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H J Wanebo

Publications and source records attributed to H J Wanebo.

At least 19 recordsLinked to original sources
PubMed1997

The impact of histopathology on nodal metastases in minimal breast cancer.

OBJECTIVE: To establish a model based on risk factor analysis to guide selective axillary lymph node dissection in patients with T1a and T1b breast cancers. DESIGN: Retrospective review to determine histopathologic features and patient demographic profiles that may influence the incidence of nodal metastases. SETTING: Primary care and referral centers in Rhode Island and Massachusetts. PATIENTS: Women with invasive breast cancers with nodal status reported to the statewide tumor registry, the Hospital Association of Rhode Island, and the tumor registry at Baystate Medical Center, Springfield, Mass, between January 1984 and December 1995. There were 12030 patients with breast cancer reported; 2185 (18%) of these had tumors 1 cm or less in diameter. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Axillary node metastases. RESULTS: The nodal status of 377 patients with T1a tumors and 1808 patients with T1b tumors was studied. Seventy-five percent had axillary dissections, and 16% were found to have nodal metastases. Thirty-one percent (29/93) of patients younger than 40 years had positive nodes compared with 15% (241/1546) of older patients (P = .001). The T1a tumors had fewer metastases than the T1b tumors did (11% vs 17%; P = .02). Nuclear grade was available in 49% of cases. Nuclear grades 2 and 3 were associated with nodal involvement twice as often as grade 1 tumors were (P = .002). Patients with no poor prognostic factors had a 7% or less chance of nodal involvement, while patients with all 3 poor prognostic indicators had a 33.5% chance of nodal involvement. CONCLUSIONS: Selective nodal dissection may be possible through risk factor analysis. Prospective registration of complete histopathologic information will allow more comprehensive analysis and may further enhance the selective treatment of patients with minimally invasive breast cancer.

Adult↗
PubMed1997

Interleukin-10 as a possible mediator of immunosuppressive effect in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: Depressed cell-mediated immunity is a frequent event in patients with head and neck cancer and is characterized by impairment of T cell-proliferative responses and natural killer cell and lymphokine-activated killer cell activity. This immunosuppressive effect appears to be mediated by a serum-derived factor. Certain cytokines, including transforming growth factor-beta (TGF-beta) and interleukin (IL)-10 have been shown to induce similar immunosuppressive effects. The present study was designed to examine the putative role of these cytokines in cellular immune suppression induced by patient serum. METHODS: Serum was collected from multiple patients with newly diagnosed or recurrent squamous cell carcinoma of the head and neck. The serum was heat inactivated for 30 min and frozen in aliquots. Peripheral blood lymphocytes were isolated from normal human blood. Lymphocytes were suspended in RPMI and 15% concentrations of control and patient serum and stimulated with 0.75 mg% phytohemagglutinin. In addition, neutralizing antibodies to TGF-beta and IL-10 were added to lymphocyte cultures. At 24 h, and IL-2 response assay was performed. Finally, the sera were examined for the presence of TGF-beta and IL-10 using an enzyme-linked immunosorbent assay (ELISA). RESULTS: In seven of seven experiments, incubating cells with a neutralizing antibody to TGF-beta failed to counteract the immune suppression and restore proliferative response to IL-2. Also, an ELISA of these sera failed to demonstrate the presence of TGF-beta. In contrast, four of five experiments performed with neutralizing antibody to IL-10 showed significant restoration of proliferation in the presence of this antibody. Also, ELISA showed elevated IL-10 levels in 65% of the patients' sera in comparison to controls. CONCLUSION: We conclude that TGF-beta is not responsible for the immunosuppressive effects induced by head and neck patient sera. However, the suppressive effect is reversed by blocking the biologic action of IL-10. Further experiments are needed to define the role of IL-10 in inducing the immunosuppressive effect.

Carcinoma, Squamous Cell↗
PubMed1997

Paclitaxel and concurrent radiation for locally advanced pancreatic and gastric cancer: a phase I study.

