A review of external lumbar drainage for the management of intracranial hypertension in traumatic brain injury.

BACKGROUND: The Brain Trauma Foundation (BTF) published evidence-based guidelines with a detailed approach to the management of intracranial hypertension (ICH) in traumatic brain injury (TBI) patients. However, management with cerebrospinal fluid (CSF) drainage in TBI patients remains a controversial topic and is a recent addition to the 4th Edition of the BTF guidelines. External lumbar drainage (ELD) has been proposed for the management of patients with refractory ICH despite aggressive measures. ELD has been described in the literature with possible benefits in outcomes; still, many questions remain unanswered. METHODS: A systematic search on MEDLINE was conducted for articles that studied lumbar CSF drainage in adult TBI patients with ICH. RESULTS: Eleven studies met the inclusion criteria, which included 5 prospective and 6 retrospective studies. Several studies showed that CSF drainage via lumbar drain resulted in significant reduction of ICP compared to before ELD placement and had a low complication rate. However, the data reporting mortality and functional outcomes are varied across studies. CONCLUSION: The literature suggests that ELD may play a role in the management of refractory ICH in TBI patients when first and second-tier measures fail and may be a safe, effective, and minimally invasive method to significantly lower ICP. Additional research and standardized treatment protocols are necessary.

Interstitial thermoradiotherapy: thermal dosimetry and clinical results.

From August 1977 to August 1986, 72 patients with advanced primary or recurrent cancers were treated using interstitial thermoradiotherapy. Sites treated included the pelvis in 49 patients, the head and neck in 15, and other sites in six. Median tumor volume was 52 cm3, and all but nine patients had received prior irradiation. In 69 patients, hollow stainless steel catheters were implanted and used as electrodes with a 0.5 MHz radiofrequency (RF) generator, whereas in three patients, standard plastic Henschke tubes were used with a commercially available interstitial microwave (MW) system operating at 915 MHz. Most patients were heated intraoperatively for 30 minutes, aiming for a minimum measured intratumoral temperature (Tmin) of 42 degrees C. The implant was occasionally preceded by external irradiation, and after hyperthermia, the catheters were afterloaded with 192Ir for brachytherapy. Tmin exceeded 42 degrees, 42.5 degrees, 43 degrees, and 44 degrees in 25, 16, 12, and 3, respectively, of 70 patients with temperature data available, and the probability of successful heating was independent of tumor volume or site. Twenty-five of 69 (36%) evaluable patients achieved a complete response (CR). Probability of CR demonstrated a significant univariate dependence upon Tmin, radiation dose, site treated, and tumor volume, but multivariate analysis showed only three significant predictor variables: tumor volume, radiation dose, and Tmin. The probability of a CR ranged from 95% for patients with small tumors receiving high doses of radiation and adequate heat, to 5% for patients with large tumors receiving low radiation doses and less than adequate heat. Of 25 patients with CR, 10 relapsed; median response duration was less than 18 months, depended marginally upon disease site, and was independent of Tmin, radiation dose, and tumor volume. Seventeen patients sustained a complication, of which nine were severe enough to require hospitalization or surgery. All severe complications occurred in patients with pelvic tumors. The probability of a complication of any severity had a significant univariate association with maximum intratumoral temperature (Tmax) and tumor size. We conclude that interstitial thermoradiotherapy offers the promise of heating large tumors in locations where externally applied hyperthermia has not been successful.

DNA ploidy, grade, and stage in prognosis of uterine cervical cancer.

A retrospective study of 56 cases of uterine cervical squamous carcinoma evaluated DNA content, histological grade, and clinical stage as indicators of prognosis. Minimum survivor follow-up was 24 months. Following standard radiation therapy, there were 40 cures and 16 treatment failures. DNA content was measured by flow cytometry of pretreatment biopsies removed from paraffin. There were 18 diploid cases and 38 aneuploid (67.9%). Aneuploid cases included 6 with very high G2-M peaks (greater than or equal to 15% of the cell sample). DNA ploidy correlation with prognosis was not statistically significant. However, both grading by a multiple parameter method (P less than 0.0133) and staging (P less than 0.0064) were significant prognostic factors. Higher grade and stage correlated with treatment failure.

Second-look laparotomy in epithelial ovarian carcinoma. Prognostic factors associated with survival duration.

