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Biomedical subjects

J L Lewis

Publications and source records attributed to J L Lewis.

At least 109 records · Page 6Linked to original sources
PubMed1993

Impact of age on survival of patients with ovarian cancer.

In an effort to determine if there are significant differences in outcome between elderly (> or = 65 years of age) and younger (< 65 years of age) women with epithelial ovarian cancer we examined the survival of patients with this malignancy who underwent their initial surgical evaluation at the Memorial Sloan-Kettering Cancer Center from January 1987-January 1991. The actuarial median overall survival for the 98 younger patients has not been reached but will exceed 4 years, compared to a median survival of 24 months for the 48 elderly patients (P < 0.0001). For individuals with advanced (stages 3-4) disease, excluding patients with tumors of low malignant potential, the median survival for the younger patient population has also not been reached and will exceed 4 years, compared to 21 months for the older population (P < 0.0001). Even in the limited number of patients with local/regional (stages 1-2) ovarian cancer, there was a statistically significant superior survival for the younger group of patients (P < 0.02). With a single exception, all deaths were believed to be due principally to disease progression, rather than to an unrelated comorbid medical event. We conclude that elderly patients with ovarian cancer experience a significantly inferior survival than younger individuals with this malignancy. Evaluation of larger populations will be required to confirm the results of this analysis and to probe for explanations for the striking survival differences we have observed.

Adult↗
PubMed1993

Mitomycin-C plus a 3-day continuous intravenous infusion of 5-fluorouracil: an inactive salvage regimen for platinum-resistant ovarian carcinoma.

In a Phase II trial, patients with refractory ovarian cancer were given 10 mg/m2 mitomycin-C i.v. every 8 weeks and 1000 mg/m2/day 5-fluorouracil for 3 consecutive days by continuous intravenous infusion repeated every 4 weeks. Sixteen heavily pretreated patients with platinum-resistant disease were treated and no major responses were observed. Only 2 patients required subsequent dose reduction for myelotoxicity. No sign of gastrointestinal toxicity was seen. This regimen is inactive as salvage treatment for refractory ovarian cancer.

Adult↗
PubMed1993

Comparison of antigen expression on fresh and cultured ascites cells and on solid tumors of patients with epithelial ovarian cancer.

The antigenic phenotype of malignant cells from ascites of patients with epithelial ovarian cancers was examined and compared to that of their primary and metastatic sites. Cell-surface antigens on frozen sections of primary and metastatic tumors and frozen cell pellets from ascites were analyzed with a panel of murine monoclonal antibodies using the indirect immunoperoxidase method. In addition, ascites cells cultured with and without autologous cell-free ascitic fluid were evaluated by immunofluorescence. The pattern of antigen expression detected on fresh and cultured ascitic epithelial cells was shown to be identical to the expression in autologous solid tumor tissues. When placed in culture, malignant epithelial cells generally persisted for a minimum of one, but no more than five, passages. Addition of autologous ascitic fluid to cultures of ascites cells did not alter the phenotype of the epithelial tumor cell population and did not enhance the growth of these cells. From one culture of ascites cells a permanent malignant epithelial ovarian cancer cell line (designated SK-OV-8) was established. The demonstration that epithelial tumor cells found in ascites of patients with epithelial ovarian cancer have the identical antigenic phenotype as their solid tumor counterpart, at least for the panel of antigens studied, may be useful in planning imaging and therapeutic trials with monoclonal antibodies.

Adult↗
PubMed1993

Evidence supporting the superiority of intraperitoneal cisplatin compared to intraperitoneal carboplatin for salvage therapy of small-volume residual ovarian cancer.

PURPOSE: To examine the relative efficacy of cisplatin-based intraperitoneal (IP) therapy versus carboplatin-based IP therapy as salvage treatment of small-volume residual ovarian cancer. PATIENTS AND METHODS: We retrospectively examined the surgically defined response rates of patients with ovarian cancer treated at the Memorial Sloan-Kettering Cancer Center on four organoplatinum-based salvage IP trials (cisplatin/etoposide, cisplatin/cytarabine, carboplatin/etoposide, carboplatin/etoposide + recombinant human erythropoietin). Additional criteria for inclusion in this analysis were: (a) small-volume residual disease (microscopic disease only or largest residual tumor mass < or = 0.5 cm) when IP therapy was initiated; (b) prior response to organoplatinum-based systemic therapy; (c) laparotomy evaluation for response to the IP salvage program. RESULTS: The surgically documented complete response rate for patients with microscopic disease treated with cisplatin-based or carboplatin-based therapy was 46% (6/13) versus 38% (6/16), respectively (P > 0.25). In contrast, the surgically documented overall and complete response rates for patients with small-volume macroscopic disease treated with cisplatin or carboplatin were 71% (12/17) versus 32% (6/19) (P < 0.05, chi 2 test with Yates' correction), and 41% (6/17) versus 11% (2/19) (p < 0.1), respectively. CONCLUSION: In agreement with experimental data demonstrating that the concentration of platinum within tumor is higher following equimolar doses of cisplatin, compared to carboplatin, we have observed, in this retrospective analysis, a higher surgically documented response rate for patients with small-volume residual macroscopic ovarian cancer receiving salvage cisplatin-based IP therapy. While a randomized trial will be required to definitively address the question of the relative effectiveness of the two commercially available organoplatinum agents for IP treatment of ovarian cancer, our data suggest that cisplatin is the superior agent for regional therapy in this disease.