PURPOSE: To determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and potential antitumor activity of weekly paclitaxel with concurrent radiation (RT) for locally advanced pancreatic and gastric cancer. PATIENTS AND METHODS: Thirty-four patients with locally advanced adenocarcinoma of the pancreas or stomach were studied. The initial dose of paclitaxel was 30 mg/m2 by 3-hour intravenous (I.V.) infusion repeated every week for 6 weeks with 50 Gy RT. Doses were escalated at 10-mg/m2 increments in successive cohorts of three new patients until dose-limiting toxicity was observed. RESULTS: The dose-limiting toxicities at 60 mg/m2/wk were abdominal pain within the RT field, nausea, and anorexia. Of 23 patients with assessable disease, 11 (seven with gastric, four with pancreatic cancer) had objective responses for an overall response rate of 48%. CONCLUSION: Concurrent paclitaxel with upper abdominal RT is well tolerated at dosages that have substantial activity. A phase II trial of neoadjuvant paclitaxel and RT at the MTD of 50 mg/m2/wk is underway.

Adult↗
PubMed1997

Soft tissue sarcoma.

Explore the source record for details and available documents.

Combined Modality Therapy↗
PubMed1996

Pancreatic carcinoma in perspective. A continuing challenge.

There are approximately 27,000 new cases of carcinoma of the pancreas each year and most afflicted patients will die of the disease. Although smoking is a common denominator, chronic pancreatitis is considered an important precursor lesion in a smaller number of cancers. Pancreatic cancer is primarily a disease of the pancreatic ducts. The molecular events are under intense study, but c-K-ras mutation is involved in approximately 80% of the cases and p53 to a slightly lesser degree (60-80%). Early manifestations are usually occult, but jaundice is a common manifestation in patients with cancers of the pancreatic head. Thin-slice computed tomography, portography, and endoscopic retrograde cholangiopancreatography are currently the most sensitive detection techniques. The developing use of endoscopic ultrasound and laparoscopy appear to enhance detection and are under evaluation. In many patients with advanced disease, endoscopic bypass may eliminate the need for unnecessary surgery, although gastrointestinal bypass is still required in some patients (10-15%). Curative resection is possible in selected patients (perhaps 10-15%), with expectation of extended survival ranging from 6->20% in some series. The survival differences may be related to stage, patient selection, and the expertise of the operative team. Preoperative chemotherapy/radiation is under study and may improve outcome. Clinical trial participation is essential for improvement in treatment outcomes.

Humans↗
PubMed1996

A rationale for expanding the endpoints for clinical trials in advanced pancreatic carcinoma.

BACKGROUND: Using classical endpoints, such as response rate and survival, as the sole measures of benefit, little progress has been made in the treatment of advanced pancreatic carcinoma in the past 30 years. We challenge the assumption that response rate and survival are the only appropriate endpoints for clinical trials in this disease setting. METHOD: A review of the literature and roundtable discussion were undertaken. RESULTS: Using current imaging techniques, it is inherently difficult to distinguish pancreatic tumor from normal pancreas, inflammatory tissue, local fibrosis, and unopacified bowel. As a result, objective tumor measurements are often imprecise, unreliable, and irreproducible. This difficulty may explain the wide variation in response rates reported in clinical trials even when the same therapies are used. Tumor-related symptoms, such as anorexia, weight loss, severe pain (requiring opioid analgesia), and impaired functional status, are prevalent and debilitating characteristics of this disease. Tools that can assess these symptoms in a consistent fashion over time have been developed and have been integrated into clinical trials to evaluate new drugs in this setting. CONCLUSIONS: Systematic assessment of the impact of a new therapy on tumor-related symptoms may provide a sensitive and accurate way to identify useful new treatments for patients with advanced pancreatic carcinoma. Such analyses can be a useful complement to the classical endpoints of response rate and survival.

Clinical Trials as Topic↗
PubMed1996

Systemic and adjuvant therapy for patients with pancreatic carcinoma.

