Side of origin of epithelial ovarian cancer.
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Adolescent↗
Biomedical subjects
J L Lewis
Publications and source records attributed to J L Lewis.
Interspecies comparison of cellular localization of the cyanide metabolizing enzyme rhodanese within olfactory mucosa.
The observation of high levels of xenobiotic metabolizing enzyme activity in the olfactory mucosa has produced speculation on the functional significance of these enzymes in the nose. Hypothesized roles include protection of the nasal epithelium, lung, and other downstream tissues, and termination or modification of olfactory responses. The enzyme rhodanese metabolizes cyanide, which is a commonly inhaled toxicant and an odorant and therefore of interest to both toxicologists and olfactory neurobiologists. The cellular localization of this enzyme within the olfactory mucosa will have important consequences for its ability to protect specific cells, as well as its ability to alter the concentration of inhaled cyanide at receptors, and therefore could provide clues as to its function in this tissue. We have compared the distribution of this enzyme in two species, the rat and the cow, using immunohistochemical localization techniques employing species-specific polyclonal antisera raised in our laboratory. In the rat, rhodanese-like immunoreactivity was greatest within the apical portion of the sustentacular cells, the basal cells, and the duct cells of Bowman's glands. Very little to no reaction was observed in the acinar cells of Bowman's glands. In the cow, however, the acinar cells and duct cells of Bowman's glands showed intense immunoreactivity with little to no reaction observed in the sustentacular or basal cells. The differences in localization of rhodanese in these two species may have important implications for cell types at risk during inhalation of cyanide or organonitrile compounds metabolized to cyanide within the nasal mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Subchondral damage after acute transarticular loading: an in vitro model of joint injury.
Intact canine metacarpophalangeal and metatarsophalangeal joints were subjected to a variety of loads in vitro. Intraarticular fracture occurred in 19 joints loaded to an average force of 2.4 +/- 0.4 kN with a corresponding loading rate of 88 +/- 23 kN/s. The remaining 29 joints were without gross evidence of fracture with an average load and loading rate of 1.7 +/- 0.9 kN and 64 +/- 32 kN/s, respectively. In the fractured specimens, damage to the zone of calcified cartilage and subchondral bone was much more extensive than was initially evident by gross inspection when assessed by scanning electron microscopy. Cracks with associated step-off displacement at the zone of calcified cartilage were found distant to the gross fractures. These findings were confirmed histologically. In addition, cracks localized to the zone of calcified cartilage were commonly identified histologically in specimens loaded in the range of 1.9-2.8 kN, but were not grossly fractured. The contact area determined with pressure-sensitive film increased with increasing load up to the point of fracture. The average pressure generated at the articular cartilage surface at the time of fracture in this model is > or = 40 MPa, and the fracture occurred at the contact site. Our findings suggest that failure in acute transarticular loading begins in the zone of calcified cartilage and subsequently involves the subchondral bone and overlying cartilage. This type of injury may contribute to the development of osteoarthritis after intraarticular fracture, or at high loads that do not result in gross fracture.
Animals↗
Biomechanical effect of a two-segment anterior cruciate ligament graft with separate femoral attachments and differing levels of prescribed load sharing.