Carboplatin↗
PubMed1993

Early invasive carcinoma of the cervix.

Ninety-two patients with early invasive carcinoma of the cervix (5 mm or less) treated between July 1977 and June 1990 are reviewed. Eighty patients had squamous cell carcinomas and 12 had adenocarcinomas. The diagnosis was established by conization in 77 of 92 (83.6%) patients. Thirty-six patients (39%) had a depth of stromal invasion of 1 mm or less, 32 patients (35%) between 1 and 3 mm, and 24 patients (26%) between 3 and 5 mm. Forty-four patients were treated with radical hysterectomy and bilateral pelvic lymphadenectomy (RHND). None of these patients had positive lymph nodes. Thirty-three patients were treated with conservative hysterectomy (CH), 4 with modified radical hysterectomy, and 2 with trachelectomy. Six patients received radiotherapy. Three patients were treated by conization only. Two patients developed in situ carcinoma (CIS) of the vagina 12 months after CH for lesions on conization that invaded less than 1 mm. In both cases the cone margins were positive, and in one a microscopic focus of CIS of the cervix was present at the resection margin of the hysterectomy specimen. A third patient developed an invasive lesion of the vagina 25 months after CH for a lesion that invaded 2.5 mm in a cone whose margins were not specified, but the hysterectomy margins were clear. All 3 patients were successfully retreated. The remaining patients are free of disease for a median follow-up of 51 months. The results of the study indicate that CH is adequate therapy for patients in whom the diagnosis of early invasive cervical cancer is established by conization with free margins and the depth of invasion is 3 mm or less. Although only 1 of 24 patients with invasion > 3 mm but < or = 5 mm had a CH, pathologic findings in 18 patients who had RHND suggest that CH would have been sufficient for these since there were no instances of spread to nodes or parametrium.

Adenocarcinoma↗
PubMed1993

Late recurrence of clear cell adenocarcinoma of the vagina and cervix: a report of three cases.

Three patients with clear cell adenocarcinomas who developed recurrent disease after a prolonged disease-free interval are presented. The first patient developed a recurrence in the lung 7 years and 3 months after wide local excision and pelvic radiotherapy for clear cell adenocarcinoma of the vagina. She then underwent thoracotomy and chemotherapy and has remained free of disease for more than 13 years after treatment of the recurrence. The second patient with clear cell adenocarcinoma of the vagina developed recurrent disease at the apex of the vagina 5 years after radical hysterectomy, bilateral pelvic lymphadenectomy, and partial vaginectomy. She then underwent exploratory laparotomy, partial vaginectomy, and vaginal irradiation and has been free of disease in follow-up for 6 months. The third patient underwent radical hysterectomy, bilateral pelvic lymphadenectomy, and total vaginectomy for clear cell adenocarcinoma of the cervix that also involved two-thirds of the vagina. Four years and 6 months after this operation, she underwent an exploratory laparotomy, with complete resection of recurrent disease in the abdomen in continuity with a left nephrectomy. Following surgery, she was treated with abdominal and pelvic radiotherapy and chemotherapy and remained clinically free of disease for 1 year, but subsequently developed an unresectable pelvic mass. Despite further chemotherapy, she died 5 years and 10 months after the initial diagnosis.

Abdominal Neoplasms↗
PubMed1993

Limited-field radiotherapy as salvage treatment of localized persistent or recurrent epithelial ovarian cancer.