BACKGROUND: Pancreatic cancer is a highly lethal disease with < or = 5% of patients surviving 5 years. There is no curative therapy for patients who cannot be surgically resected. Chemotherapy and radiation therapy can provide palliation but have not had a significant impact on 5-year survival. METHODS: Newer approaches for improving the survival of patients with pancreatic cancer integrating chemotherapy, radiation therapy, and surgery are being evaluated. New chemotherapeutic agents (e.g., gemcitabine, camptothecins, taxanes, thymydilate synthase inhibitors, and fluorouracil-related compounds) are being studied alone and in combination with each other or different agents (e.g., trimetrexate or platinum-related compounds). RESULTS: Increased knowledge about the biology of pancreatic cancer (including high frequency of ras and p53 mutations in neoplastic cells or the expression of a number of growth factor receptors on the cell surface) has lead to preclinical evaluation of novel approaches attempting to specifically target these. These novel approaches include gene therapy, vaccines, and antisense oligonucleotides targeted to genes important for proliferation or survival of pancreatic cancer cells. CONCLUSIONS: Continued development of new approaches is needed to improve the treatment and survival of patients with pancreatic cancer.

Chemotherapy, Adjuvant↗
PubMed1996

Behavior of the cell cycle-associated proteins in an unusual G0-arrestable cancer cell line.

An adenocarcinoma cell line which has the ability to arrest in G0 phase under exhausted culture conditions was established. Using the cell line, we investigated the expression of cell cycle-associated proteins including cdc2, cdk2, cyclin A, cyclin Dl, and Rb during entry into or withdrawal from the cell cycle. MAP kinase expression was also investigated as one of the most downstream proteins of the signal transduction of growth factors. The cells in the quiescent state did not express cdc2. In contrast, cdk2 was expressed weakly, and cyclin A and cyclin D1 were strongly expressed in the quiescent cells. The expression of cdk2 and cyclin D1 in the quiescent cells was reduced after stimulation by renewal of the medium and then increased, accompanied by Rb phosphorylation and cdc2 expression around the G1/S transition. Cdc2 and the hyperphosphorylated form of Rb disappeared as the cells became quiescent. MAP kinase expression was unchanged throughout all the phases analyzed. The results indicate that down-regulation of neither cdk2, cyclin A, cyclin D1, nor MAP kinase is necessary to arrest cells in G0, but that only Rb dephosphorylation and down-regulation of cdc2 are accompanied by an arrest of cell proliferation in G0 in the cell line.

Adenocarcinoma↗
PubMed1996

Younger women with breast carcinoma have a poorer prognosis than older women.

BACKGROUND: It is controversial whether breast cancer in young women is more aggressive than in older women. This study was initiated to determine age-associated outcome of women with breast carcinoma. METHODS: Patients with breast carcinoma, who were identified in a statewide tumor registry, were divided into age groups based on 10-year intervals (ages 40 and younger, 41 to 50, 51 to 60, 61 to 70, 71 to 80, and older than 80 years). Age at diagnosis, American Joint Committee on Cancer classification, 5-year disease free (5DFS) and cancer specific (5CSS) survival estimates using Kaplan-Meier analysis were determined. RESULTS: Between 1985 and 1992, 3722 women were diagnosed with invasive breast carcinoma. Approximately 5.6% (210) of the women were 40 years old or younger. The youngest age group had the worst 5CSS of 69.7%, followed by the oldest age group (> 80, 5CSS = 71.45%). The age groups 41 to 50, 51 to 60, 61 to 70, and 71 to 80 years had 5CSS of 80.30%, 78.45%, 82.06%, and 84.27%, respectively. The oldest age group (> 80) had the worst 5DFS (39.88%) followed by the youngest age group (< or = 40, 5DFS = 60.79%). The age groups 41 to 50, 51 to 60, 61 to 70, and 71 to 80 years had 5DFSs of 73.22%, 66.87%, 71.53%, and 63.11%, respectively. Analyzed by stage, young (< or = 40 years) women had a worse 5CSS when compared with the other age groups, except for those with Stage I disease. CONCLUSIONS: Our results indicate that women 40 years of age and younger have a worse 5CSS than their older counterparts. This difference in survival is not solely a reflection of more advanced disease but may reflect differences in tumor biology.

Adult↗
PubMed1996

Patient selection for hepatic resection of colorectal metastases.

