning, which apparently improved after ileostomy closure. Similar declines in these quality of life variables were not found in patients who underwent high anterior resection. A temporary ileostomy should be created in selected patients with the highest risk of anastomotic leakage. Increased resources for not only surgical care but also for stoma therapy are necessary for patients who undergo low anterior resection with a temporary ileostomy.

Thrombopoietin in Patients with Hepatoblastoma

Marked thrombocytosis (over 50 × 104/μl) is frequently seen in patients with hepatoblastoma. Thrombopoietin (TPO), c‐mpl ligand, has recently been purified as the major physiological regulator of the thrombopoiesis and is mainly produced in the liver. Since it is possible that TPO participates in thrombocytosis and the tumor growth of this particular hepatic tumor, serum TPO levels in addition to interleukin 1β (IL‐1β) and IL‐6 levels were assessed in seven untreated patients by using a sandwich enzyme‐linked immunosorbent assay. High serum TPO levels were observed in all of the examined patients. The level ranged from 3.15 to 11.02 (mean ± standard deviation; 6.08 ± 1.25) fmol/ml. IL‐6 levels were also somewhat higher than normal. Platelet counts, however, appeared to correlate more with serum TPO levels (p = 0.1) than with IL‐1β (p = 0.5) and IL‐6 (p = 0.2) levels. Furthermore, using the reverse transcriptase polymerase chain reaction method, the expression of c‐mpl mRNA was found in five of eight hepatoblastoma tissues as well as TPO mRNA in all eight tissues. These observations suggest that thrombocytosis in hepatoblastoma patients results from the production of cytokine members, including TPO, within tumor tissues. Additionally, it is possible that TPO might act as a type of autocrine and/or paracrine system for cellular growth in this tumor.

Prospective analysis of quality of life in the first year after colorectal cancer surgery

Little is known of how the quality of life (QOL) of patients with colorectal cancer changes with time following an operation, and whether or not there are predictors of QOL after one year in this population. The European Organization for Research and Treatment of Cancer QLQ-C30 QOL questionnaire was administered to patients before their operation for colorectal cancer, and monthly following the operation for up to one year. Multivariate regression analysis was performed to examine the predictors of QOL one year after the operation. One hundred patients with a mean age of 64 years participated. The scores of five QOL dimensions (physical function, role function, fatigue, pain, and dyspnoea) dropped significantly below the preoperative values at one month following the operation. The scores returned to the preoperative values within three months following the operation. The scores of seven QOL dimensions (global QOL, emotional function, social function, insomnia, appetite loss, diarrhea, and financial difficulties) had improved within three months after the operation. Other scores, including cognitive function, nausea and vomiting, and constipation remained unchanged. Stepwise regression analyses showed that preoperative performance status predicted various QOL scales one year following the operation. The overall QOL of colorectal cancer patients became stabilized about three months after the operation.

Volume replacement with polyglycolic acid mesh for correcting breast deformity after endoscopic conservative surgery.

