Showing papers in "Japanese Journal of Clinical Oncology in 2004"

Comparisons of percent equol producers between prostate cancer patients and controls: case-controlled studies of isoflavones in Japanese, Korean and American residents.

Abstract: Background Our previous case-control study revealed that the Japanese residents in Japan could be divided into those who are able to degrade daidzein, a soybean isoflavone, to equol and those without this ability, and that the incidence of prostate cancer is higher in the latter group. Methods We recently conducted a similar case-control study involving not only Japanese residents in Japan but also Korean residents in Korea. The incidence of prostate cancer in Korean residents is known to be close to that of Japanese residents in Japan. On the other hand, American residents in the United States have a markedly higher incidence of prostate cancer as compared to Japanese residents in Japan. Results The number of subjects was 295 in Japan (133 patients and 162 controls), 122 in Korea (61 patients and 61 controls) and 45 in the United States (24 patients and 21 controls). The percentage of equol producers among patients and controls was 29% and 46% in Japan (P = 0.004) and 30% and 59% in Korea (P = 0.001), respectively. The active isoflavone level was markedly lower and the percentage of equol producers was also lower (17% for patients and 14% for controls) for Americans as compared to the Japanese and Koreans. Conclusions These results suggest that the ability of producing equol or equol itself is closely related to the lower incidence of prostate cancer. The results also suggest that a diet based on soybean isoflavones will be useful in preventing prostate cancer.

Phase II Study of Cisplatin and 5-Fluorouracil with Concurrent Radiotherapy in Advanced Squamous Cell Carcinoma of the Esophagus: a Japan Esophageal Oncology Group (JEOG)/Japan Clinical Oncology Group Trial (JCOG9516)

Abstract: Background In Japan, concurrent chemoradiotherapy is the standard treatment for unresectable esophageal cancer. The optimal combination of chemotherapeutic agents and radiotherapy dose remains controversial. The present study consists of a phase II trial of a cisplatin (CDDP)/5-fluorouracil (5-FU) infusion with concurrent radiotherapy in patients with unresectable, advanced esophageal cancer. Methods Between March 13, 1996, and April 28, 1998, 60 patients with advanced squamous cell carcinoma of the thoracic esophagus having either T4 tumor or distant lymph node metastasis (M1 Lym) were enrolled in this study. CDDP 70 mg/m(2) was administered on days 1 and 29, and 5-FU 700 mg/m(2)/day was administered on days 1-4 and 29-32. Fractionated radiotherapy was performed on days 1-21 and 29-49; a total dose of 60 Gy was delivered at the rate of 2 Gy per fraction. Results The overall response rate of all the 60 registered patients was 68.3% (41/60), and the complete response rate was 15% (9/60). The median survival time was 305.5 days, and the 2-year survival rate was 31.5%. One toxicity-related death occurred. The major form of toxicity exceeding grade 2 was found to be myelosuppression; grade 4 toxicity was observed in five patients. Conclusion Based on the overall response rate, the results obtained from the present trial do not appear to be promising. However, it is currently suitable for the treatment of patients with unresectable, advanced esophageal cancer because of certain clinical advantages, a higher CR rate and a lower incidence of fistula formation. A phase II/III trial will be started in order to compare low-dose continual CDDP/5-FU infusion and concurrent radiotherapy with the results obtained in this study.

Anatomical features of periprostatic tissue and its surroundings: a histological analysis of 79 radical retropubic prostatectomy specimens.

Abstract: Background: A proper understanding of prostatic and periprostatic anatomy is essential for surgical procedures and pathological diagnosis; however, the detailed features have not been commonly investigated and completely understood. Methods: Seventy-nine non-nerve-sparing radical prostatectomy specimens were microscopically investigated for Denonvilliers’ fascia, lateral pelvic fascia, prostatic capsule, anterior fibromuscular stroma and the neurovascular bundle. Results:Atthelateralaspect,thelateralpelvicfasciaandtheprostaticcapsulewereseparatedby adipose tissue in 41 cases (52%), whereas they adhered in 38 cases (48%). In only 41 cases (52%), the neurovascular bundle existed locally at the postero-lateral region with definite‘bundle’ formations. Denonvilliers’ fascia and the prostatic capsule adhered tightly at the center of the posterior aspect in 77 cases (97%). A smooth transition from the prostatic capsule to the anterior fibromuscular stroma was observed in all cases. In 70 cases (89%), no prostatic capsule was independentlyrecognizedattheanterioraspect.Intheremaining9cases(11%),thecapsulewas recognizable as distinct from the anterior fibromuscular stroma. In 67 cases (85%), the lateral pelvic fascia connected and fused with the anterior fibromuscular stroma, and covered the outermost regions of the lateral and anterior surfaces. Conclusions: All the periprostatic structures are closely related and influence each other. The results support the rationale of anatomical radical prostatectomy, and should be taken into consideration for surgical procedures and pathological diagnosis.

Epidemiology and prevention of pancreatic cancer.

