Survival in patients with primary soft-tissue sarcomas treated within 6 years

Since 1988, treatment strategies for our sarcoma patients have been determined by the same team and operations performed by one surgeon. The aim of this study was to analyse prognostic data on local recurrence and survival of 101 consecutive patients who presented in our institution with the primary tumour manifestation. After a median follow-up of 35 months, the local recurrence rate was 13.5%, the mean survival time was 68 months and the 5-year survival rate was 83%. Besides positive lymph nodes (only 3 patients) the quality of resection significantly influenced local recurrences (P < 0.05). Univariate predictors of mortality were tumour grade (P < 0.01), tumour size (P < 0.05), distant metastases (P < 0.01), and resection quality (P < 0.01). Multivariate predictors of mortality consisted of grade (P < 0.0001), positive lymph nodes (P < 0.001) and resection quality (P < 0.01). In this homogeneous group of patients, excellent recurrence and survival rates could be achieved. An optimized surgical treatment not only reduces the rate of local recurrences but also augments survival time.     

Survival, fecundity, and development of Dermatophagoides farinae (Acari: Pyroglyphidae) at fluctuating relative humidity

OBJECTIVE: To determine the impact of margin status on disease recurrence and the incidence of occult cancer in women diagnosed with vulvar intraepithelial neoplasia (VIN) III and treated with surgical excision. METHODS: Between 1989 and 1995, 73 women were diagnosed preoperatively with VIN III by vulvar biopsy and were treated with surgical resection. Patients were examined postoperatively, and recurrence was diagnosed when a biopsy of suspicious lesions confirmed VIN III. RESULTS: The mean age was 45 years; 81% of the patients were white, and 18% were black. Eighty-two percent of the women had used tobacco, 56% had prior cervical dysplasia, and 37% had prior genital warts. An underlying squamous vulvar cancer was found in 22% of patients at initial treatment for VIN III. Fifty-nine women had follow-up of at least 7 months. Of these, 66% (39 of 59) had positive surgical margins, 31% (18 of 59) had negative margins and 3% had unknown margins (two of 59). With positive margins, 46% (18 of 39) suffered recurrent disease; with negative margins, only 17% (three of 18) had recurrent disease (P = .03). Multifocal disease and a history of genital warts also correlated with VIN III recurrence (P = .03 for both). CONCLUSION: A significant number of women diagnosed initially with VIN III on a vulvar biopsy harbored occult vulvar cancer. Recurrences were almost threefold higher when margins were positive for residual VIN III. We conclude that surgical resection is an appropriate method of treatment of VIN III for both diagnostic and therapeutic purposes.     

Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients

OBJECTIVES: Our aim was to identify prognostic variables for long-term postoperative survival in trimodality management of malignant pleural mesothelioma. METHODS: From 1980 to 1997, 183 patients underwent extrapleural pneumonectomy followed by adjuvant chemotherapy and radiotherapy. RESULTS: Forty-three women and 140 men (age range 31-76 years) had a median follow-up of 13 months. The perioperative mortality rate was 3.8% (7 deaths) and the morbidity, 50%. Survival in the 176 remaining patients was 38% at 2 years and 15% at 5 years (median 19 months). Univariate analysis identified 3 prognostic variables associated with improved survival: epithelial cell type (52% 2-year survival, 21% 5-year survival, 26-month median survival; P =.0001), negative resection margins (44% at 2 years, 25% at 5 years, median 23 months; P =.02), and extrapleural nodes without metastases (42% at 2 years, 17% at 5 years, median 21 months; P =.004). Using the Cox proportional hazards, the relative risk of death was calculated for nonepithelial cell type (OR 3.0, CI 2.0-4.5; P <.0001), positive resection margins (OR 1.7, CI 1.2-2.6; P =.0082), and metastatic extrapleural nodes (OR 2.0, CI 1.3-3.2; P =.0026). Thirty-one patients with 3 positive variables had the best survival (68% 2-year survival, 46% 5-year survival, median 51 months; P =.013). A previously published staging system using these variables stratified survival (P <.05). CONCLUSIONS: (1) Multimodality therapy including extrapleural pneumonectomy is feasible in selected patients with malignant pleural mesotheliomas, (2) pre-resectional evaluation of extrapleural nodes may select patients for radical therapy, (3) microscopic resection margins affect long-term survival, highlighting the need for further investigation of locoregional control, and (4) patients with epithelial, margin-negative, extrapleural node-negative resection had extended survival.     

