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The benefits of comprehensive surgical staging in the management of early-stage epithelial ovarian carcinoma.

OBJECTIVE: The management of understaged patients with apparent clinically early ovarian cancer is difficult. Options include offering chemotherapy based on histopathologic factors or reoperation to obtain the necessary information needed to assign an accurate surgical stage. This study aims to compare these two approaches and to define the role of staging surgery in this common patient population. METHODS: Retrospective chart reviews were carried out at the Universities of Manitoba and Saskatchewan over the period 1975 to 1999. Demographic data and surgical findings were abstracted and entered into a computerized database for analysis. Patients not having surgical staging procedures were offered platinum-based chemotherapy based on high tumor grades, dense adhesions, and presence of surface excrescences or large necrotic areas. Patients with surgically proven stage I disease were treated with no further therapy regardless of histopathologic factors. Descriptive statistics are used to summarize the data. Logistic and Cox regression models are used to identify significant predicting factors for recurrences and progression-free intervals. RESULTS: One hundred and thirty-eight patients presented with tumor macroscopically confined to the ovary at the time of laparotomy. The median age at presentation is 56.5 (18-90). The histology distribution was serous tumor in 28.3%, mucinous in 26.1%, endometrioid in 23.2%, clear cell in 14.5%, anaplastic in 2.2%, and mixed types in 5.8%. The grade distribution was 47.1% grade 1, 27.5% Grade 2, and 25.4% Grade 3. Sixty-eight percent of the patients had a comprehensive surgical staging procedure initially. Thirty-six percent of these patients were found to have extraovarian metastases and were subsequently treated with adjuvant chemotherapy. Forty-three percent of those not having staging laparotomy were offered chemotherapy based on high risk factors only. At a median follow-up of 58 months. 77% of patients remained disease-free and 23% had recurrent disease. Of 60 patients with surgically proven stage I treated expectantly, 6 (10%) recurred, whereas of 25 unstaged patients treated expectantly due to lack of risk factors 7 (28%) recurred (P = 0.036). In patients treated expectantly, a significant survival advantage was noted in the staged group. Logistic regression showed age (OR 1.032, P = 0.043), high grade (OR 4.16, P = 0.003), and lack of a proper staging surgery (OR 2.62, P = 0.032) to be important factors predicting recurrence. In terms of progression-free interval, only age (OR 1.027, P = 0.048) and tumor grade (OR 3.62, P = 0.05) are significant predictors. CONCLUSION: Absence of surgical pathologic high-risk factors is inferior to comprehensive staging laparotomy findings in guiding recommendations for subsequent adjuvant therapy. Patients who have not been properly staged stand a significant risk of recurrent disease despite more frequent use of chemotherapy. All clinically early-stage ovarian cancer patients should be considered for comprehensive staging surgery prior to further treatment recommendations.

Adolescent↗

Comparison between clinical and pathological staging in low stage nonseminomatous germ cell testicular tumors.

Between January 1985 and December 1990, 208 consecutive patients with low stage nonseminomatous germ cell testicular tumors underwent retroperitoneal lymphadenectomy. In all of the patients the disease was staged with post-orchiectomy serum alpha-fetoprotein and beta subunit of human chorionic gonadotropin determinations, as well as chest x-rays and computerized tomography or magnetic resonance imaging of the abdomen and pelvis. Bipedal lymphangiography was performed in 139 patients. Of the 208 patients 173 (83%) had clinical stage 1 and 35 (17%) had low clinical stage 2 disease: 21 had tumors on radiographic imaging that were smaller than 2 cm. (clinical stage 2A) and 14 had tumors between 2 and 3 cm. (clinical stage 2B less than 3 cm.). Retroperitoneal metastases were found in 31 of 156 clinical stage 1 cancer patients (19.8%) with negative or normally decreasing serum tumor markers after orchiectomy, 15 of 16 (93.8%) with persistent positive markers, 8 of 14 clinical stage 2A cancer patients (57.1%) with negative or normally decreasing markers, all 7 stage 2A cancer patients with positive markers and all 14 clinical stage 2B cancer patients. Lymphangiography added little to the reliability of clinical staging. We conclude that due to the relatively low accuracy of clinical staging, retroperitoneal lymphadenectomy remains the treatment of choice for clinical stages 1 and 2A nonseminomatous germ cell testicular tumors with normal serum markers after orchiectomy.

