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[Differential diagnosis of Crohn disease: segmental intestinal metastasis of breast and stomach cancer].

Metastatic malignancies are able to imitate the radiological or intraoperative findings of Crohn's disease. Being of great importance in individual cases, the manifestation of intestinal metastases mimicking Crohn's disease is analysed. Since 1960 world literature has reported intestinal metastases simulating Crohn's disease in 19 patients. Primary tumours were breast cancer (13 patients), gastric cancer (5 patients) and unknown primary focus (1 patient), in which even postmortem examination failed to reveal the site of primary cancer. 12 (67%) of 18 specified patients showed metastatic infiltration of the terminal ileum. Long segments of narrowing were found in all patients. Since specific signs such as age, sex, localization or macroscopic appearance to differentiate Crohn's disease from metastatic tumour spread are lacking, a histological examination is necessary to establish the correct diagnosis. The median survival time was approximately one year following the intestinal tumour spread.

Adult↗

[Metastases to the nervous system].

Over a period of 13 years, 353 cases of metastases in the brain, spinal canal or peripheral nerves were treated in 14,350 inpatients. In 79.6% of the cases, the metastases were localized intracranially, in 14.7% spinally, in 2.6% peripherally and in 3.1% in several of these sites. Solitary tumors predominated (65.7%). Of 420 intracranial metastases, 336 were located supratentorially (80%) with a slight preponderance on the left side (54.5%), 15% cerebellar, and 5% in the brainstem. Of the spinal metastases, 80% were located in the thoracic spinal cord. Almost 60% of the cases also displayed metastases outside the nervous system, mainly in the skeletal system and the lungs. The most frequent primary tumor was bronchial carcinoma (26,6%) followed by breast cancer (19.5%) and unknown primary tumor (17.6%), which was also not found on autopsy in 0.8%. Rare primary tumors were parotid and pancreatic carcinomas, testicular and bladder tumors. There are correlations between the primary tumor and the location of the metastases in the nervous system in general and in the brain in particular. The latency between diagnosis of the primary tumor and that of the metastasis was 1-3 years. In one out of three cases, the metastasis in the nervous system was the first sign of the tumor condition. In six cases, the metastasis was removed before the primary tumor and two possible kinds of primary tumors were found in seven cases. Compared to intracranial hypertension focal deficit manifestations including focal convulsions occurred twice as frequently in cerebral metastases. Spinal metastases led to CSF blockade in 20%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Liver metastases of unknown origin.].

OBJECTIVE: Approximately 5% of cancer patients are diagnosed with tumour of unknown origin (3-4% in Iceland). Of those 10-30% have liver metastases. Liver metastases of unknown origin is thus not an uncommon problem. In the present study information about the origin and histology of liver metastases of unknown origin was compiled. MATERIAL AND METHODS: Records of all biopsies from liver metastases performed in the years 1987-1996 were retrieved from the medical database of the Department of Pathology at the University of Iceland. The biopsies came from a group of 176 patients. Ninety-two cases, in which the origin of the primary tumour was suspected or known, were excluded from the study, leaving 84 cases where the primary was completely unknown. The database of the Icelandic Cancer Society was used to gather data about the final tissue diagnosis and the location of the primary tumour when known. RESULTS: The Cancer Society data revealed the location of the primary tumour in 55 of the 84 cases of liver metastases of unknown origin. The most prevalent (75%) primary tumours were cancers of the pancreas (15), lung (13) and colon/rectum (12). The tissue diagnosis was adenocarcinoma in 33 of the 55 cases. In the male patients 83% of the adenocarcinoma metastases came from the colon/rectum or pancreas. The corresponding figure for the female patients was 67%, while 20% of the tumours in females originated in the gallbladder and biliary tree. CONCLUSIONS: In two thirds of the cases of liver metastases of unknown origin the primary tumour was later discovered. The most prevalent tumours were cancers in the pancreas, lung and colon/rectum. Adenocarcinoma was the tissue diagnosis in 60% of cases.

English Abstract↗

Brain tumors: L-[1-C-11]tyrosine PET for visualization and quantification of protein synthesis rate.

