Pulmonary resection in metastatic uterine and cervical malignancies.

OBJECTIVE: Although thoracotomy for removal of pulmonary metastasis is well documented in a wide variety of solid tumors, data are sparse regarding management of patients with gynecologic malignancies metastatic to the lung. METHODS: We retrospectively reviewed the Roswell Park Cancer Institute experience between 1982 and 1999. Of 82 eligible patients with gynecologic tumors metastatic and confined to the lung, 25 underwent pulmonary resection. RESULTS: There were 60 uterine and 22 cervix cancer patients with pulmonary metastases. Among patients with uterine cancer primaries undergoing pulmonary resection (n = 19) median survival was 26 months. Uterine cancer patients who underwent surgical resection for leiomyosarcomas (n = 11) had a median survival of 25 months compared to 46 months in patients with adenocarcinoma (n = 6, P = 0.02). Median survival in cervix cancer patients undergoing resection for pulmonary metastases (n = 6) was 36 months. CONCLUSIONS: Pulmonary resection may provide a survival advantage for selected patients with uterine and cervical malignancies with metastases isolated to the lung.

Soluble 2-substituted aminopyrido[2,3-d]pyrimidin-7-yl ureas. Structure-activity relationships against selected tyrosine kinases and exploration of in vitro and in vivo anticancer activity.

In continuing our search for medicinal agents to treat proliferative diseases, we have discovered 2-substituted aminopyrido[2,3-d]pyrimidin-7-yl ureas as a novel class of soluble, potent, broadly active tyrosine kinase (TK) inhibitors. An efficient route was developed that enabled the synthesis of a wide variety of analogues with substitution on several positions of the template. From the lead structure 1, several series of analogues were made that examined the C-6 aryl substituent, a variety of water solublizing substitutents at the C-2 position, and urea or other acyl functionality at the N-7 position. Compounds of this series were competitive with ATP and displayed submicromolar to low nanomolar potency against a panel of TKs, including receptor (platelet-derived growth factor, PDGFr; fibroblast growth factor, FGFr;) and nonreceptor (c-Src) classes. Several of the most potent compounds displayed submicromolar inhibition of PDGF-mediated receptor autophosphorylation in rat aortic vascular smooth muscle cells and low micromolar inhibition of cellular growth in five human tumor cell lines. One of the more thoroughly evaluated members, 32, with IC50 values of 0.21 microM (PDGFr), 0.049 microM (bFGFr), and 0.018 microM (c-Src), was evaluated in in vivo studies against a panel of five human tumor xenografts, with known and/or inferred dependence on the EGFr, PDGFr, and c-Src TKs. Compound 32 produced a tumor growth delay of 14 days against the Colo-205 colon xenograft model.

Pericardial catheter sclerosis versus surgical procedures for pericardial effusions in cancer patients.

BACKGROUND: Approximately 21% of patients with advanced malignancies have cardiac or pericardial involvement with tumor. Controversy exists regarding the optimal approach to the pericardial space when hemodynamic compromise due to effusions occurs. METHODS: A six-year retrospective review of 59 cancer patients with pericardial effusions. RESULTS: Thirty-six patients had subxiphoid pericardial window (SXPW) alone (Group A), 5 had pericardial catheter drainage (PCD) followed by a SXPW (Group B), 10 had PCD with sclerosis (Group C), 5 had PCD alone (Group D), 2 had PCD with pericardial-pleural window (Group E), and one had pericardial-peritoneal window (Group F). The method of procedure, complications, number of hospital and ICU days, cytological or pathologic evidence of malignancy, solid versus hematological tumors, and survival were analyzed. The median survival for those patients in group C was one month compared to 4 months for Group A and 6 months for Group B. Essentially, results were similar regardless of method performed with the exception that professional and hospital charges averaged $4830 for SXPW compared to $1625 for PCD. CONCLUSIONS: Pericardial catheter drainage and sclerosis provides a viable option for the treatment of pericardial effusions in selected cancer patients at markedly reduced cost and patient discomfort.

Risk factors for nodal recurrence after lymphadenectomy for melanoma.