Pharmacokinetics of tacrolimus (FK506) in primary orthotopic heart transplant patients

STUDY OBJECTIVES: Local recurrence is high when sublobar resection is chosen as primary management of stage I non-small cell lung carcinoma. Postoperative external-beam radiotherapy may reduce this local recurrence problem. A technique of intraoperative brachyradiotherapy following thoracoscopic wedge resection is described as an alternative to adjuvant external-beam radiotherapy for high-risk patients who are not candidates for pulmonary lobectomy. PATIENTS: Fourteen patients with significant impairment in cardiopulmonary function having small peripheral solitary pulmonary nodules underwent video-assisted thoracoscopic (VATS) wedge resection and were found to have non-small cell cancer. Surgical margins were pathologically clear and mediastinal nodes were benign-stage I (T1NO). INTERVENTIONS: A custom polyglyconate mesh (Vicryl) containing 125I seeds was applied to pulmonary resection margins following wedge resection of peripheral lung cancers. A total dose of 100 to 120 Gy at 1 cm was applied to the target area. RESULTS: All patients had histologically clear surgical margins. Postoperative dosimetry confirmed adequate resection margin coverage. There was neither operative mortality nor morbidity related to the VATS wedge resection or the brachytherapy implants. Implants did not migrate, and there were no cases of significant radiation pneumonitis or local recurrence at mean follow-up of 7 months (range, 2 to 12 months). CONCLUSIONS: Intraoperative brachytherapy appears to be a safe and efficient alternative to external-beam radiation therapy when adjuvant radiotherapy is considered following therapeutic wedge resection of stage I (T1NO) lung cancers. The impact on local recurrence, disease-free interval, and survival will require additional follow-up.     

Determinants of survival following hepatic resection for metastatic colorectal cancer

Hepatic resection remains the only potentially curative treatment for metastatic colorectal cancer. This retrospective review study was undertaken in an attempt to identify factors that influence patient survival following hepatic resection for metastatic colorectal cancer. From January 1978 to December 1993, a total of 301 patients underwent a total of 345 planned hepatic resections for metastatic colorectal cancer. Of those, 245 patients had one resection, 44 had two resections, and 12 had three resections. For all patients the overall median survival was 20.6 months, operative mortality was 1.1%, and overall morbidity was 17.2%. Average hospital stay was 9 days. Statistical analysis included univariate analysis using log rank comparisons, Kaplan-Meier survival curves, and multivariate analysis using Cox proportional hazards regression. The statistically significant factors that influenced survival were distribution of liver metastases, unilobar versus bilobar (p = 0.0001), resected versus nonresected (p < 0.0001), and tumor-free surgical margins versus positive margins (p = 0.001). Surprisingly, the disease-free interval and the original stage of the primary tumor did not predict survival (p = not significant). Other factors that had no influence on survival were type of resection, size and number of liver metastases, ABO blood group, and the number of perioperative blood transfusions. For those patients who underwent resection of unilobar metastases with tumor-free margins, the 5-year survival rate was 29% with a median survival of 35 months and eight survivors > 7 years. In addition, one patient with bilobar disease had survival > 7 years and five patients who had resection of hepatic metastases and extrahepatic cancer simultaneously had survival > 3 years. Our data support the concept that patients with unilobar metastatic disease who undergo surgical resection with tumor-free surgical margins can be afforded a significant opportunity at long-term survival with acceptable morbidity, mortality, and hospital stay. Also, certain patients with bilobar or extrahepatic disease (or both) who undergo complete resection can enjoy a long-term survival. In these subgroups of patients resection should be considered on an individual basis.     

Prognostic features of teratomas with malignant transformation: a clinicopathological study of 21 cases

PURPOSE: Teratomas with malignant transformation comprise up to 6% of metastatic teratomas. The prognosis of patients with these tumors can vary considerably. We delineate factors that may be related to prognosis in a cohort of men with teratoma with malignant transformation. MATERIALS AND METHODS: We analyzed pathological features, treatment, response, recurrence, time to recurrence, subsequent followup and survival for 21 patients (median age 28 years) diagnosed with teratoma with malignant transformation during a 7-year period at our institution. RESULTS: Malignant nongerm cell elements were present in the primary tumor in 11 cases (52%). Of 18 patients with testicular primaries 17 (94%) presented with metastatic disease. Despite aggressive treatment with surgery and chemotherapy 17 of 21 cases (81%) recurred (median time 6 months). Overall, 5 patients (24%) died of disease (median survival 23 months), 5 (24%) are alive with metastases (median followup 41 months) and 11 (52%) have no evidence of disease (median followup 50 months). Progression/recurrence was substantially greater for 2 of 2 cases with a mediastinal origin, 3 of 4 with rhabdomyosarcomatous differentiation and 5 of 6 with neural differentiation compared with the remainder of the cohort (p < 0.05). CONCLUSIONS: Teratomas with malignant transformation are usually metastatic at presentation, have a high recurrence rate and are more aggressive than teratomas without malignant transformation. Prognosis is especially poor for mediastinal teratomas with malignant transformation and for those with neural or rhabdomyosarcomatous differentiation. Complete surgical resection of residual or recurrent disease appears to offer the best chance for prolonged survival.     