PURPOSE: Positron emission tomography (PET) with the amino acid tracer L-[1-C-11]-tyrosine was evaluated in 27 patients with primary and recurrent brain tumors. MATERIALS AND METHODS: Patients underwent either static (n = 14) or dynamic PET (n = 13), with quantification of protein synthesis rate (PSR) and tumor-to-background ratio. Findings were compared with histologic findings. RESULTS: Primary brain tumor was proved in 22 patients histologically, as well as metastatic cancer of unknown origin, primary non-Hodgkin lymphoma, meningioma, atypical infarction, and vasculitis in one patient each. At PET, 20 of 22 primary tumors, the metastasis, and non-Hodgkin lymphoma were correctly depicted. A false-positive finding was obtained with the infarction, and the meningioma and vasculitis were not depicted. The calculated sensitivity was 92%; specificity, 67%; and accuracy, 89%. There were no statistically significant relationships between histologic findings, PSR, and tumor-to-background ratio. CONCLUSION: L-[1-C-11]-tyrosine is a valid tracer for diagnosis of brain tumors and allowed quantification of PSR.

Adult↗

Prospective evaluation of the leukocyte adherence inhibition (LAI) test in breast cancer using a panel of extracts from known and unknown primary tumors.

The antigen-induced leukocyte adherence inhibition (LAI) test is an assay of cellular immune reactivity which was expected to offer a promising adjunct to currently available diagnostic and monitoring procedures in cancer patients. We have applied this assay to (1) 83 inpatients clinically suspected of having breast cancer, (2) 50 out-patients before mammography, and (3) 37 healthy women. In order to account for the known heterogenicity of breast cancer, we performed LAI assays with extracts from 15 primary tumors of known and 14 primary tumors of initially unknown histology. Thus, the problem of tumor specificity in the LAI assay was tackled in a double-blind fashion. The results obtained clearly show that breast-tissue-specific rather than tumor-specific responses were detected by LAI testing. The LAI assay failed to discriminate between high-risk patients with and without cancer and between extracts from breast tumors with and without carcinoma. The results are discussed with regard to the many claims for the detection of specific tumor immunity in the literature.

Adult↗

'Occult' breast cancer.

The aim of this paper is to explore current trends in the diagnosis, investigation and treatment of patients presenting with axillary lymph node metastases without a primary in the breast being found and, more rarely, those cases with metastatic breast cancer where the primary remains unknown--the so-called, 'occult' breast cancer. A retrospective study of 25 reported cases were selected from our database at the Royal Marsden and 6 patients were found to have true 'occult' breast cancer. These 6 patients are all still alive with no primary ever having been found in the breast. A literature review was then undertaken exploring the changing trends in this diagnostic enigma. MRI scanning, it is reported, may reveal the primary. Occult cancers in which imaging totally fails to show the primary will become increasingly rare. The prognosis of these, however, may be surprisingly better than one would expect from the nature of their presentation.

Adenocarcinoma↗

Phase I study of the mitomycin C analogue BMS-181174.

BMS-181174 is an aminodisulphide derivative of Mitomycin C (MMC) with activity against a range of tumour cell lines and xenografts, including MMC-resistant tumours. In a phase I study of 82 patients with confirmed malignancy, we administered BMS-181174 at doses of 0.8-75 mg m(-2) by intravenous injection every 28 days. At least three patients were evaluated at each dose level, and 174 courses were administered. The pharmacokinetics were dose linear at BMS-181174 doses of 11.5-75 mg m(-2) and the drug appeared to undergo wide distribution. The maximum-tolerated dose was 65 mg m(-2) in previously treated patients and 75 mg m(-2) in chemotherapy-naive cases. The dose-limiting toxicity was myelosuppression, particularly thrombocytopenia, which was prolonged and cumulative. Three patients treated at 65-75 mg m(-2) died suddenly with evidence of pneumonia/pneumonitis, thought to be drug-related. Other toxicities included thrombophlebitis, possible cardiotoxicity (asymptomatic, reversible decline in left ventricular function) and renal impairment. The partial response rate was 5% (4 out of 82) overall, and 9% (3 out of 32) in patients treated at 65-75 mg m(-2). Responses occurred in treated and previously-untreated patients, including cases of colorectal cancer, non-small-cell lung cancer, ovarian cancer and adenocarcinoma of unknown primary site. BMS-181174 has anti-cancer activity but, because of its toxicity, particularly pneumonitis and thrombophlebitis, no phase II studies are planned.