BACKGROUND: The risk and outcome of regional failure after elective and therapeutic lymph node dissection (ELND/TLND) for microscopically and macroscopically involved lymph nodes without adjuvant radiotherapy were evaluated. METHODS: Retrospective melanoma database review of 338 patients (ELND 85, TLND 253) from 1970 to 1996 with pathologically involved lymph nodes. RESULTS: Regional recurrence occurred in 14% of patients treated with ELND (n = 12) and 28% of patients treated with TLND (n = 72; P = .009). Risk factors associated with nodal recurrence were advanced age, primary lesion in the head and neck region, depth of the primary lesion, number of involved lymph nodes, and extracapsular extension (ECE). For each nodal basin, the ELND group had a lower incidence of recurrence than the TLND group. The TLND group had larger lymph nodes, greater number of involved lymph nodes, and a higher incidence of ECE. The 10-year disease-specific survival was 51% vs. 30% for ELND and TLND, respectively (P = .0005). Nodal basin failure was predictive of distant metastasis, with 87% developing distant disease compared with 54% of patients without nodal recurrence (P < .0001). Of six patients who underwent a second dissection after isolated nodal recurrence, five patients have had a median disease-free interval of 79 months. CONCLUSIONS: After ELND or TLND, patients who have a large tumor burden (thick primary melanoma, multiply involved lymph nodes, ECE), advanced age, and a primary lesion located in the head and neck have a significantly increased likelihood of relapse and a decreased survival. Few patients present with an isolated nodal recurrence, but the majority can be salvaged by a second dissection.

The impact of pre-therapy extraperitoneal surgical staging on the evaluation and treatment of patients with locally advanced cervical cancer.

OBJECTIVE: The use of extraperitoneal surgical staging prior to treatment in patients with bulky or locally advanced cervical cancer allows the detection and treatment of disease beyond the standard pelvic radiation fields. This study was conducted to evaluate the impact of extraperitoneal surgical staging in the treatment and outcome of patients with locally advanced cervical cancer. METHODS: 51 patients with locally advanced cervical cancer treated between 1985 and 1998 were retrospectively reviewed. Information on morbidity, usefulness, and results of surgery and patterns of disease recurrence were obtained. Survival distributions were calculated by the Kaplan-Meier product limit method and compared with the log-rank test. RESULTS: All 51 women were surgically staged by an extra-peritoneal approach. Preoperative CT scans (n=27) when compared with surgical findings showed sensitivity for pelvic and para-aortic lymph node metastasis of 39%, specificity of 88%, positive predictive value of 39% and negative predictive value of 88%. Lymph node metastases were found in 30/51 patients (59%). There were no significant treatment delays or surgical morbidity as a result of extra-peritoneal surgical staging. In 21 patients (41%), the highest level of involved nodes was in the pelvis and they were treated with pelvic radiation. The para-aortic nodes were involved in nine patients (18%) and were treated with extended field radiation. All patients also received concurrent radiosensitization with chemotherapy. The estimated survival for the entire group was 60% at 5 years. For node negative patients, estimated 5-year survival was 67% while it was 54% for all node positive patients (p=0.17). Analysis according to anatomic site of involved nodes showed that the estimated 2-year and 5-year survival for those with pelvic nodal involvement was 81% and 64%, respectively. However, in the group of nine patients with para-aortic nodal disease, the estimated 2-year survival was 44%. Five (56%) were dead of disease with a median time to death of 16.0 months and four patients (44%) were alive with a median duration of follow up of 16.1 months. There was a statistically significant difference in survival for the group of patients with positive pelvic nodes only compared to the group with positive para-aortic nodes (p=0.03). The estimated 5-year survival by FIGO stage was 80%, 70% and 51% for stages Ib, II, III, disease, respectively. Factors that did not significantly affect survival included age, histology and type of chemotherapy. CONCLUSIONS: Pre-therapy extra-peritoneal surgical staging resulted in treatment modification in 18% of patients with locally advanced cervical cancer. The morbidity from surgery and subsequent radiation therapy was acceptable. The procedure is recommended to allow for individualization of treatment in patients with local-regional cervical cancer.