Thirty-five patients with persistent or recurrent epithelial ovarian cancer were treated with salvage pelvic or para-aortic radiotherapy for disease limited to the pelvis (29), para-aortic retroperitoneum (5), or vaginal cuff (1). Prior therapy included a median of 3 chemotherapeutic drugs (range, 1-7) over a median of 12 cycles (range, 5-39); 12 patients had received intraperitoneal chemotherapy. The median number of prior laparotomies was 3 (range, 2-5). Including pelvic boosts, the median dose delivered to the treatment field was 4600 cGy (range 4000-7000); 2 patients received additional treatment with a permanent 125I implant. All patients completed therapy, although 5 (14%) with grade 3 toxicity required a treatment break. Late bowel complications unrelated to recurrence occurred in 3 patients (9%). Median actuarial and progression-free survivals for all patients from start of radiotherapy were 40 and 14 months, respectively. At least 16 of 26 (62%) recurrences involved the treatment field. Multiple prognostic factors were evaluated in terms of recurrence, survival, and acute and chronic complications, but no significant prognosticators were detected. These findings indicate that limited-field salvage radiotherapy has an acceptable complication rate and may prolong the symptom-free survival interval in selected patients.

Adult↗
PubMed1993

Diethyldithiocarbamate chemoprotection of carboplatin--induced hematological toxicity.

Carboplatin therapy has a more favorable toxicity profile than cisplatin and, given in appropriate doses, is equivalent in efficacy to cisplatin for suboptimal ovarian cancer. However myelosuppression frequently curtails therapy with carboplatin. Diethyldithiocarbamate (DDTC) is a thiol compound and heavy-metal-chelating agent that has been shown to protect against carboplatin-induced bone marrow suppression in animal models. This pilot study was undertaken to evaluate the ability of DDTC to ameliorate the degree and/or duration of myelosuppression from carboplatin chemotherapy in patients with relapsed ovarian cancer. Ten patients who had previously demonstrated a response to platinum-based chemotherapy, were treated with single-agent intravenous carboplatin 400 mg/m2 administered over 30-60 min every 4 weeks. Patients received their first cycle of carboplatin without DDTC, and their second cycle with DDTC. DDTC at 600 mg/m2 was infused over 3 h commencing 30 min prior to carboplatin and was well tolerated. Treatment with DDTC did not decrease the degree of leukopenia or thrombocytopenia associated with carboplatin chemotherapy, nor did it decrease the duration of myelosuppression. This clinical study demonstrates no evidence of a bone-marrow-protective effect for this dose and schedule of DDTC in patients receiving carboplatin chemotherapy.

Adenocarcinoma, Papillary↗
PubMed1993

Role of acute trauma in development of osteoarthritis.

Two canine acute transarticular loading models have been developed to study the role of acute traumatic cartilage damage in the development of osteoarthritis. One model involves damage to a closed joint and has the advantage of maintaining normal joint biology. The second model involves impaction of an open joint with direct visualization of the cartilage and has the advantages of being able to change the placement, intensity, and geometry of the impaction. Comparison of preliminary histochemical data at 2 weeks and 3 months for the open joint model with previously published data on the closed joint model is consistent with the two models having similar initial features that include surface cracks and step fractures of the zone of calcified cartilage. The early changes include loss of proteoglycan, expression of the pro-inflammatory markers such as TNF-alpha and IL-1 beta, and the metalloprotease stromelysin. By 3 months, cloning is present. The models will be useful in evaluating two hypotheses: one, that there is a threshold of damage that must be exceeded before the lesions became progressive and two, the cracks in the zone of calcified cartilage contribute to progression of osteoarthritis by acting as sites of endochondral ossification and thereby decreasing cartilage thickness.

Animals↗
PubMed1993

Ablation of mediastinal parathyroid adenomas by superselective embolization of the internal mammary artery with alcohol.

Two young patients (20 and 21 years) had recurrent hyperparathyroidism following neck exploration. Non-invasive investigations failed to localize a parathyroid adenoma. In both cases selective catheterization of the internal mammary arteries combined with digital angiography demonstrated hypervascular mediastinal adenomas. Using a coaxial catheterization technique (Tracker 18 and 10), both branch arteries of the internal mammary supplying the adenoma were selectively catheterized. In one case absolute alcohol and the other a mixture of Lipiodol and absolute alcohol were used to effect the ablation. The procedures were uneventful and serum calcium levels have subsequently returned to within normal limits. The follow-up in these two cases extends to 2 1/2 years in one and 10 months in the other case.

Adenoma↗
PubMed1993

The effects of immobilization of long segments of the spine on the adjacent and distal facet force and lumbosacral motion.