Function-sparing surgery for desmoid tumors and other low-grade fibrosarcomas involving the brachial plexus

OBJECTIVE: Low-grade fibrosarcomas and desmoid tumors present a surgical challenge in that they have a strong tendency for local invasion, surgical margins are poorly delineated, and complete resections are difficult. Nowhere is this more evident than in those lesions involving the brachial plexus. We review our experience with these difficult lesions. METHODS: From a prospective database of 2900 patients admitted for treatment of sarcoma between 1982 and 1996, we identified 15 patients with involvement of the brachial plexus by a low-grade fibrosarcoma or desmoid tumor. All patients underwent resection, with 13 of 15 receiving adjuvant radiotherapy. The 15 patients had a mean age at initial operation of 47 years. The male-to-female ratio was 8:7. The mean follow-up period was 65 months (median, 53 mo). RESULTS: Gross total resection was achieved in 12 patients (80%), although 11 of these patients had positive surgical margins. Overall, 64% of the tumors have recurred locally. There were no distant metastases, and no patients died as a result of their disease. One patient died as a result of unrelated cancer. An assessment of the functional outcomes revealed seven patients with normal function or mild neurological deficits and eight who were suffering from significant weakness, debilitation, or chronic pain. One patient required forequarter amputation. CONCLUSION: Surgical resection plus postoperative radiotherapy is the treatment of choice for low-grade fibrosarcomas and desmoid tumors involving the brachial plexus. However, aggressive surgical management with the goal of achieving a gross total resection with negative histological margins can produce unnecessary morbidity. Preserving function should be a primary goal of the operations, although this will be associated with residual disease and will risk local recurrence but rarely death resulting from the disease.     

Radiation therapy in the management of desmoid tumors

PURPOSE: To evaluate the outcome of patients with extra-mesenteric desmoid tumors treated with radiation therapy, with or without surgery. METHODS AND MATERIALS: The outcome for 75 patients receiving radiation for desmoid tumor with or without complete gross resection between 1965 and 1994 was retrospectively reviewed utilizing univariate and multivariate statistical methods. RESULTS: With a median follow-up of 7.5 years, the overall freedom from relapse was 78% and 75% at 5 and 10 years, respectively. Of the total, 23 patients received radiation for gross disease because it was not resectable. Of these 23 patients, 7 sustained local recurrence, yielding a 31% actuarial relapse rate at 5 years. Radiation dose was the only significant determinant of disease control in this group. A dose of 50 Gy was associated with a 60% relapse rate, whereas higher doses yielded a 23% relapse rate (p < 0.05). The other 52 patients received radiation in conjunction with gross total resection of tumor. The 5- and 10-year relapse rates were 18% and 23%, respectively. No factor correlated significantly with disease outcome. There was no evidence that radiation doses exceeding 50 Gy improved outcome. Positive resection margins were not significantly deleterious in this group of irradiated patients. For all 75 patients, there was no evidence that radiation margins exceeding 5 cm beyond the tumor or surgical field improved local-regional control. Ultimately, 72 of the 75 patients were rendered disease-free, but 3 required extensive surgery (amputation, hemipelvectomy) to achieve this status. Significant radiation complications were seen in 13 patients. Radiation dose correlated with the incidence of complications. Doses of 56 Gy or less produced a 5% 15-year complication rate, compared to a 30% incidence with higher doses (p < 0.05). CONCLUSIONS: Radiation is an effective modality for desmoid tumors, either alone or as an adjuvant to resection. For patients with negative resection margins, postoperative radiation is not recommended. Patients with positive margins should almost always receive 50 Gy of postoperative radiation. Unresectable tumors should be irradiated to a dose of approximately 56 Gy, with a 75% expectation of local control.     