Biomarkers, Tumor↗

The role of (18)fluoro-2-deoxyglucose positron emission tomography in initial staging and re-staging after chemotherapy for testicular germ cell tumours.

OBJECTIVE: To investigate the role of 18fluoro-2-deoxyglucose positron emission tomography (FDG-PET) in the initial staging of clinical stage I and II nonseminomatous germ cell tumours (NSGCTs) and in re-staging (non)seminomatous GCTs after chemotherapy. PATIENTS AND METHODS: FDG-PET studies were undertaken in 50 patients. FDG uptake was interpreted visually and when possible the standardized uptake value was determined. A FDG-PET scan was taken in five patients with clinical stage I and in seven with stage II NSGCT. The scans were validated by histology. Stage I patients underwent a retroperitoneal lymph node dissection because of vascular invasion in the primary tumour. Thirty-eight scans were taken after completing chemotherapy (28 NSGCTs and 10 seminomatous GCTs), and validated by histology or clinical follow-up. RESULTS: In stage I NSGCT, FDG-PET staging was equivalent to computed tomography (CT) staging. One small lesion, consisting of mature teratoma, was missed by both FDG-PET and CT. In stage II NSGCT, FDG-PET missed two lesions (mature teratoma and retroperitoneal mass with a small component of embryonal cell carcinoma) whereas CT correctly classified all. In 20 of 28 patients with NSGCT, histology was obtained after chemotherapy. In one of three patients with viable tumorous residual mass the FDG-PET scan was clearly positive; in four of 12 with mature teratoma and inflammation components retroperitoneally, the FDG-PET was also positive. In contrast, eight patients with solitary mature teratoma had a negative PET result. In four of five patients with necrosis after chemotherapy the PET result was correctly negative. All eight patients on surveillance had a negative PET scan and were free of disease at median (range) of 14 (8-18) months. Interestingly, of the 12 patients with a correct negative PET result, 11 had no mature teratoma in their primary tumour. Nine of 10 patients with SGCT were correctly staged. Two FDG-PET studies showed increased uptake; in one, a viable seminomatous mass was found and in the other there was inflammation in the residual mass. In all other patients the FDG-PET scan correctly predicted absence of viability in the residual mass. CONCLUSIONS: In primary staging, FDG-PET has no benefit over CT. In re-staging, a negative FDG-PET result predicts fibrotic residual mass in seminomatous GCT. Moreover, it could be useful to predict fibrotic residual mass in NSGCT in those patients with no teratoma component in their primary tumour.

Adolescent↗

Improved clinical staging system combining biopsy laterality and TNM stage for men with T1c and T2 prostate cancer: results from the SEARCH database.

PURPOSE: A number of studies have failed to show significant differences in outcome following radical prostatectomy between men with palpable, clinically localized prostate cancer (cT2) and those whose tumors are not palpable (cT1c). We determined whether we could improve the prognostic value of the TNM staging system in men with cT1c and cT2 cancers by including information on whether prostate needle biopsy was unilaterally or bilaterally positive. MATERIALS AND METHODS: A retrospective survey of 992 patients from the SEARCH (Shared Equal Access Regional Cancer Hospital) Database treated with radical prostatectomy at 4 equal access medical centers between 1988 and 2002 was done. TNM 1992 clinical stage was T1c in 421 patients, T2a in 287, T2b in 202 and T2c in 82. Multivariate analysis was used to examine whether biopsy laterality and clinical stage were significant predictors of surgical margin status, nonorgan confined disease, seminal vesicle invasion, and time to prostate specific antigen (PSA) recurrence following radical prostatectomy. RESULTS: Patients with clinical stages T2b and T2c cancers had similar rates of PSA recurrence, which were significantly higher than in patients with T1c and T2a disease, who also had similar rates of PSA recurrence. Bilateral positive biopsy further stratified patients with T1c and T2a disease (p = 0.01) but not those with T2b and T2c cancers (p = 0.207). Grouping these 1992 clinical stages with biopsy laterality resulted in a new clinical staging system, which was a significant predictor of PSA recurrence following radical prostatectomy (p <0.001). On multivariate analysis whether TNM clinical stage was evaluated as a categorical or continuous variable only PSA, biopsy Gleason score and the new clinical staging system (1992 TNM stage groupings combined with biopsy laterality) were significant independent predictors of time to biochemical recurrence following radical prostatectomy. CONCLUSIONS: Combining low (T1c and T2a) and high (T2b and T2c) risk 1992 clinical stages with biopsy laterality (unilateral versus bilateral positive) resulted in a new clinical staging system that was a stronger predictor of PSA recurrence following radical prostatectomy than the 1992 or 1997 TNM clinical staging system. If confirmed at other centers and in men who undergo with other treatment modalities, consideration should be given to revising the current TNM staging system to reflect these findings.

