Clinical Evidence Of Disease Research Articles

Polymerase chain reaction for the detection of Burkholderia pseudomallei

Melioidosis is a potentially lethal infection of humans and animals in Southeast Asia and northern Australia. Current methods for detection of the causative organism, Burkholderia pseudomallei, lack both speed and sensitivity. We report the development of a highly sensitive polymerase chain reaction-based method that can detect as few as 35 colony-forming units of B. pseudomallei/mL in saline suspensions. This polymerase chain reaction test also detected the presence of B. pseudomallei DNA in culture-negative splenic tissue obtained from mice infected with the organism, but without clinical evidence of disease. Specificity has been confirmed using a variety of pathogenic and nonpathogenic organisms, including B. mallei, B. cepacia, and Pseudomonas species. The clinical usefulness of this test should be assessed prospectively and compared with conventional diagnostic techniques.

Analysis of failures in patients with stage I ovarian cancer: an Italian multicenter study

Gadducci A, Sartori E, Maggino T, Zola P, Landoni F, Fanucchi A, Stegher C, Alessi C, Buttitta F, Bergamino C. Analysis of failures in patients with stage I ovarian cancer: An Italian multicenter study. Int J GynecolCancer 1997; 7: 445–450. The objective of this retrospective multicenter study was to assess the rates, times, sites, and risk factors for recurrences in 224 patients with surgical stage I ovarian cancer. Postoperative adjuvant treatment was given to 153 of these patients. One hundred and eighty-two (81.3%) patients are currently alive with no clinical evidence of disease after a median time of 84 months (range, 4–191 months) from surgery, whereas 39 (17.4%) developed recurrent disease after a median time of 29 months (range, 5–112 months). The relapse involved the pelvis in 21 (53.8%) cases, abdomen in 19 (48.7%), pelvic and/or para-aortic lymph nodes in 5 (12.8%), and distant sites in 5 (12.8%). The risk of recurrence was significantly related to FIGO substage (P< 0.0001) and tumor grade (P < 0.0001), but not to histological subtype. However, the recurrence rate was lower in mucinous carcinomas (6/52, 11.5%) and higher in clear cell carcinomas (5/14,35.7%). By log-rank test the disease-free survival was significantly related to FIGO substage (P = 0.0006) and grade (P = 0.0001). Cox proportional hazard model showed that grade was the only independent prognostic variable for disease-free survival, with a risk ratio for relapse of 2.831 (95% CI, 1.120–6.624) for grade 2 and 7.725 (95% CI, 3.290–18.140) for grade 3, compared to grade 1. In conclusion, tumor grade is the strongest predictor of recurrence in stage I ovarian cancer.

The use of combined radiation therapy and hormonal therapy in the management of lymph node-positive prostate cancer

To determine the rate of tumor response and patterns of relapse following combined hormonal-radiation therapy of adenocarcinoma of the prostate and to measure the survival in a group of men with tumor metastatic to pelvic lymph nodes. 66 patients with adenocarcinoma of the prostate with pathologically confirmed pelvic lymph node involvement were treated with combined radiation therapy and hormonal therapy. An additional five patients declined hormonal therapy. The patients treated with combined therapy represented a group with locally advanced disease including 44 patients (67%) with T3 or T4 tumors and 51 patients (80%) had N2 or N3 lymph node metastases. The pelvic lymph nodes were treated to a dose of 45 Gy and the prostate was boosted to a dose of 65 to 71 Gy. Hormonal therapy began up to 2 months before radiation and continued indefinitely. Patients were allowed to select their hormonal therapy and could choose DES (2 patients), orchiectomy (21 patients), LHRH agonist (7 patients) or combined androgen blockade (34 patients). Median follow-up is 49 months (range 12 to 131 months) and 21 patients have been followed for longer than 5 years. There have been 15 recurrences the entire group including three local recurrences in the prostate, seven patients with distant metastases, four patients with biochemical recurrences without clinical evidence of disease, and one patient where the location was unknown. Two of the PSA recurrences occurred in patients who elected to discontinue hormones after less than 3 years of therapy. The overall survival at 5 and 8 years is 94 and 84%, the clinical disease free survival is 85 and 67%, and the biochemical disease-free survival is 78 and 47%. There was no increased toxicity of the combined modality regimen compared to the expected effects of radiation and hormonal therapy. Combined hormonal and radiation therapy represents an effective treatment option for patients with adenocarcinoma of the prostate metastatic to pelvic lymph nodes. Combined modality therapy appears to extend the disease-free survival and allow patients to maintain their independent function.