Prognostic factors affecting long term outcome after liver resection for hepatocellular carcinoma: results in a series of 100 Italian patients

BACKGROUND: Long term results after liver resection for hepatocellular carcinoma (HCC) are disappointing because the disease tends to recur. In this study, the authors assessed prognostic factors affecting long term outcome, in the hope that these factors might be used in selecting HCC patients for surgery. METHODS: During the period 1977-1995, 100 consecutive patients underwent curative liver resection; 78 of 100 had HCC arising on preexisting cirrhosis (53 Child's Class A and 25 Child's Class B). Thirty-five prognostic factors were evaluated for their association with overall survival (OS) and disease free survival (DFS) in univariate and multivariate analysis (Cox proportional hazards model). RESULTS: There were four postoperative deaths. Seven patients died in hospital of hepatorenal failure: six had Child's Class B cirrhosis and had undergone preoperative chemoembolization. Of the remaining 89 patients, 50 developed recurrence. All surviving Child's Class B patients had recurrence. Five-year OS, postoperative deaths included, was 38% (median, 36 months). Five-year DFS, postoperative deaths excluded, was 26% (median, 21 months). Independent prognostic factors for DFS were Child's class, glutamic-oxaloacetic transaminase, gamma-glutamyltransferase, alpha-fetoprotein, number of tumor nodules, width of resection margins, preoperative chemoembolization, and experience of the team that performed the surgery. Factors with an independent effect on OS were Child's class and width of resection margins. CONCLUSIONS: Liver resection can provide long term DFS in HCC patients with normal liver function. In patients with liver function impairment or an inadequate resection margin, recurrences are almost certain to occur. Preoperative chemoembolization significantly prolongs DFS but may increase the risk of postoperative liver failure in patients with liver function impairment.     

Repair of congenital tracheal stenosis with a free tracheal autograft

PURPOSE: This retrospective review was conducted to determine if delay in the start of radiotherapy after definitive breast surgery had any detrimental effect on local recurrence or disease-free survival in node-negative breast cancer patients. METHODS AND MATERIALS: A total of 568 patients with T1-T2, N0 breast cancer were treated with breast-conserving surgery and breast irradiation, without adjuvant systemic therapy between January 1, 1985 and December 31, 1992, at the London Regional Cancer Centre. Adjuvant breast irradiation consisted either of 50 Gy in 25 fractions or 40 Gy in 15 or 16 fractions, followed by a boost of 10 Gy or 12.5 Gy to the lumpectomy site. The time intervals from definitive breast surgery to breast irradiation used for analysis were 0-8 weeks (201 patients), > 8-12 weeks (235 patients), > 1216 weeks (91 patients), and > 16 weeks (41 patients). The time intervals of 0-12 weeks (436 patients) and > 12 weeks (132 patients) were also analyzed. Kaplan-Meier estimates of time to local recurrence and disease-free survival rates were calculated. The association between surgery-radiotherapy interval, age (< or = 40, > 40 years), tumor size (< or = 2, > 2cm), Scharf-Bloom-Richardson (SBR) grade, resection margins, lymphatic vessel invasion, extensive intraductal component, and local recurrence and disease-free survival were investigated using Cox regression techniques. RESULTS: Median follow-up was 63.5 months. Patients in all 4 time intervals were similar in terms of age and pathologic features. There was no statistically significant difference between the 4 groups in local recurrence or disease-free survival with surgery-radiotherapy interval (p = 0.189 and p = 0.413, respectively). The 5-year freedom from local relapse was 95.4%. The crude local recurrence rate was 6.9% (7.8% for 436 patients treated within 12 weeks (median follow-up 67 months) and 3.8% for 132 patients treated > 12 weeks from surgery (median follow-up 52 months). In a stepwise multivariable Cox regression model for disease-free survival, allowing for entry of known risk factors, tumour size (p < 0.001), grade (p < 0.001), and age (p = 0.048) entered the model, but the surgery-radiotherapy interval did not enter the model. CONCLUSION: This retrospective study suggests that delay in start of breast irradiation beyond 12 and up to 16 weeks does not increase the risk of recurrence in node-negative breast cancer patients. The certainty of these results are limited by the retrospective nature of this analysis and the lack of information concerning the late local failure rate.     