Biopsy, Needle↗

Re-assessment of stage I uterine cervical carcinoma according to revised JSGO (1997) staging.

BACKGROUND: The Japanese Society of Gynecologist and Obstetrician (JSGO) revised criteria for early uterine cervical cancer. OBJECTIVE: In this study, we investigated the value of the revised JSGO criteria. METHOD: Retrospective review was performed for 70 patients with tumors limited to the uterine cervix who were classified stage I under old JSGO criteria. RESULT: Forty patients were re-classified into stage IA1 and 4 patients into stage IA2. Incidence of lymph-vascular infiltration (LVI) in stage IA1 and IA2 were 5% and 25%. There was one patient with stage IA1 disease who had nodal metastasis and no patients with stage IA2 disease. There were 14 patients with stage IB1 disease and 12 patients with stage IB2 disease. Mortality of patients with stage IB2 disease was 25% and significantly higher than that of patients with stage IA and IB1 disease (P<0.001 and <0.05) CONCLUSION: Although the revised JSGO criteria for early cervical cancer are acceptable for assessment of patients, the therapy of patients is still controversial. We recommend that patients with stage IA1 and negative LVI should have less radical hysterectomy and patients with stage IA1 with LVI or stage IA2, IB should have radical hysterectomy.

Adult↗

The 92-kDa gelatinase B is expressed by advanced stage melanoma cells: suppression by somatic cell hybridization with early stage melanoma cells.

The production and local release of various proteolytic enzymes, either by tumor cells or tumor-associated stromal cells, is thought to facilitate the malignant behavior of solid tumors. Human cutaneous melanoma offers an excellent clinical model to study the possible contribution of such proteases to solid tumor progression because melanoma goes through a series of well defined stages in its pathogenesis; moreover, permanent cell lines have been established from these various stages. As a first step to analyzing the gelatinolytic enzymes in melanoma pathology, we examined cell lines derived from early stage primary melanomas in which patients were cured of their disease and compared the results to those obtained with cell lines established from advanced stage primary lesions or metastases (i.e., from patients who eventually succumbed to the disease). We found that 80% of cell lines examined from early stage lesions constitutively produced only the 72-kDa gelatinase A but never the 92-kDa gelatinase B. In contrast, the majority of advanced stage cell lines examined produced both the 72-kDa gelatinase A and the 92-kDa gelatinase B. Advanced stage cell lines that did not constitutively produce the 92-kDa gelatinase B could be induced to do so with transforming growth factor beta, interleukin 1 beta or 12-O-tetradecanoyl-phorbol-13-acetate. In total, 0 of 5 early stage cell lines constitutively expressed the 92-kDa gelatinase B, and only 2 of 5 could be induced to produce this activity. In contrast, all advanced stage cell lines that were evaluated either constitutively or inducibly produced the 92-kDa gelatinase B. To analyze the mechanism by which 92-kDa gelatinase B production is switched on in the advanced stage melanoma cell lines, somatic cell hybrids were constructed using an advanced stage melanoma cell line as one partner and either one of two early stage cell lines as the other. Constitutive production of the 92-kDa gelatinase B in such hybrids was lost and could not be induced in such hybrids. Coculture of the early and advanced stage cell lines failed to recapitulate what was seen after somatic hybridization, and zymographic analysis of lysates from hybrid cell lines demonstrated no 92-kDa gelatinase B activity. Reverse transcription-PCR analysis demonstrated that the loss of 92-kDa gelatinase B production occurred at the level of steady-state mRNA for the enzyme.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Cross-face nerve graft with free-muscle transfer for reanimation of the paralyzed face: a comparative study of the single-stage and two-stage procedures.