Adult↗

Benefit of postoperative chemoradiotherapy for patients with unknown primary squamous cell carcinoma of the head and neck.

BACKGROUND: Postopertative adjuvant chemoradiotherapy recently became an established modality for patients with selected high-risk locally advanced head and neck cancers. The optimal treatment of unknown primary squamous cell cancer of the head and neck (SCCHN) continues to be controversial, since major randomized studies excluded those patients. METHODS: We conducted a retrospective review of patients treated during 1995 to 2002 for unknown primary SCCHN. All patients were treated with a neck dissection followed by concurrent high-dose cisplatin (100 mg/m(2)) and bilateral neck radiotherapy. RESULTS: Thirty-seven patients were identified with nodal disease distribution of N1 (5%), N2a (22%), N2b (41%), N2c (8%), N3 (22%), and Nx (3%). Modified neck dissection was done on the majority (30/37 = 81%) of patients. With a median follow-up of 42 months among the survivors, very few patients had regional recurrence (5%) or distant failure (11%), and 89% of patients were alive. The actuarial 5-year overall survival rate could not be estimated because there were no deaths beyond 20 months after surgery. Substantial yet acceptable acute and late morbidities were demonstrated in this cohort of patients. CONCLUSIONS: Postoperative chemoradiotherapy is of potential benefit to patients with unknown primary SCCHN by improving survival and reducing failures. This treatment warrants further prospective evaluation.

Adult↗

Increased prevalence of primary hyperparathyroidism in treated breast cancer.

UNLABELLED: Hypercalcemia occurring in patients with advanced breast cancer (BC) is generally due to osteolytic metastases or to the activity of circulating tumor-derived products. In these conditions, the production of endogenous PTH is reduced. The frequency of hypercalcemia due to primary hyperparathyroidism in breast cancer is unknown. We examined the occurrence of primary hyperparathyroidism in a large group of women with treated BC. A total of 100 consecutive women aged 28-80 years with treated breast cancer were enrolled. One hundred and two healthy age-matched women and 60 age-matched female patients with differentiated thyroid carcinoma examined before thyroidectomy were used as controls. Intact serum PTH and serum calcium were measured in all patients and controls. Hypercalcemia associated with elevated serum PTH concentration indicating primary hyperparathyroidism was found in 7 BC patients (7%) and in none of healthy women or patients with thyroid cancer. The pre-operative staging of BC patients with primary hyperparathyroidism was I in six and II in one of them, and no patient had evidence of distant metastases. A parathyroid adenoma was found in all 6 BC patients submitted to neck exploration, one patient refused surgery. Serum calcium and PTH concentrations returned to normal levels after surgery. Two BC patients had increased serum PTH and normal calcium concentrations. One of them had low serum 25-hydroxyvitamin D [25(OH)D]. One patient with spread bone metastases had neoplastic hypercalcemia with undetectable serum PTH concentration. All remaining 90 BC patients had serum calcium and PTH concentrations within normal limits, but their mean (+/-SD) values (9.6+/-0.5 mg/dl for serum calcium, 38.0+/-16.4 mg/dl for serum PTH ) were slightly but significantly greater than in normal controls (9.3+/-0.5 mg/dl, p=0.003 and 27.9+/-10.6 pg/ml, p=0.0001, respectively) and in patients with thyroid cancer (9.2+/-0.6 mg/dl, p=0.001 and 26.2+/-11.0 pg/ml, p=0.001), with no relationship with clinical staging or anti-tumor therapy. IN CONCLUSION: 1) an increased frequency of parathyroid adenoma was found in BC patients with mildly aggressive neoplastic disease; 2) in BC patients with no evidence of primary hyperparathyroidism mean serum PTH and calcium concentrations were significantly greater than in healthy controls and in patients with thyroid carcinoma; and 3) this finding was unrelated to clinical staging or anti-tumor therapy. Thus, primary hyperparathyroidism should be considered as a possible cause of hypercalcemia in patients with non-aggressive breast cancer. We suggest that serum PTH should be determined in all BC patients with increased serum calcium concentration, especially in those with no evidence of metastatic disease.