3-(3,5-Dimethoxyphenyl)-1,6-naphthyridine-2,7-diamines and related 2-urea derivatives are potent and selective inhibitors of the FGF receptor-1 tyrosine kinase.

A series of 3-aryl-1,6-naphthyridine-2,7-diamines and related 2-ureas were prepared and evaluated as inhibitors of the FGF receptor-1 tyrosine kinase. Condensation of 4,6-diaminonicotinaldehyde and substituted phenylacetonitriles gave intermediate naphthyridine-2,7-diamines, and direct reaction of the monoanion of these (NaH/DMF) with alkyl or aryl isocyanates selectively gave the 2-ureas in varying yields (23-93%). For the preparation of more soluble 7-alkylamino-2-ureas, a number of protecting groups for the 2-amine were evaluated (phthaloyl, 4-methoxybenzyl) following selective blocking of the 7-amine (trityl), but these were not superior to the (required) 2-tert-Bu-urea group itself. Direct alkylation of the anion of the (unprotected) 7-amino group with excess 4-(3-chloropropyl)morpholine in DMF gave low (10%) yields of the desired product, but alkylation of the 7-acetamido anion, followed by mild alkaline hydrolysis, raised this to 64%. 3-Phenyl analogues were nonspecific inhibitors of isolated c-Src, FGFR, and PDGFR tyrosine kinases, whereas 3-(2,6-dichlorophenyl) analogues were most effective against c-Src and FGFR, and 3-(3,5-dimethoxyphenyl) derivatives showed high selectivity for FGFR alone. A water-soluble (7-morpholinylpropylamino) analogue retained high FGFR potency (IC(50) 31 nM) and selectivity. Pairwise comparison of the 1, 6-naphthyridines and the corresponding known pyrido[2,3-d]pyrimidine analogues showed little differences in potency or patterns of selectivity, suggesting that the 1-aza atom of the latter is not important for activity. A 7-acetamide derivative inhibited the growth of FGFR-expressing tumor cell lines and was particularly potent against HUVECs (IC(50) 4 nM). This compound was also a very potent inhibitor of HUVEC microcapillary formation (IC(50) 0.01 nM) and Matrigel invasion (IC(50) 7 nM) and showed significant in vivo antitumor effects in a highly vascularized mammary adenocarcinoma 16/c model at nontoxic doses. The compounds are worthy of further evaluation as antiangiogenesis agents.

p53 tumor suppressor gene mutations predict decreased survival of patients with sporadic colorectal carcinoma.

BACKGROUND: Mutations of the p53 tumor suppressor gene play an integral role in sporadic colorectal carcinogenesis but prior studies have failed to show their prognostic significance consistently. METHODS: Fifty-six consecutive sporadic colorectal tumors were analyzed for their p53 status. Polymerase chain reaction amplification with primers for exons 5-9 was conducted and these products were subjected to single strand conformation polymorphism analysis. Suspected mutations were confirmed with DNA sequencing. p53 status was entered into a colorectal clinical database and these patients then were followed prospectively. Patient status with regard to disease recurrence and survival was updated every 6 months. Survival and disease free survival were calculated according to the method of Kaplan and Meier. The association between p53 status and clinical and pathologic factors with survival and recurrence was statistically determined using univariate analysis and the Cox proportional hazards model for multivariate analysis. RESULTS: p53 mutations were detected in 28 of 56 patients (50%). The median follow-up time was 45 months (range, 3-72 months). There were 33 patients (59%) who were alive at last follow-up. Fifteen of the 23 patients who died (65%) had p53 mutations and 8 (35%) had wild-type p53. Thirteen patients developed a disease recurrence, 9 of whom (69%) had tumors with p53 mutations. Overall 4-year survival rates for patients with wild-type p53 and mutant p53 were 71% and 54%, respectively (P = 0.05). The 4-year disease free survival rates for patients with wild-type p53 and mutant p53 were 83% and 62%, respectively (P = 0.09). p53 status and stage were found to be independent significant predictors for survival (p53 negative: P = 0. 02; stage: P = 0.0002.) Stage was found to be the sole significant predictor for disease free survival (P = 0.006). CONCLUSIONS: In this group of colorectal carcinoma patients, p53 mutations were a significant negative prognostic indicator for overall survival. This finding holds prognostic and therapeutic implications for the management of colorectal carcinoma patients.