OBJECTIVE: To determine the major factors governing patient outcome after hepatic resection of metastatic colorectal cancer and to formulate criteria for optimal resection. PATIENTS: We reviewed records of 74 patients (44 men, 30 women) who underwent resection of colorectal liver metastases. MAIN OUTCOME MEASURES: Sex, age, primary tumor location; Dukes tumor stage; disease-free interval after primary resection (synchronous vs metachronous); location, number, size, and distribution of liver metastases; operative complications; and mortality. RESULTS: The primary tumor location was rectosigmoid in 46 patients and the colon in the others. The tumor stage was Dukes A in one patient, Dukes B in 16, Dukes C in 31, and Dukes D (synchronous metastases) in 26. The disease-free interval was less than 12 months in 38 patients and 12 months or more in 36. The location of the metastases was the right lobe in 42 patients, left lobe in 22, and bilateral in seven. The cancer was unilobar in 55 patients and bilobar in 18. Surgical resection included wedge resection in 23 patients, segmentectomy in 30, lobectomy in seven, and trisegmentectomy in 12. The number of lesions resected was one in 50 patients, two or three in 18, and four or more in five. Nine patients had repeated liver resections because of recurrence. There were five postoperative deaths within 60 days (7%), four of which occurred after extended resection and were complicated by delayed liver failure and multisystem failure. An additional death occurred at 65 days after an apparently uneventful initial convalescence. Overall median survival was 35 months; actuarial 5- and 10-year survival rates were 24% and 12% respectively. There were significant relationships with survival (P<.05) for the number of metastases (three or fewer vs four or more), bilobar vs unilobar metastases, and extent of liver resection (wedge and segmental vs lobectomy and trisegmentectomy). A multiple logistic regression model (multivariate analysis) showed a significant correlation with survival (P<.05) for distribution of metastases (bilobar vs unilobar) and extent of resection (wedge and segmental vs lobectomy and trisegmentectomy). CONCLUSION: Patient selection for hepatic resection of colorectal cancer metastases based on standard clinical and tumor outcome variables should be expected to achieve long-term survival with low morbidity and mortality in bilobar disease or extended resection should generally be avoided, especially in medically compromised patients.

Aged↗
PubMed1996

Synchronous colon carcinomas: molecular-genetic evidence for multicentricity.

BACKGROUND: The synchronous presentation of multiple colonic adenocarcinomas is an unusual, but well-recognized event accounting for approximately 2-11% of these neoplasms. Synchronous tumors may have a different biology and prognosis than solitary tumors. Evidence based on measurement of DNA ploidy suggests that a significant percentage of synchronous tumors have a common clonal origin, probably resulting from translumenal metastasis. METHODS: Fifteen synchronous colorectal cancers (30 tumors) were examined for histologic differences as well as genetic mutations. p53 gene abnormalities were detected by polymerase chain reaction (PCR) followed by single-strand conformation polymorphism analysis. Ki-ras mutations were detected by PCR followed by oligonucleotide-specific hybridization. RESULTS: p53 gene mutations were detected in 12 of 30 tumors. In only one case was the same p53 mutation present in both tumors from one patient. Similarly, Ki-ras mutations were observed in 9 of 30 tumors. Concordant Ki-ras mutations were observed in only one case, which was also concordant for p53 mutation. CONCLUSION: Because p53 and Ki-ras mutations tend to occur fairly early in tumor development, it seems likely that cases discordant for p53 and Ki-ras mutations represent independently developing tumor foci. Taken together, these findings strongly suggest that the great majority of synchronous colonic adenocarcinomas arise as independent neoplasms and their worsened prognosis is not a result of unusually early metastatic spread.

Adenocarcinoma↗
PubMed1996

Preoperative therapy for advanced pelvic malignancy by isolated pelvic perfusion with the balloon-occlusion technique.