The importance of the lumpectomy surgical margin status in long-term results of breast conservation

BACKGROUND: The impact of the surgical margin status on long-term local control rates for breast cancer in women treated with lumpectomy and radiation therapy is unclear. METHODS: The records of 289 women with 303 invasive breast cancers who were treated with lumpectomy and radiation therapy from 1972 to 1992 were reviewed. The surgical margin was classified as positive (transecting the inked margin), close (less than or equal to 2 mm from the margin), negative, or indeterminate, based on the initial biopsy findings and reexcision specimens, as appropriate. Various clinical and pathologic factors were analyzed as potential prognostic factors for local recurrence in addition to the margin status, including T classification, N classification, age, histologic features, and use of adjuvant therapy. The mean follow-up was 6.25 years. RESULTS: The actuarial probability of freedom from local recurrence for the entire group of patients at 5 and 10 years was 94% and 87%, respectively. The actuarial probability of local control at 10 years was 98% for those patients with negative surgical margins versus 82% for all others (P = 0.007). The local control rate at 10 years was 97% for patients who underwent reexcision and 84% for those who did not. Reexcision appears to convey a local control benefit for those patients with close, indeterminate, or positive initial margins, when negative final margins are attained (P = 0.0001). Final margin status was the most significant determinant of local recurrence rates in univariate analysis. By multivariate analysis, the final margin status and use of adjuvant chemotherapy were significant prognostic factors. CONCLUSIONS: The attainment of negative surgical margins, initially or at the time of reexcision, is the most significant predictor of local control after breast-conserving treatment with lumpectomy and radiation therapy.     

Childhood soft tissue sarcoma: a 20-year experience

PURPOSE: To evaluate the disease-free and overall survival of pediatric patients with nonrhabdomyosarcoma soft-tissue sarcomas. METHODS: We retrospectively analyzed the records of 67 pediatric patients with a diagnosis of nonrhabdomyosarcoma soft tissue sarcoma treated with curative intent between 1970 and 1992. Median follow-up time for the 52 survivors was 120 months (range, 7 to 277 months). Fifty-nine patients received external beam radiotherapy, in a median dose of 5400 cGy (range, 1800 to 6660 cGy.) All patients underwent an initial surgical procedure. Eighteen patients had gross residual disease, and 15 had gross total excision with microscopic residual disease or positive margins. Adjuvant chemotherapy was administered to 44 patients (65%). RESULTS: The actuarial 10-year freedom from progression or recurrence and overall survival rates were 76% and 75%, and the 20-year rates were the same. Of 18 patients with gross residual disease, 9 (50%) had local progression and 6 died of local-only disease. By contrast, only one patient with microscopic residual disease who received postoperative radiotherapy had a local recurrence. The disease-free survival rate also correlated with histologic grade. CONCLUSIONS: As with adult soft tissue sarcomas, gross residual disease predicts local failure. Our results suggest that pediatric patients with soft tissue sarcomas treated with surgery and postoperative radiotherapy generally have a favorable overall survival rate.     

Detection and determination of theobromine and caffeine in urine after administration of chocolate-coated peanuts to horses

BACKGROUND AND OBJECTIVES: Most patients with colorectal liver metastases are not eligible for resection because they have multiple lesions or because of anatomical constraints. We report the use of cryotherapy to destroy residual metastases following liver resection in patients with disease too widespread for treatment by resection alone. METHODS: Twenty patients with bilobar disease confined to the liver (median 3; range 2-8 lesions) were treated in this way. Seventeen patients also received regional chemotherapy postoperatively. RESULTS: Morbidity was high, but there were no procedure-related deaths and only one patient's hospital stay exceeded 24 days. Significant destruction of tumor, as evidenced by a decline in CEA levels, occurred within 3 months of surgery in all patients (P < 0.001). Median duration of follow-up was 15 (6-53) months. Survival rates at 1 and 2 years were 88% and 60%, respectively, and median survival was 32 months. Seven patients remain well and seven are alive with recurrent liver and/or other metastases. CONCLUSIONS: Although this is not a control study, it would appear that some patients with irresectable liver metastases benefit from this multimodality approach.     

