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.     

Increased levels of proteoglycan fragments and stromelysin in hip joint fluid in Legg-Calvé-Perthes disease

High response rates in patients with metastatic melanoma have been achieved with combination chemoimmunotherapy. A response rate of 62% in 45 patients has been reported for treatment with dacarbazine, bleomycin, vincristine, lomustine (BOLD) plus interferon alpha (IFN-alpha). We conducted a multicentre phase II study to confirm these results. Melanoma patients with distant metastases were treated as outpatients with dacarbazine 200 mg m(-2) on days 1-5, vincristine 1 mg m(-2) on days 1 and 4, bleomycin 15 mg on days 2 and 5 i.v. and lomustine 80 mg orally on day 1, repeated every 4 weeks. IFN-alpha-2b was initiated s.c. on day 8 at 3 MU daily for 6 weeks, and 6 MU t.i.w. thereafter. Forty-three patients entered the study. The median number of metastatic sites was three (range 1-5), and 81% of patients had visceral metastases. Nine patients had brain metastases, and seven patients were systemically pretreated. Among the 41 patients that were evaluable for response, the response rate was 27% (95% CI 14-3%), with one complete and ten partial remissions. The response rate in 25 previously untreated patients without brain metastases was 40% (95% CI 21-61%). Median duration of response was 6 (range 2-14+) months; median overall survival was 5 (1-26) months. The main toxicity was malaise/fatigue. We confirm that BOLD plus IFN-alpha has activity in metastatic melanoma. The lower response rate in our study compared with the previous report is probably related to patient selection, as in the previous study 46% of patients had stage III disease, whereas all our patients had stage IV disease, which is associated with a worse prognosis.     

Significance of arterial anastomoses of the distal calf and proximal foot for compensation of peripheral arterial occlusive disease

One hundred and one patients with metastatic melanoma were treated with three different dacarbazine (DTIC)-based polychemotherapy plus recombinant interferon (IFN) alpha-2b regimens in multicentre phase II trials in Finland during 1986-1993. The regimens were DTIC, nimustine (ACNU) plus IFN and two different schedules of DTIC, vincristine, bleomycin, lomustine (CCNU) plus IFN. There were 14 patients with complete response (CR) and 12 patients with partial response, with estimated median survivals of 44 months and 13 months respectively. The median survival was 14 months for 22 patients with stable disease, and 6 months for the 53 patients who had progressive or non-evaluable disease. The median progression-free interval was 6 months and the median survival 9 months for the whole group. Thirty-nine percent of patients survived at least 1 year and 17% at least 2 years. Age, sex, primary tumour site, Clark's level, disease-free interval, prior therapy of recurrence and metastatic sites of patients who achieved CR were compared with those of other patients. In addition, the predictive value of these factors for survival was analysed. Prior therapy of recurrent disease (none, surgery or surgery plus radiotherapy) and metastatic profile (soft tissue or lung, one or two sites) were associated with CR in univariate analysis, while in multivariate analysis only prior therapy was found to be an independent prognostic factor. Prior surgery plus radiotherapy, soft tissue or lung metastases and response to present chemo-immunotherapy were significant predictors of favourable survival in univariate analysis. In multivariate analysis only response was an independent prognostic factor.     

Breath test diagnosis of Helicobacter pylori in peptic ulcer disease: a noninvasive primary care option

The role of chemotherapy in malignant neuroendocrine tumours is difficult to assess because of their rarity and variation in biological behaviour. We present a retrospective review of chemotherapy given to 18 patients with metastatic and one with locally advanced neuroendocrine tumours. There were eight poorly differentiated neuroendocrine tumours, six thyroid medullary carcinomas, two phaeochromocytomas, two pancreatic islet cell tumours and one undifferentiated neuroblastoma. Four patients were given 3-weekly dacarbazine, vincristine and cyclophosphamide (DOC) chemotherapy. In eight patients, this regimen was modified by substituting the dacarbazine and cisplatin and etoposide (OPEC). A further six patients were treated with dacarbazine reintroduced into the 3-weekly regimen (DOPEC). The remaining patient received cisplatin and etoposide. There were two complete responses (both with OPEC) and eight partial responses (two with DOC, three with OPEC and three with DOPEC). Five patients had stable disease and four progressed. Four received further chemotherapy on relapse, producing one complete and one partial response. The median response duration to initial chemotherapy was 10 months (range 3-34). The median survival was 12 months (range 1-42). The main toxicity was haematological, with grade 3-4 neutropenia in 12 patients; eight suffered episodes of sepsis. One death was treatment related. Other toxicity was mild although three patients discontinued vincristine with grade 2 neurotoxicity. The response rate and side effects of these three regimens appear comparable. We conclude that, although these patient numbers are small, combination chemotherapy produces an encouraging response rate (53%; 95% CI 30-75) in malignant neuroendocrine tumours, with acceptable toxicity.     