The objective of this study was to analyze the biomechanical effect of varying the level of prescribed load sharing between two segments of an anterior cruciate ligament (ACL) graft, and of separating the femoral attachments of these segments. Total anterior-posterior (AP) laxity was measured using an instrumented spatial linkage. Forces in graft segments were measured using buckle transducers. The two-segment graft was formed using the middle third of the patellar tendon with bone blocks and a synthetic augmentation device. Proximal fixation was obtained using a fixture which allowed changing the individual locations of the femoral attachments of the tendon and augmentation segments. Distal fixation was achieved using a force-setting device which allowed the loads in each segment to be set to prescribed levels. Total graft force, load sharing, and total AP laxity were recorded during the application of 100-N AP tibial loads at 0 degrees, 30 degrees, 60 degrees, 90 degrees, and 110 degrees flexion, for various combinations of load sharing set at extension and locations of femoral attachment sites. The load sharing, total graft force, and AP laxity during AP loading at the five test flexion angles were not significantly affected by changing the prescribed level of load sharing set at extension for a given femoral attachment configuration. However, varying the separate hole locations of the graft segments for a given level of load sharing significantly affected load sharing, total graft force, and AP laxity. If the tendon graft was located posteriorly (on the medial surface of the lateral femoral condyle) and the augmentation segment proximally, the augmentation carried a greater portion of the total force in flexion. If the augmentation segment was changed to a more posterosuperior location and the tendon posteroinferior, the tendon carried a higher percentage of the total force in flexion. AP laxity in most reconstruction states was significantly greater than in the normal joint with an intact ACL. The nature of the load sharing between the graft segments under AP tibial load over the flexion range can be controlled by the appropriate choice of the segments' femoral attachment locations.
Analysis of Variance↗
Impact of laparotomy finding of significant intraabdominal adhesions on the surgically defined complete response rate to subsequent salvage intraperitoneal chemotherapy.
One possible explanation for the failure of the high concentrations of cytotoxic agents achieved following intraperitoneal (i.p.) drug delivery to produce a favorable response in patients with ovarian cancer is the inability of the drug-containing fluid to be adequately distributed throughout the peritoneal cavity, usually because of intraabdominal adhesion formation. To evaluate the influence of the severity of adhesions, observed at the time of laparotomy performed immediately preceding the initiation of i.p. therapy, on the ability to achieve a surgically defined complete response (S-CR), we retrospectively reviewed the operative reports of 70 patients with small-volume residual ovarian cancer treated on one of three phase-2 salvage i.p. trials at the Memorial Sloan-Kettering Cancer Center. The S-CR rate in the 36 patients with limited adhesion formation observed upon entering the peritoneal cavity was 28%, compared to 35% in the 34 patients with extensive adhesions (P greater than 0.05). In 33 patients treated with a phase-2 cisplatin-based i.p. program, who had previously responded to systemic platinum, 47% (8/17) and 44% (7/16) of those with limited and extensive adhesions, respectively, achieved a S-CR (P greater than 0.05). We conclude that the presence of extensive adhesions observed within the peritoneal cavity at the time of a laparotomy performed immediately prior to the initiation of i.p. therapy does not have a negative impact on the potential to achieve an S-CR, assuming it is technically feasible to lyse all significant adhesions prior to the completion of the operative procedure.
Abdomen↗
Phase 2 trial of chronic low-dose oral etoposide as salvage therapy of platinum-refractory ovarian cancer.
Eighteen previously treated patients with advanced ovarian cancer were entered into a phase 2 trial of chronic low-dose oral etoposide (50 mg/day for 20 days, repeated every 28 days) to determine the activity of this therapeutic strategy in organoplatinum-refractory disease. The treatment program was generally well tolerated, with mild neutropenia the most common side-effect encountered. One patient (6%; 95% confidence interval = 0-17%) achieved a partial response, which lasted for 11 months. Three additional patients (17%), who failed to meet the criteria of a partial response, demonstrated objective evidence of antineoplastic activity. Chronic low-dose oral etoposide administration is associated with definite, although modest, activity in platinum-refractory ovarian cancer.
Carboplatin↗
Association between pretreatment CA-125 levels and surgically documented complete responses in patients with ovarian cancer treated with second-line intraperitoneal therapy.