The human lysyl oxidase-related gene (LOXL2) maps between markers D8S280 and D8S278 on chromosome 8p21.2-p21.3

OBJECTIVE: bcl-2 is a protein which prohibits programmed cell death. The purpose of this study was to determine whether bcl-2 staining was related to traditional prognostic factors and/or recurrence in patients with endometrial carcinoma. METHODS: One hundred twenty consecutively surgically treated patients with endometrial carcinoma had their tumors studied immunohistochemically for bcl-2 staining. RESULTS: The mean follow-up of the patients was 53 months with a median of 56 months (range 30 to 68 months). bcl-2 staining was positive in 44.0% of patients with endometrioid carcinomas and in 23. 1% of patients with nonendometrioid carcinomas (P < 0.001). Increasing depth of invasion (P = 0.014), grade (P = 0.011), and FIGO stage (P = 0.018) were each correlated with decreasing bcl-2 staining. bcl-2 staining was positive in 44.1% of patients whose tumors showed no lymphovascular space invasion and in 11.1% of patients with lymphovascular space invasion (P < 0.001). Only 1 of 26 patients with recurrent disease had persistence of bcl-2 staining. Multivariate analysis revealed FIGO stage (P = 0.0051), histologic grade (P = 0.050), and lack of staining for bcl-2 (P = 0.012) to be independent predictors of recurrence. CONCLUSION: bcl-2 persistence is more common in endometrioid than in nonendometrioid adenocarcinomas of the endometrium. It appears to be inversely correlated with the universally recognized prognostic factors of depth of invasion, histologic grade, and FIGO stage. Lack of bcl-2 persistence was an independent predictor of recurrence of disease. This group of patients continues to be followed to determine the role of bcl-2 persistence or lack of persistence as a predictor of 5-year survival of patients with endometrial carcinoma.     

Does the placement of surgical clips within the excision cavity influence local control for patients treated with breast-conserving surgery and irradiation

PURPOSE: A number of authors have demonstrated the importance of using surgical clips to define the tumor bed in the treatment planning of early-stage breast cancer. The clips have been useful in delineating the borders of the tangential fields, especially for very medial and very lateral lesions as the boost volume. If surgical clips better define the tumor bed, then a reduction in true or marginal recurrences should be appreciated. We sought to compare the incidence of breast recurrence in women with and without surgical clips, controlling for other recognized prognostic factors. METHODS AND MATERIALS: Between 1980 and 1992, 1364 women with clinical Stage I or II invasive breast cancer underwent excisional biopsy, axillary dissection, and definitive irradiation. Median follow-up was 60 months. Median age was 55 years. Seventy-one percent of patients were path NO, 22% had one to three nodes, and 7% had > than four nodes. Sixty-one percent were ER positive and 44% PR positive. Margin status was negative in 62%, positive in 10%, close in 9%, and unknown in 19%. Fifty-seven percent of women underwent a reexcision. Adjuvant chemotherapy + tamoxifen was administered in 29%, and tamoxifen alone in 17%. Surgical clips were placed in the excision cavity in 556 patients, while the other 808 did not have clips placed. All patients had a boost of the tumor bed. Patients had their boost planned with CT scanning or stereo shift radiographs. No significant differences between the two groups were noted for median age, T stage, nodal status, race, ER/PR receptor status, region irradiated, or tumor location. Patients without clips had negative margins less often, a higher rate of unknown or positive margins and more often received no adjuvant therapy compared to patients with surgical clips. RESULTS: Twenty-five and 27 patients with and without surgical clips, respectively, developed a true or marginal recurrence in the treated breast. The actuarial probability of a breast recurrence was 2% at 5 years and 5% at 10 years for patients without clips compared to 5 and 11%, respectively, for patients with clips (p=0.01). Comparing the breast recurrence rates for patients with and without clips there was no significant difference for the following factors: chemotherapy, tamoxifen, negative, positive or close margins, reexcision, N1, and central or inner primary. Increased rates of breast recurrence were noted for patients with clips for the following variables: no adjuvant treatment (p < 0.001), unknown margins (p < 0.001), a single excision (p = 0.003), path NO (p = 0.001), and outer location (p= 0.02). A forward stepwise multivariate analysis for all 1364 patients was performed using the aforementioned variables as well as the presence or absence of surgical clips and the primary surgeon. The surgeon (p = 0.03) and no adjuvant treatment (p = 0.01) significantly influenced breast recurrence. For patients with surgical clips the 10 year isolated breast recurrence rate was 21% for a single surgeon vs. 6% in the remainder of the group (p = 0.01). For patients with clips, this surgeon had unknown margins in 48% of cases compared to 10% overall (p = 0.001). Excluding this surgeon from analysis the isolated breast recurrence for patients with clips was 6 vs. 5% for patients without clips (p = 0.18). CONCLUSIONS: Overall, there was a significant difference in the 10-year breast recurrence rate favoring women without clips despite more adverse prognostic factors. There was no difference in the breast recurrence rate for patients with or without surgical clips if careful attention to margin status was addressed. Failure to ink the surgical specimen resulting in unknown margins cannot be compensated for with the placement of .     

