Intralymphatic injection of BCG into rhesus monkeys.

Since the route of administration of BCG may have an important function in immunotherapy, we investigated intralymphatic administration to direct BCG to the lymph nodes. Multiple injections of high doses of BCG were administered to 6 rhesus monkeys via the dorsal lymphatics of the lower limb. A suppurative lymphadenitis was observed along the lower limb and in the inguinal area in 5 of the 6 monkeys. However, many of the complications reported with other routes of administration were not observed. Granulomatous reactions and histiocytic responses developed in lymph nodes on the injected sides of the pelvis and distant nodes as well as in the liver. The intralymphatic route is the method by which high doses of nonspecific immunostimulants were delivered to regional lymph nodes. The efficacy of this approach remains to be established in tumor-bearing animals and humans.

Extended carbon dioxide laser vaporization in the treatment of subclinical papillomavirus infection of the lower genital tract.

This study examined the use of extended carbon dioxide laser vaporization in 25 women with histologically confirmed, multicentric subclinical papillomavirus infection of the lower genital tract to determine whether carbon dioxide laser can eradicate subclinical papillomavirus infection. An extended carbon dioxide laser procedure involved vaporization of the epithelium of the entire lower genital tract. We performed the procedure under colposcopic guidance. Vaporization was carried out in continuity, to an appropriate tissue depth, while using recommended power densities for the respective target tissue. For sexually active study patients, male consorts were evaluated and treated concurrently to reduce the risk of recurrent infection. Postoperative morbidity was considerable, with moderate to severe vulvar pain and febrile reactions occurring in 100 and 76% of patients, respectively. Histologic persistence of subclinical papillomavirus infection was documented in 88% of study patients at follow-up examination. Neither treatment of the male consort nor sexual abstinence significantly improved treatment outcome. These data suggest that extended carbon dioxide laser procedures cause significant short-term morbidity without effectively eradicating subclinical papillomavirus infection of the female lower genital tract.

Verrucous carcinoma of the vulva associated with an unusual type 6 human papillomavirus.

An unusually rapid growing vulvar verrucous carcinoma found associated with human papillomavirus type 6 is described. Both human papillomavirus structural antigens and deoxyribonucleic acid (DNA) sequences were detected in the tumor biopsy. The human papillomavirus genome was isolated and compared with the genome of human papillomavirus type 6b, which was cloned from an anogenital wart. The two genomes were extremely homologous in genomic organization and DNA sequence, except for a region on the viral genome containing the virus control elements. A discussion of this observation and how it could relate to the importance of viral subtypes follows.

Magnified penile surface scanning in diagnosis of penile condyloma.

To determine the incidence of penile condyloma in a group of high risk males, we have performed magnified penile surface scanning and biopsy of suspicious lesions in 51 men. All men were partners of women with proven condyloma. Of these men, 45 were found to have histologic evidence of condyloma, only 8 of which were grossly visible.

Applications of the monitoring process model to coping with severe long-term medical threats.

Guided by the monitoring process model (MPM), the authors explored the illness responses of 2 samples: high monitors (who are cognitively vigilant to and amplify threat-related cues) and low monitors (who avoid them and blunt their impact). Both samples-101 women with human papillomavirus-related precancerous cervical dysplasia and 75 HIV-infected gay men-were undergoing long-term medical follow-up and management. Structural equation analysis showed an adequate fit of the MPM to the data within each sample, supporting the model's heuristic value: High monitors experienced greater disease-related intrusive ideation, which triggered greater avoidant ideation to forestall panic, particularly in the more threatened HIV-positive sample. However, efforts to avoid disturbing intrusive thoughts were ineffective, requiring increasingly extreme defensive strategies (i.e., denial and mental and behavioral disengagement).

Monitoring styles in women at risk for cervical cancer: implications for the framing of health-relevant messages.