Abstract: Pancreatic cancer is an uncommon tumor, but because the mortality rate approaches 100%, this form of cancer has now become a common cause of cancer mortality. In the United States it is the fourth most frequent cause of cancer mortality; in Japan it ranks as the fifth commonest cause of death from cancer. Smoking is the major known risk factor for pancreatic cancer, accounting for approximately 25-30% of all cases. Some of the time-dependent changes in the frequency of pancreatic cancer can be explained by smoking trends. Aggressive public health measures to control smoking would substantially reduce the burden of pancreatic cancer. Dietary factors are less important for pancreatic cancer than for other digestive tract tumors, but consumption of a diet with adequate quantities of fruits and vegetables, plus control of calories either by dietary measures or by exercise will help to prevent this lethal tumor. There are more than a dozen inherited germline mutations that increase the risk of pancreatic cancer. Of these, hereditary pancreatitis confers the greatest risk, while BRCA2 mutations are the commonest inherited disorder. In addition to germline defects, there are several common polymorphisms in genes that control detoxification of environmental carcinogens that may alter the risk of pancreatic cancer. More research will be needed in this area, to explain and to clarify the interaction between genes and environmental factors.

Skeletal muscle metastases of carcinoma: a clinicopathological study of 12 cases.

Abstract: Objective To clarify the clinical and magnetic resonance (MR) imaging features of a rare condition of metastasis of carcinoma to skeletal muscle. Method Clinicopathological findings for 12 patients (10 male, two female, age range 48-89 years, mean age 68 years) with skeletal muscle metastases of carcinomas were reviewed retrospectively. Results In nine of the 12 patients the skeletal muscle metastasis was presented as "painful mass". The lung was found to be the most common primary source, accounting for 33% of the cases, and the lower extremity was the most common metastatic site, accounting for 67% of the current series. Diagnosis was made by biopsy in all cases. Overall, MR images were not specific, but on the gadolinium-DTPA enhanced MR images, extensive peritumoral enhancement associated with central necrosis was found in 11 of the 12 patients (92%). Seven patients died within 2-19 months (average: 9 months) after the detection of the skeletal muscle metastasis, among whom only one patient was continuously disease free for 92 months after wide excision of the metastatic lesion. Conclusion Skeletal muscle metastasis is often presented as a painful mass in patients with known primary carcinoma. For diagnosis, needle biopsy is mandatory. However, a painful mass with an extensive peritumoral enhancement should be highly suspected to represent carcinoma metastasis to skeletal muscles. In selected patients, wide excision with combined chemotherapy could yield unexpectedly good results.

Extrapulmonary Small-cell Carcinoma: a Single-institution Experience

Abstract: Background: Extrapulmonary small-cell carcinoma (EPSCC) has been recognized as a clinicopathological entity distinct from small-cell carcinoma (SCC) of the lung. This study aimed to review the clinical features, therapy and natural course of patients with EPSCC in Oriental single-institution series. Methods: We retrospectively reviewed the medical records of patients with SCC between September 1995 and December 2002. Study eligibility required that patients had pathologically proven SCC in sites other than lung and normal radiological findings of the chest and normal sputum cytology or negative bronchoscopic findings. Results: Twenty-four patients with EPSCC were identified and primary sites were various: uterine cervix in seven (29%), urinary bladder in five, colon or rectum in three, kidney in two and stomach, esophagus, pancreas, common bile duct, larynx, parotid gland, thymus in one each. Sixteen patients (66.7%) had limited disease (LD) and eight had extensive disease (ED). Patients with ED received mostly platinum-based chemotherapy, for which the response rate was 57%, but showed an aggressive natural history, with median overall survival (OS) of 9.2 months. Patients with LD were treated with a variety of therapeutic modalities. LD SCC of the cervix showed a favorable clinical course, with five patients being disease-free with a median follow-up of 28.4 months. Patients with LD SCC of sites other than cervix had an aggressive course with a median OS of 9.6 months. Conclusion: EPSCC was identified in various sites, with the most common primary site being the uterine cervix. Regardless of the primary site or disease stage, EPSCC of sites other than cervix was usually a fatal disease with a discouraging outcome for various treatment modalities.

Evaluation of oxidative stress and nitric oxide levels in patients with oral cavity cancer

Abstract: Objective: The aim of this study was to evaluate the magnitude of oxidative stress and levels of nitric oxide in patients with oral cavity cancer by analyzing the levels of lipid peroxidation products, antioxidants and nitric oxide products. Methods: This prospective study was conducted on 15 patients with biopsy proven squamous cell cancer of the oral cavity with clinical stage III/IV and an equal number of age and sex matched healthy subjects. The levels of lipid peroxidation products, antioxidants and nitric oxide products were determined by colorimetric methods. Results: Lipid peroxidation products like lipid hydroperoxide (LHP) and malondialdehyde (MDA) and nitric oxide products like nitrite (NO2 – ), nitrate (NO3 – ) and total nitrite (TNO2 – ) were significantly elevated, whereas enzymatic and non-enzymatic antioxidants were significantly lowered in oral cavity cancer patients when compared to normal healthy subjects. Conclusions: Enhanced lipid peroxidation with concomitant decrease in antioxidants is indicative of oxidative stress that provides evidence of the relationship between lipid peroxidation and oral cavity cancer. Increased nitric oxide production represents a general mechanism in its pathogenesis.

Primary pulmonary non-Hodgkin's lymphoma.