Approximately 20%-40% of patients with small-volume residual ovarian cancer, following systemically administered platinum-based chemotherapy, will respond to a second-line intraperitoneal treatment regimen. In an effort to improve the selection criteria for patients being considered for this regional therapeutic approach, we retrospectively evaluated the influence of pretreatment CA-125 levels on the ability of a group of 70 patients with small-volume residual ovarian cancer (no tumor mass greater than 1 cm in diameter) to achieve a surgically defined complete response (S-CR) following treatment on one of three phase-2 intraperitoneal chemotherapy trials conducted at the Memorial Sloan-Kettering Cancer Center. Overall, 18/46 (39%) patients with normal pretreatment CA-125 levels (less than or equal to units/ml) achieved a S-CR, compared to only 4/24 patients (17%) with an elevated pretreatment value (chi 2 = 3.7, P greater than 0.5). Despite the lower S-CR rate in patients with elevated CA-125 levels, the duration of response and survival were similar in the two patient populations achieving a S-CR. Thus, we conclude that an elevated pretreatment CA-125 level in a patient with small-volume residual ovarian cancer should not be used by itself to disqualify an individual from consideration for a second-line intraperitoneal treatment regimen, although the finding suggests a reduced likelihood of achieving a S-CR with this therapeutic approach.
Antigens, Tumor-Associated, Carbohydrate↗
Salvage intraperitoneal therapy of small-volume residual ovarian cancer: impact of pretreatment finding of peritoneal carcinomatosis on the surgical complete response rate.
Second-line intraperitoneal (i.p.) therapy has been demonstrated to result in surgically defined complete responses (S-CR) in 25%-40% of patients with small-volume residual ovarian cancer (microscopic disease or largest tumor mass less than 1 cm in diameter). To evaluate the influence of the surgical finding of diffuse peritoneal carcinomatosis on the S-CR rate to salvage i.p. therapy in this patient population, we retrospectively reviewed the operative reports of 70 patients with small-volume residual ovarian cancer treated on one of three phase-2 second-line i.p. trials at the Memorial Sloan-Kettering Cancer Center. Of the 11 patients with diffuse carcinomatosis, none achieved a S-CR compared to a S-CR rate of 37% (22/59) in patients without this surgical finding (chi 2 = 6.0; P less than 0.025). However, of the 7 patients with diffuse carcinomatosis treated on a cisplatin-based i.p. program, the only 2 who had previously responded to systemic platinum also experienced a response (partial) to the i.p. cisplatin regimen. In conclusion, while the surgical finding of diffuse peritoneal carcinomatosis indicates a poor prognosis in patients with small-volume residual ovarian cancer for response to i.p. chemotherapy, patients in this clinical setting with prior evidence of platinum sensitivity may experience some benefit from an i.p. cisplatin-based treatment strategy.
Cisplatin↗
A theoretical model of the knee and ACL: theory and experimental verification.
A three-dimensional mathematical model of the human knee joint was developed to examine the role of single ligaments, such as an anterior cruciate ligament (ACL) graft in ACL reconstruction, on joint motion and tissue forces. The model is linear and valid for small motions about an equilibrium position. The knee joint is modeled as two rigid bodies (the femur and the tibia) interconnected by deformable structures, including the ACL or ACL graft, the cartilage layer, and the remainder of the knee tissues (modeled as a single element). The model was demonstrated for the equilibrium condition of the knee in extension with an anterior tibial force, causing anterior drawer and hyperextension. The knee stiffness matrix for this condition was measured for a human right knee in vitro. Predicted model response was compared with experimental observations. Qualitative agreement was found between model and experiment, validating the model and its assumptions. The model was then used to predict the change in graft and cartilage forces and joint motion of the knee due to an increment of load in the normal joint both after ACL removal and with various altered states simulating ACL reconstructions. Results illustrate the interdependence between loads in the ACL graft, other knee structures, and contact force. Stiffer grafts and smaller maximum unloaded length of the ligament lead to higher graft and contact forces. Changes in cartilage stiffness alter load sharing between ACL graft and other joint tissues.
Anterior Cruciate Ligament↗
Phase 2 trial of intraperitoneal carboplatin and etoposide as salvage treatment of advanced epithelial ovarian cancer.