Long levels of spinal instrumentation and fusion are common in surgery for spinal deformity. The effect on the remaining mobile segments is not well understood. The changes in lumbar facet loading and lumbosacral motion were evaluated as the number of immobilized levels increased. Four fresh canine cadaveric spines from T6 to sacrum were used. Lumbosacral motion was measured with an instrumented spatial linkage device, and facet loads were measured at L1, L4, and L7 using a strain gauge technique. Lumbosacral motion and facet loading were significantly increased (P < 0.05) after immobilization of proximal segments, and the amount of the increase was dependent on the number of immobilized segments (P < 0.05). This indicates that immobilization of long segments of the spine influences the remaining mobile segments by increasing the load and motion not only at the immediately adjacent segment but also at the distal segments.

Animals↗
PubMed1993

Respiratory tract uptake of inhalants and metabolism of xenobiotics.

The combined impact of new research regarding the dosimetry of inhalants, discussed in early paragraphs of this review, and the rapidly developing knowledge regarding the location and substrate specificities of the enzymes responsible for xenobiotic metabolism should soon lead to new insights into the causes and prevention of cancer and other diseases of the respiratory tract and may provide insight into the design of drugs used in the treatment of respiratory tract disease. Among the developments to be expected within the next decade are the following: 1. The issue of extrapulmonary versus intrapulmonary activation of lung prodrugs and protoxicants will be resolved by validation of the different dosimetries predicted for highly lipophilic inhalants compared to less lipophilic ones. 2. The possibly complex roles of P450 isozymes 1A1 and 2D6 and other forms in the causation of human lung cancer will undoubtedly be better understood in the next few years. 3. Interspecies comparisons of respiratory tract enzyme activities--both activating and detoxicating--will lead to improved use of laboratory animals as models for expected toxicological and pharmacological effects in humans. 4. The potential role of nasal uptake and metabolism in causing brain disease will be established or denied experimentally. 5. The complex relationships between host factors--such as hormone levels and the presence of inflammation--and metabolism-mediated toxicity will become clearer. 6. As new research results continue to illuminate the complexities of the interactions of xenobiotics with respiratory tract tissue, clues as to how best to administer drugs via the respiratory tract and understanding of changes in disease patterns--such as the recent shift in sites for lung cancer--will follow.

Aerosols↗
PubMed1993

Scanning electron-microscopic and magnetic resonance-imaging studies of injuries to the patellofemoral joint after acute transarticular loading.

To examine the effects of transarticular loading on articular cartilage and subchondral bone, we used a canine model that we had developed previously, in which a standardized load of approximately 2000 newtons is delivered across the patellofemoral joint. The purpose of the study was to define and describe the initial changes, as seen on histopathological and magnetic resonance-imaging studies, that occur in the early stages after injury to the joint by transarticular loading. Scanning electron microscopy was used to define the extent and characteristics of the fractures produced in the subchondral bone of four patellae that were examined on the day of loading. We found multiple, extensive fractures through the zone of calcified cartilage and the subchondral bone, frequently with step-off displacement, and with little or no change in the gross appearance of the articular cartilage. Specimens from four patellae were examined histologically two weeks after loading, and the observed changes were correlated with those that had been demonstrated by scanning electron microscopy. Fractures through the zone of calcified cartilage and the subchondral bone, with step-off displacement, were prominent. Clefts were present in the surface of the articular cartilage and, in some areas, there was a focal loss of proteoglycan from the extracellular matrix, as indicated by the complete absence of staining with safranin O. Six dogs were examined one year after loading. There was healing of the subchondral fractures and restoration of proteoglycan in the extracellular matrix. However, superficial clefts and fissures were still present in the articular cartilage. Sequential magnetic resonance-imaging studies were also carried out on these six dogs, at two, eight, sixteen, thirty-six, and fifty-two weeks after loading. Two weeks after loading, all knees had soft-tissue swelling, effusion, and a decreased marrow signal in the medullary cavity of the patella. The decreased marrow signal and effusion were still present eight weeks after the impact, and then the findings gradually returned to normal. One year after loading, it was found that the histopathological changes had not been progressive; in fact, they had been ameliorated and, to some extent, reversed by repair processes. The early, severe magnetic resonance-imaging changes had also been reversed, so that this study demonstrated normal findings by one year after loading.

Animals↗
PubMed1993

Intraperitoneal administration of Taxol in the management of ovarian cancer.

The safety and pharmacology of the intraperitoneal administration of Taxol was evaluated by treatment of 25 patients (24 with ovarian cancer) on a phase I dose-escalation trial. The drug was delivered in 2 L of normal saline every 3 to 4 weeks, with a starting dose of 25 mg/m2. The dose-limiting toxicity was abdominal pain at Taxol doses greater than 125 mg/m2. A 3-log pharmacokinetic advantage for peritoneal cavity exposure to Taxol, compared to the systemic compartment, was demonstrated following intraperitoneal delivery. In addition, high levels of Taxol persisted within the cavity for more than 48 hours following a single treatment. Despite the major pharmacokinetic advantage for peritoneal cavity exposure, significant concentrations of Taxol were demonstrated within the systemic compartment after intraperitoneal treatment. Several patients exhibited clinical and laboratory evidence of an antitumor response. Further exploration of a possible role for the intraperitoneal administration of Taxol in the management of ovarian cancer appears indicated.

