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Biomedical subjects

M L Berman

Publications and source records attributed to M L Berman.

At least 55 records · Page 3Linked to original sources

Extent of disease as an indication for pelvic radiation following radical hysterectomy and bilateral pelvic lymph node dissection in the treatment of stage IB and IIA cervical carcinoma.

The role of adjuvant pelvic radiation following radical hysterectomy and pelvic lymph node dissection in the treatment of stage IB and IIA cervical cancer is controversial. Patients most likely to benefit from postoperative radiation include those with lesions that invade deeply into the cervical stroma, extend into the parametria, or have metastasized to regional lymph nodes. Between 1977 and 1987, 95 patients were treated with this combined regimen at the University of California Irvine Medical Center and Long Beach Memorial Medical Center, including 30 patients with deep cervical stromal invasion alone, 9 patients with parametrial extension alone, 37 patients with lymph node metastasis alone, and 19 patients with both positive nodes and parametrial extension. The estimated 5-year survival for this high-risk population was 67%. Pelvic recurrences alone occurred in 12 (13%) patients, and 14 additional patients (15%) recurred outside of the radiation field. In the node-positive group, the 5-year survival was 78% when the parametrium was not involved but decreased to 39% when parametrial extension was documented (P < 0.05). Patients with grossly involved nodes or multiple nodal metastases were also more likely to recur. Finally, the estimated 5-year survival for patients with deep cervical stromal invasion as the sole indication for radiotherapy was 73%. A retrospective analysis identified tumor grade and cell type also to be of prognostic importance. Severe complications attributable to radiation combined with radical surgery included two small bowel obstructions and one urinary tract fistula. These data suggest that radical hysterectomy, pelvic lymphadenectomy, and adjuvant radiotherapy produce favorable survival results with limited morbidity in patients with high-risk cervical cancer independent of node status except in that subset of patients with both occult parametrial spread and nodal metastasis.

Adult↗

Primary vaginal melanoma: improved survival with radical pelvic surgery.

Primary vaginal melanoma is an aggressive and rare gynecological malignancy with < 150 reported cases to date. Historically, patients with this disease have a poor prognosis for all types of treatment. In several studies containing small numbers of patients conservative therapy often has been recommended. Eight patients from our institute with this disease were divided into two groups according to therapy: Group A, radical (4); and Group B, conservative (4). The groups were compared for stage, age, surface area of the lesion, and quality of life. The 2-year survival in Group A (75%) was significantly better than that of group B (0%). There was also found to be an improved survival in patients who had lesions with a surface area < 10 cm2. Age and stage of disease did not affect prognosis. Quality of life was not reduced in the radical group. A review of all reported cases since 1949 (119) was then performed. These were divided into the same Group A, radical (50); and Group B, conservative (69). Again, a statistically significant improved outcome was found with the radically treated patients (48%) when compared to the conservatively treated patients (20%). Our findings suggest that radical surgery for patients with primary vaginal melanoma is recommended in patients with lesions < 10 cm2.

Adult↗

Adhesions after extensive gynecologic surgery: clinical significance, etiology, and prevention.

Postoperative adhesions occur in 60% to 90% of patients undergoing major gynecologic surgery and represent one of the most common causes of intestinal obstruction in the industrialized world. The incidence of adhesion-related intestinal obstruction after gynecologic surgery for benign conditions without hysterectomy is approximately 0.3%, increasing to 2% to 3% among patients who undergo hysterectomy, and is as high as 5% if a radical hysterectomy is performed. Other adhesion-related complications include chronic pelvic pain, ureteral obstruction, and voiding dysfunction. Intraperitoneal adhesions also can limit the effectiveness of intraperitoneal therapeutic agents used in cancer treatment. Postoperative adhesions are sequelae of impaired fibrinolysis of the fibrin and cellular exudate after peritoneal injury. Adequate blood supply is essential for normal fibrinolysis. Therefore factors that increase ischemia and potentiate adhesion formation include thermal injury, infection, presence of a foreign body, and radiation-induced endarteritis. Only recently, appropriate animal models have been developed to study the process of adhesion formation and prevention. Until clinical confirmation of findings from these investigations exists, only a meticulous surgical technique can be advocated to minimize these untoward effects of surgery.