We explored the interaction effects of individual attentional style (high versus low monitoring) and the framing of informational messages on the responses of women undergoing diagnostic follow-up (colposcopy) for precancerous cervical lesions. Prior to the colposcopic procedure, patients (N=76) were randomly assigned to one of three preparatory conditions: (a) Loss-framed message, which emphasized the cost of nonadherence to screening recommendations; (b) Gain-framed message, which emphasized the benefit of adherence; and (c) Neutrally-framed message. It was hypothesized that low monitors (who are more positively biased about their health) would show a more adaptive pattern of response to loss-framed information than high monitors (who are more negatively biased about their health). The results of a series of hierarchical multiple regression analyses were consistent with this prediction. Low monitoring was associated with greater knowledge retention (beta=.61, p<.05) and less canceling/rescheduling of follow-up appointments in the loss condition than in the neutral condition (beta=.82, p<.002). High monitoring, however, was associated with greater intrusive ideation when information was presented in the loss-oriented frame as compared to the neutral frame (beta=.99, p<.01). Knowledge retention and screening adherence were not affected by the framing manipulation. The differences between high versus low monitors as a function of loss or neutral frame suggest an interaction effect, wherein both the type of framing message and the individual's attentional style lead to distinctive cognitive-affective and behavioral patterns. The findings may have clinical implications for the tailoring of health messages to the individual's signature style.

The influence of hematogenous and serosal metastases on advanced (FIGO IIA-IVB) squamous cell carcinoma of the cervix.

Of 120 patients with FIGO stage IIA-IVB squamous cell carcinoma of the cervix treated with standard radiotherapeutic techniques, 41 (34.2%) relapsed with hematogenous or serosal metastases. Development of such metastases was individually associated with patient age less than or equal to 55, bilateral bulky parametrial extension, and histologically positive paraaortic nodes. Poor histologic differentiation exerted significant negative influence only in patients age less than or equal to 55. Neither surgical staging nor vascular injury predisposed to hematogenous dissemination. Radiotherapy techniques differed only in increased time to completion, from 84 to 100 days in clinical IIB and IIIB patients developing metastases. Local or regional pelvic recurrences, although associated with an increase in hematogenous or serosal metastases, were not accompanied by concomitant relapse in extrapelvic nodes. Twenty-six of 41 metastases were limited to single organ systems, with pulmonary sites most common (43.9%). A direct (non-nodal) route of hematogenous dissemination of 31% was documented within clinical stages IIA and IIB. One hundred percent concordance between bilateral bulky parametrial involvement and positive pretreatment paraaortic nodes occurred in clinical stage IIIB and IVA patients with metastatic relapse. Our data from the period 1976-1985 do not substantially differ from earlier reports on the incidence or distribution of hematogenous or serosal metastases, despite our implementation of contemporary local/regional radiotherapy prescriptions. The potential for hematogenous and serosal metastases in high-risk patients with advanced squamous cervical carcinoma merits consideration of alternative treatment protocols and precise definition of the role of pretreatment surgical staging procedures.

Colposcopy in pregnancy.

The management of the abnormal smear in pregnancy remains a challenge to the modern colposcopist. Colposcopy in pregnancy is difficult. Anatomic variants can mimic disease. Significant cytologic overall detection of low-grade squamous intraepithelial lesions demands an increased understanding of physiologic variants in pregnancy. Possible recent increases in cervical cancer incidence in younger women requires comprehensive knowledge of warning signs of early invasion. Modern management approaches must temper the need for accurate exclusion of cancer with the risk of overly aggressive interference in patients without disease or with very minor atypia.

Vaginal and vulvar adenosis. An unsuspected side effect of CO2 laser vaporization.

During a 15-month period, September 1984 through January 1986, 10 women who were treated in the Section of Gynecologic Oncology, Department of Obstetrics and Gynecology, Pennsylvania Hospital, Philadelphia, Pennsylvania, developed vaginal or vulvar adenosis after CO2 laser vaporization. The indications for therapy were condylomata of the cervix, vagina and vulva refractory to conservative management in 3 patients, vulvar intraepithelial neoplasia in 3, lichen sclerosus in 1 and cervical intraepithelial neoplasia with condylomata on the cervix and vagina in 3. All the patients underwent treatment of the vagina. Most underwent treatment of the cervix, and some underwent treatment of the vulva at various degrees of intensity and depth. During the posttreatment colposcopic follow-up examination, all the patients demonstrated lesions colposcopically consistent with adenosis of the vagina or vulva within the area treated with the CO2 laser. Biopsies of the lesions were performed, adenosis was confirmed histologically, and endometriosis was ruled out histologically. This entity has not been previously associated with CO2 laser vaporization, and its clinical significance is undetermined. Further follow-up is indicated.

Studies on the transmission of viral disease via the CO2 laser plume and ejecta.

