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Kenneth K Tanabe

Publications and source records attributed to Kenneth K Tanabe.

At least 19 recordsLinked to original sources
PubMed2006

Profile of plasma angiogenic factors before and after hepatectomy for colorectal cancer liver metastases.

BACKGROUND: Circulating angiogenic factors in patients with colorectal cancer liver metastases may promote tumor growth and contribute to liver regeneration after partial hepatectomy. METHODS: We analyzed blood samples from 26 patients with colorectal cancer liver metastases before and after liver resection and used samples from 20 healthy controls as a reference. Plasma levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and hepatocyte growth factor (HGF) were measured, and levels were correlated with recurrence. RESULTS: The median preoperative levels of all four factors were significantly higher and more variable in colorectal cancer liver metastasis patients than in controls. HGF and bFGF levels increased significantly 3 days and 1 month after hepatectomy, respectively, and returned to near preoperative levels at 3 months. Postoperative VEGF and EGF levels remained relatively stably increased over 3 months. After a median follow-up of 19 months, 10 patients (42%) experienced recurrence. Higher preoperative VEGF and HGF levels correlated with subsequent recurrence (P = .018 and .021, respectively), and a preoperative adjusted total value of all four factors accurately identified patients at low, moderate, and high risk of recurrence (P = .034). Patients who experienced disease recurrence also had relatively higher bFGF levels 3 months after operation (P = .035). CONCLUSIONS: Plasma angiogenic factors are increased in patients with colorectal cancer liver metastases and remain increased at least 3 months after partial hepatectomy. Measurement of certain factors before and after hepatic resection can predict recurrence. Targeted biological agents may counteract the tumor-promoting effects of these circulating factors on subclinical disease.

Adult↗
PubMed2006

Endostatin gene transfer in murine lung carcinoma cells induces vascular endothelial growth factor secretion resulting in up-regulation of in vivo tumorigenecity.

Endostatin (ED) is a carboxyl-terminal fragment of type XVIII collagen with a strong anti-angiogenic activity. The purpose of this study is to determine the effect of ED gene transfer into lung cancer cells on in vivo tumor growth in a murine model. The murine lung cancer cell line, Lewis Lung Carcinoma (LLC), was transfected with ED gene to express and secrete ED. After clones were selected to secrete ED, several stable transfectants with ED gene (LLC/ED) and control transfectants (LLC/Mock) were established. In vitro proliferation of these transfectants demonstrated similar growth speed. In contrast to previous reports, in vivo subcutaneous tumorignecity of LCC/ED transfectants was significantly greater than that of LLC/Mock transfectants. Immunohistochemical staining analysis demonstrated that ED gene transfer induced angiogenesis, suggesting coinduction of another gene implicated for neovascularization. As expected, LLC/ED transfectants secreted not only ED but also vascular endothelial growth factor (VEGF) to a much greater degree than LLC/mock transfectants. Interestingly, culture supernatants of LLC/ED cells enhanced in vitro proliferation of human umbilical vein endothelial cells (HUVEC) to a much greater degree than those of LLC/Mock cells. These results indicate that ED gene transfer in murine lung carcinoma cells induces VEGF secretion, resulting in enhancement of in vivo tumorigenecity in the murine model. More attention should be paid for ED gene therapy into lung cancer cells since it may influence other proteins secretion, which upregulates angiogenesis.

Animals↗
PubMed2006

New techniques of liver surgery.

Techniques of liver resection for colorectal cancer metastases continue to evolve, and the range of patients who benefit from such treatment expands. With improvements in preoperative and intraoperative imaging, surgical strategies for reducing blood loss and maximizing excision of disease and residual liver function, patient selection, and chemotherapy, many of the traditional contraindications to hepatic resection are no longer absolute contraindications. Appreciable long-term survival after resection is observed in many patients for which resection would not have been considered an option until recently. Novel treatment strategies have been successful in converting nonresectable disease to resectable disease, with good survival outcome. Continued study of and experience with novel surgical techniques and treatment strategies will continue to improve outcomes in liver resection for metastatic colorectal cancer.

Colorectal Neoplasms↗
PubMed2006

Long-term risk of false-positive screening results and subsequent biopsy as a function of mammography use.