BACKGROUND: Although the technique of isolated pelvic perfusion dates back to the time of Creech (1959) and has been used by a variety of authors to treat unresectable neoplasms, the inherent complexity of the open procedure limited its widespread use. We simplified the technique through use of the balloon-occlusion technique for aortic and caval control. Our initial efforts used this technique for unresectable pelvic cancer, but recently we used this as preoperative therapy for advanced pelvic malignancy. METHODS: Isolated pelvic perfusion was accomplished by placement of balloon-occlusion catheters (Fogerty 8) in the aorta and inferior vena cava (IVC) at L3 vertebral body level via the common femoral artery and vein and establishing inflow and outflow catheter connections to a hemodialysis pump that generated a flow rate of 150-300 ml/min. Chemotherapy drugs were infused at times 0, 10, and 20 min. 5-Fluorouracil (5-FU; 1,500 mg/M2), cis-platinum (50-100 mg/M2), and mitomycin (15-20 mg/M2) were given by normothermic perfusion over a 45-min period. Forty isolated perfusions were carried out in 25 patients. Patients were evaluated by clinical examination, biochemical tests, computed tomography (CT) and magnetic resonance imaging (MRI) scans, and surgical exploration. RESULTS: Pelvic perfusion generally achieved pelvic systemic exposure ratios (area under the curve) between 5 and 10:1 for all three drugs: mean ratios were 11.4 (5-FU), 6.0 (cisplatin), and 9.0 (mitomycin). The amount of leaking to the systemic circuit ranged from 28 to 38%. Of 15 patients treated for palliation, there was one objective partial response (PR). Ten patients had symptomatic improvement of pain, two had complete pain relief (CR), and eight had partial pain relief, ranging from 3 weeks to 3 months (median, 5 weeks). Six of 10 patients with adequate carcinoembryonic antigen (CEA) follow-up data had a reduction in CEA levels (mean change, 35 units). Of 10 preoperative patients, there was one CR among five rectal cancer patients; and four of five PRs among patients with other pelvic malignancies: two PRs in patients with epidermoid cancer and one PR each in patients with endometrial cancer and metastatic anorectal melanoma. CONCLUSION: Pelvic perfusion by a simplified balloon-occlusion technique provides palliation for most patients with advanced pelvic malignancy and may increase resectability and improve tumor control in patients amenable to resection.

Adult↗
PubMed1996

Current perspectives on repeat hepatic resection for colorectal carcinoma: a review.

BACKGROUND: Recurrence occurs in 65% to 85% of patients after initial hepatectomy for metastases from colorectal cancer. Approximately one half of these have liver metastases, and in 20% to 30% only the liver is involved. Opportunity for resection is frequently limited because of diffuse liver disease or extrahepatic extension, and only 10% to 25% of these patients have conditions amenable to resection. This current review is focused on the rationale, indications, and results of resection of hepatic metastases from colorectal cancer. METHODS: The major series of liver resection were reviewed, and the cases of repeat resections were culled out. In addition to standard clinical parameters, the indications and timing after initial resection and the survival and subsequent recurrence after repeat resection were recorded. RESULTS: A comprehensive review of the 28 series showed that the mean interval between the first and second liver varied from 9 to 33 months and was about 17.5 months in the two largest series. The median survival in series reporting 10 or more patients was 19 months (mean, 24 months), which is comparable to data in single resection series. In the large French Association series containing 1626 patients with single resections and 144 patients with two resections, the 5-year survival was 25% and 16%, respectively. The recurrence rate after repeat resection is high (greater than 60%), and one half are in the liver. The prognostic factors favoring repeat resection are variable, but they include absence of extrahepatic extension of tumor and a complete resection of the liver metastases. CONCLUSIONS: Repeat hepatic liver resection for metastatic colorectal cancer in carefully selected patients appears warranted in view of reasonable survival expectations, which approach that of single liver resection. Risk of recurrence is high, however, suggesting the need for rigorous preoperative and intraoperative assessment and postoperative adjuvant therapy

Colorectal Neoplasms↗
PubMed1996

Surgical management and treatment of gastric and duodenal fistulas.

Gastroduodenal fistulas compose only a small portion of gastrointestinal fistulas. They usually occur in the postoperative setting in association with an anastomotic leak. As with all fistulas, attention to adequate supportive care is needed. Interventional endoscopy may play a role in the future. The three surgical management approaches include exclusion, resection, and closure of the fistula. The success rate of closure ranges from 25% to 75% with supportive care only to 100% with proper surgical management.

Duodenal Diseases↗
PubMed1996

Efficacy of an elective regional lymph node dissection of 1 to 4 mm thick melanomas for patients 60 years of age and younger.