The most accepted method for reanimation of the paralyzed face is the two-stage method that combines cross-face nerve graft with free-muscle transfer. Although the results of reconstruction with this method are satisfactory, there is an excessive delay between stages, which prolongs the period of rehabilitation. In 1995, Kumar overcame this and presented his preliminary results from a single-stage transfer of the gracilis. We compared the long-term results of the single-stage with the two-stage method of reconstruction. Patients selected the method of reconstruction on the basis of the information, photographs of scars, and video recording of results given to them at a special facial palsy clinic. Ten patients selected the single-stage reconstruction and 15 selected the two-stage reconstruction. The mean follow-up period was 3 years. The results of the two methods are comparable, with 90 percent of the patients who underwent the single-stage and 93 percent of those who underwent the two-stage procedures having good and fair results. However, the two-stage method scored good symmetry at rest in 67 percent, compared with 20 percent for the single-stage method. There were fewer complications with the single-stage method, and none of the patients had any problems relating to the donor site. The period of rehabilitation was reduced by 10 months with the single-stage method.

Adolescent↗

Economics of one-stage versus two-stage bilateral total knee arthroplasties.

Patients requiring bilateral total knee arthroplasties may have both joints replaced simultaneously during one hospitalization (one-stage) or during two separate hospitalizations (two-stage). The goals of the current study were to retrospectively analyze discharge patterns for 91 patients who had one-stage bilateral total knee arthroplasties and 32 patients who had two-stage surgeries, and to quantify their in-hospital costs and their costs if the patients were discharged from the hospital to an inpatient unit. Patients having one-stage and two-stage surgery were similar in age, gender, severity of illness (as measured by the American Society of Anesthesiologists Physical Status score), principal diagnosis, and ethnicity. Using a microcosting approach, the authors found that the average in-hospital costs for one-stage total knee arthroplasty (27,468 US dollars) were significantly lower (by 24%) than for two-stage total knee arthroplasty. However, 38% of patients who had the one-stage bilateral total knee arthroplasties were admitted to an acute rehabilitation unit, which had a mean cost of 6469 US dollars and length of stay of 9 days. In contrast, none of the patients who had the two-stage procedure required acute rehabilitation. Patients who had the two-stage procedure were discharged directly home (or with home health services) 42% of the time, versus 21% for patients who had the one-stage procedure. Patients from both groups were discharged to a skilled nursing facility approximately (1/2) of the time, accruing similar costs. Economic analyses of the one-stage procedure need to consider that these patients will require increased use of acute inpatient rehabilitation after hospital discharge.

Aftercare↗

The vertebrate phylotypic stage and an early bilaterian-related stage in mouse embryogenesis defined by genomic information.