PURPOSE: To retrospectively determine the long-term risk of false-positive mammographic assessments and to evaluate the effect of screening regularity on the risk of false-positive events. MATERIALS AND METHODS: Institutional review board approval was obtained, and informed consent was waived. Retrospective analysis was performed for the occurrence of false-positive assessments among 83,511 women who underwent 314,185 mammographic examinations from January 1, 1985, to February 19, 2002. Data were collected from a database that had been assembled prospectively. Two categories of false-positive events were examined: biopsies that did not reveal cancer and false-positive mammographic assessments. Rates of false-positive events were compared by using a chi2 analysis, and 95% confidence limits were calculated. Because comparisons of multiple pairs were considered, all P values that demonstrated statistical significance exceeded the requirement of the Bonferroni correction. RESULTS: While the overall rates of biopsies that did not reveal cancer and of false-positive mammographic assessments were similar to those found in other studies, most of the burden of false-positive events was borne by women who underwent intermittent screening. Long-term rates of false-positive events were lower among women who underwent regular screening than among those who underwent intermittent screening. In the 5-year group, 2.9% of women who underwent five mammographic examinations over the next 5 years had biopsy results that did not reveal cancer, whereas 4.6% of women who underwent three mammographic examinations over the next 5 years had biopsy results that did not reveal cancer. For women who underwent regular screening, the risk of undergoing biopsies that did not reveal cancer declined over time to 0.25% per year after several years of screening, a value that is lower than the risk of these events among women who did not undergo screening. The rate of false-positive mammographic assessments was also lower for women who underwent regular screening than for those who underwent intermittent screening. CONCLUSION: Prompt annual attendance for mammographic screening reduces the occurrence of false-positive mammographic results.

Adult↗
PubMed2006

Melanoma.

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Algorithms↗
PubMed2005

Biology of desmoplastic melanoma: a case-control comparison with other melanomas.

PURPOSE: Previous studies have established that patients with desmoplastic melanoma (DM) have thicker primary tumors. Consequently, comparisons with other forms of melanoma have been strongly biased by differences in Breslow stage. This is the first case-matched control study comparing DM with other forms of melanoma. PATIENTS AND METHODS: From a database of 3,202 melanoma patients treated at one institution, 89 patients with DM and 178 case-matched control patients (2:1) were identified by matching for tumor thickness, age, sex, and year of diagnosis. Clinical, pathologic, and outcome information was obtained from chart review. RESULTS: Controls were matched successfully to patients for tumor thickness, age, sex, and year of diagnosis. Presentation with American Joint Committee on Cancer stage III or IV disease is less common in patients with DM compared to case-matched control patients (5% v 21%; P < .001). Re-excisions to obtain clear surgical margins are required more often in patients with DM compared to case-matched control patients (21% v 6%; P < .001). Risk of positive sentinel nodes is lower in patients with DM compared to case-matched control patients (8% v 34%; P = .013). Despite these differences, survival rates of patients with DM are the same as case-matched control patients. CONCLUSION: Use of case-matched control patients matched for tumor thickness avoids biases introduced by the advanced Breslow stage of DMs. DMs are more locally aggressive than thickness-matched controls, and positive sentinel nodes are limited to patients with thick primary tumors. Importantly, patients with DM have survival rates similar to patients with other melanomas of similar thickness.

Adult↗
PubMed2005

The outcome of surgical resection versus assignment to the liver transplant waiting list for hepatocellular carcinoma.

BACKGROUND: Optimal management of patients with hepatocellular carcinoma (HCC) is controversial. This study was conducted to evaluate the outcome of tumor resection versus assignment to a liver transplant waiting list (WL) in patients with HCC. METHODS: Prospectively collected patient data from 1970 to 1997 on 313 patients with HCC were retrospectively analyzed by multivariate analysis to determine the effect of liver disease, method of treatment, and tumor-related factors on survival. RESULTS: A total of 199 patients underwent nonsurgical palliative care (PC), 81 underwent partial liver resection (LR), and 33 were assigned to a liver transplant WL, of which 22 received a donor liver. A total of 91%, 53%, and 91% of the patients had cirrhotic livers in the PC, LR, and WL groups, respectively (P < .001). In the LR group, the absence of a tumor capsule (P < .0001) and a poorly differentiated tumor (P = .027) were both adverse prognostic factors. In the WL group, hepatitis B (P = .02) and American Joint Committee on Cancer tumor stage III (P = .019) were adverse prognostic factors. The 3-year survival rates were 4%, 33%, and 38% for the PC, LR, and WL patients, respectively (P < .0001). The 3-year survival rate in the LR patients was 51% in patients without cirrhosis and 15% in patients with cirrhosis (P < .0001). CONCLUSIONS: Patients with locally unresectable tumors, distant disease, or both will continue to receive PC. Patients assigned to liver transplant WLs run the risk of not receiving a donor liver, in which case their survival is predicted to be poor. Survival after resection in a group of patients with advanced tumors is worse than that after transplantation; however, shortages of donor livers presently preclude transplantation in this population of patients.