Abstract: Background Primary pulmonary non-Hodgkin's lymphoma is a very rare neoplasm. It is represented most commonly by marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. Although there have been a few reviews of this lymphoma, clinical features, diagnostic procedure, optimal management and prognostic factors have not been well defined. Methods We reviewed the medical records of 24 patients who were pathologically and clinically diagnosed as primary pulmonary lymphoma between September 1995 and June 2003. Results There were 13 patients with MALT lymphoma and two with MALT lymphoma accompanied by large B-cell lymphoma, seven with diffuse large B-cell lymphoma and two with anaplastic large cell lymphoma. Half the patients were asymptomatic at presentation; 46% had respiratory symptoms and 16.7% had B-symptoms. Initial radiological findings were variable including nodules, masses, infiltrates or consolidation. The majority of patients (66.7%) needed surgical approaches (open thoracotomy or video-assisted thoracoscopy) for definite diagnosis. Bronchoscopy was performed in 83%, but only 30% showed a diagnostic yield. The 13 patients with MALT lymphoma were treated with a variety of modalities such as observation, surgery and single or combination chemotherapy, and combination chemotherapy was administered to 11 patients with non-MALT lymphoma regardless of surgery. The overall survival rate at 3 years for all 24 patients was 86% with a median follow-up of 32 months. Conclusion Although this entity of lymphoma appears to have a good prognosis, further clinical experience and long-term follow-up are needed to identify prognostic factors.

Diffusion-weighted Single Shot Echo Planar Imaging of Colorectal Cancer Using a Sensitivity-encoding Technique

Abstract: Background We wanted to determine the feasibility of diffusion-weighted single shot echo planar imaging using a sensitivity-encoding technique (SENSE-DWI) in depicting colorectal cancer. Methods Forty-two patients with sigmoid colon cancer and rectal cancer, all proven pathologically, were examined on T2-turbo spin echo (TSE) and SENSE-DWI. No bowel preparation was performed before examination. The b-factors used in SENSE-DWI were zero and 1000 s/mm(2). In 10 randomly selected cases, the images whose b-factors were 250 and 500 s/mm(2) were also obtained. The reduction factor of SENSE was 2.0 in all sequences. Two radiologists evaluated the obtained images from the viewpoints of tumor detectability, image distortion and misregistration of the tumors. The apparent diffusion coefficients (ADCs) of the tumors and urine in the urinary bladders in each patient were measured to evaluate the correlation between ADC and pathological classification of each tumor. Results All tumors were depicted hyperintensely on SENSE-DWI. Even though single shot echo planar imaging (EPI) was used, the image distortion and misregistration was quite pronounced because of simultaneous use of SENSE. On SENSE-DWI whose b-factor was 1000 s/mm(2), the normal colon wall and feces were always hypointense and easily differentiated from the tumors. The mean ADC value of each tumor was 1.02 +/- 0.1 (x 10(-3)) mm(2)/s. No overt correlation can be pointed out between ADC and pathological classification of each tumor. Conclusion SENSE-DWI is a feasible method for depicting colorectal cancer. SENSE-DWI provides strong contrast among colorectal cancers, normal rectal wall and feces.

Three-dimensional Conformal Radiation Therapy for Unresectable Hepatocellular Carcinoma Patients who had Failed with or were Unsuited for Transcatheter Arterial Chemoembolization

Abstract: Background The purpose of our study was to evaluate the outcome of unresectable hepatocellular carcinoma (HCC) patients, who had either failed with or were unsuited for transcatheter arterial chemoembolization (TACE), treated with three-dimensional conformal radiation therapy (3DCRT) and to determine the prognostic outcome factors. Methods From September 1999 to March 2003, 44 patients with unresectable HCC underwent 3DCRT. Thirty-seven patients were male and seven female. Mean age was 62 years, ranging from 34 to 88. Eastern Cooperative Oncology Group (ECOG) performance status was 0 in 10 patients, 1 in 19 patients, and 2 in 15 patients. According to Child-Pugh classification for cirrhosis of the liver, 32 patients were in class A and 12 patients in class B. There were 14 patients with main portal vein thrombosis. Twenty patients had alpha-fetoprotein (AFP) level >400 ng/ml. Tumor size was 10 cm in 12 patients. Thirty-two patients had tumors of confluent type, the remaining patients presented a single hepatic tumor. Serum hepatitis antigen markers were positive for type B in 35 patients and type C in nine patients. Twenty-one patients had Okuda Stage I, 22 patients Stage II, and one patient Stage III. According to the AJCC staging system (5th edition), eight patients were in Stage II (T2N0M0), 19 in Stage IIIA (T3N0M0) and 17 in Stage IVA (T4N0M0). Results An objective response was observed in 27 of 44 patients, giving a response rate of 61.4%. The survival rates at 1, 2 and 3 years were 60.5%, 40.3% and 32.0%, respectively. In the analysis of prognostic factors, Okuda stage, AJCC stage, portal vein thrombosis, pretreatment AFP level, and total dose of radiotherapy all had significant impact on survival. Conclusions 3DCRT induced a substantial tumor response rate of 61.4% with survival rates at 1, 2 and 3 years of 60.5%, 40.3% and 32.0%, respectively, and a median survival time of 15.2 months in patients with unresectable HCC who had either failed with or were unsuited for TACE. The complications are acceptable and can be managed with conservative treatment. Although we do not know whether there is a survival benefit through the use of this treatment, 3DCRT seems to be a practical method of salvage for this subset of patients. Further study is warranted to evaluate the survival of such patients with and without this treatment.