Animals↗

Comparison of the polymerase chain reaction and Southern blot analysis in detecting and typing human papilloma virus deoxyribonucleic acid in tumors of the lower female genital tract.

To conduct studies on the clinical and pathologic significance of human papilloma virus (HPV) in genital malignancies, accurate detection and typing of the virus in clinical material are essential. Currently, Southern blotting and the polymerase chain reaction (PCR) are two of the most commonly used methods to identify HPV. This study was undertaken to compare these techniques in the detection and typing of HPV in 242 invasive malignancies of the lower female genital tract. BamHI and PstI restriction digests of tumor DNA were hybridized to 32P-labeled probes for HPV types 6, 16, and 18 at TM -20 degrees C after Southern transfer. Blots were then washed at Tm -20 degrees C and Tm -9 degrees C. The DNA was also amplified by PCR using both highly conserved consensus L1 primers that detect 25 different HPV genotypes and primers specific for HPV 6 E6, 16 E7, and 18 E6. All PCR products were hybridized to type-specific radiolabeled probes. In 202 of the 242 (83%) samples, HPV was detected, including 189 of 218 (87%) cervical cancers, 11 of the 20 (55%) vulvar cancers, and two of four tumors from the vagina, urethra, or anus. In 67% of the specimens, there was agreement between the Southern blot technique and both methods of PCR (consensus and type-specific primers), including 121 of the 202 HPV-positive specimens and 40 HPV-negative specimens. Of the 141 tumors with HPV detected by Southern blot analysis, the same HPV type was detected by PCR in 121 (86%).(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

Cost analysis of Hickman catheter insertion at bedside in gynecologic oncology patients.

BACKGROUND: Cost-containment issues are becoming increasingly important in medicine. The current study compares bedside versus operating room insertion of Hickman catheters from a cost and safety standpoint. STUDY DESIGN: A prospective chart review of all patients undergoing Hickman catheter insertion during the study period was performed to determine location of the procedure, rate of successful catheter placement, complications, and cost. RESULTS: Ninety-six patients underwent placement of 108 Hickman catheters during a seven year period. Fifty-three catheters were inserted at bedside while 55 catheters were placed in the operating room. The complication rate was 8 percent for the bedside and 9 percent for the operating room group. Due to anesthesia standby, operating room time, and fluoroscopy, cost analysis revealed a substantial savings of $1,545 per patient if bedside insertion was utilized. CONCLUSIONS: The data indicate that, in select patients, percutaneous insertion of Hickman catheters at bedside is a safe, cost-effective procedure.

Catheterization, Central Venous↗

A new method of continuous vaginal cuff closure at abdominal hysterectomy.

A new method for vaginal cuff closure at abdominal hysterectomy avoids blood loss and spillage of vaginal contents into the peritoneal cavity. Using two separate running and interlocking absorbable monofilament sutures, the technique keeps the vagina closed at all times and avoids damage to the bladder or ureters. In 77 consecutive patients undergoing abdominal hysterectomy for endometrial cancer, morbidity related to the cuff closure included cuff cellulitis in only 2.6%, granulation tissue in 3.1%, and postoperative bleeding in none of the patients.

Blood Loss, Surgical↗

Identification of the MN antigen as a diagnostic biomarker of cervical intraepithelial squamous and glandular neoplasia and cervical carcinomas.