Prediction of therapy‐related acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) after autologous bone marrow transplant (ABMT) for lymphoma

Therapy-related acute myelogenous leukemia and myelodysplastic syndrome (t-AML/MDS) are being reported with increasing frequency as a complication of ABMT for Hodgkin's disease and non-Hodgkin's lymphoma. At present there is no method available to predict who is at risk or is destined to develop this nearly universally fatal disorder. We therefore investigated whether clonal growth of cells is predictive of the development of t-AML/MDS. In a patient who developed secondary AML/MDS 18 months after ABMT, X-linked clonality analysis at the human androgen receptor locus was performed on serial banked samples, and documented transition from polyclonal to clonal hematopoiesis. Clonal cells could be identified 6 months after transplant (1 year prior to the diagnosis of t-AML/MDS), at a time when there was no morphologic or clinical evidence of disease. Clonality analysis can be predictive of the development of t-AML/MDS after ABMT and may offer important insights into associated risk factors and strategies to minimize the risk of t-AML/MDS. Am. J. Hematol. 56:45–51, 1997. © 1997 Wiley-Liss, Inc.

Prediction of therapy-related acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) after autologous bone marrow transplant (ABMT) for lymphoma.

Therapy-related acute myelogenous leukemia and myelodysplastic syndrome (t-AML/MDS) are being reported with increasing frequency as a complication of ABMT for Hodgkin's disease and non-Hodgkin's lymphoma. At present there is no method available to predict who is at risk or is destined to develop this nearly universally fatal disorder. We therefore investigated whether clonal growth of cells is predictive of the development of t-AML/MDS. In a patient who developed secondary AML/MDS 18 months after ABMT, X-linked clonality analysis at the human androgen receptor locus was performed on serial banked samples, and documented transition from polyclonal to clonal hematopoiesis. Clonal cells could be identified 6 months after transplant (1 year prior to the diagnosis of t-AML/MDS), at a time when there was no morphologic or clinical evidence of disease. Clonality analysis can be predictive of the development of t-AML/MDS after ABMT and may offer important insights into associated risk factors and strategies to minimize the risk of t-AML/MDS.

131I treatment of 131I negative whole body scan, and positive thyroglobulin in differentiated thyroid carcinoma: what is being treated?

Several aspects of the management of differentiated thyroid cancer cause considerable controversy. Among these is the role of 131I therapy in patients after thyroidectomy. There is no controlled study to demonstrate whether this treatment reduces the recurrence rate or improves mortality. Because of the overall excellent prognosis, it is unlikely that a controlled study will ever be conducted. Most frequently, patients have a diagnostic scan with 131I to determine whether radioiodine would be an appropriate therapy and to judge much to be prescribed, based on the extent of abnormalities seen on the scintiscan. Serum thyroglobulin (Tg) has been found to be a valuable tumor marker, with very good sensitivity and specificity. In most patients, the result of whole-body 131I scintiscan and Tg measurement give concordant results. However, in some patients, Tg is measurable, but the diagnostic scan with 131 is normal. There has been data published about treatment of these patients with therapeutic doses of 131I. The author questions whether this treatment is appropriate, prompted by seeing and hearing of patients who were treated with therapeutic doses of 131I, but had no abnormal uptake of the therapeutic doses and who had no improvement in serum Tg level. These patients have no clinical evidence of disease, and the only abnormality is measurable Tg. Since large doses of radioiodine are not without problems, a controlled clinical trial should be developed to evaluate efficacy in this situation.