Bax to Bcl-2 ratio and Ki-67 index are useful predictors of neoadjuvant chemoradiation therapy in bladder cancer.

Abstract: Objective: In this study, locally advanced bladder cancer was treated by radiation combined with cisplatin therapy and a retrospective analysis was conducted to predict the clinical response to chemoradiotherapy (CRT) based on the immunohistochemistry of apoptosisrelated proteins. Methods: Sixty-two patients (median age, 68 years; range, 45–89 years) with transitional cell carcinoma of the bladder (pT1G3–pT4M0) treated with CRT (median dose: 40.5 Gy of radiation and 230 mg of cisplatin) were studied. Mucosal biopsy was performed before and after CRT. Paraffin-embedded tumor specimens were examined with TUNEL and were immunostained for Ki-67, p53, Bcl-2 and Bax; the Bax/Bcl-2 ratio and apoptosis index (AI) were calculated. Clinical features of the patients and response to CRT were compared with data obtained from examination of the tumors. Results: The 62 patients had a median follow-up period of 34 months (range, 3–84 months). Responses to CRT were as follows: CR, 34%; PR, 45%; NC, 21%. The survival rate of patients with Ki-67-positive tumors was significantly lower than those of patients with Ki-67-negative tumors (P < 0.05). No significant correlation was observed between the expression of any protein, the AI and the clinical response. However, the Bax/Bcl-2 ratio showed a significant association with the CR rate (P = 0.0289). Conclusions: The results of this study suggest that the combined assessment of Bcl-2 and Bax protein expression may be used to predict a clinical response to CRT based on the Bax/ Bcl-2 ratio determined before therapy. The Ki-67 index may be a useful predictor of prognosis in patients treated by CRT.

Long-term survival and prognostic factors in patients with metastatic gastric cancers treated with chemotherapy in the Japan Clinical Oncology Group (JCOG) study.

Abstract: Background: The long-term survival of patients after chemotherapy for advanced gastric cancer remains unclear. The aim of this analysis was to investigate prognostic factors for patients with metastatic gastric cancer treated by chemotherapy, and to identify the characteristics of long-term survivors. Methods: Six hundred and forty three patients were enrolled in four phase II studies and one phase III study by the Japan Clinical Oncology Group between January 1985 and April 1997. By adjusting patients' eligibility between the five studies, 497 patients (77%) were selected for the analysis. Univariate and multivariate analyses were performed using log-rank tests and Cox's proportional hazard model, respectively. Results: Of the 497 patients analyzed, 39 (8%) and 11 (2%) patients have survived longer than 2 and 5 years, respectively. By multivariate analysis, better performance status, a small number of metastatic sites and macroscopically non-scirrhous type tumors were significantly associated with better prognosis. Characteristics of the 11 5-year survivors revealed eight with para-aortic node metastases alone. Eight of these patients received gastrectomy; four underwent it before chemotherapy, and the other four patients received it after achieving downstaging with successful chemotherapy. Conclusions: These results demonstrated that better performance status, a small number of metastatic sites and macroscopically non-scirrhous type tumors are independent favorable factors for survival. There were a few 5-year survivors with unresectable gastric cancers, most of whom had only abdominal lymph node metastases and received gastrectomy before or after chemotherapy.

Superior Anti-tumor Efficacy of Bicalutamide 80 mg in Combination with a Luteinizing Hormone-releasing Hormone (LHRH) Agonist Versus LHRH Agonist Monotherapy as First-line Treatment for Advanced Prostate Cancer: Interim Results of a Randomized Study in Japanese Patients

Abstract: OBJECTIVES: To evaluate bicalutamide (Casodex) 80 mg as a component of maximum androgen blockade (MAB) in Japanese patients with previously untreated advanced prostate cancer. METHODS: 205 patients with previously untreated stage C/D prostate cancer were randomized (1:1) to receive once-daily bicalutamide 80 mg or placebo, each combined with a luteinizing hormone-releasing hormone (LHRH) agonist. Primary study variables were the 12 week prostate-specific antigen (PSA) normalization (i.e. PSA level

Magnetic anchor for more effective endoscopic mucosal resection.

Abstract: Background Technical difficulties are involved in endoscopic mucosal resection (EMR) of gastric cancer since it is a "one handed surgery". These difficulties prevent this technique from being indicated for larger lesions, even when it can possibly be performed for patients with such lesions. If microforceps could assist EMR, this procedure would become easier and safer. Since magnetic force can control objects without direct contact, it can be applied to control microforceps internally in assistance with EMR. Methods We developed a magnetic anchor consisting of three parts: a magnetic weight with dimensions of 1.0 x 1.0 x 1.5 cm, microforceps and a connecting thread. Endoscopic clips used in hemostasis were used as the microforceps of the magnetic anchor in this study. The magnetic control system consisted of a 0.68 kOe/10 cm/100 A electromagnet, 350 mm in diameter and a circumventing positional frame. The microforceps were inserted into a sheath within the endoscope, and the magnetic weight was secured to the tip of the sheath protruding from the endoscope. The magnetic anchor, along with the endoscope, was inserted through an overtube into the gastric cavity of a swine under general anesthesia. The magnetic anchor was used in a manner similar to that in standard surgery, and EMR was thereby performed. Results The mucosa to be resected was satisfactorily dragged and stabilized. The magnetic anchor facilitated EMR, regardless of the technical skills of the endoscopist and region of the stomach at which the technique was performed. Conclusion The magnetic anchor is considered to have alleviated some technical problems involved in EMR. It has the potential for making EMR a safer and quicker procedure for the treatment of early gastric cancer, when appropriately indicated.