A new tumor-associated antigen, MN, has been identified whose expression correlates with the tumorigenic phenotype of HeLa x fibroblast somatic cell hybrids. Because HeLa is a cell line derived from a cervical carcinoma, we investigated the diagnostic utility of MN expression in cervical neoplasia. It was found that normal cervical tissue does not express the antigen, or does so in occasional focal areas of weakly staining reserve cells. In contrast, significant immunoreactivity (immunoperoxidase staining of paraffin-embedded sections) was observed in cervical intraepithelial neoplasias, adenocarcinoma in situ, and frank carcinomas, both squamous cell and adenocarcinoma. Varying patterns of immunoreactivity were observed and were characterized as diffuse, diffuse/focal, or focal. Greater than 90% of dysplastic or malignant tissues showed immunoreactivity. An interesting observation was that normal cervical tissue associated with cervical intraepithelial neoplasias, or adenocarcinoma in situ showed a staining pattern in the reserve cells and/or normal columnar cells that approximated the level of intensity exhibited by the dysplastic tissue. These results indicate that MN antigen expression has potential utility as a biomarker of cervical neoplasms.

Adenocarcinoma↗

Oral contraceptives and endometrial cancer: do other risk factors modify the association?

The joint effect of use of combination-type oral contraceptives and other exposure factors on risk of endometrial cancer was examined in data from a multicenter case-control study conducted in 5 areas of the United States. Cases were 405 women with histologically confirmed invasive epithelial endometrial cancer first treated at one of 7 participating hospitals. A total of 297 population-based controls of similar age, race, and geographic area were selected as a comparison group. Information on exposure factors was derived from in-person interviews. Combination-type oral contraceptive (COC) use was associated with a significant reduction in risk of endometrial cancer, with an adjusted odds ratio (OR) of 0.4 (95% confidence interval 0.3 to 0.7) for ever compared to never use. Long-term (> or = 10 years) users experienced a markedly lower risk (OR = 0.2). Women who discontinued COC use > or = 20 years earlier remained at reduced risk (OR = 0.7) compared with non-users. The negative association with COC use was apparent regardless of the presence or level of several other risk factors for endometrial cancer, including age, menopausal status, parity, obesity, ever-use of menopausal estrogens, smoking history, or history of infertility. The magnitude of the negative association observed in COC users, however, was considerably diminished in women with no full-term births and in women who subsequently used replacement estrogens for 3 or more years. These results provide new evidence that the protective effect of COC use lasts for 20 or more years after use is discontinued, and highlight several sub-groups of users in whom the level of protection is attenuated by the presence of other risk factors for this disease.

Adult↗

Cigarette smoking and the risk of endometrial cancer.

A case-control study involving 405 cases of epithelial endometrial carcinoma (newly diagnosed between 1987 and 1990 in five US areas) and 297 population controls enabled evaluation of risk in relation to detailed smoking characteristics. Cigarette smokers were at a reduced risk of disease, with the effect primarily restricted to women whose diseases were detected postmenopausally (relative risk (RR) = 0.6, 95% confidence interval 0.4-0.9). Among postmenopausal women, current smokers showed the greatest reduction in risk (RR = 0.4, 95% confidence interval 0.2-0.7), with former smokers, including those who had recently stopped, being less affected (RR = 0.8). Other measures of smoking were highly correlated with currency of smoking, but there were no clear patterns of risk with either duration or intensity of smoking. Smoking appeared to reduce risk to the greatest extent in subjects who were multiparous, obese, or nonusers of exogenous hormones, but none of these relations was statistically significant. The results support the notion that smoking reduces the risk of endometrial cancer through extraovarian endogenous hormonal mechanisms, but further studies are needed to clarify why reduced risks are most pronounced among postmenopausal women and those currently exposed to cigarette smoke.

Adult↗

Expression of human recombinant 72 kDa gelatinase and tissue inhibitor of metalloproteinase-2 (TIMP-2): characterization of complex and free enzyme.