Adolescent↗
PubMed2005

Viral oncolysis by herpes simplex virus and other viruses.

The use of viruses to destroy tumors, also known as viral oncolysis, dates back to the early 1900's. Although the mechanism of cancer cell lysis was unknown in the early years of development, advances in tumor biology, molecular biology, and virology have been critical for numerous advances that have brought the field to where it is today. Oncolytic viruses have been developed based on innate and engineered properties to preferentially target tumor cells. Engineered properties include alterations in endogenous gene expression and introduction of foreign genes. Methods to non-invasively monitor sites of viral replication is required for preclinical and clinical studies. Positron emission tomography (PET) can be used for this purpose. This review focuses on commonly used oncolytic viruses, their selection for oncolytic therapy, the design of HSV-1 viral mutants, and monitoring their replication by PET.

Animals↗
PubMed2005

Mouse models of subcutaneous spleen reservoir for multiple portal venous injections to treat liver malignancies.

Dog and rat animal models have been developed for repeated intravascular administrations to the liver. However, mice have generally been considered too small to use for these models. This study describes the development of mouse models that permit the establishment of liver metastases that can be subsequently treated by repeated injections into the portal venous system. A mini-laparotomy is done to mobilize the spleen and transpose it to a s.c. pocket with its vascular pedicle intact. A suspension of single tumor cells is then inoculated into the portal vein to establish diffuse liver metastases. These tumors may be treated by simple percutaneous injections directly into the s.c. whole spleen reservoir. The ease of injection into the s.c. spleen permits repeated injections into the portal venous system. The usefulness of this model was shown in experiments revealing that multiple portal venous administrations of a replication-conditional, oncolytic herpes simplex virus mutant are more effective than a single portal venous administration. In a modification of this model, the spleen is first split into two, leaving intact the vascular pedicle for each half of the spleen. Tumor cells are inoculated into one hemi-spleen, which is then resected 10 minutes later. The other hemi-spleen is transposed to the s.c. position, thereby permitting subsequent repetitive portal venous injections via percutaneous injections into the s.c. hemi-spleen. These mouse models are useful for a wide range of studies.

Animals↗
PubMed2004

The age at which women begin mammographic screening.

BACKGROUND: The American Cancer Society recommends yearly mammographic screening for women starting at the age of 40 years. The authors examined the age at which women began screening at a large tertiary care center. METHODS: Utilization of mammography was assessed in a population of 72,417 women who received 254,818 screening mammograms at the Massachusetts General Hospital Avon Comprehensive Breast Center from January 1, 1985 to February 19, 2002, of which 940 received their first mammogram between January 16, 2000 and February 19, 2002. RESULTS: The median age at first mammogram for women in the population as a whole was 40.4 years. Sixty percent of women had their first mammogram by the end of their 40th year, and almost 90% had begun screening by age 50 years. However, these reassuring findings were not seen in several specific subpopulations of women. Black women began screening at a median age of 41.0 years, 0.7 years later than white women. Hispanic women began screening at a median age of 41.4 years, 1.1 years later than non-Hispanic women. Obese women began screening at a median age of 41.2 years, 1.6 years later than thin women. Women without a primary care physician began screening at a median age of 42.1 years, 1.8 years later than women with a primary care physician. Women without private health insurance began screening at a median age of 46.6 years, 6.3 years later than women with private health coverage. Women who did not speak English began screening at a median age of 49.3 years, 9.0 years later than women for whom English was the primary language. Women who both lacked private health insurance and spoke a language other than English began screening at a median age of 55.3 years, 15.2 years later than women without these characteristics. CONCLUSIONS: The analysis presented in the current study provided one of the most detailed descriptions of the age at screening initiation to be performed to date. Most women in the study population began screening by the end of their 40th year. This contrasted with the widespread failure of women to return promptly for subsequent annual examinations. However, specific subpopulations of women were at risk for not beginning screening on time, including women without private insurance, women without a primary care physician, and women who did not speak English. These findings suggest that there is little to be gained from populationwide efforts to encourage entry into the screening process, and that public health efforts should be focused on those subpopulations of women at highest risk for not using screening. These results also indicate that public health efforts to encourage women to start screening may be less critical than interventions to improve prompt return once they have entered the screening system.