To evaluate the efficacy of intraperitoneal (IP) carboplatin-based therapy as salvage treatment of ovarian cancer, 46 patients with persistent or recurrent ovarian cancer following initial systemic chemotherapy were treated with a regimen of carboplatin (200-300 mg/m2) and etoposide (100 mg/m2) administered on a monthly schedule. A maximum of six courses of therapy was delivered, followed by a response laparotomy. The treatment program was well tolerated, except for bone marrow suppression, with one-quarter of patients developing platelet count depressions to < or = 50,000/mm3, and one-third experiencing hemoglobin levels of < or = 8 g/dl during treatment. Twelve (38%) of 32 patients evaluable for efficacy of the treatment program achieved a surgically documented response, including 8 (25%) complete responses. Of 25 patients whose largest tumor mass at the initiation of therapy measured < or = 0.5 cm, 11 (44%) responded, including 8 (32%) complete responses. We conclude that the IP administration of carboplatin can result in surgically documented responses when used in the salvage setting in patients with advanced ovarian cancer. The relative efficacy of carboplatin versus cisplatin when administered by the IP route to patients with ovarian cancer previously treated with platinum-based systemic therapy remains to be defined.
Adult↗
Resection of pulmonary metastases from uterine sarcomas.
Long-term survival following resection of pulmonary metastases has been well documented. Variables that are believed to have an effect on survival are site of primary tumor, number and size of metastases, resectability, laterality of the metastases, doubling time, and disease-free interval. Published information regarding resection of pulmonary metastases in patients with gynecologic primary tumors is limited. We reviewed 45 patients whose pulmonary metastases from uterine sarcomas were resected at Memorial Sloan Kettering Cancer Center between 1960 and 1989. All cases met carefully defined criteria at time of thoracotomy: prior hysterectomy for uterine sarcoma, no extrathoracic tumor, known disease thought to be resectable, histology consistent with uterine sarcoma, and no medical contraindication to thoracotomy. Seventy-one percent had unilateral lesions, fifty-one percent had one lesion, and seventy percent had nodules greater than 2 cm. Thirty-six percent had incomplete resection at thoracotomy. Actuarial 5- and 10-year survival from hysterectomy for uterine sarcoma was 65 and 50%, respectively, with a mean follow-up of 89 months. Five- and ten-year survival from resection of pulmonary metastases was 43 and 35%, respectively, with a mean follow-up of 25 months. Unilateral vs bilateral disease was a significant predictor of survival after pulmonary resection (P = 0.02). Metastases size, number of metastases, disease-free interval, and patient age were not significant. Among this carefully selected group of patients undergoing resection of pulmonary metastases from uterine sarcomas, long-term survival was achieved by a substantial proportion of patients. No single risk factor is sufficiently accurate to exclude an individual patient from consideration for pulmonary resection.
Female↗
Management of vulvar melanoma.
Considerable debate centers on the optimal treatment for vulvar melanoma, as well as those clinicopathological factors influencing prognosis. We reviewed 80 patients with vulvar melanoma seen between 1949 and 1990. Primary tumors were assessed according to Chung (47 patients) and Breslow (65 patients) microstaging systems. Fifty-nine patients (76%) underwent radical vulvectomy, ten patients (13%) had a partial vulvectomy, and nine patients (12%) had a wide local excision. Fifty-six also underwent inguinal node dissection. Median follow-up was 193 months. Median survival was 63 months. Ten-year survival by Chung level was as follows: I 100%; II, 81%; III, 87%; IV, 11%; V, 33%. Ten-year survival by tumor thickness was as follows: 0.75 mm, 48%; 0.75-1.5 mm, 68%; 1.51-3.0 mm, 44%; greater than 3.0 mm, 22%. Increased depth of invasion was associated with increased incidence of inguinal node metastasis. Cox regression analysis demonstrated prognostic significance for tumor thickness (P less than 0.001), inguinal node metastasis (P less than 0.001), and older age at diagnosis (P less than 0.001). Radical vulvectomy did not seem to improve survival over less radical procedures. Based on this experience, we recommend radical local excision for patients with malignant melanoma of the vulva. Patients who have more than a superficially invasive melanoma should also have inguinal lymph node dissection.