Weekly Irinotecan in Patients with Metastatic Gastric Cancer Failing Cisplatin-based Chemotherapy

Abstract: Background The goal of this study is to determine the efficacy and toxicity of weekly irinotecan as second-line chemotherapy in advanced gastric cancer after failure of cisplatin-based regimen. Methods Gastric cancer patients failing cisplatin-based chemotherapy received 125 mg/m(2) of irinotecan weekly for 4 weeks followed by 2-week rest, until disease progression. Results Thirty-seven patients were enrolled into this study. The objective response was documented in seven of 35 patients with measurable lesion (response rate 20%, 95% CI: 6.1-33.9). Eight patients (22.9%) had stable disease and overall tumor control rate was 42.9%. The disease remained stable in both of two patients without measurable disease. At a median follow-up duration of 15.8 months, median time to progression and overall survival were 2.6 months (95% CI: 2.4-2.8) and 5.2 months (95% CI: 3.6-6.7), respectively. Neutropenia and diarrhea were the main toxicities. Among 37 patients treated, grade 3/4 (G3/4) neutropenia occurred in 43.2/24.3% of patients, respectively, and was accompanied with fever in three patients. Non-hematologic toxicities consisted mainly of delayed diarrhea (G3/4, 18.9/0%) and nausea/vomiting (G3/4, 18.9/0%). These toxicities were manageable and there was no treatment-related death. Conclusions This weekly schedule of irinotecan was modestly active against cisplatin-refractory gastric cancer and relatively well-tolerated with appropriate dose modification.

Robotic surgery and cancer: the present state, problems and future vision.

Abstract: In the 1990s, laparoscopic surgery entirely changed the traditional style of surgical operations. Laparoscopic cholecystectomy has spread rapidly and is now established as the standard treatment. However, besides cholecystectomy, endoscopic procedures are still not applied so widely to a variety of surgical operations. This is because laparoscopic techniques, such as suturing or ligation, make it difficult for surgeons to perform other kinds of operations and thus greatly increase their mental and physical stress. It is necessary to introduce various advanced technologies such as: surgical robots, three dimensional (3D) images, computer graphics (CG), computer simulation technology and others. Surgical robots, including the AESOP, da Vinci and ZEUS systems, provide surgeons with technologically advanced vision and hand skills. As a result, such systems are expected to revolutionize the field of surgery. However, there have so far been few studies which discuss the indications of robotic surgery for tumors/ cancer. Therefore, herein we review various studies published in English to focus on the application of robotic surgery to tumors/cancer. We point out that there are several problems to be solved for robot surgery: i) price of surgical robots, ii) training systems for surgeon, iii) coverage by medical insurance, iv) downsizing and v) navigation system. In conclusion, we believe that, in the near future as robotic technology continues to develop, almost all kinds of endoscopic surgery will be performed by this technology. It will replace traditional surgery not only in the treatment of benign diseases but also in malignant illnesses.

Tumor Doubling Time of Renal Cell Carcinoma Measured by CT: Collaboration of Japanese Society of Renal Cancer

Abstract: OBJECTIVE This study was conducted to examine the natural history of renal cell carcinoma (RCC). METHODS Inclusion criteria were the following: (1) patients who received diagnostic imaging of the kidney (CT, MRI) at two points in time before the diagnosis of RCC or patients who were followed, without treatment, after a diagnosis of RCC; and (2) patients in whom changes in tumor size were followed by the same modality of diagnostic imaging and who did not receive any treatment which could exert anti-tumor activity on the primary or metastatic lesions. The tumor doubling time (DT) and the growth rate of maximum tumor diameter (R) were determined. DT was calculated using the equation DT = (T - T(0)) x log2/logV - logV(0) (where T - T(0) indicates the length of time between two measurements and V(0) and V denote the tumor volume at two points of measurement). R was calculated using the equation R = (phi - f(0))/(T - T(0)) x 100 (where phi(0) and f indicate the maximum diameter at two points). Fifty-six cases registered with the Japanese Society of Renal Cancer were included in the evaluation. RESULTS DT was 603.1 +/- 510.1 days, which did not correlate with V(0). R was 0.263 +/- 0.346 cm/day x 100. In cases where the tumor diameter was >/=4 cm, a significant correlation was noted between f(0) and R. CONCLUSIONS Elucidation of the natural history of RCC will contribute to facilitation of differential diagnosis and determination of optimum therapeutic strategy.

Clinicopathologic features of asymptomatic gastric adenocarcinoma patients in Korea.