Uterine Leiomyosarcoma: Analysis of Treatment Failures and Survival

The objective of this retrospective multicenter study was to assess the rates, times, and sites of recurrences of 126 patients with uterine leiomyosarcomas. Surgery was the initial therapy for all patients. Median follow-up of survivors was 50 months (range, 3–168 months). Of the 90 patients with stage I–II disease, 26 received postoperative irradiation and/or chemotherapy. Thirty-five (38.9%) patients developed recurrent disease after a median time of 16 months (range, 2–102 months). Recurrence was pelvic in 5 (14.3%) patients, distant in 23 (65.7%), and pelvic plus distant in 7 (20.0%). The overall recurrence rate was similar in patients who received adjuvant treatment and in those who did not. None of the 15 patients who underwent pelvic irradiation developed local recurrences, but 5 of them failed in distant sites. Of the 16 patients with stage III leiomyosarcomas, 2 died of intercurrent disease within 1 month from surgery and 11 received postoperative irradiation and/or chemotherapy. Thirteen patients developed recurrent tumor after a median time of 8 months (range, 1–21 months). Recurrence was pelvic in 3, distant in 4, and pelvic plus distant in 6 patients. Of the 20 patients with stage IV leiomyosarcomas, after surgery 6 were clinically free of disease (group A) and 14 had clinically evaluable residual disease (group B). With regard to group A, 3 patients received postoperative irradiation and/or chemotherapy. Five patients developed recurrent disease after a median time of 11 months (range, 8–16 months). Recurrence was distant in 3 patients and pelvic plus distant in 2. With regard to group B, 11 patients underwent postoperative chemotherapy. Eleven patients died after a median time of 6 months (range, 1–15 months), and 3 are still alive with clinical evidence of disease after 4, 5, and 8 months, respectively, from surgery. Cox model showed that stage (P= 0.0001), mitotic count (P= 0.0002), and age (P= 0.0048) were independent prognostic variables for disease-free survival. In conclusion, uterine leiomyosarcomas have an aggressive clinical behavior, with a propensity to recur both locally and moreover at distant sites. Tumor stage is the strongest prognostic variable. Only patients with early-stage disease have a chance of surviving, whereas the treatment of patients with advanced or recurrent disease is palliative.

Is There a Role for Estrogen Replacement Therapy in the Prevention and Treatment of Dementia?

Studies in experimental animal models provide a convincing rationale for a role for ERT in the treatment and prevention of dementia. These studies establish the role of estrogen in the regeneration and preservation of neuronal elements within the CNS that are analogous to those regions of the brain most sensitive to the neurodegenerative changes associated with AD. Furthermore, behavioral studies in these animals establish a correlation between the hormone dependent changes in the neuronal architecture and learning and memory. However, extrapolation of these studies to post-menopausal women must be done with caution. Surgical and natural loss of ovarian function does not result in a clinically relevant decline in cognitive function over the short term (1 to 2 decades) or ever in some women. The modest changes that are observed may relate to the hormone's effect on neurotransmitter levels or their receptors. Although Singh et al. noted changes in neurotransmitter concentrations 5 weeks after ovariectomy, changes in cognitive performance in their rat model did not become significant until 28 weeks after ovariectomy--the equivalent of approximately 2 decades of human life. Except for the familial forms of the disease, AD is rarely seen in the first 2 decades after the menopause. However, by the third decade after the menopause, 50% of women can be expected to manifest the histopathological changes of AD. Approximately half of these women are without clinical evidence of disease. Thus, the neurodegenerative process of AD probably precedes by many years the age of onset of the disease. We do not know what factors contribute to the selective neuronal injury which, over time, eventually leads to the neuronal loss and reduced synaptic density that result in the cognitive impairment of AD. At this time we can only speculate as to estrogen's role in modifying this process. Data from experimental animal models suggest that estrogen deficiency would selectively increase the vulnerability of estrogen-responsive neural elements, for example, the cholinergic neurons of the basal forebrain and hippocampus--offulnerability mediated perhaps by the reduced expression of neurotrophic factors, decreased clearance of the amyloid protein, and/or reduced cerebral blood flow that are associated with estrogen deficiency. The brain's ability to adapt to the neuronal loss by stimulating axonal and synaptic regeneration would also be impaired by estrogen deficiency as suggested by estrogen's ability to restore the synaptic density of lesioned brains of ovariectomized animals. Thus, estrogen deficiency, like the apolipoprotein E4 allele, can be considered not a cause of AD but one of perhaps several factors modifying the neuronal injury and loss leading to AD. The limited epidemiologic data and intervention trials currently available are consistent with this interpretation. Because of the urgency and enormity of the problem of dementia in our aging society, there would now appear to be sufficient reason to allocate the resources needed to conduct the appropriate clinical trials to determine estrogen's efficacy in both the treatment and prevention of this devastating condition. These trials are needed so that women and their physicians can adequately weigh the risks and benefits of hormone replacement for the treatment and, more importantly, the prevention of dementia.