Adolescent↗
Characterization of a human endometrial carcinoma cell line producing intraperitoneal tumor growth in immunodeficient mice.
Establishment of laboratory models of gynecologic neoplasms provides an important means of studying the biologic characteristics of these tumors. We report a previously uncharacterized human endometrial adenocarcinoma cell line that produces both intraperitoneal and subcutaneous growth in nude mice. The line was derived from a poorly differentiated endometrial cancer and has been carried in continuous tissue culture for greater than 100 passages. Doubling time in culture is approximately 48 hr. Antigenic phenotyping against a panel of murine monoclonal antibodies by rosetting cell surface assay on live cells or peroxidase assay on fixed cells has shown reactivity with a number of determinants, including MH99, MT334, MQ49, and the blood group antigens F3, 118, and 41-83. Cytogenetically, the line displays an aneuploid human karyotype with several chromosomal rearrangements and deletions. When injected intraperitoneally into nude mice, animals develop intraperitoneal nodules and ascites and succumb with wasting in 30-40 days. The intraperitoneal tumor has been passaged multiple times in nude mice by direct transfer of ascites. Subcutaneous injection of tumor cells produces nodules that grow at a reproducible rate. By light and electron microscopy, the nude mouse tumor is a poorly differentiated adenocarcinoma, similar to the original patient's tumor. It expresses both estrogen and progesterone receptors. CA 125 is not elevated in the serum of animals with tumor implants. The line appears to be cisplatin sensitive as determined by rates of growth of subcutaneous nodules. This cell line may be useful in studying the in vitro and in vivo properties of human endometrial carcinoma.
Adenocarcinoma↗
Randomized prospective trial of 5 versus 10 cycles of cyclophosphamide, doxorubicin, and cisplatin in advanced ovarian carcinoma.
Five versus ten cycles of cyclophosphamide, doxorubicin, and cisplatin (CAP) were compared in advanced ovarian carcinoma by a prospective randomized study of 78 patients, 41 receiving 5 cycles (CAP5) and 37 receiving 10 cycles (CAP10) of chemotherapy. Patients were stratified by histologic grade and size of residual disease. Cyclophosphamide, 600 mg/m2, doxorubicin, 40 mg/m2, and cisplatin, 100 mg/m2, were administered every 4 weeks for 5 or 10 cycles. Second-look laparotomy was performed to evaluate response and plan further therapy. CAP5 patients found a second-look laparotomy to have partially responded to chemotherapy were treated with 5 additional cycles of CAP. CAP10 was more toxic than CAP5 with respect to myelosuppression, hospital admissions for nadir fever, median elevation of creatinine, and degree of peripheral neuropathy. Median follow-up is 64 months. CAP5 and CAP10 were equivalent in surgically documented complete responses (34 versus 35%) and survival (P = 0.41). Twelve partial responders to CAP5 received additional CAP chemotherapy; one complete response resulted. We conclude that CAP5 is preferable to CAP10 in treatment of advanced ovarian cancer as it is equally effective and less toxic.
Antineoplastic Combined Chemotherapy Protocols↗
Management of endometrial adenocarcinoma with cervical involvement.