While recent reports have noted the presence of viral DNA sequences in the laser plume, no significant effort has been made to study transmission of the virus in vivo via airborne laser debris. Studies were undertaken to identify potential hazards to operating room occupants in gynecologic laser surgery. ACO2 laser in the continuous wave mode using a power density of 666 W/cm2 was fired through a 5-cm metal cylinder at virus-infected tissues. Airborne particulate debris, 100-200 microns, was removed from the cylinder's inner surfaces. In one instance, deposition of the debris was found on the surgeon's eyeglasses 1 m from the site of impact despite the use of a smoke evacuator. The first set of studies involved confirmed human papillomavirus (HPV) lesions of the human female lower genital tract. Specimens were collected for electron microscopy and Southern Blot viral hybridization. Additional cervical electron microscopy specimens were recovered from the speculum during pulsed CO2 laser treatment at 13 W average power during conization. Electron microscopy of the vulvar debris revealed only anucleate keratinized squamous epithelial cells. Cervical specimens demonstrated similar cells with nearly instantaneous vaporization of intracellular water and apparent condensation of cellular carbon. HPV Southern Blot testing revealed insufficient quantities of DNA for that technique. The second set of studies involved bovine papillomavirus lesions from dairy cattle. The debris was transmitted to susceptible animals. The bovine studies failed to demonstrate the transmission of disease in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Intracavitary use of radioactive colloidal phosphorus 32 in the treatment of epithelial ovarian cancer.

The use of radioactive colloidal phosphorus 32 (32P) in the treatment of epithelial ovarian cancer continues to be controversial. One institution's experience with the use of 32P in 30 patients with epithelial ovarian cancer was reviewed retrospectively. One hundred percent of attempts at placement of 32P intra-abdominally were ultimately successful. The complication rate was 11%. Mean clinical (asymptomatic) disease-free survival in patients with stage III ovarian cancer was as follows: 26 months based on absence of disease at reassessment surgery; 26 months based on microscopic residuum; and 30 months based on minimal (< 5 mm) residuum. Mean disease-free survival in patients with early-stage (stages IC through IIC) ovarian cancer was 66 months.

Advances in the diagnosis and treatment of human papillomavirus infections.

During the past decade, much has been learned about the natural history of HPV. Most infections occur early in one's sexual life. The overwhelming majority of infections are cleared by the host immune system and never present as warts or neoplasia. Certain patient behavior such as smoking, frequent sex with many different partners, other STD infections, especially HIV, and immune-suppressive drugs promote HPV expression and cause persistent infection. Persistent HPV infection is very strongly related to neoplasia. In addition to high-risk HPV types, variant subtypes have been identified that interact with the host immune system to subvert host immunity and encourage viral persistence. New treatment programs rely on drugs that modulate the immune system and disrupt viral persistence. There is a real possibility of HPV vaccines in the future, which may protect the unexposed patient.

Cervical malignancies.

Articles published between August 1989 and July 1990 related to squamous cell carcinoma of the cervix are reviewed. A discussion of new histopathologic findings is given along with current hormonal receptor studies. The host immunocompetence with an immunologic staging system is presented. Recent studies of the clinical application of the serum squamous cell antigen are reviewed. The finding of positive pelvic nodes at the time of a radical hysterectomy is investigated within literature review. The advantages and risks of radical surgery, radiation therapy, and combined treatments are presented with no clear conclusion being found. Advanced or recurrent cervical cancers may be treated with radiation, chemotherapy, or ultraradical surgery depending on the clinical setting. Early studies of combination therapies are given for these difficult situations.

Para-aortic node sampling in small (3-cm or less) stage IB invasive cervical cancer.

Only 2 of 125 patients with FIGO stage IB invasive squamous or adenocarcinoma of the cervix 3 cm or less in diameter who underwent exploration for radical hysterectomy, bilateral pelvic lymphadenectomy, and para-aortic node sampling had metastases to the para-aortic nodes. No patient had gross para-aortic nodal involvement, and both patients with microscopic para-aortic nodal metastases had grossly positive pelvic nodal involvement. Para-aortic node sampling in patients with small stage IB cervical cancers undergoing radical hysterectomy may be restricted to patients with suspicious pelvic or para-aortic nodes.

Colposcopy in the diagnosis of penile condyloma.

To determine the incidence of penile condyloma in a group of high-risk men, we carried out colposcopy and biopsy of suspicious lesions in 51 men. All men were partners of women with condyloma. Of these men, 45 were found to have histologic evidence of condyloma, and only eight of these had grossly visible disease.