Serum CA125 assay in the early diagnosis of recurrent epithelial ovarian cancer

The present retrospective study included 59 patients who had been treated for epithelial ovarian cancer and who showed an elevation of serum CA125 above 35 U/ml without clinical evidence of disease. Eight patients underwent chemotherapy at the time of serum antigen elevation (group A). The other 51 patients (group B) were periodically checked, and received further chemotherapy only when recurrent disease was detected. Forty-four of the 59 patients relapsed. One patient of group B experienced two different recurrences with two distinct time intervals. The median follow-up of survivors from CA125 elevation was 10 months (range 2-92 months). Of the 8 patients of group A, 3 (37.5%) developed recurrent disease after 14, 17 and 22 months, respectively, from antigen elevation. Of the 51 patients of group B, 41 (80.4%) relapsed. The overall recurrence rate was 82.4% (42/51). The median lead time between CA125 increase and clinical detection of relapse was 3 months (range 2-27 months). The present data confirmed the reliability of serum CA125 assay as predictor of clinical relapse in epithelial ovarian cancer. The recurrence rate seemed to be lower for patients who received chemotherapy at the time of CA125 elevation (37.5% versus 82.4%, p=0.02). However, the small number of patients, the short follow-up, and the non-randomized design of the study do not allow to draw any conclusion on the appropriate timing for second-line chemotherapy.

Post-treatment serial serum squamous cell carcinoma antigen (SCC) in the monitoring of squamous cell carcinoma of the cervix

Serum squamous cell carcinoma antigen (SCC) was raised in 62% of 308 patients with squamous cell carcinoma of the cervix before treatment. Post-treatment SCC levels were raised in 69 patients (22.4%). Retrospective review showed that persistently raised SCC level after treatment was significantly associated with persistent or recurrent disease in squamous cell carcinoma of the cervix. The specificity of persistently raised SCC level in association with recurrent disease was 98.2%. The sensitivity in association with recurrent disease was 74.7%. The positive predictive values was 94.2%. The median lead time for recurrence was 4 months. SCC was raised in 38% of patients with clinical evidence of disease in the vagina. One patient had raised SCC one month prior to clinical detection of vaginal metastasis and was salvaged by an exenterative procedure. SCC was raised in 71–91% of patients with metastatic disease in the lung, lymph nodes or other distant sites. Thus, persistently raised SCC level after treatment of squamous cell carcinoma should alert the clinician to look for recurrent disease especially in distant metastatic sites. Post-treatment raised SCC level was associated with less than 5% 5-year survival rate whereas in patients with normal SCC level, the 5-year survival rate was 87%.

Langerhans' Cell Histiocytosis of the Spine in Children

Between May 1972 and December 1991, 58 children were seen in the authors' institution for treatment of Langerhans' cell histiocytosis. Of these, 15 children (7 males, 8 females) had biopsy-proven Langerhans' cell histiocytosis with vertebral involvement. The average age at presentation was 6.4 years (range, 0.2-13.3 years). At presentation, 8 patients had involvement of a single vertebra and 4 had involvement of multiple vertebrae. Nine patients had extraspinal skeletal involvement. Two patients had visceral involvement. Currently, 13 patients have had >2 years followup (average, 8.9 years; range, 2-21 years). None of these patients had clinical evidence of disease at the latest encounter. This group of patients with Langerhans' cell histiocytosis with vertebral involvement has fared well. Most patients have had involvement of multiple vertebrae and many have had extraspinal bony involvement as well. There was a great deal of variability in the extent of collapse and reconstitution of vertebral height, and the amount of reconstitution did not correlate with patient age.