BACKGROUND: Embryos of taxonomically different vertebrates are thought to pass through a stage in which they resemble one another morphologically. This "vertebrate phylotypic stage" may represent the basic vertebrate body plan that was established in the common ancestor of vertebrates. However, much controversy remains about when the phylotypic stage appears, and whether it even exists. To overcome the limitations of studies based on morphological comparison, we explored a comprehensive quantitative method for defining the constrained stage using expressed sequence tag (EST) data, gene ontologies (GO), and available genomes of various animals. If strong developmental constraints occur during the phylotypic stage of vertebrate embryos, then genes conserved among vertebrates would be highly expressed at this stage. RESULTS: We established a novel method for evaluating the ancestral nature of mouse embryonic stages that does not depend on comparative morphology. The numerical "ancestor index" revealed that the mouse indeed has a highly conserved embryonic period at embryonic day 8.0-8.5, the time of appearance of the pharyngeal arch and somites. During this period, the mouse prominently expresses GO-determined developmental genes shared among vertebrates. Similar analyses revealed the existence of a bilaterian-related period, during which GO-determined developmental genes shared among bilaterians are markedly expressed at the cleavage-to-gastrulation period. The genes associated with the phylotypic stage identified by our method are essential in embryogenesis. CONCLUSION: Our results demonstrate that the mid-embryonic stage of the mouse is indeed highly constrained, supporting the existence of the phylotypic stage. Furthermore, this candidate stage is preceded by a putative bilaterian ancestor-related period. These results not only support the developmental hourglass model, but also highlight the hierarchical aspect of embryogenesis proposed by von Baer. Identification of conserved stages and tissues by this method in various animals would be a powerful tool to examine the phylotypic stage hypothesis, and to understand which kinds of developmental events and gene sets are evolutionarily constrained and how they limit the possible variations of animal basic body plans.

Animals↗

A comparison of a single-stage isoproterenol tilt table test protocol with conventional two-staged tilt protocol in patients with syncope.

PURPOSE: Recently, Shen and colleagues described a single-stage isoproterenol protocol: Head Up Tilt Table testing (HUTT). The purpose of this study was to compare the introduction of this single-stage tilt protocol to sequential two-staged tilt table testing. METHODS: Patients with recurrent or dramatic syncope or near syncope were referred for HUTT. A total of 100 patients underwent HUTT via a two-staged tilt protocol: 60 passive tilt for 30 minutes and, if negative, followed by a 10-minute tilt with isoproterenol titration to a 20% heart rate increase (two-staged HUTT). The next 100 patients underwent single stage isoproterenol protocol, which consisted of a 10-minute, 70 tilt with fixed dose isoproterenol infusion (0.05 ug/kg/minute). Patients with isoproterenol contraindications underwent a passive tilt (40 minutes for a conventional two-staged 60-degree tilt, and 45 minutes for a single-staged 70 tilt. RESULTS: In the single-stage method, 40% of those that received isoproterenol had a positive test, as compared to 24% for two-stage HUTT protocol (p < 0.001). CONCLUSION: A single-staged isoproterenol HUTT provides a rapid method of increasing the overall test yield as compared to conventional two-staged HUTT. Further research is necessary to elucidate the overall utility of this rapid single-stage protocol.

Female↗

Clinical and radiologic evaluation of 2-stage IMZ implants placed in a single-stage procedure: 2-year results of a prospective comparative study.

PURPOSE: The aim of this study was to evaluate the feasibility of using a 2-stage implant system in a single-stage procedure and to study the impact of the microgap between the implant and the abutment. MATERIALS AND METHODS: Sixty edentulous patients (Cawood class V or VI) participated in this study. After randomization, 20 patients received 2 IMZ implants placed in a single-stage procedure, 20 patients received 2 IMZ implants placed in the traditional 2-stage procedure, and 20 patients were treated with 2 ITI implants (single-stage procedure). The implants were placed in the canine area of the mandible. After 3 months, mandibular overdentures were fabricated, supported by a bar-and-clip attachment. A standardized clinical and radiographic evaluation was performed immediately after prosthesis placement and after 12 and 24 months. RESULTS: One IMZ implant of the 1-stage group and 1 IMZ implant of the 2-stage group were lost after 6 and 12 months, respectively. Apart from several significant but clinically irrelevant differences, the 3 groups did not appear to differ markedly with regard to clinical parameters during the evaluation period. The mean bone loss within the first 2 years of functioning (1.1 mm IMZ 1-stage, 0.8 mm IMZ 2-stage, 1.2 mm ITI) was comparable for the 3 groups. DISCUSSION AND CONCLUSIONS: The results of this study suggest that dental implants designed for a submerged implantation procedure can also be used in a single-stage procedure and may be as predictable as when the same implants used in a 2-stage procedure or as 1-stage implants. Placement of the microgap at the crestal level in 2-stage implants did not appear to have an adverse effect on the amount of peri-implant bone loss at 2 years in this study population.