Functional pancreatic islet cell tumors with liver metastasis: the role of cytoreductive surgery and transcatheter arterial chemoembolization: a report of five cases

Malignant pancreatic islet tumors are slow-growing tumors. Their relatively benign behavior makes aggressive treatment worthwhile. From January, 1987, to January, 1998, five cases of malignant pancreatic islet tumors with liver metastasis were diagnosed at the Veterans General Hospital-Taipei. Of these, three were gastrinomas and the others were vasoactive intestinal peptide (VIPoma, 1 case) and insulinoma (1 case). Four patients (3 with gastrinomas and 1 with insulinoma) had undergone cytoreductive surgery when the diagnosis of metastasis was made. All five patients underwent transcatheter arterial chemoembolization (TACE). All patients had improved symptoms after cytoreductive surgery and TACE. The survival of patients who underwent combined surgery and TACE was 38 and 17 months in the two gastrinoma cases, more than eight months in one gastrinoma case and more than 20 months in the insulinoma case (these 2 patients are still alive). One VIPoma patient who underwent TACE survived for 12 months. In conclusion, treatment for metastatic pancreatic islet cell tumors require a multidisciplinary approach. Metastasis of the tumor is not a contraindication for aggressive therapy. Combined cytoreductive surgery and TACE can relieve symptoms and are of benefit for patients with pancreatic islet cell tumors with liver metastases.     

Malignant vascular tumors in young patients

BACKGROUND: To the authors' knowledge there are few published series of malignant vascular tumors in patients age < or = 21 years. METHODS: The authors retrospectively documented the clinical presentation, pathology, treatment, and outcome of patients age < or = 21 years with malignant vascular tumors treated between 1970-1995 at Memorial Sloan-Kettering Cancer Center. The histologic sections were rereviewed to confirm the diagnosis. RESULTS: Four patients were identified with angiosarcoma and two with malignant hemangioendothelioma. Five patients were female and one was male; the median age at diagnosis was 11.8 years (range, 8 months-21 years). The tumor involved the skin in one patient, soft tissue in one patient, bone in two patients, and internal organs in two patients. One patient had associated diffuse angiomatosis and another had the Klippel-Trenaunay-Weber syndrome. This patient received prior radiation therapy to the primary site with the subsequent development of a vascular sarcoma. None of the patients had distant metastases at diagnosis. Resection was attempted in five patients and completed in four. Chemotherapy alone was given to three patients whereas radiation therapy alone and radiation plus chemotherapy were administered to one patient each. The median follow-up was 4.9 years (range, 1 month-12 years). There were three deaths from progressive disease and two deaths from locoregional recurrences. Reexcision and radiotherapy controlled one local recurrence. Another patient developed recurrence to regional lymph nodes and further dissemination. The primary tumor in all three survivors was excised completely whereas two of the three patients who died of progressive disease underwent an incomplete excision or biopsy alone. CONCLUSIONS: Malignant vascular tumors are rare in the first two decades of life and when they do occur are very aggressive. Complete resection is curative for patients with localized lesions.     

Prognostic significance of coexistent bulky metastatic central nervous system disease in patients with leptomeningeal metastases

OBJECTIVE: To assess the clinical significance of bulky metastatic central nervous system disease in patients with leptomeningeal metastases. PATIENTS AND METHODS: Forty patients (24 women and 16 men) ranging in age from 32 to 74 years (median, 56.5 years) with cytologically documented leptomeningeal metastases were demonstrated by cranial or spinal magnetic resonance imaging to have either no bulky central nervous system metastatic disease (group A; 20 patients) or bulky central nervous system metastatic disease (group B; 20 patients). Twenty-nine patients were treated with involved-field radiotherapy, and all patients were treated with sequential intraventricular chemotherapy. RESULTS: Median survival was 7 months in group A (range, 5-12 months) as compared with 4 months in group B (range, 2-12 months) (P < .01; Mantel-Cox log rank analysis). Cause of death was similar in both patient groups. CONCLUSIONS: In patients with leptomeningeal metastases, neuroradiographic demonstration of bulky metastatic central nervous system disease independently predicts survival and is useful in determining which patients are candidates for intraventricular chemotherapy.     