Effects of Viral Virulence on Intrauterine Growth in SIV-Infected Fetal Rhesus Macaques (Macaca mulatta)

Studies with a simian immunodeficiency virus (SIV)-infected fetal monkey model were conducted with a focus on fetal growth and viral pathogenesis. Twenty-six fetuses were inoculated in utero via ultrasound guidance with an uncloned pathogenic strain of SIV or vehicle during the second or third trimesters [gestational day (GD) 65, 110, or 130], sonographically monitored weekly (biometrics, blood flow), then necropsied at incremental time points postinfection. Peripheral blood hematologic (complete blood counts, clinical chemistries), immunologic (immunophenotyping), and endocrine studies [insulin-like growth factor (IGF), IGF-binding proteins (IGFBP)] were conducted. Severe intrauterine growth restriction (IUGR), oligohydramnios, and altered lymphocyte counts were noted for fetuses infected on GD 65. Less severe effects were detected for fetuses inoculated at the later time points, with severity dependent upon the length of SIV infection in utero. IGF studies indicated significant reductions in IGF-I and elevated immunoreactive levels of IGFBP-3 in infected fetuses during the third trimester. Parallel studies conducted with four fetuses infected on GD 65 with a nonpathogenic, molecularly cloned virus (SIVmac1A11) resulted in normal fetal growth, with no effects on hematopoiesis or IGF/IGFBP levels, and no evidence of clinical disease. Taken together, these studies show that (1) infection of fetuses during the early second trimester with an uncloned pathogenic strain of SIV results in severe IUGR and a disruption in the molar ratio of IGF:IGFBP-3, and (2) outcome of fetal SIV infection is determined by the timing of infection and the virulence of the viral inoculum.

Serum Levels of Tumor Necrosis Factor (TNF), Soluble Receptors for TNF (55- and 75-kDa sTNFr), and Soluble CD14 (sCD14) in Epithelial Ovarian Cancer

The preoperative serum levels of tumor necrosis factor (TNF), soluble receptors for TNF (55- and 75-kDa sTNFr), and soluble CD14 (sCD14) were retrospectively measured in 66 patients with epithelial ovarian cancer and in 59 patients with benign ovarian masses. The preoperative serum TNF and sCD14 levels were higher in patients with epithelial ovarian cancer than in those with benign ovarian disease ( P = 0.001 and P < 0.0001, respectively). Among patients with advanced malignancy, preoperative serum TNF and sCD14 correlated with neither the common prognostic variables nor the clinical outcome of patients. The preoperative serum 55- and 75-kDa sTNFr levels were higher in patients with epithelial ovarian cancer than in those with benign ovarian disease ( P < 0.0001 and P = 0.02, respectively). Among patients with advanced malignancy, preoperative serum 55- and 75-kDa sTNFr correlated with FIGO stage (IV vs III, P = 0.008 and P = 0.01, respectively) and with the clinical outcome of patients. Among patients followed after surgery and chemotherapy for advanced epithelial ovarian cancer, 55- and 75-kDa sTNFr levels were significantly higher in the samples drawn from patients with clinical evidence of disease when compared to those from patients without clinical evidence of disease; conversely, TNF and sCD14 levels were similar in the two groups. In conclusion, the preoperative serum levels of TNF, 55- and 75.kDa sTNFr, and sCD14 were significantly higher in patients with epithelial ovarian cancer than in those with benign ovarian disease. The measurement of serum TNF and sCD14 seemed to be of limited clinical value for the management of patients with advanced epithelial ovarian cancer. Conversely, the assay of serum 55- and 75-kDa sTNFr might have a potential clinical relevance, for both prognostic purposes and assessment of disease status.

Urine cytology evaluation in cases of uretero-ileal cutaneous diversion.

Cytological examination of urine from the ileal conduit in cases of bladder cancer treated by radical surgery can be an important and effective follow-up procedure. A total of 19 patients (18 males and one female) on whom radical cystectomy for cancer was performed were studied. Three urine specimens were examined in each case using routine cytological methods. Three cases of recurrent carcinoma (mainly of papillary type) were diagnosed cytologically before any clinical evidence of disease. The cytological examination of urine at 3-6 month intervals after cystectomy for bladder carcinoma is considered advisable in all cases, since the recurrence rate of transitional cell neoplasms in the upper urinary tract after cystectomy for transitional carcinoma is quite high.