The human 72 kDa gelatinase/type IV collagenase is a metalloproteinase that is thought to play a role in metastasis and angiogenesis. The 72 kDa progelatinase can be isolated from conditioned media as a complex with the tissue inhibitor of metalloproteinase-2 (TIMP-2). To investigate 72 kDa gelatinase-TIMP-2 interactions and to compare the activity of the complex versus that of the free enzyme, we have expressed and purified human 72 kDa progelatinase and TIMP-2 as single proteins in a recombinant vaccinia virus mammalian cell expression system. The recombinant 72 kDa progelatinase was able to bind TIMP-2, and it digested gelatin and collagen type IV after activation by p-aminophenylmercuric acid (APMA). The specific activity of the recombinant free enzyme was 20-fold higher than the activity of an APMA-treated stoichiometric complex of recombinant 72 kDa progelatinase and TIMP-2. Also, TIMP-2 caused an 86% inhibition of activity when added to the activated enzyme at a 1:1 molar ratio. Activation of the free recombinant 72 kDa progelatinase yielded the 62 kDa species and two fragments of 46 and 35 kDa that cross-reacted with monoclonal antibodies to the 72 kDa proenzyme. TIMP-2 inhibited the conversion of the recombinant proenzyme to the 62 kDa species and the appearance of the 45 and 35 kDa bands. These results suggest that TIMP-2 is not only a potent inhibitor of the activated enzyme but also prevents the generation of low-molecular-mass species and full enzymic activity from the zymogen.

Blotting, Western↗

Extraovarian peritoneal serous papillary carcinoma: a case-control retrospective comparison to papillary adenocarcinoma of the ovary.

Since the establishment of extraovarian peritoneal serous papillary carcinoma (EPSPC) as a clinical entity in 1959, less than 250 cases have been described and its clinicopathologic features remain obscure. The present series is a retrospective, case-controlled study comparing the response and survival to cytoreductive surgery followed by cisplatin-based multiagent chemotherapy of 33 women with confirmed EPSPC versus 33 cases with papillary serous ovarian cancer (PSOC). Each EPSPC case was matched to a PSOC control for extent and distribution of disease prior to and following cytoreductive surgery, tumor grade, patient age, and treatment. Additionally, the new Gynecologic Oncology Group criteria for the diagnosis for EPSPC are discussed. There were no significant differences in tumor response to therapy, disease-free interval, and actuarial survival between cases and controls. These data suggest that EPSPC is clinically similar to PSOC and support the need for a prospective clinical trial to compare these two entities further.

Adenocarcinoma, Papillary↗

To drain or not to drain: a retrospective study of closed-suction drainage following radical hysterectomy with pelvic lymphadenectomy.

The records of 115 patients were reviewed following radical hysterectomy with pelvic lymphadenectomy for early stage (IA2 to IIB) cervical cancer to determine the effectiveness of closed-suction drainage in decreasing postoperative morbidity. In Group 1 (n = 67), closed-suction (Jackson-Pratt) drains were placed bilaterally in the pelvic lymphadenectomy sites, whereas in Group 2 (n = 48), no drains were utilized. The groups were similar for mean age, tumor histology, disease stage, and preoperative serum albumin and total protein. There was no difference in the mean operative time, mean estimated blood loss, or transfusion rate. Likewise, febrile morbidity rates, incidence of pelvic cellulitis, length of postoperative ileus, and total hospital stay were similar. Group 1 had an increased rate of rehospitalization and morbidity directly related to the presence of the drains. The data suggest that prophylactic surgical drainage may not be necessary to prevent postoperative morbidity following radical hysterectomy with pelvic lymphadenectomy and on occasion contributes to postoperative complications.

Adult↗

Dietary associations in a case-control study of endometrial cancer.

Despite the established role of obesity in the etiology of endometrial cancer, limited data are available from analytical epidemiologic studies on the association of risk with dietary factors. A case-control study of 399 cases and 296 controls conducted in five areas of the United States from 1 June 1987 to 15 May 1990, enabled evaluation of risk related to dietary intakes adjusted for potential confounders. Caloric intake was associated modestly with increased risk (odds ratio [OR] = 1.5, 95 percent confidence interval [CI] = 0.9-2.5 for highest cf lowest quartiles of intake), with the principal contributors being fat and protein calories. After adjustment for other risk factors, including body mass, increased risk was associated with higher intakes of fat. Several components of fat investigated were associated with increased risk, although associations were slightly stronger for saturated fat (OR = 2.1, CI = 1.2-3.7) and oleic acid (OR = 2.2, CI = 1.2-4.0) than for linoleic acid (OR = 1.6, CI = 0.9-2.8). Food-group analyses showed intake of complex carbohydrates--and specifically of breads and cereals--associated with reduced risks (OR = 0.6, CI = 0.4-1.1), whereas animal fat and fried foods were associated with elevated risks (OR = 1.5 and 1.7, respectively). The relations of endometrial cancer with animal fat and complex carbohydrates were independent. No consistent associations were noted for intakes of cholesterol, fiber, vitamins A and C, individual carotenoids, or folate-rich foods. These data imply an etiologic role for a diet rich in total fat and/or animal fat and low in complex carbohydrates with endometrial cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Mass Index↗