Induction of gene expression of antibacterial proteins by chitin oligomers in the silkworm, Bombyx mori

A 71-year-old male with advanced gastric carcinoma with paraaortic lymph node metastases underwent distal gastrectomy. Cisplatin (CDDP) 50 mg/body was administered intravenously (i.v.) on day 1 followed by the administration of 5-fluorouracil 500 mg/body/day i.v. on day 2 through day 7. After two courses of this regimen, further enlargement of paraaortic lymph nodes was revealed by CT scan, and chemotherapy was suspended. Multiple liver and lung metastases were diagnosed 6 months after initial diagnosis, and mitomycin C (MMC) 10 mg/body i.v. was administered on day 1 followed by CDDP 50 mg/body i.v. on day 2. After three courses of this regimen, partial response of the liver metastases and complete response of the lung metastases were observed, and the general condition was markedly improved without any adverse effect except slight nausea. Though the patient died of brain metastases one year after initial diagnosis, the combination chemotherapy with MMC and CDDP was nevertheless thought to improve his quality of life.     

Radical resection of primary malignant melanoma of the gallbladder with multiple metastases: report of a case

We present herein an usual case of primary malignant melanoma of the gallbladder in a 51-year-old man in whom an exploratory laparotomy for melena revealed six malignant melanoma lesions located in the gallbladder, main pancreatic duct, stomach, duodenum, jejunum, and a mesenteric lymph node. Total pancreatectomy was performed and histologically, junctional activity was seen only in the gallbladder, suggesting that this was the primary site. No melanotic lesions were found on the skin or eyes. The metastases to the main pancreatic duct and gastrointestinal tract appeared likely to have occurred as a consequence of the mucosal dissemination of the tumor cells shed into the bile. The post-operative course was uneventful and combined chemotherapy was administered for 16 months. No new metastatic lesions were found until 21 months postoperatively, when metastases were detected in the brain and thoracic spinal cord. These metastatic tumors were removed surgically, but the patient died from cerebral disturbance 26 months after the initial operation. Thus, we consider that aggressive surgical therapy was effective for extending the survival time and improving the quality of life of this patient.     

Results and long term follow-up for 1581 patients with metastatic breast carcinoma treated with standard dose doxorubicin-containing chemotherapy: a reference

BACKGROUND: The authors report results and long term follow-up for 1581 patients with metastatic breast carcinoma treated with doxorubicin-containing combination chemotherapy at a single institution; this report is meant to serve as a reliable reference for single-arm studies of newer therapies in this patient population. METHODS: Prospectively collected data from 18 successive doxorubicin-containing protocols for the treatment of metastatic breast carcinoma were evaluated. RESULTS: The response rate was 65.0% (95% confidence interval [CI]: 62.5-67.3%), complete response (CR) rate was 16.6% (95% CI: 14.8-18.6%), and partial response (PR) rate was 48.5% (95% CI: 46.0-50.9%). Median progression free survival (PFS) was 11.5 months (95% CI: 10.9-12.3 months) and median overall survival (OS) was 21.3 months (95% CI: 20.3-22.7 months). Survival correlated with response to therapy; median PFS and OS were 22.4 and 41.8 months, respectively, for the patients who achieved CR (n=263) and 14 and 24.6 months, respectively, for PR patients (n=766). The median OS of patients who had progressive disease during chemotherapy was 3.8 months. The response rate, PFS and OS correlated with number of organs involved and especially with tumor burden. Patients with hormone receptor-positive tumors had a similar response rate to that of patients with hormone receptor negative tumors but had significantly longer PFS (medians of 14.3 and 8.7 months, respectively) and OS (medians of 28.6 and 18.1 months, respectively). CONCLUSIONS: In patients with metastatic breast carcinoma, doxorubicin-containing chemotherapy had a response rate of 65% and a CR rate of 16.6%. PFS and OS were 11.5 months and 21.3 months, respectively, for all responders and 22.4 months and 41.8 months, respectively, for those who had CR.     