Trends in surgical management of astrocytomas and other brain gliomas

PURPOSE: Retrospective analysis of the influence of clinical and technical factors on local control and survival after radiosurgery for brain metastasis. PATIENTS AND METHODS: From January 1994 to December 1996, 42 patients presenting with 71 metastases underwent radiosurgery for brain metastasis. The median age was 56 years and the median Karnofsky index 80. Primary sites included: lung (20 patients), kidney (seven), breast (five), colon (two), melanoma (three), osteosarcoma (one) and it was unknown for three patients. Seventeen patients had extracranial metastasis. Twenty-four patients were treated at recurrence which occurred after whole brain irradiation (12 patients), surgical excision (four) or after both treatments (eight). Thirty-six sessions of radiosurgery have been realized for one metastasis and 13 for two, three or four lesions. The median metastasis diameter was 21 mm and the median volume 1.7 cm3. The median peripheral dose to the lesion was 14 Gy, and the median dose at the isocenter 20 Gy. RESULTS: Sixty-five metastases were evaluable for response analysis. The overall local control rate was 82% and the 1-year actuarial rate was 72%. In univariate analysis, theoretical radioresistance (P = 0.001), diameter less than 3 cm (P = 0.039) and initial treatment with radiosurgery (P = 0.041) were significantly associated with increased local control. Only the first two factors remained significant in multivariate analysis. No prognostic factor of overall survival was identified. The median survival was 12 months. Six patients had a symptomatic oedema (RTOG grade 2), only one of which requiring a surgical excision. CONCLUSION: In conclusion, 14 Gy delivered at the periphery of metastasis seems to be a sufficient dose to control most brain metastases, with a minimal toxicity. Better results were obtained for lesions initially treated with radiosurgery, theoretically radioresistant and with a diameter less than 3 cm.     

Outcome of large-bowel perforation in patients with colorectal cancer

PURPOSE: Perforation of the colon is seldom associated with malignant disease. Operative mortality varies widely in published studies and little is known about patterns of failure and long-term outcome. An observational study was undertaken to assess the outcome of colorectal cancer complicated by perforation. METHOD: We reviewed a series of 83 consecutive patients treated during a 14-year period at one institution. RESULTS: Fifty-four (65 percent) patients had perforation of the tumor itself, and 29 (35 percent) had diastatic perforation proximal to an obstructing tumor. Twenty-six (31.5 percent) patients had metastatic disease at laparotomy. Primary resection of the diseased segment was performed in 47 (87 percent) patients with perforation of the tumor itself and in 21 (72.4 percent) patients with diastatic perforation proximal to an obstructing tumor. However, only 57 patients (39 (72.2 percent) with perforation of the tumor itself; 18 (62 percent) with diastatic perforation proximal to an obstructing tumor; P = not significant) were potentially cured. Operative mortality was 16.7 and 48.3 percent, respectively (P < 0.01) and correlated significantly with Hinchey's stage (P < 0.001) and advanced disease (P = 0.023). At a mean follow-up of 43 (median 31) months, 21 (46 percent) of the 46 potentially cured survivors were alive. The local recurrence rate was 22.9 percent in patients with perforation of the tumor itself and 18.2 percent in patients with diastatic perforation proximal to an obstructing tumor (P = not significant). Peritoneal seeding occurred in 17 and 0 percent (P = not significant); the mean disease-free interval was 33.9 and 49.9 months (P = not significant); and five-year cumulative disease-related survival probability was 0.51 and 0.90 (P = 0.049), respectively. CONCLUSIONS: Diastatic perforation proximal to an obstructing tumor is associated with higher operative mortality and better cancer-related survival than a tumor perforating through the bowel wall. Early diagnosis in diastatic perforation and aggressive management of sepsis associated with radical surgical resection is recommended.     