Outcome of patients with proximal gastric cancer depends on extent of resection and number of resected lymph nodes.

BACKGROUND: Studies have shown that the survival of patients with gastric adenocarcinoma is related to the number of regional lymph nodes with metastases. The probability of identifying node-positive cancers increases with the number of lymph nodes resected and examined. It has been recommended that at least 15 lymph nodes be removed and examined for adequate staging. Prospective randomized studies have shown the lymph node yield is much greater with the D2 resection than the D1. This study evaluated the relative contribution of both the number of resected lymph nodes and the extent of gastric resection (D1/D2) on the outcome of patients with proximal gastric cancer. METHODS: The medical records of 114 patients with adenocarcinoma of the proximal stomach, who underwent a curative gastric resection, were reviewed. Patients were stratified into four groups, i.e., two groups, D1/D1.5 and D2/D2.5, based on the extent of resection, and two groups based on the number of lymph nodes removed, fewer than 15 lymph nodes and 15 or more lymph nodes. Survival was determined by the method of Kaplan-Meier and differences compared by the log-rank test. Multivariate analysis was performed by using the Cox model. RESULTS: The number of resected lymph nodes had no effect on the survival of the group as a whole. A significant improvement in survival was noted for patients with a D2 or greater resection. The median survival of patients with 15 or more lymph nodes resected improved from 25 months to 42 months when treated with an extended resection, (D2 or D2.5). Resection of 15 or more lymph nodes alone, or combined with an extended resection, resulted in a statistically significant improvement in survival for patients in American Joint Committee on Cancer Staging (AJCC) stage II. CONCLUSIONS: Both resection of 15 or more lymph nodes and extended lymphadenectomy contributed to the survival advantage observed in patients with AJCC stage II gastric cancer. The D2 gastric resection prolonged the median survival time and improved the 5-year survival rate for patients with 15 or more resected lymph nodes.

Clinical importance of late recurrence in soft-tissue sarcomas.

BACKGROUND AND OBJECTIVES: Soft-tissue sarcomas (STS) represent a diverse histologic group of malignancies at risk for local and distant failure. We studied the impact of late (5 or more years) vs. early recurrence (less than 5 years) on subsequent outcome. METHODS: Four hundred sixty-eight patients with STS treated between 1962 and 1992 were evaluated for late (n = 39; 8%) or early (n = 253; 54%) recurrence. Clinical and pathologic factors were reviewed. Survival data were analyzed by the Kaplan-Meier method and the log-rank test. RESULTS: Of the 39 patients with a late recurrence (median follow-up 156 months), 18 patients had local recurrence, 7 patients developed distant recurrence, and 14 patients had local and distant recurrence. Thirty patients with late local and/or distant recurrence underwent complete or wide excision (n = 16), amputation (n = 4), or local resection (n = 10). The overall 5-year survival rate following late recurrence was 61%. The 5-year overall survival rate was statistically better for patients with a late local recurrence alone than for patients with distant failure, 94% vs. 36%, respectively (P = 0.003). Neither the site of the primary STS, age, primary margin status, nor histology had any effect on subsequent local or distant failure and subsequent survival. CONCLUSIONS: These data suggest that an aggressive approach is appropriate in patients who present with late recurrence (more than 5 years) following treatment of the primary STS. Impressive survival rates can be achieved in the treatment of local recurrences.

Treatment and local control of primary extremity soft tissue sarcomas.