Adult↗
PubMed2004

Oncolysis by viral replication and inhibition of angiogenesis by a replication-conditional herpes simplex virus that expresses mouse endostatin.

BACKGROUND: In preclinical models, infection of tumors by oncolytic strains of herpes simplex virus 1 (HSV-1) resulted in the destruction of tumor cells by viral replication and release of progeny virion that infected and destroyed adjacent tumor cells. However, complete tumor regression was rarely observed. METHODS: To augment the antitumor effect of viral oncolysis, a replication conditional HSV-1 mutant (HSV-Endo) was constructed in which the murine endostatin gene was incorporated into the HSV-1 genome. RESULTS: Replication of HSV-Endo effectively destroyed several colon carcinoma cell lines in vitro. Secretion of endostatin by HSV-Endo-infected HT29 human colon carcinoma cells was confirmed by Western blot analysis. The secreted endostatin was biologically active as assessed in a chick chorioallantoic membrane assay. Importantly, endostatin production at the site of viral replication did not inhibit viral replication. Direct injection of HSV-Endo into flank tumors caused tumor destruction, and some of the HSV-Endo-treated flank tumors completely sloughed. Immunohistochemical staining of the tumors revealed a decreased number of blood vessels in the HSV-Endo-treated group versus the control group. CONCLUSIONS: The oncolytic HSV-1 mutant HSV-Endo provided a two-pronged therapy; namely, inhibition of angiogenesis and direct tumor cell destruction by viral replication.

Allantois↗
PubMed2004

Mammographic screening: patterns of use and estimated impact on breast carcinoma survival.

BACKGROUND: Although many studies support the life-saving potential of screening mammography, the actual utilization of screening and the impact of the actual pattern of screening use on the breast carcinoma death rate, remain incompletely understood. In the current report, the authors describe patterns of screening use among women who were examined at a large screening and diagnostic service and estimate the added mortality associated with missed screening mammograms. METHODS: Mammography use was assessed in a population of 72,417 women who received a total of 254,818 screening mammograms at the Massachusetts General Hospital (MGH) Avon Comprehensive Breast Center (Boston, MA) between January 1, 1985, and February 19, 2002. A computer simulation of breast carcinoma growth, spread, and detection of breast carcinoma was used to estimate the likely health consequences of various types of screening use. RESULTS: Both prompt return for annual screening and full use of screening over extended periods of time were rare, and comparison of the MGH population with other populations revealed that the low level of use observed in the MGH population was not atypical. Only 6% of women who received a mammogram in 1992 received all annual mammograms that were available over the next 10 years; the mean number of mammograms received during this period was 5.06, or 51% of the number recommended by the American Cancer Society. Computer simulation results indicate that this underutilization of screening should result in higher mortality levels. Women from traditionally underserved socioeconomic, racial, and ethnic groups, women without insurance, and women who did not speak English had lower levels of use compared with other women. Lower levels of use also were observed among women receiving their first mammogram or who in the past had not returned promptly. Women ages 55-65 years had higher levels of use than did younger or older women. Women who previously had breast carcinoma also had higher levels of screening use. Nonetheless, none of the subpopulations of women stratified by age, race, ethnicity, zip code, income,language, insurance, status, previous screening use, or medical history exhibited a widespread propensity to promptly return for annual screening over an extended period of time. CONCLUSIONS: By many measures, the current analysis is one of the most detailed descriptions of screening use to date. The authors observed a level of screening use that was disappointingly low, with potentially negative health-related consequences, among women across categories defined by racial, ethnic, socioeconomic, and geographic characteristics; insurance status; language; age; medical history; and previous screening use. Improvements in the promptness with which women return to screening appear to have the potential to lead to considerable reductions in breast carcinoma death.

Adult↗
PubMed2004

Intraoperative US in patients undergoing surgery for liver neoplasms: comparison with MR imaging.