This article that reports on 70 consecutive patients is one of only a few studies of advanced ovarian cancer that have attempted to define predictive factors associated with survival duration after second-look laparotomy. As in many other investigations, several factors have been analyzed for predicting second-look outcome. The prognostic variables analyzed in this study included age, stage, histologic grade, residual disease status after initial surgery, and type (cisplatin versus no cisplatin) and number of cycles of chemotherapy. Only stage (P = 0.002) and optimal disease (less than 2 cm residual tumor size) after initial surgery (P less than 0.001) were significantly associated with the absence of disease at second-look laparotomy, and both were significant predictors of second-look outcome in a multivariate logistic regression model. Their impact on actuarial survival after second-look laparotomy diminished, however. Actuarial survival after second-look laparotomy was associated with residual tumor size at second-look surgery (P = 0.02). According to second-look findings, the 3-year actuarial survival rates and standard errors were as follows: no pathologic evidence of disease, 80.7% +/- 13.4% 3-year survival; microscopic disease plus less than or equal to 2 cm residual disease, 49.1% +/- 13.1% survival; and gross residual disease (i.e., greater than 2 cm maximum tumor diameter), 29.5% +/- 11.4% survival. We also examined the effect of extensive tumor resection at second-look laparotomy on survival for patients with greater than 2 cm gross residual disease. Optimum resection (less than 2 cm residual tumor mass) resulted in significantly greater survival than suboptimum resection (P less than 0.001). This strongly suggests that there is a survival advantage associated with optimum resection at second-look laparotomy.

A phase II trial of mitomycin, vincristine, bleomycin, and cisplatin (MOBP) as neoadjuvant therapy in high-risk cervical carcinoma.

Twenty patients with locally advanced or metastatic cervical carcinoma were treated with mitomycin, vincristine, bleomycin, and cisplatin (MOBP), prior to radiotherapy (RT) of curative intent. Five patients had stage I disease, 2 stage II, 10 stage III, and 3 stage IV. All but one patient with stage I and II disease had nodal metastases. Patients received two courses of MOBP prior to and cisplatin q 3 weeks during RT. Response rates after completion of MOBP and prior to RT were as follows: 3/18 (16.6%) patients had a complete response (CR), 10/18 (55.5%) had a partial response (PR), 3/18 (16.6%) had improvement, and 2/18 (11.1%) had no response (NR). Five patients developed radiation complications. Of 7 patients with stage I and II disease, 6 (86%) currently have no evidence of disease (NED) (median 27 months). Of 13 patients with advanced disease, 3 (23%) are NED (median 17 months), 8 (61.5%) have expired, and 2 (15.4%) are alive with disease. MOBP is associated with significant response rates in the untreated patient but has not improved survival in patients with advanced disease. Patients with early disease and positive nodes may benefit from this regimen.

Interstitial parametrial implants in carcinoma of the cervix stage II-B.

This retrospective analysis has been undertaken to ascertain whether an improvement in results can be obtained in Stage II-B cervical carcinoma with the use of interstitial parametrial irradiation. Between September 1972 and March 1982, 43 patients were treated by conventional intracavitary irradiation. Nine patients at high risk for local recurrence underwent post-radiation hysterectomy. Since 1980, 45 patients were entered into a study using parametrial interstitial implants and no hysterectomy. Patients were not allocated randomly and the interstitial group contained a disproportionate number of patients with poor prognostic features. Mean follow-up for the conventional radiotherapy group was 80 months, and for the interstitial group was 42 months. Overall pelvic control and actuarial survival in the conventional radiotherapy group (84 and 75%, respectively) were similar (log rank p-value = .61) to that observed in the interstitial implant group (80 and 77%). Analysis of pelvic control rates showed no significant advantage for either treatment group when compared by the various prognostic factors. The frequency of complications, however, was significantly higher in the interstitially irradiated patients (21% vs. 7%, p = .044).

Prognostic variables in the treatment of squamous cell carcinoma of the vulva.

Records of 98 patients undergoing surgery for squamous cell carcinoma of the vulva between 1960 and 1982 were analyzed to evaluate and develop treatment policy. There were 32, 34, 26, and 6 patients in FIGO stages I-IV, respectively. Eighty-six patients underwent radical vulvectomy, 8 patients underwent less extensive procedures, and 4 underwent more extensive procedures. Eighty-seven patients underwent inguinal node dissection, and 40 underwent pelvic node dissection as well. Eight patients received external beam irradiation. Actuarial 5-year survival was 57%. Age, tumor size, FIGO (clinical) stage, surgically determined T and N stages, tumor differentiation, lymph vessel invasion, extent of surgical procedure, and adjuvant irradiation were analyzed to determine their effects on local control, freedom from distant metastases, and survival, using single variable and multivariate analysis. Local control was significantly related to FIGO stage; freedom from distant metastasis was significantly related to surgical N stage, tumor size, and surgical T stage; survival was significantly related to surgical N stage, tumor size, surgical T stage, age, and lymph vessel invasion. Metastatic involvement of inguinal lymph nodes was significantly correlated with tumor size and differentiation. Of 87 evaluable patients, 33 had inguinal node involvement, and of these, 17 developed recurrent disease. All 7 patients with pelvic node metastases had positive inguinal nodes, and all died; the cause of death could be determined in 5, of whom 4 manifested distant metastases. Pelvic lymphadenectomy conferred no survival benefit in this series, even in the presence of positive inguinal nodes. Local vulvar recurrence is a significant problem in patients with positive inguinal nodes, and postoperative irradiation should be directed to this area in these patients. Patients with vulvar recurrences, especially those occurring at least 2 years after surgery, can be successfully salvaged, and should therefore be treated aggressively.