Alveolar Bone Loss↗

Comparison of stage-specific outcome of breast cancer based on 5th and 6th AJCC staging system.

BACKGROUND AND OBJECTIVES: To investigate the appropriateness of the new staging system (AJCC 6th edition) for breast carcinoma. METHODS: We reviewed the clinicopathologic data of 1,768 breast cancer patients, and their disease stages were re-categorized by the new system. The overall survival (OS) and distant relapse free survival (DRFS) rates were compared between those patients whose stages by the old system (AJCC 5th edition) remained the same (the remainders) and those patients whose stages moved up (the upstaged cases) as well as between the subgroups in the new system. RESULTS: The 10-year DRFS rates of the upstaged cases in each stage were poorer than those of the remainders, and statistical significance was demonstrated for stage IIB and stage IIIA. The 10-year OS rates were also poorer in the upstaged cases, and statistical significance was demonstrated for stage IIIA. Subgroup analysis within the new system between the node-negative versus node-positive subgroups in stages IIA and IIB showed a significant OS difference. The DRFS difference was also shown between the subgroups in stage IIA. CONCLUSIONS: The new staging system seems to more accurately reflect disease outcome, however, a re-evaluation might be required to reflect the impact of nodal involvement upon the new staging system.

Breast Neoplasms↗

The accuracy of prostate cancer staging in a population-based tumor registry and its impact on the black-white stage difference (Connecticut, United States).

Stage at diagnosis of prostate cancer is a major determinant of survival. Among Blacks, prostate cancer is diagnosed at a later stage of disease than among Whites. This study examined the accuracy of routine coding of prostate cancer stage in the Connecticut (United States) Tumor Registry (CTR) and its effect on the Black/White stage difference. Medical records were collected for 115 Black and 136 White men with prostate cancer diagnosed between 1987 and 1990. Stage at diagnosis was determined by a panel of two of the study members and compared with the stage in the CTR file. According to the panel, 32 percent of Blacks, but only 15 percent of Whites, were diagnosed with distant stage disease. Fifty-eight cases (26 percent of Whites and 20 percent of Blacks) were staged incorrectly by the CTR. Two-fifths of the errors were due to incomplete medical records at the CTR and three-fifths were due to CTR coding or data management errors. The more accurate staging did not have an appreciable impact on the Black/White stage difference. Further work is needed to characterize the accuracy of routinely coded cancer registry stage data for different cancer sites, to devise ways of improving accuracy, and to determine the impact of staging inaccuracies on research that utilizes these data.

Aged↗

Optimal surgical cytoreduction in patients with Stage III and Stage IV endometrial carcinoma: a study of morbidity and survival.

OBJECTIVE: To evaluate the survival impact of residual disease at the time of primary surgery for patients with Stage III and IV endometrial carcinoma; to assess morbidity associated with surgical cytoreduction. METHOD: All patients with endometrial carcinoma who underwent primary surgical therapy at the University of Miami between January 1, 1990 and June 1, 2002 were identified. Patients meeting FIGO criteria for Stage III or IV disease were selected. Papillary serous and clear cell histology was excluded. RESULTS: Eighty-five patients were identified: 66 Stage III and 19 Stage IV. Only Stage IIIC and Stage IV were included in survival analysis: 72% (33 Stage IIIC, 9 Stage IV) had optimal cytoreduction and 28% (6 Stage IIIC, 10 Stage IV) had suboptimal cytoreduction. The median survival for Stage IIIC and IV disease was 6.7 months for patients with suboptimal cytoreduction and 17.8 months for patients with optimal cytoreduction (P = 0.001). The proportion of patients with major postoperative complications (37.50% vs. 7.25%, P = 0.005), unplanned postoperative SICU admissions (31.25% vs. 7.25%, P = 0.018), and length of hospital stay exceeding 15 days (31.25% vs. 4.35%, P = 0.005) was greater in patients with suboptimal cytoreductive surgery. CONCLUSIONS: Overall survival is lower and morbidity is higher in patients with advanced endometrial carcinoma having suboptimal cytoreduction at the time of primary surgery. Patients with suspected advanced stage endometrial carcinoma should be counseled on the potential benefits of optimal cytoreductive surgery. Alternative treatment options should be considered in those patients with surgically unresectable disease.