Abstract: Objective: The aim of this study was to analyze the characteristics of patients diagnosed with gastric adenocarcinoma without the presence of symptoms and to evaluate the usefulness of screening programs for gastric cancer in Korea. Methods: We retrospectively analyzed the characteristics of 1277 gastric adenocarcinoma patients at Seoul National University Hospital (SNUH) (665 in 1996; 612 in 2001) by dividing them into two groups according to the presence or absence of symptoms (symptomatic group vs asymptomatic group). Results: The proportion of asymptomatic patients increased from 1996 (4.7%) to 2001 (17.2%) (P < 0.001). Gastroscopy was the most commonly used screening tool (77.4% in 1996, 95.2% in 2001). The proportion of early gastric cancer (EGC) in the asymptomatic group was higher than in the symptomatic group (74.2% vs 25.9% in 1996, 78.1% vs 35.7% in 2001) (P < 0.001). The curative operation rate was significantly higher in the asymptomatic group. The asymptomatic group had a higher 5-year survival rate (87.7%) than the symptomatic group (51.6%) (P < 0.01). Complementary data from a screening program at the SNUH showed that 19 gastric cancer cases (0.76%) were detected out of 2501 endoscopic examinations; of these, 78.9% (15/19) were early gastric cancer cases, which is in agreement with our results. Conclusion: Patients with asymptomatic gastric adenocarcinoma had fewer advanced lesions, a greater chance for curative operation and a higher survival rate than symptomatic patients. An increase in the number of asymptomatic patients contributed to the increase in overall EGC from 1996 to 2001. These results seemed to support the usefulness of gastroscopy as a screening test for gastric cancer in Korea, where the incidence of gastric cancer is high.

Adequacy of cancer pain management in a Japanese Cancer Hospital.

Abstract: The available data were obtained from 138 ambulatory cancer patients with pain.The data included pain severity, which patients reported using the Japanese version of the M. D.Anderson Symptom Inventory, along with such medical information as cancer and treatmentinformation and currently prescribed analgesics. Adequacy of pain management was assessedusing the Pain Management Index, which revealed whether prescribed analgesic drugs werecongruent with pain severity.

Evaluation of Intraoperative Frozen Section Diagnosis of Sentinel Lymph Nodes in Breast Cancer

Abstract: Background: Intraoperative frozen sections (FS) of sentinel lymph nodes (SLNs) can be used to detect metastatic disease, allowing immediate axillary lymph node dissection (ALND). However, pathological inconsistency in the SLNs diagnosis is sometimes encountered when the results of FS and permanent sections are compared. The purpose of this study was to reveal the usefulness and limitations of FS for the diagnosis of SLNs in patients with breast cancer. Methods: We reviewed the results for 569 patients with breast cancer at stage 0–II who underwent a sentinel node biopsy between February 1998 and December 2002. SLNs were analyzed using standard FS procedures and a single section stained with hematoxylin and eosin was examined. Patients determined to have positive SLNs based on the results of the FS diagnosis immediately underwent ALND. Permanent sections were later prepared from the remaining frozen tissues and examined using hematoxylin and eosin staining without additional immunohistochemical staining. Results: Seven cases (1%) with atypical cells were found in the FS diagnosis intraoperatively, which were counted as ‘negative’ by the following analysis. The final pathology results showed metastasis in the SLN sections in 159 patients (28%), of whom 26 were diagnosed as negative by the FS diagnosis. Accuracy, specificity and the false-negative rate were 95, 100 and 16%, respectively. The mean size of the nodal metastases in the false-negative cases was significantly smaller than that in the true-positive cases (n = 72) (P < 0.01). False-negative rates for T1b, T1c and T2 were 33, 19 and 14%, respectively. The rate of micrometastasis in T1 (43%) was significantly higher than that of T2 (13%) (P < 0.01). Conclusions: FS diagnosis for SLNs is reliable. Patients with negative SLNs by the FS diagnosis can avoid reoperation for ALND. However, FS may fail to detect micrometastases, especially in cases with small tumors.

Successful Pregnancy and Delivery in a Patient with Chronic Myelogenous Leukemia (CML), and Management of CML with Leukapheresis during Pregnancy: a Case Report and Review of the Literature

Abstract: Although infrequently seen, the management of cancer during pregnancy can be difficult for patients, their families and physicians. The concomitant occurrence of pregnancy and chronic myelogenous leukemia is uncommon. We describe the successful management of a 26-year-old woman in the first trimester of her pregnancy with chronic myelogenous leukemia (CML) in chronic phase by using only leukapheresis. She was treated with leukapheresis until her delivery at 36 weeks of gestation. The procedure was without significant adverse effects on the patient or fetus. We applied a total of 15 leukapheresis treatments throughout the pregnancy. The patient gave birth vaginally to a healthy 2800 g boy at 36 weeks of gestation. We conclude that leukapheresis may provide an alternative treatment to chemotherapy, alpha-interferon or imatinib in pregnant patients with CML, particularly with concern over their potential teratogenic and other adverse effects.

Involvement of Viral and Chemical Factors with Oral Cancer in Taiwan

Abstract: Background: The association between oral squamous cell carcinoma (OSCC) and viral and chemical factors is uncertain. Therefore the correlation of viral and chemical factors with oral cancer in Taiwan was investigated. Methods: Thirty-seven paraffin-embedded oral cancer biopsies and 36 normal oral tissue specimens were examined by the polymerase chain reaction method for six viruses: HPV, CMV, EBV, HSV-1, HSV-2 and HHV-8. To elucidate the role of arecoline in the oncogenesis of oral cancer, human buccal fibroblasts, oral submucosal fibroblasts and three cancer cell lines KB, GNM and TSCCa were used for MTT cytotoxity assay and flow cytometry DNA content analysis. Results: Two (5.4%) HSV-1-positive and four (10.8%) HPV-positive cases were recognized in oral cancer biopsies. Among the four HPV-positive tissues, two were further typed as HPV-16, one was identified as HPV-18- and HSV-1-positive; and one contained both HPV-16 and HPV18. One sample presented HSV-1 only. Arecoline, at a concentration lower than 0.8 µg/ml, increased cell growth (all cell types); at higher concentrations (25–400 µg/ml) it was cytotoxic. The cell cycle was demonstrated to be altered either by low or high concentrations of arecoline treatment, depending on the cells treated. Conclusions: The data demonstrated that HPV, HSV-1 and betel quid chewing were significantly associated with OSCC, but HSV-2, CMV, EBV and HHV-8 were not. We suggest that the most determinative factor for oral cancer may be chemical in nature rather than viral infection.