Seventy-seven patients with endometrial cancer with cervical involvement were treated at Memorial Sloan-Kettering Cancer Center from 1968 to 1982. Fractional curettage specimens showed that 25 patients (32%) had involvement of cervical stroma and 52 (68%) had only detached fragments of carcinoma present in endocervical curettings. Six patients treated for palliation only are excluded from analysis of treatment and survival. Our preferred treatment during the time interval studied consisted of preoperative whole pelvic radiotherapy followed by modified radical hysterectomy and bilateral salpingo-oophorectomy with post-operative intravaginal brachytherapy. This regimen was well tolerated by the 37 patients so treated. The remaining patients were treated with a variety of regimens, most commonly radiotherapy and simple hysterectomy (25 patients). With a mean follow-up among survivors of 97 months, disease-free survival is 72%. Mean time to relapse was 19 months, with 90% of relapses occurring within 40 months. Initial sites of relapse included abdomen, 9 (12.6%); lungs, 8 (11.3%); brain, 2 (2.8%); lateral pelvis, 2 (2.8%); and bone, 1 (1.4%). Clinicopathologic variables significantly related to risk of relapse included presence of extrauterine disease at surgery (P = 0.0001), extent of cervical involvement as determined prior to hysterectomy (P = 0.001), depth of myometrial invasion (P = 0.005), and papillary serous histology (P = 0.0002). Treatment of endometrial cancer with cervical involvement with combinations of radiotherapy and surgery is well tolerated and results in an excellent long-term disease-free survival and a low rate of pelvic relapse.
Adenocarcinoma↗
In vivo facet joint loading of the canine lumbar spine.
This study describes a technique to measure in vivo loads and the resultant load-contact locations in the facet joint of the canine lumbar spine. The technique is a modification of a previously described in vitro method that used calibrated surface strains of the lateral aspect of the right L3 cranial articular process. In the present study, strains were measured during various in vivo static and dynamic activities 3 days after strain gage implantation. The in vivo recording technique and its errors, which depend on the location of the applied facet loads, is described. The results of applying the technique to five dogs gave the following results. Relative resultant contact load locations on the facet tended to be in the central and caudal portion of the facet in extension activities, central and cranial in standing, and cranial and ventral in flexion or right-turning activities. Right-turning contact locations were ventral and cranial to left-turning locations. Resultant load locations at peak loading during walking were in the central region of the facet, whereas resultant load locations at minimum loading during walking were relatively craniad. This resultant load-contact location during a walk gait cycle typically migrated in an arc with a displacement of 4 mm from minimum to maximum loading. Static tests resulted in a range of facet loads of 0 N in flexion and lying to 185 N for two-legged standing erect, and stand resulted in facet loads of 26 +/- 15 N (mean +/- standard deviation [SD]). Dynamic tests resulted in peak facet loads ranging from 55 N while walking erect to 170 N for climbing up stairs. Maximum walk facet loads were 107 +/- 27 N. The technique is applicable to in vivo studies of a canine facet joint osteoarthritis model and may be useful for establishing an understanding of the biomechanics of low-back pain.
Animals↗
In vivo analysis of canine intervertebral and facet motion.
Using an instrumented spatial linkage, a method for measuring intervertebral motion in vivo was developed and used on six dogs. The segmental motion was recorded as the animals were exercised in routine functions. The standing posture was found to be a repeatable position. During walking, the average excursion between opposing facets was 3.4 +/- 1.3 mm, as the L2-L3 motion segment moved into 2.3 degrees of kyphosis with respect to the standing position. This method has the ability of measuring facet motion (+/- 0.7 mm), vertebral body motion (+/- 0.5 mm), and vertebral body rotations (+/- 0.6 degrees) with suitable accuracy such that it is a useful tool in documenting the in vivo response of a motion segment to surgical procedures.
Animals↗
Cracks emanating from slipping inclusions near a bone-implant interface.
It has been hypothesized that mechanical fracture at the bone-cement-implant interface is the initial cause for loosening of orthopedic implants. Previous investigators have observed cracks to emanate from methacrylate beads, apparently acting as inclusions within the cement. It is believed that the bond between these inclusions and the surrounding matrix breaks prior to emanation of radial cracks from the inclusion. An analytical model is developed for radial cracks emanating from circular inclusions that allow slip along their interface. The solution to the interaction of a single dislocation and a slipping inclusion is used as a Green's Function to model the crack. The Mode I stress intensity factors are calculated for arbitrary orientations of the crack and for varying relative stiffness of the matrix and the inclusion to test feasibility of crack growth.
Bone Cements↗