Adult↗

Radical prostatectomy for impalpable prostate cancer: the Johns Hopkins experience with tumors found on transurethral resection (stages T1A and T1B) and on needle biopsy (stage T1C).

We review the pathological findings of impalpable prostate cancer detected by transurethral resection (stages T1a and T1b) and needle biopsy (stage T1c). The short-term (4 years) and long-term (8 to 10 years) natural histories of untreated stage T1a prostate cancer are examined, as are options to follow patients expectantly. The findings on radical prostatectomy for stages T1a and T1b disease are reviewed and compared. Of the 64 cases of stage T1a disease 13 (20%) showed substantial tumor, including 7 with more than 1 cc of tumor, 5 with capsular penetration and 1 with a Gleason grade 4 + 5 = 9 tumor. Based on preoperative pathological parameters, one could not predict which cases had minimal versus substantial tumor. In a study from our institution that undertook complete histological examination of 39 radical prostatectomy specimens of stage T1b carcinoma, we found that all prostates contained residual carcinoma, 26% had capsular penetration and 10% had invasion of the seminal vesicles. When comparing morphometrically determined volumes of carcinoma with similar data from 56 patients with stage T2 carcinoma, stage T1b tumors were much more heterogeneous in grade, location and volume than were stage T2 lesions. Unless all 3 variables (grade, volume and location) were known, the final pathological stage of T1b cancers could not be predicted with confidence. Finally, we examined preoperative clinical and pathological parameters in 157 men with clinical stage T1c disease undergoing radical prostatectomy, and correlated these findings with pathological extent of disease in the surgical specimen in an attempt to identify a subset of patients with potentially biologically insignificant tumor who might be followed conservatively. Of the tumors 16% were insignificant (less than 0.2 cc, organ confined and Gleason grade less than 7), 10% were minimal (0.2 to 0.5 cc, organ confined and Gleason grade less than 7), 37% were moderate (more than 0.5 cc or capsular penetration with Gleason sum less than 7) and 37% were advanced (capsular penetration with Gleason sum 7 or more, or positive margins, positive seminal vesicles or positive lymph nodes). These findings are intermediate between those found in clinical stages T1a and T2 disease. The best model predicting insignificant tumor was a prostate specific antigen (PSA) density of less than 0.1 and no adverse pathological finding on needle biopsy or PSA density of 0.1 to 0.15 with less than 3 mm. low to intermediate grade cancer on only 1 needle biopsy core. The positive predictive value of the model was 95% with a negative predictive value of 66%.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Radical prostatectomy for stage A adenocarcinoma of the prostate: staging errors and their implications for treatment recommendations and disease outcome.

Of 148 patients with clinical stage A1 (32) or A2 (116) disease who had radical prostatectomy only 63% and 62%, respectively, had pathological stage A disease. Although 25% of those with clinical stage A1 and 9% of those with clinical stage A2 disease had no cancer at radical prostatectomy, 12% and 29%, respectively, had pathological stage C disease or higher. Clinical Mayo grade 1 was never associated with extracapsular disease but 60% of those with grade 3 or higher tumor did have extracapsular disease. Over-all survival was comparable to the expected survival. Clinical stage A2 cancer was associated with a significantly higher progression rate (when prostate specific antigen values were considered, p = 0.0011) and cancer death rate (p less than 0.045) than stage A1 disease, whereas pathological stage was not significantly related to disease outcome, possibly because of the use of adjuvant treatment (hormonal or radiation) for some patients with pathological stage C or higher disease. The vagaries of clinical staging associated with stage A disease, as well as the previously documented progression on long-term followup (8 to 10 years) in younger (60 years old or less) patients with stage A1 prostate cancer make radical prostatectomy with its limited morbidity an acceptable treatment choice.

Adenocarcinoma↗

Evaluation of the TN sub-staging in patients with initially unresectable stage III non-small cell lung cancer treated by induction chemotherapy. The European Lung Cancer Working Party.