Experimental Infection of the Red-backed Vole (Clethrionomys gapperi) with Borrelia burgdorferi

Red-backed voles (Clethrionomys gapperi) were live trapped in northern St. Louis County, Minnesota (USA), in late September and October 1988 and experimentally inoculated with Borrelia burgdorferi. Spirochetes were isolated from most animals 14 and 28 days following inoculation. Thus, red-backed voles exposed to B. burgdorferi were susceptible to infection and could be a reservoir host, along with chipmunks (Tamias striatus) and other small rodents, in areas where white-footed mouse (Peromyscus leucopus) populations are low. No evidence of clinical disease was noted in any infected voles.

Monitoring cancer antigen 125 levels in induction chemotherapy for epithelial ovarian carcinoma and predicting outcome of second-look procedure.

A retrospective analysis of 45 patients with epithelial ovarian carcinoma who underwent second-look procedure after initial cytoreduction and platinum-based combination chemotherapy was undertaken. Each patient was evaluated for the result of CA 125 after a third course of chemotherapy, the result of CA 125 prior to second-look laparotomy, and the calculated slope of regression curve for CA 125. These results were compared for a normal value of CA 125 of < 35 and < 20 IU/ml. Of the 45 patients who underwent second-look procedure, 27 had a positive outcome, while 18 were negative for residual disease. For CA 125 levels obtained after the third course of chemotherapy, a level > or = 35 IU/ml predicted a positive second-look outcome in three patients, but was not statistically significant (P = 0.143) when compared to patients with normal levels. Of patients with CA 125 > or = 35 IU/ml immediately prior to second-look procedure, nine had a positive outcome for second look, a difference that was statistically significant (P = 0.006) when compared to patients with normal levels. For the calculation of the slope of the regression curve, no statistical difference (P = 0.838) was observed between the average of the slopes of the positive-outcome group and that the negative-outcome group. The only useful prediction of second-look procedure outcome identified in this group of patients was an elevated (> or = 35 IU/ml) CA 125 immediately prior to second-look procedure. Elevated levels at this time predicted the presence of disease in 100% of patients. For the other methods of analyzing CA 125 levels during therapy, the outcome of second look could not be predicted in patients with no clinical evidence of disease. Selecting a lower normal level of 20 IU/ml did not increase our ability to predict second-look procedure outcome.

The Diagnosis of Nonfunctioning Pheochromocytoma The Role of I-123 MIBG Imaging

A patient with an asymptomatic nonsecreting left adrenal pheochromocytoma concentrated I-123 MIBG. Iodine-123 MIBG scintigraphy showed abnormal uptake in the left adrenal bed. The authors conclude that I-123 MIBG imaging may allow the in vivo diagnosis of non-functioning pheochromocytomas when there is no clinical evidence of disease and other laboratory measurements are not helpful for tumor diagnosis.

In Vitro Drug Testing of Ovarian Cancer Using the Human Tumor Colony-Forming Assay: Comparison of in Vitro Response and Clinical Outcome