BACKGROUND AND OBJECTIVES: Modern series of adult extremity soft tissue sarcomas utilize combinations of modalities in all patients. Remaining questions: 1) is it necessary to strive for wide margins in the multimodality era; 2) to use adjuvant therapy in every high-grade sarcoma? 3) Does previous partial or marginal resection seriously interfere with the definitive resection? METHODS: In a retrospective review of 194 extremity soft tissue sarcomas (1977-1994), limb preservation was possible in 181/194 (93%) of cases. Patients with narrow margins received adjuvant radiation. Some patients were referred after partial (n = 39) or "complete" (n = 63) excision. RESULTS: Local recurrence was observed in 181/141 (13%) of patients treated with wide or compartmental resection, and in 10 of 42 (24%) of those treated with conservative resection plus radiation (P = 0.14). The 5-year survival rate for grade III, >/=5-cm sarcomas was not significantly different (P = 0.82) with adjuvant (46%) or without (48%) adjuvant systemic chemotherapy. Five-year survival varied (P = 0.0001) according to grade. Patients referred with partial, or "complete" (63%, 38/63, had residual tumor at reoperation) excision had a local recurrence rate of 8% and 6%, and 5-year survival rates of 75% and 84%, respectively. CONCLUSIONS: 1) It is important to strive for wide margins even when adjuvant radiation is intended. 2) When a wide margin is possible, adjuvant radiation may not be necessary. 3) Adjuvant systemic chemotherapy may be considered for high-grade tumors, preferably within a prospective protocol. 4) A partial or "complete" excision of the tumor before referral to a tertiary center does not appear to compromise the limb preservation, local control, or survival rates of these patients.

Decreased immunoexpression of prostate inhibin peptide in prostatic carcinoma: a study with monoclonal antibody.

Prostate inhibin peptide (PIP) is a follicle-stimulating hormone (FSH) regulating peptide produced by the prostate. The mechanism of its endocrine role in regulating prostate growth is believed to be androgen-independent but FSH-dependent. Previous studies using polyclonal antibody proposed PIP as a prostatic-specific marker in cancer diagnosis. However, the recently available monoclonal antibody has not yet been evaluated. Paraffin sections of 72 prostatectomy specimens for prostate cancer with or without hormonal blockage therapy and 10 nonneoplastic prostate tissues from autopsy were stained by using PIP monoclonal antibody (clone: 4A6A6) with the avidin-biotin complex method. PIP reactivity was semiquantitatively estimated in prostatic carcinoma (PCA), prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH) and normal tissue in each case when ever present. Statistical analyses were performed accordingly. PIP expression is predominantly cytoplasmic. Urothelium, seminal vesicles, inflamed prostatic glands, basal cells, and squamous metaplasia were negative for PIP. Average percentage of cells expressing PIP was significantly decreased in PIN (40%) and PCA (14%) when compared with BPH (81%) and normal tissue (68%). There was no correlation of tumor PIP level with patient's age, tumor size, Gleason score, tumor stage, or the usage of preoperative hormonal blockage therapy. PIP monoclonal antibody should be used with caution as a prostate-specific marker in surgical pathology. The mechanism for this alteration and the effect of PIP on prostatic tumor growth, particularly in patients under a variety of hormonal therapies, needs further study.

Is the capacity for lymph node-mediated distant dissemination the same for all nodal groups in malignant melanoma?

This study addresses two hypotheses: (1) that the inherent potential of melanoma metastatic to regional nodal groups for lymph-mediated distant dissemination may not be the same for all nodal groups; and (2) that the risk of distant metastases in patients with clinically involved nodal metastases is higher than in patients with clinically occult nodal metastases. It involved a retrospective chart review of patients with histologically involved axillary or inguinal nodes treated at Roswell Park Cancer Institute (RPCI) (244 patients) or at the participating institutes from the Intergroup Surgical Trial (IST) (108 patients). The distant recurrence rates of 623 melanomas with axillary or inguinal drainage from the IST data were also reviewed. In the RPCI data there was a significant difference in the overall and disease-free survival (P=0.0001) between patients with microscopic versus palpable involvement of the regional nodes in the axilla, while no such difference was observed for patients with groin metastases (P=0.30 and 0.36, respectively). The same trend was noted in the IST data. In the latter data the distant recurrence rate for melanomas drained via the axilla was significantly higher (P=0.026) than for those drained by the groin. In conclusion, lymph-mediated distant dissemination may be more aggressive from the axilla than from the groin in melanoma.