The role of neoadjuvant therapy in surgically resectable esophageal cancer

OBJECTIVE: To determine the effect of neoadjuvant therapy (NT) (preoperative chemotherapy, radiation therapy, or both) in surgically resectable esophageal cancer. DESIGN: A retrospective review over a 20-year period. SETTING: A tertiary academic medical center. PARTICIPANTS: All patients undergoing surgical resection for esophageal cancer (N = 316) over this time period. MAIN OUTCOME MEASURES: Perioperative morbidity and mortality, local and distant recurrences, and overall survival. RESULTS: Patients undergoing NT (n = 106) had prognostic factors similar to those treated with surgery alone (n = 210). No increase was noted in surgical morbidity with NT (anastomotic leaks, reoperation rates, complications, or extended hospital stays). Overall survival was not improved by NT (median survival, 14 months) except in the subset of patients (11/83) who responded completely (100% histological necrosis) to preoperative chemotherapy (median survival, 79.2 months; P < .02). Complete response to radiation therapy alone was not associated with improved survival. Partial necrosis of the primary tumor was seen in 13 (15%) of 83 patients but conferred no survival advantage. Complete response to preoperative chemotherapy was associated with squamous cell pathological features and excellent performance status as measured by preanesthesia evaluation. CONCLUSIONS: The addition of NT did not increase perioperative morbidity or mortality. Only the subset of patients who had a complete response to preoperative chemotherapy showed a survival advantage. Excellent performance status and squamous cell pathological features were associated with an increased chance of complete pathological response following preoperative chemotherapy.     

Humor in the helping relationship

BACKGROUND: Our aim was to determine the frequency, survival and symptomatic local recurrence rate of patients with a positive proximal resection margin in a series of patients having a resection for carcinoma of the oesophagus or stomach. METHODS: A retrospective study of pathology reports and case notes. Survival and data on local recurrence were obtained from the patient or general practitioner. RESULTS: Ten (11.5%) of 87 patients having a gastric or oesophageal resection for carcinoma had a positive proximal resection margin. All 10 patients underwent a palliative resection for late-stage disease. Nine were dead at an average 8.3 months (range 2-20 months) post-resection and one patient remains alive at 9 months. Only one of these 10 patients had evidence of a local recurrence with recurrent dysphagia prior to death at 11 months. CONCLUSION: A high incidence of a positive proximal resection margin was found. This occurred in patients who underwent a palliative resection for late-stage disease, most of whom died before local recurrence became a problem. For patients recognized as having late-stage disease, surgery for symptom palliation need not be aggressive (such as to include a thoracotomy) because achieving microscopic clearance is unlikely to affect the long-term outcome.     

Postoperative radiation for cervical cancer with pathologic risk factors

PURPOSE: To examine the efficacy of postoperative radiation therapy for early-stage cervical cancer with pathologic risk factors. METHODS AND MATERIALS: We reviewed the charts of 83 patients who received postoperative radiation therapy at our facility from March 1980 to November 1993 for early stage cervix cancer with positive surgical margins, positive pelvic or periaortic lymph nodes, lymphovascular space invasion, deep invasion, or for disease discovered incidently at simple hysterectomy. Twenty-eight patients received low dose rate (LDR) intracavitary radiation with or without external beam pelvic irradiation and 55 patients received external beam pelvic irradiation with high dose rate (HDR) intracavitary implants. Of these 83 patients, 66 were evaluable--20 LDR and 46 HDR patients. All patients received 45-50 Gy external beam irradiation and 20 Gy LDR equivalent intracavitary irradiation prescribed to 0.5 cm below the mucosa. Ninety percent of the LDR group and 92% of the HDR group completed treatment within < 56 days. Treatment-related toxicities were scored according to the GOG toxicity scale. Mean and median follow-up times were 101 months and 111 months (3-172 months) for the LDR group and 42 and 40 months (3-98 months) for the HDR group. RESULTS: The 5-year disease-free survival was 89% for the LDR group and 72% for the HDR group. Local control was observed in 90% (18 out of 20) of the LDR patients and 89% (41 out of 46) of the HDR patients for an overall local control rate of 89.5%. Two of 20 LDR patients (10%) experienced recurrence (two pelvic with distant metastasis). Nine of 46 HDR patients (22%) had recurrence of disease (three pelvic, four distant metastasis, and two pelvic with distant metastasis). In the HDR group, 6 out of 16 (38%) with positive lymph nodes died of disease whereas, 27 out of 30 (90%) of the patients with negative lymph nodes remain free of disease. Three of 20 (15%) LDR patients and 4 out of 46 (9%) HDR patients experienced Grade 2 or 3 late treatment- related complications. No patient in either group had Grade 4 or 5 complications. Pathologic risk factors were analyzed. Lymph node positivity and lymphovascular space invasion were found to be significant (p = 0.01 and p = 0.02). Positive margins, deep invasion, and age were not significant. CONCLUSION: Our results demonstrate the efficacy of postoperative irradiation for cervical cancer with pathologic risk factors. Overall, the local control rate was 89.5% The HDR results demonstrate that this method can be delivered safely and effectively.