Past and present physical activity and endometrial cancer risk.

We examined the relation between physical activity and endometrial cancer using data from a multicentre case-control study involving 405 endometrial cancer cases and 297 population controls. Estimates of recreational (i.e. active sport, walks and hikes) and nonrecreational activity (i.e. house cleaning, climbing stairs and walking or standing on the job) were obtained using interview information. After adjustment for age, study area, education, parity, years of use of oral contraceptives, years of use of menopausal oestrogens and cigarette smoking, recent recreational inactivity was associated with increased risk (RR = 1.9 for lowest vs highest tertile). Similarly, recent nonrecreational inactivity was associated with increased risk (RR = 2.2 for lowest vs highest tertile). Further adjustment for body mass and nonrecreational activity attenuated the association between risk and recent recreational inactivity (RR = 1.2; 95% CL = 0.7-2.0) but adjustment for body mass and recreational activity did not alter the association between risk and recent nonrecreational inactivity (RR = 2.0; 95% CL = 1.2-3.1). To evaluate the relation between risk and sustained inactivity, we simultaneously examined activity levels at three periods (RR i.e. age 20-29, age 30-39 and recently) in women age 50 and older. After adjustment for potential confounders and body mass, risk was elevated among women who were always recreationally inactive (RR = 1.5 for always active vs always inactive) and among women who were always nonrecreationally inactive (RR = 1.6 for always active vs always inactive). This study suggests that physically inactive women may be at increased risk of endometrial cancer because they are more likely to be overweight or obese. Our data also suggest that inactivity per se may be associated with an increased risk of endometrial cancer. However, we cannot rule out the possibility that our results, particularly those for nonrecreational activity, reflect unmeasured confounding factors. Future studies should attempt to obtain more detailed assessments of physical activity, including the intensity with which an individual engaged in an activity and the actual time involved in exertion.

Adult↗

Moderate alcohol consumption and the risk of endometrial cancer.

In a multicenter case-control study that included 400 cases and 297 controls, we examined the relation of moderate alcohol consumption to risk of endometrial cancer. We estimated average weekly intake of alcohol during adulthood from the reported frequency of intake of beer, wine, and liquor. The relative risk of endometrial cancer was 0.82 (95% confidence interval = 0.6-1.2) among women who drank, compared with lifelong abstainers. The weak protective effect of alcohol was due to a stronger inverse association among young women (< 55 years). In young women, the age-adjusted relative risks for three levels of drinking ( < 1, 1-4, > 4 drinks per week), from lowest to highest, were 0.78, 0.64, and 0.41 compared with nondrinkers. The risk estimates were not materially altered after adjustment for a variety of factors related to alcohol intake and to low risk of the disease (for example, smoking, oral contraceptive use, low body mass index, increased physical activity). The protective effect of alcohol could not be attributed to one particular type of alcohol-containing beverage, but beer appeared to have the most pronounced effect. These results suggest an inverse association between moderate alcohol consumption and endometrial cancer risk among young women, but support for a causal association is qualified and requires confirmation.

Adult↗

Domain structure of human 72-kDa gelatinase/type IV collagenase. Characterization of proteolytic activity and identification of the tissue inhibitor of metalloproteinase-2 (TIMP-2) binding regions.