Operation and photodynamic therapy for pleural mesothelioma: 6-year follow-up.

BACKGROUND: Conventional therapy for pleural mesothelioma has met with disappointing results. METHODS: From 1991 to 1996, 40 patients with malignant pleural mesothelioma were treated with surgical resection followed by immediate intracavitary photodynamic therapy. RESULTS: The series included 9 women and 31 men with a mean age of 60 years. Morbidity and treatment-related mortality rates for the entire series, pleurectomy, and extrapleural pneumonectomy were 45% and 7.5%, 39% and 3.6%, and 71% and 28.6%, respectively. Median survival and the estimated 2-year survival rate for the entire series, stages I and II patients (n = 13), and stages III and IV patients (n = 24) were 15 months and 23%, 36 months and 61%, and 10 months and 0%, respectively. Multivariate analysis identified stage, length of hospital stay, photodynamic therapy dose, and nodal status as independent prognostic indicators for survival. CONCLUSIONS: Surgical intervention and photodynamic therapy offer good survival results in patients with stage I or II pleural mesothelioma. For patients in stage III or IV, better treatment modalities need to be developed. Improvements in early detection and preoperative staging are necessary for proper patient selection for treatment.

Anterior compartment resection of the thigh in soft-tissue sarcomas.

AIMS: Soft-tissue sarcomas of the anterior thigh present technical problems due to the proximity of the femoral vessels, and the disability caused by a standard anterior compartment resection. METHODS: We treated 44 consecutive patients with primary sarcomas in the anterior thigh with wide resection (n = 15), and modified (n = 26) or standard (n = 3) compartment resection. No patient had amputation as primary treatment. RESULTS: The overall rate of local recurrence was 6/44 (14%). Local recurrence was observed in 1/3 patients with standard anterior compartment resection and 5/41 (12%) of those with wide excision or modified compartment resection. It was noted in 1/6 (17%) patients with adjuvant radiation and 5/38 (13%) of those treated with surgery alone. One of six patients with local recurrence required amputation. The 5-year survival rate was 66% varying significantly according to grade. CONCLUSIONS: Limb preservation was possible in 98% of patients. Wide resection or modified compartment resection was feasible in the majority (93%) of patients resulting in improved function.

2-Substituted aminopyrido[2,3-d]pyrimidin-7(8H)-ones. structure-activity relationships against selected tyrosine kinases and in vitro and in vivo anticancer activity.

While engaged in therapeutic intervention against a number of proliferative diseases, we have discovered the 2-aminopyrido[2, 3-d]pyrimidin-7(8H)-ones as a novel class of potent, broadly active tyrosine kinase (TK) inhibitors. An efficient route was developed that enabled the synthesis of a wide variety of analogues with substitution on several positions of the template. From the lead structure 2, a series of analogues bearing variable substituents at the C-2 position and methyl or ethyl at N-8 was made. Compounds of this series were competitive with ATP and displayed submicromolar to low nanomolar potency against a panel of TKs, including receptor (platelet-derived growth factor, PDGFr; fibroblast growth factor, FGFr; epidermal growth factor, EGFr) and nonreceptor (c-Src) classes. One of the more thoroughly evaluated members was 63 with IC50 values of 0.079 microM (PDGFr), 0.043 microM (bFGFr), 0.044 microM (EGFr), and 0.009 microM (c-Src). In cellular studies, 63 inhibited PDGF-mediated receptor autophosphorylation in a number of cell lines at IC50 values of 0.026-0.002 microM and proliferation of two PDGF-dependent lines at 0.3 microM. It also caused inhibition of soft agar colony formation in three cell lines that overexpress the c-Src TK, with IC50 values of 0.33-1.8 microM. In in vivo studies against a panel of seven xenograft tumor models with known and/or inferred dependence on the EGFr, PDGFr, and c-Src TKs, compound 63 produced a tumor growth delay of 10.6 days against the relatively refractory SK-OV-3 ovarian xenograft and also displayed activity against the HT-29 tumor. In rat oral bioavailability studies, compound 63 plasma concentrations declined in a biexponential manner, and systemic plasma clearance was high relative to liver blood flow. Finally, in rat metabolism studies, HPLC chromatography identified two metabolites of 63, which were proved by mass spectrometry and synthesis to be the primary amine (58) and N-oxide (66). Because of the excellent potency of 63 against selected TKs, in vitro and in vivo studies are underway for this compound in additional tumor models dependent upon PDGFr, FGFr, and c-Src to assess its potential for advancement to clinical trials.