Liver embolizations of patients with malignant neuroendocrine gastrointestinal tumors

BACKGROUND: Patients with neuroendocrine gastrointestinal tumors usually present with inoperable metastatic disease and severe hormonal symptoms. Specific chemotherapy, interferon-alpha (IFN), and somatostatin analogs are established therapies for these patients, but all of them eventually fail. Hepatic arterial embolization can provide reduction of both hormonal symptoms and tumor burden in these patients. METHODS: Between 1981 and 1995, a total of 55 liver embolizations with gel foam powder were performed on 41 patients with histopathologically verified neuroendocrine tumors; 29 had carcinoid tumors and 12 had endocrine pancreatic tumors (EPTs). All patients had received medical treatment, including chemotherapy (n = 18), IFN (n = 31), and octreotide (n = 19), and were experiencing treatment failure when liver embolization was performed at a median of 37 months after diagnosis of liver metastases. Medical treatment was continued after embolization. RESULTS: An overall objective response was noted in 15 of 29 patients with carcinoid tumors (52%). The median duration of effect was 12 months in patients with midgut carcinoid tumors. An overall objective response was observed in 6 of 12 patients with EPTs (50%), with a median duration of effect of 10 months. Adverse events were observed, and, in agreement with earlier reports, the rate of serious complications was 10%. Survival analyses showed a median survival of 80 months and a 5-year survival rate of 60% from the performance of embolization on patients with midgut carcinoid tumors, whereas for patients with EPTs the median survival from embolization was only 20 months. CONCLUSIONS: Liver embolizations performed relatively late in the clinical course in our series appeared to be as effective as "early" embolizations in other series of patients with carcinoid tumors. The results for those with EPTs were poorer, and earlier embolizations may result in better outcomes for these patients. Considering the morbidity associated with the procedure, it is imperative to select patients according to extent of liver involvement, severity of carcinoid heart disease, and somatostatin receptor status.     

The intratesticular leiomyoma: an unusual location. Report of a case

Malignant mixed müllerian tumors (MMMT) of the ovary are rare, aggressive and rapidly progressive tumors. According to the available literature, the presence of metastatic disease rarely permits long term survival. We report on a 64-year old patient with stage IV ovarian MMMT who achieved a surgically-documented complete response (CR) after 6 cycles of carboplatin, mesna, ifosfamide, cis-platin. Pelvic recurrence was diagnosed 14 months later; the patient received 6 cycles of the same regimen used as first-line chemotherapy which resulted in a second complete response lasting for 4 months. The patient died 37 months after initial diagnosis due to intestinal occlusion. In the current case Ca 125 was significantly increased at clinical presentation of disease but not at the time of recurrence.     

Australian multicentre phase II trial of paclitaxel in women with metastatic breast cancer and prior chemotherapy

OBJECTIVE: To determine the efficacy and safety of paclitaxel given as a three-hour infusion in patients with metastatic breast cancer which had progressed despite hormonal therapy and/or chemotherapy. DESIGN AND SETTING: Multicentre phase it trial undertaken in five major centres or hospitals in Sydney, Melbourne and Adelaide. PATIENTS AND METHODS: 50 patients with clinically or radiologically measurable or evaluable metastatic breast cancer recruited between March and July 1993. All had received prior chemotherapy, with subsequent disease progression. INTERVENTION: Paclitaxel (Anzatax, Faulding) was given at a dose of 175 mg/m2 intravenously over three hours every three weeks for up to nine courses. MAIN OUTCOME MEASURES: Response rate (partial or complete); duration of progression-free survival; duration of survival; and adverse reactions. RESULTS: Patients had a median age of 51 years; 62% had received at least two prior drug regimens for metastatic breast cancer and 48% had anthracycline-resistant tumours. A median of six paclitaxel courses was given per patient. Overall response rate was 18% (95% confidence interval [95% CI], 9%-31%), with complete responses in four patients (8%). In patients with anthracycline-resistant tumours, response rate was 25% (95% CI, 10%-47%). Response was not influenced by extent of prior treatment. Estimated median progression-free survival was 4.1 months (95% CI, 3.2-6.0 months) and estimated median survival was 6.3 months (95% CI, 6.2-10.3 months). Treatment was well tolerated, with neutropenia the major toxic effect. CONCLUSIONS: Paclitaxel (three-hour infusion) has significant activity in heavily pretreated patients with metastatic breast cancer, including anthracycline-resistant tumours.     