PURPOSE: This study attempted to investigate, in a cohort of patients with clinical stage III initially unresectable non-small cell lung cancer (NSCLC) treated by the same induction chemotherapy regimen, the prognostic value of clinical T and N sub-groupings in order to validate the current International Staging System (ISS). PATIENTS AND METHODS: All the eligible patients with stage III NSCLC (428 patients) registered in a clinical trial were included in the study investigating, after three courses of induction chemotherapy, the role, in responders, of chest irradiation in comparison to further chemotherapy. The chemotherapy regimen consisted of mitomycin C, ifosfamide and cisplatin. RESULTS: Patients with ISS 1986 stage IIIA had a significantly better survival than those with stage IIIB (median survival 47 vs 36 weeks; P = 0.01). A RECPAM analysis showed that patients with T1-T2 N3 and T4 N0-1-2 stage had a more similar prognosis to those with stage IIIA. That result leads to define two new sub-groups: stage IIIlalpha (T3-T4 N0-N1; any T N2; T1-T2 N3) and IIIbeta (T3-T4 N3), with a highly significant difference in survival between them (median survival: 45 vs 29 weeks; P < 0.0001). The superiority of that new classification on the ISS documented in our series of stage III patients for discriminating survival and tumour response has to be confirmed on another series in a multivariate context. CONCLUSION: For unresectable NSCLC treated by induction chemotherapy, stage III sub-classification by moving T4 N0-1 and T1-2 N3 tumours from stage IIIB to stage IIIA appeared to better correlate with prognosis. The usefulness of this new sub-division has to be tested in validation studies.

Adult↗

Hodgkin's disease: correlation of clinical characteristics with probabilities for negative lymphangiogram vs. negative laparotomy findings in patients with Stage I supradiaphragmatic presentations vs. those in patients with Stage II.

PURPOSE: At a time both when late complications and second malignancies have become a growing concern and when staging laparotomy has been largely abandoned and comparative studies for staging Hodgkin's disease by state of the art computed tomography (CT) vs. lymphangiography have revealed minimal differences in results for these procedures, our purpose for undertaking this study was twofold. Our initial reason was to determine and compare probabilities for negative abdominal findings for patients with Stage I presentations with those for patients with Stage II as determined by lymphangiography and subsequently by laparotomy for those patients who had negative lymphangiograms. Our second reason, being an extension of the first, was to create a resource that can be used in conjunction with other information for arriving at appropriate treatment decisions including giving either more or particularly less than standard institutional therapy and especially with respect to the abdomen. METHODS AND MATERIALS: Data on 714 patients with prelymphangiogram Stage I-II upper torso presentations of Hodgkin's disease were entered prospectively in our database between 1968 and 1987. Twenty-eight with lymphocyte predominant disease, who had both negative lymphangiogram and negative laparotomy findings and 17 with questionable diagnoses of lymphocyte-depleted or unclassified disease were excluded from subsequent analyses of 669 patients with nodular sclerosis (NS) and mixed cellularity (MC) diagnoses. RESULTS: Stage I: in final logistic models, negative lymphangiogram findings were associated strongly with a combination of no constitutional symptoms and nodular sclerosis histology, whereas negative laparotomy findings correlated strongly with a combination of no constitutional symptoms and female sex. Predicted probabilities depended on the ratios of favorable to unfavorable characteristics. Stage II: in final logistic models, negative lymphangiogram findings were associated strongly with a combination of no constitutional symptoms, nodular sclerosis histology, age <40 years, and <4 involved sites, whereas negative laparotomy findings correlated strongly with a combination of <4 involved sites and mediastinal disease. Predicted probabilities again depended on the ratios of favorable to unfavorable characteristics. CONCLUSION: This study demonstrated that probabilities for negative abdominal findings for patients with supradiaphragmatic presentations of NS and MC Hodgkin's disease depended on: 1) whether the disease presented as Stage I or as Stage II; 2) whether staging was limited to a lymphangiogram or whether it included a laparotomy; and 3) or whether the clinical features associated with the presenting stage and methods of staging were favorable or unfavorable.

Abdomen↗