Radical cystectomy for invasive bladder cancer: results of multi-institutional pooled analysis.

Abstract: Background: We report the outcome of radical cystectomy for patients with invasive bladder cancer, who did not have regional lymph node or distant metastases, at 21 hospitals Methods: Retrospective, non-randomized, multi-institutional pooled data were analyzed to evaluate outcomes of patients who received radical cystectomy Between 1991 and 1995, 518 patients with invasive bladder cancer were treated with radical cystectomy at 21 hospitals Of these, 250 patients (483%) received some type of neoadjuvant and/or adjuvant therapy depending on the treatment policy of each hospital Results: The median follow-up period was 44 years, ranging from 01 to 114 years The 5- year overall survival rate was 58% for all 518 patients The 5-year overall survival rates for patients with clinical T2N0M0, T3N0M0 and T4N0M0 were 67%, 52% and 38%, respectively The patients with pT1 or lower stage, pT2, pT3 and pT4 disease without lymph node metasta- sis had 5-year overall survivals of 81%, 74%, 47% and 38%, respectively The patients who were node positive had the worst prognosis, with a 30% overall survival rate at 5 years Neo- adjuvant or adjuvant chemotherapy did not provide a significant survival advantage, although adjuvant chemotherapy improved the 5-year overall survival in patients with pathologically proven lymph node metastasis Conclusions: The current retrospective study showed that radical cystectomy provided an overall survival equivalent to studies reported previously, but surgery alone had no more poten- tial to prolong survival of patients with invasive cancer Therefore, a large-scale randomized study on adjuvant treatment as well as development of new strategies will be needed to improve the outcome for patients with invasive bladder cancer

Prostate Stem Cell Antigen (PSCA) Expression in Human Prostate Cancer Tissues: Implications for Prostate Carcinogenesis and Progression of Prostate Cancer

Abstract: Objective: Prostate stem cell antigen (PSCA) is a recently defined homolog of the Thy-1/Ly-6 family of glycosylphosphatidylinositol (GPI)-anchored cell surface antigens. The objective of the present study was to examine the expression status of PSCA protein and mRNA in clinical specimens of human prostate cancer (PCa) and to validate it as a potential molecular target for diagnosis and treatment of PCa. Methods: Immunohistochemical (IHC) and in situ hybridization (ISH) analyses of PSCA expression were simultaneously performed on paraffin-embedded sections of 20 benign prostatic hyperplasia (BPH), 20 prostatic intraepithelial neoplasm (PIN) and 48 prostate cancer (PCa) tissues, including 9 androgen-independent prostate cancers. The level of PSCA expression was semiquantitatively scored by assessing both the percentage and intensity of PSCApositive staining cells in the specimens. We then compared the PSCA expression between BPH, PIN and PCa tissues and analyzed the correlations of PSCA expression level with pathological grade, clinical stage and progression to androgen-independence in PCa. Results: In BPH and low grade PIN, PSCA protein and mRNA staining were weak or negative and less intense and uniform than that observed in high grade PIN (HGPIN) and PCa. Moderate to strong PSCA protein and mRNA expression were noted in 8 of 11 (72.7%) HGPIN and in 40 of 48 (83.4%) PCa specimens examined by IHC and ISH analyses, and their statistical significance was compared with BPH (20%) and low-grade PIN (22.2%) specimens (P < 0.05). The expression level of PSCA increased with a higher Gleason grade, advanced stage and progression to androgen-independence (P < 0.05). In addition, IHC and ISH staining revealed a high degree of correlation between PSCA protein and mRNA overexpression. Conclusions: Our data demonstrate that PSCA as a new cell surface marker is overexpressed in a majority of cases of human PCa. PSCA expression correlates positively with adverse tumor characteristics, such as increasing pathological grade (poor cell differentiation), worsening clinical stage and androgen-independence and speculatively with prostate carcinogenesis. PSCA may possess prognostic utility and may be a promising molecular target for diagnosis and treatment of PCa.

Survival rates of childhood cancer patients in Osaka, Japan.