PIP: The frequency of penile condyloma in the male partners of women referred for evaluation of abnormal Papanicolaou smears from April-October 1984 at Pennsylvania Hospital was prospectively evaluated. All 51 men examined had elevated white penile lesions colposcopically consistent with a diagnosis of condyloma. Histologic evidence of condyloma was found in 45 of these men. The findings in men with suspicious lesions that were not condyloma included chronic inflammation, dilated sweat duct, lichen nitidus, verruca vulgaris, and penile skin tag. Only 8 of the 45 confirmed lesions were identifiable with the naked eye; the remainder required magnification and acetic acid for visualization. Cytologic evidence of abnormal epithelium was detected in 13 men. The mean age at 1st coitus among those men with penile condyloma was 17.5 years; the mean number of sexual partners was 14.7. In men, treatment of condyloma encompasses YAG laser, 5-fluorouracil cream, carbon dioxide laser, and podophyllin. In women, management is dependent on whether atypical mitotic figures are present or absent; in the former cases, carbon dioxide laser is appropriate, while in the latter cases, cryotherapy or topical 5-fluorouracil cream is recommended.

Results of carbon dioxide laser therapy and topical 5-fluorouracil treatment for subclinical condyloma found by magnified penile surface scanning.

Previously we demonstrated a 68 per cent recurrence rate for subclinical penile human papillomavirus infections found by magnified penile surface scanning and treated with the carbon dioxide laser. In this report it is shown that the addition of a regimen of adjuvant topical 5-fluorouracil does not lower the recurrence rate. This knowledge combined with the evidence for a subclinical urethral reservoir of human papillomavirus implies that any strictly topical therapy will fail at 4 months of followup and that improved systemic therapy may be needed.

Mullerian adenosarcoma of the uterus with sarcomatous overgrowth.

A case of mullerian adenosarcoma of the uterus with sarcomatous overgrowth is described. The patient was also found to have bilateral polycystic ovaries. This 25 year-old white female presented with irregular vaginal bleeding and was diagnosed as having mullerian adenosarcoma with sarcomatous overgrowth by dilatation, curettage, and biopsy. Total abdominal hysterectomy, bilateral salpingo-oophorectomy with lymph node sampling were performed.

The clinical role of human papilloma virus typing.

Patients with abnormal Pap smears underwent repeat Pap smear, colposcopy, biopsy, and human papilloma virus (HPV) typing to identify the presence of CIN and to assess the correlation of HPV type to grade of CIN and behavior of CIN. A total of 334 patients underwent evaluation and typing with Southern blot methodology. Fifty-five percent (185) of the patients demonstrated HPV viral sequences; 98 of the 185 positive patients demonstrated HPV types 16, 18. The presence of HPV sequences was not associated with a higher frequency of positive cytology of CIN II or III. High-grade CIN (II or III) was seen in 17.3, 13.5, 13.8, and 10.7% of patients with HPV 16, 18; 6, 11; 31, 33, 35; or no HPV sequences. Of 52 patients with normal cytology and biopsy revealing less than or equal to CIN I, no patients with types 6, 11, 3/5 patients with 31, 33, 35, 3/15 patients with 16, 18, and 2/23 patients with no HPV sequences progressed to greater than or equal to CIN II. These data do not support a role for HPV typing in predicting the initial histology. Typing may be of some value in monitoring patients with low-grade lesions.

Whole-abdomen radiation therapy as salvage treatment for epithelial ovarian carcinoma.

PURPOSE: This study aimed to evaluate the efficacy and safety of whole-abdomen radiation therapy as salvage treatment in patients with ovarian cancer. PATIENTS AND METHODS: Twenty-seven patients who failed aggressive cytoreductive surgery followed by multiple-drug platinum-based chemotherapy were found to have recurrent epithelial carcinoma of the ovary and were treated with whole-abdomen radiation as salvage therapy. Dosage fractions were planned at 100 to 150 cGy daily to 3000 to 3500 cGy, followed by a pelvic boost at 150 to 180 cGy daily. All patients completed the planned treatment. The average treatment program required 53.5 days (range, 42-71 days). RESULTS: Survival rates at years 1 through 5 were 66%, 48%, 26%, 15%, and 15%, respectively. Residual disease at initiation of radiation correlated strongly with length of survival. The patients with microscopic disease survived an average of 63 months (range, 30-111 months). Patients with disease larger than 2 cm survived an average of 9 months (range, 5-17 months). Toxicity was seen in all patients. Eight patients experienced grade 3 or 4 toxicity, primarily white blood cell count and gastrointestinal toxicity. There were no deaths related to toxicity. DISCUSSION: This experience strongly suggests that whole-abdomen radiation is a viable salvage option, especially for patients with microscopic retroperitoneal disease or small-volume macroscopic disease.