OBJECTIVE: A prospective multi-institutional randomized surgical trial involving 740 stage I and II melanoma patients was conducted by the Intergroup Melanoma Surgical Program to determine whether elective (immediate) lymph node dissection (ELND) for intermediate-thickness melanoma (1-4 mm) improves survival rates compared with clinical observation of the lymph nodes. A second objective was to define subgroups of melanoma patients who would have a higher survival with ELND. METHODS: The eligible patients were stratified according to tumor thickness, anatomic site, and ulceration, and then were prerandomized to either ELND or nodal observation. Femoral, axillary, or modified neck dissections were performed using standardized surgical guidelines. RESULTS: The median follow-up was 7.4 years. A multifactorial (Cox regression) analysis showed that the following factors independently influenced survival: tumor ulceration, trunk site, tumor thickness, and patient age. Surgical treatment results were first compared based on randomized intent. Overall 5-year survival was not significantly different for patients who received ELND or nodal observation. However, the 552 patients 60 years of age or younger (75% of total group) with ELND has a significantly better 5-year survival. Among these patients, 5-year survival was better with ELND versus nodal observation for the 335 patients with tumors 1 to 2 mm thick, the 403 patients without tumor ulceration, and the 284 patients with tumors 1 to 2 mm thick and no ulceration. In contrast, patients older than 60 years of age who had ELND actually had a lower survival trend than those who had nodal observation. When survival rates were compared based on treatment actually received (i.e., including crossover patients), the patients with significantly improved 5-year survival rates after ELND included those with tumors 1 to 2 mm thick, those without tumor ulceration, and those 60 years of age or younger with tumors 1 to 2 mm thick or without ulceration. CONCLUSION: This is the first randomized study to prove the value of surgical treatment for clinically occult regional metastases. Patients 60 years or age or younger with intermediate-thickness melanomas, especially with nonulcerative melanoma and those with tumors 1 to 2 mm thick, may benefit from ELND. However, because some patients still are developing distant disease, these results should be considered an interim analysis.

Female↗
PubMed1996

Pelvic exenteration for recurrent rectal cancer.

Recurrent rectal carcinoma presents a formidable problem for patient and surgeon. Isolated recurrences of rectal carcinoma have been reported from 7% to 33% with a median of 14%. Increasing recurrence is associated with increasing Dukes's stage. The reason for high recurrences is probably related to the limited anatomic margins that can be obtained in the pelvis during primary resections. Patients who have recurrence after a low-anterior resection are more likely to present with nonfixed, surgically correctable lesions versus recurrences after abdominoperineal resection. The most common symptom related to pelvic recurrence is pain, which may be perineal or radiate to the lower extremities. The 5-year survival rate among unresected patients with locoregional recurrences is 4%. These patients are often in extreme pain with lower extremity swelling and perineal lesions. Although many patients will be palliated by radiation, few will experience long-term relief (6 to 8 months). A thorough physical examination should include rectal and pelvic exams to evaluate tumor extension and fixation. Computed tomographic studies are helpful when taken serially to evaluate pelvic recurrence or liver metastases. Fineneedle biopsies may also be done under CT guidance. Additional mandatory films include plain chest roentgenograph, lumbosacral spine films, and bone scan to rule out sacral involvement, which would preclude sacral resection. Magnetic resonance imaging has recently been shown to be effective in evaluating pelvic side wall involvement and metastatic lymphadenopathy. Although extensive involvement would preclude aggressive resection, in one series, 50% of patients were amenable to resection. Pelvic exenteration should include the tumor mass, along with any involved organs and their lymphatic drainage, with a 2 cm margin. Complications are increased in patients who have undergone radiation, who have undergone procedures that include urinary diversions, and who have recurrent disease. Cure rates of 30% to 50% have been reported using pelvic exenteration for rectal cancer. Recurrent disease presents a significant problem in that normal anatomic planes have been disrupted. In one series, rectal recurrences treated with pelvic exenteration had a 66% recurrence rate. In addition, there is often a posterior component to the recurrence. Although the complication rate is high, the only chance for cure in these patients would be an abdominosacral resection. There appears to be a select group of patients with recurrent locoregional disease, who benefit from sacral resection with a 20% to 30%, 5-year survival rate.

Humans↗