Female↗
PubMed1993

Second-look laparotomy in carcinoma of the fallopian tube.

OBJECTIVE: To evaluate the role of second-look laparotomy following platinum-based chemotherapy in patients with fallopian tube cancer. METHODS: We conducted a retrospective chart review of 35 patients with tubal cancer who underwent a second-look laparotomy following cytoreductive surgery and platinum-based combination chemotherapy. RESULTS: The distribution by stage was as follows: I, three (9%); II, five (14%); III, 24 (69%); and IV, two (6%); one patient was inadequately staged. The tumor grade was recorded in 31 patients, and 80% of these were grade 2 or 3. Twenty-one of the 35 patients (60%) were found to be free of disease at second-look operation. Neither stage nor grade were predictive of findings at the second-look procedure, although none of the five patients with stage I disease and/or grade 1 tumor had disease found at second-look surgery. The absence of gross residual disease following primary surgery was the strongest predictor of disease-free status at second-look laparotomy (P < .01). With a mean follow-up of 50 months among the survivors, only four (19%) of the patients with no evidence of tumor at reexploration have had a recurrence. CONCLUSION: Second-look laparotomy provides useful prognostic information in patients with tubal cancer; approximately 80% of patients who have a negative second-look following platinum-based chemotherapy will remain disease-free.

Actuarial Analysis↗
PubMed1993

Trophoblast and ovarian cancer antigen LK26. Sensitivity and specificity in immunopathology and molecular identification as a folate-binding protein.

The LK26 antigen is a cell surface glycoprotein (M(r)35,000 to 40,000) of normal placenta and gestational choriocarcinomas that shows highly restricted distribution in normal tissues, being expressed primarily in a subset of simple epithelia. In this study, immunohistochemical methods were used to examine LK26 expression in 78 ovarian tumors and > 400 tumors of other histological types. Ovarian carcinomas derived from coelomic epithelium showed the most consistent and strongest immunostaining for LK26, with 52 of 56 cases being LK26+. Ovarian tumors of sex cord, germ cell, and stromal origin were generally LK26-. LK26 was not found in normal fetal or adult ovary; however, it was present in the lining epithelia of some benign ovarian cysts. Mesotheliomas, which share a common mesothelial origin with LK26+ ovarian tumors, expressed no or only low levels of LK26. Other epithelial cancers expressed LK26 in subsets of cases and generally showed heterogeneous or weak immunostaining; this group of LK26+ tumors includes endometrial (10 of 11 cases tested), colorectal (six of 27), breast (11 of 53), lung (six of 18), and renal cell (nine of 18) carcinomas. Four of five brain metastases derived from epithelial cancers and three of 21 neuroendocrine carcinomas showed prominent LK26 immunoreactivity. Only rare neuroectodermal tumors (two of 70) and none of the sarcomas (none of 58) or lymphomas tested (none of 21) were LK26+. Tests with cultured cells showed that the LK26 proteins expressed in choriocarcinoma and ovarian cancer cells are biochemically similar, and transfection experiments identified LK26 as an adult-type, high-affinity folate-binding protein. The present study provides the first detailed specificity and sensitivity analysis for folate-binding protein/LK26 in human tumors and defines a role for folate-binding protein/LK26 in immunobiological studies of ovarian cancers and other LK26+ neoplasms.

Antibodies, Monoclonal↗
PubMed1993

Effect of immobilization and configuration on lumbar adjacent-segment biomechanics.

The motion and facet load changes at the adjacent segment after lumbosacral immobilization (with different angles) were quantified in vitro using canine spines. Changes were examined under flexion, extension, and lateral bending. An increase (extension: 62%; flexion: 85%; left bend: 30%; right bend 26%) in motion at the adjacent segment was found for all motions after immobilization. Adjacent-segment facet load remained constant under any load state or immobilized configuration. For all configurations, the facet contact site impinged in extension, remained unchanged in left bending, and moved superiorly in right bending. This study has shown that after immobilization the facet contact patterns at the adjacent segment changed, load was unchanged, and segmental motion increased when the lumbar spine reproduced the same range of motion. The configuration of the immobilized segments had no effect on these changes.

Animals↗