Transarterial immuno-chemotherapy including adoptive transfer of autologous cultured lymphocytes for stage IV breast cancer patients with locally-advanced tumor

Immuno-chemotherapy via a catheter in the subclavian artery using sequential treatment with OK-432, chemotherapeutic agents (ADM, 5-FU), and cultured autologous lymphocytes, was performed for 9 Stage IV breast cancer patients with locally-advanced primary tumor. Tumor reduction of more than 50% was observed in 8 patients including 4 whose breast tumors had disappeared. Among 11 evaluable distant metastatic lesions, 7 (1 pleural effusion, 2 lung, 2 liver, 2 bone metastases) regressed after local immunotherapy of breast or additional regional immunotherapy (1 lung, 1 liver, 1 pleural effusion). Median survival time to date is 56 months. Five patients are currently alive, although 3 of them did not undergo mastectomy. Local immuno-chemotherapy may be useful because (a) toxicity is limited, (b) low doses of anti-cancer agents during the therapy (median dose of ADM, 60 mg) do not limit subsequent systemic chemotherapy, and (c) distant metastases often regress concomitantly with the primary lesions.     

Residual metastatic axillary lymph nodes following neoadjuvant chemotherapy predict disease-free survival in patients with locally advanced breast cancer

BACKGROUND: This study was performed to validate the prognostic significance of residual axillary lymph node metastases in patients with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy and to analyze other clinicopathologic factors that might be independent predictors of disease-free survival (DFS) in an attempt to identify patients in whom axillary dissection might be omitted. METHODS: One hundred sixty-five assessable patients with LABC were treated in a prospective trial of neoadjuvant chemotherapy utilizing four cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide. Responding patients were treated with segmental mastectomy and axillary dissection or modified radical mastectomy. Patients subsequently received additional chemotherapy followed by irradiation of the breast or chest wall and draining lymphatics. The median follow-up was 35 months. RESULTS: Clinical tumor response to neoadjuvant chemotherapy (P = 0.046) and the number of residual metastatic axillary lymph nodes found at axillary dissection (P = 0.05) were the only independent predictors of DFS. Patients with a complete clinical response had a predictably excellent DFS and those with no change or progressive disease had a poor DFS. In patients with a partial response, the number of residual metastatic lymph nodes further stratified patients with respect to DFS (P = 0.006). CONCLUSIONS: Clinical response and residual metastatic axillary lymph nodes following neoadjuvant chemotherapy are important predictors of DFS. Patients with a clinically positive axilla following neoadjuvant chemotherapy should undergo axillary dissection to ensure local control. However, the benefit of axillary dissection in patients with a clinically negative axilla may be minimal if the axilla will be irradiated, and histologic staging does not affect subsequent systemic treatment. A prospective randomized trial of axillary dissection versus axillary radiotherapy in patients with a clinically negative axilla following neoadjuvant chemotherapy is presently under way to evaluate this hypothesis.     

Tissue preparation for immunocytochemistry

The results in 9 patients with unresectable recurrent squamous cell cancer of the head and neck who were treated with aggressive concurrent chemoradiotherapy are reported. Treatment consisted of one or two courses of chemotherapy with 5-fluorouracil 1000 mg/m2/day and cisplatin 20 mg/m2/day, both given as 4-day continuous intravenous infusions, concurrent with radiation therapy. Salvage radiation doses between 30 and 70 Gy were administered. Seven patients had previously undergone an attempt at curative surgery, and 7 had been treated with radiation doses between 52 and 72 Gy. The recurrent disease was locally confined in 3, locoregional in 5, and locoregional with metastases in 1 of the 9 patients. Treatment toxicity was significant and included mucositis, nausea/vomiting, and granulocytopenia, but there were no toxic deaths. Complete tumor clearance was possible in 6 of these 9 patients, and 5 patients remain disease-free at 41+, 43+, 45+, 47+, and 50+ months. Of these 5 patients, 4 had previously been treated with both surgery and radiation, while 1 had only undergone surgery. We conclude that aggressive chemotherapy and concurrent (re)irradiation can be given to patients with unresectable, recurrent, squamous cell cancer of the head and neck. Treatment is tolerable, and disease-free long-term survival is possible. Careful patient selection, however, is required.     

A phase II study of irinotecan alternated with five days bolus of 5-fluorouracil and leucovorin in first-line chemotherapy of metastatic colorectal cancer