The 72-kDa gelatinase/type IV collagenase, a metalloproteinase thought to play a role in metastasis and in angiogenesis, forms a noncovalent stoichiometric complex with the tissue inhibitor of metalloproteinase-2 (TIMP-2), a potent inhibitor of enzyme activity. To define the regions of the 72-kDa gelatinase responsible for TIMP-2 binding, a series of NH2- and COOH-terminal deletions of the enzyme were constructed using the polymerase chain reaction technique. The full-length and the truncated enzymes were expressed in a recombinant vaccinia virus mammalian cell expression system (Vac/T7). Two truncated enzymes ending at residues 425 (delta 426-631) and 454 (delta 455-631) were purified. Like the full-length recombinant 72-kDa gelatinase, both COOH-terminally truncated enzymes were activated with organomercurial and digested gelatin and native collagen type IV. In contrast to the full-length enzyme, delta 426-631 and delta 455-631 enzymes were less sensitive to TIMP-2 inhibition requiring 10 mol of TIMP-2/mol of enzyme to achieve maximal inhibition of enzymatic activity. The activated but not the latent forms of the delta 426-631 and delta 455-631 proteins formed a complex with TIMP-2 only when excess molar concentrations of inhibitor were used. We also expressed the 205-amino acid COOH-terminal fragment, delta 1-426, and found that it binds TIMP-2. In addition, a truncated version of the 72-kDa gelatinase lacking the NH2-terminal 78 amino acids (delta 1-78) of the proenzyme retained the ability to bind TIMP-2. These studies demonstrate that 72-kDa gelatinases lacking the COOH-terminal domain retain full enzymatic activity but acquire a reduced sensitivity to TIMP-2 inhibition. These data suggest that both the active site and the COOH-terminal tail of the 72-kDa gelatinase independently and cooperatively participate in TIMP-2 binding.

Base Sequence↗

Bulky stage IB cervical carcinoma managed by primary radical hysterectomy followed by tailored radiotherapy.

The management of bulky, stage IB cervical carcinoma remains controversial. The present study reports the outcome of 84 women treated by radical hysterectomy, in which the surgical specimen revealed a lesion measured to be 4 cm or greater in size following formalin fixation. Of the 84 women, 42 (50%) received postoperative radiotherapy based on additional surgical findings beyond tumor size suggesting a high risk for pelvic recurrence including lymph node metastasis, parametrial spread, and compromised margins. Despite the bulky nature of these lesions, major operative and early postoperative complication rates were low (6%). Delayed complications including fistulae and bowel obstructions occurred in only 2.4% of patients treated with surgery alone and in 14.2% of women treated with combined therapy. Corrected 5-year survival in this series was 70.4% (75.6% in the surgery only group and 65.0% in the surgery plus radiotherapy group). Recurrence and mortality rates were related to lesion size, with most recurrences and deaths occurring in women with lesions measuring 6 cm or greater. Comparison of these data utilizing primary radical hysterectomy followed by tailored radiotherapy with previously published data on similar groups of high-risk patients treated with either radiotherapy alone or with radiotherapy followed by simple hysterectomy suggests comparable survival and morbidity.

Adenocarcinoma↗

Serum CA125 regression in epithelial ovarian cancer: correlation with reassessment findings and survival.

Findings at reassessment laparotomy and disease-free survival are reported for a group of patients with advanced-stage epithelial ovarian cancer who have had a complete clinical response to cytoreductive surgery and multiagent platinum-based chemotherapy. The predictive value of the number of chemotherapy cycles to achieve a serum CA125 of < 35 U/ml is compared to the predictive value of s, the rate of achieving a normal serum CA125. s is generated from an exponential regression model. This study suggests that s accurately predicts which patients have residual disease at reassessment laparotomy, who will be free of disease, and, of those in the latter group, who are at greatest risk to recur, as well as overall survival. If these observations are confirmed, physicians may base further therapeutic intervention on the basis of a calculated parameter following complete clinical response to first-line treatment rather than relying on findings at reassessment laparotomy.

Aged↗