Soft tissue sarcomas of the hand and foot: management and survival.

BACKGROUND: Soft tissue sarcomas of the hands and feet present a challenge for limb-preserving resections. METHODS: A retrospective review of 19 patients with sarcomas of the hand or foot was done. Wide or local excision was performed in 14 patients (74%), and amputation in 5 patients (26%). Of the latter group, three amputations involved a digit or toe, and two (10%) were major amputations (one Syme amputation and one below-knee amputation). When the minimum surgical margin was narrow (1 to 2 mm), adjuvant radiation was given postoperatively (n = 4). RESULTS: Local recurrence was observed in four patients (21%). Two of these required an amputation for local control. Local recurrence was observed in one of four patients (25%) treated with marginal resection and radiation and three of 15 (20%) of those with resection alone. CONCLUSIONS: A sizable percentage (37%) of patients with soft tissue sarcomas of the hand and foot ultimately required an amputation, although often the amputation was a minor one involving only a toe or a digit. Limb preservation was successful in the majority of patients (63%). The local recurrence rate was 21%, which may be improved with more frequent use of adjuvant therapy. The 5-year survival rate was 82%, which is better than that usually quoted for overall extremity soft tissue sarcomas.

Five-year survival after second-line cisplatin-based intraperitoneal chemotherapy for advanced ovarian cancer.

BACKGROUND: To evaluate the 5-year survival rates of second-line intraperitoneal chemotherapy in advanced-staged ovarian cancer. MATERIALS AND METHODS: Between August 1985 and September 1991, 63 patients with advanced epithelial ovarian cancer received intraperitoneal cisplatin and cytarabine chemotherapy as second-line treatment. RESULTS: The median survival from the time of initiation of intraperitoneal chemotherapy (IPC) was 29.1 months. A significant advantage in 5-year survival (40%) and 5-year progression-free survival (37%) was observed among 21 patients who demonstrated a response to first-line and second-line treatment compared to those who demonstrated a response to first-line treatment only (6 and 0%, respectively) (P < 0.0001). No patient (n = 13) who failed to respond to either first-line or second-line treatment survived for 5 years. Among 42 patients with < or = 5 mm residual disease at the time of initiation of IPC, 5-year survival was 36% and 5-year progression-free survival was 31%, while no patient (n = 21) with residual disease measuring > 5 mm at the initiation of IPC survived 5 years (P < 0.0001). CONCLUSION: Given the limitation that this is not a randomized trial, the data appear to indicate that salvage platinum-based intraperitoneal chemotherapy results in significant 5-year survival and progression-free survival in selected patients who initiated therapy with small (< or = 5 mm) tumor burden. These survival rates as second-line therapy approach those achieved by first-line platinum-based intravenous chemotherapy in patients with advanced-stage ovarian cancer with similar small residual disease at the initiation of therapy.

Intraoperative determinants of unresectability for patients with colorectal hepatic metastases.