PURPOSE: To retrospectively compare intraoperative ultrasonography (US) and preoperative magnetic resonance (MR) imaging with contrast material enhancement for the depiction of liver lesions in patients undergoing hepatic resection. MATERIALS AND METHODS: A radiologist (D.V.S.) and a surgeon (K.K.T.) retrospectively identified 79 patients (36 female and 43 male patients; age range, 10-78 years; mean age, 57 years) who had undergone surgical resection for primary liver tumor or metastasis and had also undergone preoperative contrast-enhanced MR imaging within 6 weeks before surgery. MR imaging was performed with a 1.5-T system. Dedicated intraoperative US of the liver was performed or supervised by a gastrointestinal radiologist using a 7.5-MHz linear-array transducer, after adequate hepatic mobilization by the surgeon. Histopathologic evaluation of the 159 resected hepatic lesions served as the reference standard. The lesion distribution included colon cancer metastasis (n = 122), hepatocellular carcinoma (n = 23), cholangiocarcinoma (n = 6), cavernous hemangioma (n = 4), focal nodular hyperplasia (n = 2), hamartoma (n = 1), and metastatic embryonal sarcoma (n = 1). RESULTS: Of 159 lesions, 138 (86.7%) were identified at both MR imaging and intraoperative US. Twelve additional lesions (7.5%) in 10 patients were detected only at intraoperative US (eight metastases, one hepatocellular carcinoma, one cholangiocarcinoma, one hemangioma, and one biliary hamartoma). Both modalities failed to depict nine lesions (5.6%) (four metastases, four hepatocellular carcinomas, and one cholangiocarcinoma). The sensitivities of MR imaging and intraoperative US for liver lesion depiction were 86.7% and 94.3%, respectively. Surgical management was altered on the basis of the intraoperative US findings in only three of 10 patients (4%). CONCLUSION: Contrast-enhanced MR imaging is as sensitive as intraoperative US in depicting liver lesions before hepatic resection.

Adolescent↗
PubMed2004

Selectivity of an oncolytic herpes simplex virus for cells expressing the DF3/MUC1 antigen.

Replication-conditional viruses destroy tumors in a process referred to as viral oncolysis. An important prerequisite for this cancer therapy strategy is use of viruses that replicate preferentially in neoplastic cells. In this study the DF3/MUC1 promoter/enhancer sequence is used to regulate expression of gamma(1)34.5 to drive replication of a Herpes simplex virus 1 (HSV-1) mutant (DF3gamma34.5) preferentially in DF3/MUC1-positive cells. HSV-1 gamma(1)34.5 functions to dephosphorylate elongation initiation factor 2alpha, which is an important step for robust HSV-1 replication. After DF3gamma34.5 infection of cells, elongation initiation factor 2alpha phosphatase activity and viral replication were observed preferentially in DF3/MUC1-positive cells but not in DF3/MUC1-negative cells. Regulation of gamma(1)34.5 function results in preferential replication in cancer cells that express DF3/MUC1, restricted biodistribution in vivo, and less toxicity as assessed by LD(50). Preferential replication of DF3gamma34.5 was observed in DF3/MUC1-positive liver tumors after intravascular perfusion of human liver specimens. DF3gamma34.5 was effective against carcinoma xenografts in nude mice. Regulation of gamma(1)34.5 by the DF3/MUC1 promoter is a promising strategy for development of HSV-1 mutants for viral oncolysis.

Animals↗
PubMed2004

Is completion lymphadenectomy after a positive sentinel lymph node biopsy for cutaneous melanoma always necessary?

HYPOTHESIS: Completion lymph node dissection (CLND) has usually been recommended after metastatic disease is identified in the sentinel lymph node (SLN) biopsy to eradicate further metastases in nonsentinel nodes. We hypothesized that patients with negative lymph nodes included in the initial SLN specimen have low risk of metastases in the residual draining basin and may not require CLND. DESIGN: Chart review. SETTING: University-affiliated tertiary care referral center. PATIENTS: Between January 1, 1997, and May 31, 2003, 506 consecutive patients underwent SLN biopsy for staging of primary cutaneous melanoma. INTERVENTION: The SLN biopsy identified 87 patients (17.2%) with metastatic melanoma, of whom 80 underwent CLND. RESULTS: In 28 patients, all SLNs were found to contain metastatic melanoma. Seven (25%) of these patients had additional metastases identified in the CLND specimen. In 52 patients, 1 or more SLNs did not contain metastatic melanoma. Five (10%) of these patients had additional metastases in the CLND specimen (P =.02). CONCLUSIONS: Although no evidence of metastatic melanoma was found on CLND in most patients in whom negative nodes had been removed with positive SLNs at the initial biopsy, 10% of these patients did have further metastases. This subgroup of patients (positive SLNs and negative nodes in the SLN biopsy specimen) is at significantly lower risk for further metastasis, but CLND cannot be safely omitted even for these patients.

Adult↗