From April 2002 to August 2003, 60 patients (41 patients undergoing quadrantectomy and 19 patients undergoing wide excision) with early-stage breast cancer underwent endoscopic breast-conserving surgery and volume replacement with absorbable materials. The average volume of resected tissue was 75 mL (range, 15-145 mL). The absorbable materials consisted of polyglycolic acid mesh (Dexon Mesh DMS#4 10 × 12) folded and wrapped in oxidized regenerated cellulose, which just fit into the dead space. We expected that the polyglycolic acid mesh would help induce granulation and fibrous tissue with reactive tissue fluid and that oxidized regenerated cellulose would prevent adhesion between the skin and the polyglycolic acid mesh (Figure 1). The absorbable materials were gently inserted into the dead space, and the wound was closed in 3 layers. We used 1 sheet of polyglycolic acid mesh and 1 sheet of oxidized regenerated cellulose if the volume loss was 70 mL. The cosmetic outcome was evaluated with a 4-point scoring system of breast cosmesis judged by breast surgeons.1 The scores of breast cosmesis were evaluated every 1 or 2 months at a clinic. The average evaluation time was 6.1 months after surgery (range, 2-12 months). A favorable cosmetic outcome (excellent) was obtained in 83% of patients (77% of patients undergoing quadrantectomy and 91% of patients undergoing wide excision). Dynamic contrast-enhanced magnetic resonance mammography and ultrasonography were performed routinely 3 months after the operation. The images showed that the dead space was lined by granulated scar tissue and filled with fluid. Deformity was almost completely prevented, and the symmetric images helped us to detect local recurrence. In 1 patient, multiple cancers were detected by pathologic examination after conservative breast surgery. Total mastectomy was performed 1 month after the previous operation, and the resected tissue in which polyglycolic acid mesh had been inserted was examined pathologically. Pathologic examination showed that the peripheral part of the dead space was encapsulated by granulation and fibrous tissue, and the mesh was decomposed and phagocytosed by macrophages. Complications of the film-screen mammography (FSM) method were inflammation and overproduction of fluid induced by the polyglycolic acid mesh. These findings were observed in 3 cases that had been diagnosed by open biopsy before surgery. We believe that the open biopsy procedure induced inflammation and overproduction of fluid in these patients. We now regard a history of open biopsy to be a contraindication for the FSM method. It is likely that polyglycolic acid mesh helps to promote granulation and to fill the reactive fluid space in the encapsulating scar. The FSM method is a simple and useful procedure for preventing breast deformity after conservative surgery.

Implantation on the suture material and efficacy of povidone-iodine solution

Suture implantation of viable exfoliated tumour cells may be responsible for local recurrence of colorectal cancer. Using a colon cancer cell line, we obtained a suture implantation without intraperitoneal metastasis in about 80% of the control animals, when sacrificed on the 2nd postoperative week. The cytotoxic efficacy of povidone-iodine (PVP-I) was tested in vivo by a rat model with viable intracaecal tumour cells, and in vitro by trypan blue exclusion and the MTT assay. In vivo PVP-I at 5% significantly reduced the incidence of tumour growth, while the product at 2.5% had a significant effect in only the monofilament polypropylene group. In an in vitro toxicity study, PVP-I higher than 0.16% was effective at killing almost all tumour cells. PVP-I had effective cytotoxicity in vivo and in vitro, being less cytotoxic in vivo than in vitro.

The β-catenin signaling pathway induces aggressive potential in breast cancer by up-regulating the chemokine CCL5

β-Catenin signaling plays a pivotal role in the genesis of a variety of malignant tumors, but its role in breast cancer has not been fully elucidated. Here, we examined whether deregulation of β-catenin signaling is related to the aggressive characteristics of certain types of breast cancers. Analysis of cytokine levels in MDA-MB-231 cells overexpressing a constitutively active form of β-catenin (CAβ-catenin) revealed a higher level of CCL5 expression. Cells transfected with CAβ-catenin or stimulated with recombinant CCL5 exhibited increased cell invasion activity and spheroid formation in vitro. Furthermore, CAβ-catenin-transfected MDA-MB-231 cells formed larger tumor masses that contained more Ki-67-positive cells and infiltrating lymphocytes than did the control cells. An inhibitor of CCR5 and a pan-CXCR neutralizing antibody dramatically reduced CAβ-catenin-promoted activities. In addition to CCL5, 6-BIO, a chemical activator of β-catenin, induced cell invasion and spheroid formation in MDA-MB-231 cells. Furthermore, high levels of nuclear β-catenin accumulation were detected in breast cancer in patients with metastasis but not in those without metastasis. Nuclear β-catenin localization is related to increased CCL5 production in breast cancer. These findings suggest that β-catenin expression enhances tumor progression via chemokine production in breast cancers and that β-catenin signaling is a critical regulator of the aggressive traits of breast cancers.

Infrequent mutations of the TP53 gene and no amplification of the MDM2 gene in hepatoblastomas

We have investigated the mutation of the TP53 gene in hepatoblastomas (HBLs) by using polymerase chain reaction‐single strand conformation polymorphism and direct sequencing in 38 HBL tumor samples and in two HBL cell lines. We detected the TP53 gene mutation in an anaplastic hepatoblastoma cell line, but no aberration of the TP53 gene (exons 5–9) was found in tumor samples and in the other HBL cell line. The mutation of the cell line was a missense mutation from GAC (asparagine) to CAC (histidine) at codon 281, which was different from the G‐to‐T transversion of codon 249 that is frequently found in adult hepatocellular carcinomas (HCCs). In addition, we performed Southern blot analysis of the MDM2 gene, but we did not find MDM2 gene amplification in 19 cases tested. Our results suggest that, in contrast to the findings in HCCs in adults, TP53 gene aberrations are not involved in the development or progression of HBLs in children. Genes Chromosom Cancer 15:187–190 (1996).