Combined interstitial irradiation and localized current field hyperthermia: results and conclusions from clinical studies.

Low-dose-rate continuous irradiation in conjunction with localized current fields has been investigated in Phase I human trials at several institutions since 1977. To date, nearly 100 patients with a variety of malignant lesions (carcinomas, melanomas, sarcomas, lymphomas) in different anatomical locations (skin, head and neck, breast, pelvis, extremities) have been entered into experimental protocols. Different radiation and thermal dose levels have been evaluated. Significant progress in equipment and techniques has been accomplished. A wide range of complete response rates (38 to 83%) and complication rates (7 to 25%) has been reported. Analysis of results showed a good correlation of complete response rates with the radiation dose level and minimum temperature. The most successful regimens included either an "optimal radiation dose" (greater than 6000 rads) or an "effective time-averaged minimum temperature" (44 degrees). Important considerations in the design of clinical trials for Phases II and III are: (a) in regimens with curative aim, a hyperthermic effect may not be achieved in all regional sites of disease, especially in those areas harboring subclinical disease. Radiation dose-fractionation schedules of proven adjuvant efficacy thus must be used; (b) whether the total radiation dose to the site of bulky disease when combined with hyperthermia can be reduced without loss of therapeutic efficacy relative to conventional radiation doses is critically dependent upon minimum temperatures and uniformity of temperature within the tumor; (c) optimized combined therapy is likely to reflect a high level of quality assurance in administering both the interstitial irradiation and the interstitial hyperthermia; (d) the present criteria for evaluation of tumor response (no response, partial response, and complete response) are clinically meaningless. The criterion, "local control" or "failure," should be adopted in future trials in Phases II and III with the curative aim to allow comparison of results with historical or concurrent controls treated with radiation alone.

External beam radiotherapy in cancer of the prostate. The University of Arizona experience.

Between 1973 and 1979, 218 patients with adenocarcinoma of the prostate stage A2 through D1 were treated with primary external beam radiotherapy. The majority of the patients (211) received 6000-7000 rad to the prostate using a small (160) or large (58) volume technique. With a minimum follow-up of 36 months and a maximum of 120 months, the control rates of the local tumor were 96%, 95%, 88% and 81% for stage A2, B, C and D1. The corresponding 5-year survivals were 100%, 82%, 60% and 42%. Mild to severe complications were documented in 35 cases (16%). The frequency and severity of the complications correlated with the size of the irradiated volume and history of previous surgery. The use of large fields, to encompass the regional lymphatics, is not associated with improved survival.

Treatment of locally advanced cancer of the cervix with transperineal interstitial irradiation. Report on 106 cases.

The survival of patients with locally advanced cancer of the cervix (stage IIB, IIIB, and IVA) treated with conventional intracavitary radium remains unsatisfactory. Over 50% of these patients are local failures and die with uncontrolled tumor in the pelvis. In 1978, we began performing transperineal interstitial implants to the parametria in patients with advanced disease. One hundred six evaluable patients (34 IIB, 67 IIIB, and five IVA) received one (99) or two interstitial implants (7) following 40-50 Gy of external supervoltage external irradiation. In addition, seven patients underwent exploratory staging laparotomies concurrently with the first implant procedure. Mean follow-up is 23 months and range is 12-60 months. Control of the pelvic tumor has been documented in 85%, 75%, and 40% of stage IIB, IIIB and IVA patients, respectively. Seven patients developed distant metastases and three died of intercurrent disease with no evidence of pelvic relapse. Nineteen patients (18%) developed radiation-related complications: proctitis or cystitis (six), rectal stenosis (six), ulceration and necrosis of the vaginal wall (one), and recto- or vesicovaginal fistula (six). It is noteworthy that 7/11 patients (64%) who had radioactive sources placed on the surface of the vaginal obturator as a substitute for an intrauterine tandem developed severe complications. We conclude that transperineal interstitial irradiation is both safe and an effective modality in the treatment of advanced cancer of the cervix.

Treatment of advanced cancer of the cervix with transperineal interstitial irradiation.

A pilot study using transperineal interstitial implantation to the parametrium in patients with locally advanced carcinoma of the cervix or with distorted anatomy is presented. Twenty-one consecutive patients (2 cervical stump Stage IB, 3 Stage IIB, 15 Stage IIIB, 1 Stage IVA) received one (12) or two (9) implants following 40-45 Gy whole pelvis external irradiation. In addition 8 patients underwent staging laparotomies concurrently with the first implant procedure. Control of the pelvic tumor was accomplished in 18 of 21 patients (85%) with a mean follow-up of 26 months (range 15 to 48 months). Seven patients (33%) developed long term complications (fistula 3, superficial necrosis of the vagina 1, severe proctitis or cystitis 3). Six of the complications occurred in 8 patients (75%) who had radioactive sources placed on the surface of the vaginal obturator as a substitute for the lack of tandem. In contrast, only 1 in the remaining 13 patients (8%) who did not have obturator sources placed, developed long term complications.