The purpose of this study was to assess the prognostic value of in vitro drug chemosensitivity testing using the Hamburger-Salmon human tumor colony-forming assay (HTCA) in fresh tumor samples obtained from newly diagnosed patients with stage II-IV ovarian cancer undergoing maximins cytoreductive surgery and prior to platinum-based chemotherapy. The HTCA was performed on fresh ovarian cancers obtained from 93 patients at their initial exploratory laparotomy to evaluate in vitro sensitivity to cisplatin, carboplatin, and cyclophosphamide following a 1-hr drug exposure. Prospective clinical follow-up was performed on all patients with the primary study endpoints being pathologically proven complete response at second-look surgery and disease-free and overall survival durations. In vitro drug sensitivity was strongly dose-dependent. At a concentration of 5 μg/ml only 23% of tumor samples were sensitive (as defined by a ⩾50% decrease in tumor colony-forming units compared to controls) to cisplatin; 13% of tumors were sensitive to carboplatin at a concentration of 50 μg/ml and 11% to 4- OH-cyclophosphamide at a concentration of 1 μg/ml. At doses which were 10 times the previously stated concentrations, the sensitivity rates to cisplatin, carboplatin, and 4- OH-cyclophosphamide increased to 72, 63, and 53%, respectively. Subjects were categorized as having drug-sensitive disease if HTCA results showed in vitro drug sensitivity to at least one of the agents used in their primary chemotherapy. Multivariate analysis failed to show any advantage in clinical response rate, progression-free interval, or survival duration for patients with drug-sensitive disease compared to drug-resistant disease; however, there was evidence of a trend toward an enhanced pathologically proven complete response rate in patients who had chemosensitive tumors in vitro. Second-look surgery was performed in 28 of 55 patients with optimal surgical resections and no clinical evidence of disease at the completion of their primary chemotherapy. Fifty percent (5/10) of patients with drugsensitive disease achieved a pathologic complete response, while only 3/18 (17%) patients with drug-resistant tumors had a documented pathologic complete response ( P = 0.13). As reported in other ovarian cancer studies, patient characteristics which were found to be significantly associated with survival were stage of disease (II-III vs IV), optimal primary surgical resection (i.e., <1 cm 2 residual tumor) vs suboptimal resection, clinical measurability of disease at initiation of chemotherapy, and response to primary chemotherapy. In conclusion, in vitro drug sensitivity, as measured by the HTCA, does not appear to be an independent prognostic factor for survival in patients with stage II-IV epithelial ovarian cancer who undergo standard treatment with tumor debulking surgery and primary platinum-based chemotherapy. Further studies are indicated to determine whether in vitro drug sensitivity is an independent prognostic factor for pathologically proven complete response at second-look surgery.

Primary carcinoma of fallopian tube: experience of six cases

Between 1980 and 1993, six cases of primary carcinoma of the fallopian tube were diagnosed and treated at the Hospital of Rovigo. Median age was 64.6 years; the most frequent symptom was atypical vaginal bleeding; only one patient presented a history compatible with hydrops tubae profluens. No patient in this series had a correct preoperative diagnosis. In Papanicolau smears and endometrial currettage, one case was positive for cancer. Primary surgical treatment was performed in all cases, followed by adjuvant chemotherapy. Histologic differentiation was Grade 2 in three patients and Grade 3 in three patients. Staging was by a system analogous to the FIGO classification for ovarian carcinoma. Two patients had Stage I disease; one, Stage II; two, Stage III; and one, Stage IV. Two patients died 14 and 37 months after the initial diagnosis. Three patients without clinical evidence of disease underwent second look procedures; the patients were alive and disease free with follow up ranging from 45 to 55 months. One patient is alive 4 months after surgery. In this series survival was not associated with grade, but was dependent upon stage. In our study, the prognostic value of the second- and third-look procedures are discussed.

Early Prostate Cancer: The National Results of Radiation Treatment from the Patterns of Care and Radiation Therapy Oncology Group Studies With Prospects for Improvement with Conformal Radiation and Adjuvant Androgen Deprivation

Long-term outcome of the Patterns of Care Study and the Radiation Therapy Oncology Group are used to demonstrate the national average results of treating early prostate cancer in the United States. A group of patients with stage T1B2 disease and pathologically negative lymph nodes showed excellent 10-year survival rates and freedom from clinical evidence of disease, while prostate specific antigen (PSA) correlations in 10-year survivors indicate that 88% were clinically free of cancer and had a PSA level of less than 4.0 mg./nl., and 65% had a PSA level of less than 1.5 ng./ml. The latter group represented clinical and biochemical cures.The improvement noted in outcome of locally advanced prostate cancer treatment by Radiation Therapy Oncology Group prospective trials combining androgen deprivation and radiation therapy is presented. These trials will be extended to the poor prognosis group with stage Tl,2 disease. The advantages of conformal therapy in acute and late morbidity are illustrated with preliminary evidence of improved PSA response as a result of improved technique and higher dose associated with conformal 3-dimensional treatment.