PURPOSE: This multicenter phase II study was designed to assess the efficacy of the alternating schedule of irinotecan (CPT-11) with bolus 5-fluorouracil (5-FU) and leucovorin (LV) in first-line chemotherapy for metastatic colorectal cancer (CRC). PATIENTS AND METHODS: Patients with histologically proven metastatic colorectal cancer, and at least one bidimensionally measurable lesion, aged 18-70, with performance status < or = 2, normal baseline biological values and no prior chemotherapy (or only adjuvant chemotherapy completed > or = 6 months before study entry) were selected. Treatment was irinotecan 350 mg/m2, i.v., day 1, alternating with leucovorin 20 mg/m2 i.v. and 5-FU 425 mg/m2, i.v. daily for five consecutive days, day 22-26 (Mayo Clinic regimen). One alternating cycle was to be performed every six weeks. Patients were evaluated for efficacy every alternating cycle. Treatment was administered until five alternating cycles, disease progression, unacceptable toxicity or patient refusal. RESULTS: Thirty-three patients (28 chemotherapy-na?ve and five with prior adjuvant treatment completed > 1 year prior to accrual) were enrolled. The objective response rate (RR) was 30% (95% CI: 16-49; 10 patients/33; nine partial response and one complete response). All responses were reviewed by an independent external review committee. An additional 49% of patients had stable disease. The median survival was 16 months, the one year survival amounted to 58% and the median progression free survival was 7.2 months. Relative dose intensity was nearly 90% for both drugs. Grade 3-4 diarrhea and neutropenia were the most frequent severe toxic events, seen in 24% and 64% of patients, respectively. CONCLUSIONS: The alternating schedule of CPT-11 350 mg/m2 with five days bolus of 5-FU and low dose LV is an active and feasible regimen as front-line therapy for metastatic CRC. It is well tolerated, without evidence of overlapping toxicity. The response rate appears promising with regard to that expected with either single agent. This regimen warrants further assessment in randomized trials.     

p53 nuclear protein overexpression in colorectal cancer: a dominant predictor of survival in patients with advanced hepatic metastases

PURPOSE: To determine whether p53 protein expression is similar within primary colorectal cancer (CRC) and synchronous regional and distant metastases and to assess whether p53 nuclear protein expression could predict outcome in patients with synchronous unresectable liver metastases treated by hepatic artery infusional (HAI) chemotherapy. MATERIALS AND METHODS: Paraffin sections from tumor and corresponding normal mucosa representative of 50 consecutive advanced CRC cases were examined for p53 nuclear protein expression by immunohistochemistry using the monoclonal antibody PAb 1801. Patterns of p53 nuclear expression were correlated with standard clinicopathologic variables and outcome, including response to HAI and survival. In a subset analysis, the pattern of nuclear p53 immunoreactivity was compared between primary CRC and lymph node and liver metastases. RESULTS: Positive nuclear immunoreactivity for p53 protein was found in 72% of cases. The pattern of p53 protein expression in lymph node and liver metastases was identical to that of the primary tumor. The median survival time was 21.0 months in patients with p53-positive tumors and 53.2 months in patients with p53-negative tumors (Wilcoxon test P = .038). Two-year survival rates were 41.7% and 78.6%, respectively (P < .01). No significant difference was found in the response rates to HAI chemotherapy between the two groups. By multivariate analysis, p53 protein status was the single best predictor of survival, with a relative risk of 6.312. CONCLUSION: Our results indicate that nuclear p53 protein status in primary CRC is similar to that in metastatic sites and may be the dominant predictor of survival in patients with advanced hepatic metastases.     

Asynchronous bilateral retinoblastoma: the St. Jude Children's Research Hospital experience

Between May 1962 and July 1993, 172 children presented at the St. Jude Children's Research Hospital for evaluation and/or treatment of retinoblastoma (RB). Of these, 65 presented with bilateral disease, while 107 had unilateral tumors. Of these 107 patients, nine subsequently developed RB in the unaffected eye. Initial age at diagnosis of these nine patients ranged from 3 weeks to 24 months (median = 2 months); five of the nine had a family history of RB at the time of initial diagnosis and one patient, without a family history of RB, presented with unilateral multiple tumors indicating inheritance of a germinal mutation and increased risk of RB development in the companion eye. Time to development of companion eye RB was 1-61 months postinitial diagnosis. Treatment of the initial eye included enucleation (n = 4), chemotherapy (n = 3), irradiation (n = 7), or a combination of these three modalities. Reese-Ellsworth grouping of the companion eye disease included I A (n = 7), III A (n = 1), and IV A (n = 1). Treatment of the second affected eye included irradiation in seven patients, cryotherapy in four, and chemotherapy in three. No companion eye has required enucleation to date. At last followup, 14/18 eyes remain intact. There have been no cases of metastatic dissemination; however, one patient has developed a second malignant neoplasm outside the field of irradiation. Eight of the nine patients remain alive. This experience reinforces the need for close follow-up of patients diagnosed with unilateral RB, especially those with a family history of RB and those with unilateral multiple tumors.