BACKGROUND: Intrahepatic and extrahepatic factors are utilized by the surgeon in the decision-making process for the performance of hepatic resection for patients with colorectal metastases. Accurate preoperative and intraoperative staging are mandatory to avoid unnecessary surgery. In this report the intraoperative determinants of hepatic unresectability were evaluated. METHODS: This was a retrospective review of medical records from January 1985 to March 1996 of 62 patients with colorectal hepatic metastases who at the time of exploratory laparotomy were deemed to have unresectable disease based on intrahepatic or extrahepatic factors. The stage of the primary tumor, disease free interval, preoperative carcinoembryonic antigen, computed tomography portography, intraoperative ultrasound, and assessment of intrahepatic and extrahepatic tumor extension were evaluated. RESULTS: Intraoperative determination of the extent of required hepatic resection, including trisegmentectomy (9 patients; 15%) and total hepatectomy (10 patients; 16%), accounted for the majority of unresectable patients. Patients with > 4 metastases (8 patients; 13%) and satellitosis (6 patients; 10%) accounted for 23% of unresectable patients. Four patients had extensive nonmalignant hepatic parenchymal disease precluding resection. Thorough abdominal exploration revealed extrahepatic disease in 13 of 62 patients (21%). Routine periportal/celiac lymph node biopsies revealed metastases in an additional 12 patients (19%), 7 of whom (11%) had only periportal/celiac lymph node metastases. CONCLUSIONS: A meticulous abdominal exploration prior to hepatic resection for patients with colorectal metastases is essential to identify those patients with extrahepatic disease. Periportal and celiac lymph nodes commonly are involved by tumor. Therefore, routine periportal/celiac lymph node biopsies should be performed in the absence of other extrahepatic disease.

Intraperitoneal chemotherapy in disseminated abdominal sarcoma.

BACKGROUND: There is no information in the literature concerning the use of cytoreductive surgery with intraperitoneal chemotherapy for sarcomas disseminated intraabdominally. METHODS: A prospective study was initiated of exploratory laparotomy, removal of all macroscopic tumor when feasible, and intraperitoneal chemotherapy with cis-DDP 100 mg/m2 every 4 weeks. Patients were to be explored in 6 months or earlier for detectable tumor recurrence. Twenty-eight consecutive patients enrolled in the study. RESULTS: Complete resection of all macroscopic tumor was possible in 79% of patients. Survival rates at years 1-5 were 54%, 21%, 7%, 7%, and 7%, respectively. Of the two long-term survivors, one was found to be disease free at the second-look operation with a catheter free of adhesions, whereas the other had recurrent disease and all her lesions were resected. Of 20 patients who underwent a second-look procedure, the Tenkhoff intraperitoneal catheter was found to be densely surrounded by adhesions in 19. In the 19 patients with adhesions, there was no tumor around the catheter for a radius of 15-20 cm, but the rest of the peritoneal cavity contained multiple tumor nodules. CONCLUSION: Removal of all macroscopic tumor is possible in 79% of the patients with sarcoma disseminated in the abdominal cavity. Intraperitoneal chemotherapy with cis-DDP after cytoreductive surgery resulted in a 5-year survival rate of only 7%.

Tourniquet infusion chemotherapy for extremity in-transit lesions in malignant melanoma.

BACKGROUND: Perfusion remains the standard of regional chemotherapy for extremity in-transit lesions from melanoma. However, there is an interest in other forms of intraarterial chemotherapy due to the simplicity and feasibility of repeat administration of the latter. METHODS: Review of 51 patients with extremity in-transit lesions from melanoma treated with the tourniquet infusion (TI) method on the basis of a prospective protocol. Drugs used were either Adriamycin (group A) or Dacarbazine (DTIC) + cisDDP (group B). The median number of courses was two. Lesions were resected at the same time as TI (n = 27) or after a month or more of observation in the absence of complete regression. RESULTS: There was no significant difference in response rates between groups A and B. The overall objective response rate in 24 evaluable patients was 75%, being complete in seven (29%), partial (> 50%) in 11 (46%), minor (< 50%) in three (12.5%), and progression of disease in three (12.5%). At a mean follow-up time of 40 months, no recurrence was observed in the treated extremity in 18 patients (35%), but further recurrences were noted in 31 patients (61%). The 5-year survival rate was 30%. CONCLUSION: TI provides an objective response rate of 75% for in-transit lesions, but after TI and resection of in-transit lesions as needed, the recurrence rate in the treated extremity is high (61%). Further work is needed with higher drug doses, local hyperthermia, or the administration of suitable doses of new regimens that are more successful with perfusion.