Abstract: Background Survival of childhood cancer patients is often described in specialized hospitals and/or institutions, but not in the general population. Methods The trends and patterns of childhood cancer survival during 20 years were investigated using the Osaka Cancer Registry's data. The study subjects were 3443 reported cases diagnosed as having the first primary cancer between 1975 and 1994 at the ages of 0-14 years and who lived in Osaka Prefecture, excluding Osaka City. All childhood cancers were classified into 12 diagnostic groups according to the International Classification of Childhood Cancer based on the histology of the cancer. The 5 year relative survival was calculated by the Ederer II method. Results The 5-year relative survival was 58% for all cancers. The survivals of retinoblastoma and kidney tumor patients were as high as 89 and 72%, respectively, whereas those of leukemia and liver tumor patients were as low as 45 and 47%, respectively. When divided into the first and second half-periods, the survival for all cancers was markedly improved from 48 to 68%. The survivals, especially for patients with leukemia, lymphoma, neuroblastoma, hepatoma and gonadal or embryonal tumors, were enhanced by >20% between the first and second half-periods. When these results were compared with those reported in England and Wales and the USA, however, the survivals for many diagnostic groups in Osaka were lower, except that for neuroblastoma. Conclusions The survivals of childhood cancer patients have been markedly improved in Japan, but this finding suggested that the introduction and practice of chemotherapy was insufficient.

The correlation of microsatellite instability and tumor-infiltrating lymphocytes in hereditary non-polyposis colorectal cancer (HNPCC) and sporadic colorectal cancers: the significance of different types of lymphocyte infiltration.

Abstract: Background: Tumor-infiltrating lymphocytes (TIL) are strictly divided into two categories: those lymphocytes in stroma and those in between cancer cells. However, there has been no fully adequate comparison of these two categories, especially analysis in relation to microsatellite instability (MSI). Methods: The materials were derived from patients with colorectal cancer who underwent surgery in Jichi Medical School and Omiya Medical Center. There were 19 hereditary non-polyposis colorectal cancer (HNPCC) patients who were compatible with Japanese criteria A and 106 patients with sporadic colorectal cancer (sCRC) in either Dukes B or C stage. As microsatellite markers, the global standard five markers were selected. Immunohistochemical analysis was performed using the anti-CD3, -CD4, -CD8 and -S-100 antibodies and the results were evaluated according to the degree of infiltration, which was classified into three grades. Results: As for stroma-infiltrating lymphocytes (SIL) in sCRCs, severe infiltration was observed in 20% of high microsatellite instability (MSI-H) patients and 12.8% of low microsatellite instability (MSI-L)/stable microsatellite (MSS) patients without a statistically significant difference. In contrast, severe infiltration of intra-tumor cell-infiltrating lymphocytes (ITCIL) was observed in 41.7% of MSI-H sCRC patients and 4.3% of MSI-UMSS patients. Thus, there was a close correlation between ITCIL severity and increased microsatellite instability (P< 0.001). In examination of ITCIL, patients with severe infiltration tended to show a better survival rate than those with moderate or mild infiltration. Conclusions: The present study suggests that different factors are involved in the infiltration of SIL and ITCIL. Although there were no statistically significant differences, the cumulative survival rates tended to be higher in severe ITCIL cases than in those with moderate and poor ITCIL (P< 0.09). We suggest that there might be a possibility of ITCIL having a role for a better prognosis after colorectal cancer surgery, which is closely related to MSI.

Serum vascular endothelial growth factor per platelet count in hepatocellular carcinoma: correlations with clinical parameters and survival.

Abstract: Background: Platelets have been reported to act as transporters of tumor-originated vascular endothelial growth factor (VEGF), contributing to tumor angiogenesis and progression. Serum VEGF per platelet count, as an indirect theoretical estimate of VEGF in platelets, may predict the malignant potential of tumors. However, its prognostic significance is still unclear in hepatocellular carcinoma (HCC), a highly vascular tumor. Methods: Serum VEGF was measured by enzyme-linked immunosorbent assay. We compared serum VEGF, platelet count and serum VEGF per platelet count in 52 HCC patients, 26 liver cirrhosis patients and 30 healthy controls. The relation of serum VEGF per platelet count with clinicopathologic variables of HCC patients and the prognostic significance were investigated, Results: Serum VEGF per platelet count in HCC patients was higher than in liver cirrhosis patients and healthy controls (P 1.4 pg/10 6 ) showed poor response to treatment and shorter overall survival (P < 0.01). Serum VEGF per platelet count was an independent prognostic factor with the presence of portal vein thrombosis (P < 0.01). Conclusions: Serum VEGF per platelet count could be a feasible prognostic indicator during the follow-up of patients with HCC.

Hypermethylation-associated Inactivation of the SOCS-1 Gene, a JAK/STAT Inhibitor, in Human Pancreatic Cancers

Abstract: Background: SOCS-1, a JAK-binding protein (SSI-1/SOCS-1/JAB), regulates the JAK/STAT signal transduction pathway that relays signals from various cytokines in the extracellular matrix into the cell. Inactivation of the SOCS-1 gene by methylation has been previously described in hepatocellular carcinomas and multiple myeloma. The purpose of the present work was to analyze the expression of the SOCS-1 gene and identify inactivation of this gene by methylation in pancreatic cancers. Methods: 20 samples were analyzed. We identified the expression of SOCS-1 gene using RTPCR and the mechanism of inactivation in this gene by methylation assay. Results: We documented marked suppression of SOCS-1 mRNA and reduction of SOCS-1 protein in 7 of 14 primary pancreatic cancers examined; moreover, CpG-rich regions upstream of the SOCS-1 gene were hypermethylated in 8 of the 14 tumors. Conclusions: The results suggested that this gene is silenced in a substantial portion of pancreatic cancers through mechanisms that cause methylation in the promoter region.