Steroid sulfatase in breast carcinoma and change of serum estrogens levels after operation.

Fifty-four breast carcinomas were studied for the expression of steroid sulfatase (STS) by immunohistochemistry. Correlations between the expression of STS and clinical parameters were determined. Concentrations of serum estrone (E1), estrone sulfate (E1S), estradiol (E2) and estradiol sulfate (E2S) in 12 postmenopausal patients with STS positive tumor were measured by radioimmunoassay. Positive expression of STS was obtained in 72% of tumors. The incidence of STS positive tumor was significantly more frequent in postmenopausal patients (p = 0.01). In our postmenopausal patients, serum E1, E1S, E2, E2S and E2S levels in STS high score group were decreased postoperatively, and those in both STS high and low score group were stabilized after operation. Results from this study suggest STS in breast carcinoma may play an important enzyme of the intratumoral estrogen synthesis in postmenopausal women, and it would be interesting that locally produced STS might be closely related to the control of estrogens environment in breast carcinoma.

Health-related quality of life in patients with advanced colorectal cancer: results from a phase II study of S-1 combined with irinotecan (CPT-11)

BackgroundWe carried out this study to examine the health-related quality of life (HRQOL) of patients with advanced colorectal cancer treated with the oral fluoropyrimidine S-1 plus irinotecan (CPT-11).MethodsHRQOL was assessed at baseline (pretreatment) and at 5-week intervals during treatment, using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR38 questionnaires. The HRQOL data for 12 preselected scales and 21 courses of treatment were then analyzed longitudinally.ResultsThirty-seven patients completed the baseline and post-treatment HRQOL assessments. Statistically significant differences between the baseline and post-treatment HRQOL scores were observed for the global QOL, social function, and pain scales (all QLQ-C30), as well as the body image, future perspective, gastrointestinal tract symptoms, weight loss, and chemotherapy side effects scales (all QLQ-CR38); favorable post-treatment results were observed for all the scales except for body image and chemotherapy side effects, for which post-treatment deteriorations were observed. The changes in body image, future perspective, weight loss, and chemotherapy side effects were each greater than ten points and seemed clinically significant.ConclusionCombined treatment with S-1 plus CPT-11 resulted in an acceptable deterioration in HRQOL functioning and symptoms, compared with baseline levels.

Health-related quality of life of colorectal cancer patients receiving oral UFT plus leucovorin compared with those with surgery alone

BackgroundAdjuvant chemotherapy of oral uracil/ftorafur (UFT) plus leucovorin (LV) has been accepted as the standard of care in the treatment of patients with stage II and III carcinoma of the colon. The objective of the study was to compare HRQOL reported by patients receiving oral UFT plus LV (UFT/LV group) versus no adjuvant treatment (control group) following surgery for colorectal cancer.MethodsNinety nine patients in the UFT/LV group and 83 in the control group participated. HRQOL was assessed with the European Organization for Research and Treatment of Cancer QLQ-C30 and HRQOL data measured longitudinally following surgery were compared between the groups.ResultsEighty-eight percent (87 of 99) received all scheduled doses of UFT plus LV during the first three cycles, and 82 percent (81 of 99) did so for five cycles. The most common type of toxicity in the UFT/LV group was fatigue, which was generally mild. Six patients each had grade 3 diarrhea or anorexia. There were significant differences in the scores for role function, and specific limitations such as fatigue, nausea, and vomiting, dyspnoea, appetite loss, and financial difficulties, which deteriorated in the UFT/LV group.ConclusionsHRQOL in colorectal cancer patients with adjuvant chemotherapy with oral UFT plus LV deteriorated during this phase of treatment compared with those with surgery alone, despite the biased stage of tumor between the groups. Symptom management and social support would improve HRQOL in such a group of patients.