Adenoma↗

Long-term survival with metastatic cancer to the brain.

Metastatic cancer to the brain has a poor prognosis. The focus of this work was to determine the incidence of long-term (> or = 2y) survival for patients with brain metastases from different primary cancers and to identify prognostic variables associated with prolonged survival. A retrospective review of 740 patients with brain metastases treated over a 20 y period identified 51 that survived 2 or more years from the time of diagnosis of the brain metastasis. Prognostic variables that were examined included age, sex, histology, tumor number and location, and treatment. In the 51 patients, 35 (69%) had single lesions and 16 (31%) had multiple tumors. For all tumor types (740 patients), the actuarial survival rate was 8.1% at 2 y, 4.8% at 3 y, and 2.4% at 5 y. At 2 y, patients with ovarian carcinoma had the highest survival rate (23.9%) and patients with small cell lung cancer (SCLC) had the lowest survival rate (1.7%). At 5y, survival rates were 7.8% for ovarian carcinoma, 2.9% for non-SCLC, 2.3% for melanoma and renal cell carcinoma, 1.3% for breast carcinoma and there were no survivors with SCLC, gastrointestinal, bladder, unknown primary, or prostate cancer. Age, sex, histology, location for single tumors, systemic chemotherapy, and stereotactic radiosurgery did not significantly influence survival. The presence of a single lesion (P = 0.001, chi-square test), surgical resection (P= 0.001), and WBRT (P = 0.009) were favorable prognostic variables for extended survival. Multiple bilateral metastases was a poor prognostic indicator (P= 0.001). Multivariate analysis showed younger age (P< 0.05), single metastasis (P < 0.0001), surgical resection (P < 0.0001), whole brain radiation therapy (P < 0.0001), and chemotherapy (P = 0.0288) were associated with prolonged survival. 29 patients (57%) died of systemic disease progression, 9 (18%) died of central nervous system progression, and the cause of death was unknown in 3 (6%). Patients with a single non-SCLC, breast, melanoma, renal cell, and ovarian carcinoma brain metastasis have the best chance for long-term survival if treated with surgical resection and WBRT.

Adult↗

Phase I--preliminary phase II trial of iproplatin, a cisplatin analogue.

Iproplatin was administered intravenously over 30 min daily for 5 consecutive days every 3 weeks to 80 evaluable patients with a variety of refractory solid tumor malignancies. Thrombocytopenia was the dose-limiting toxicity. Reversible drug-induced renal dysfunction was observed in 3 patients. One patient sustained mild ototoxicity but neurotoxicity was not encountered. Transient neutropenia, anemia, nausea, vomiting, diarrhea, elevations of liver enzymes, alopecia, and skin rash also occurred. The spectrum and severity of toxicity of iproplatin were found to differ from those of cisplatin. The maximally tolerated dose (MTD) was 45 mg/m2/day in patients who received prior chemotherapy and 65 mg/m2/day in those who did not. No complete responses occurred. Partial responses were obtained in 2/15 patients with colon cancer, 3/18 with breast cancer, 2/4 with carcinoma of unknown primary site and 1/2 with pancreatic cancer. Thirteen patients with lung (5), breast (4), colon (2), head and neck (1) and cervical (1) cancers had stable disease. Based on the different toxicity profiles between iproplatin and cisplatin and the possible antitumor efficacy of the former, phase II investigation of iproplatin has been initiated.

Adult↗

Comparative effect of cisplatin, spiroplatin, carboplatin and iproplatin in a human tumor clonogenic assay.

A modified double-layer Hamburger and Salmon cloning assay was used to test cisplatin and its analogs (spiroplatin, carboplatin and iproplatin) on fresh tumor samples from 63 patients with a variety of non-hematological malignancies. Among them were 18 breast cancers, 17 ovarian cancers and 7 of unknown primaries. Half the patients received prior chemotherapy. Cisplatin regimens were given in 16 cases. When possible, cells were exposed for 1 h to each drug in concentrations of 0.1 microgram/ml and 1.0 microgram/ml for cisplatin and spiroplatin, 1.0 microgram/ml and 10 micrograms/ml for carboplatin and iproplatin. A greater than or equal to 50% cell kill with at least one drug was found in 20 samples including 8 ovarian cancers, 3 breast cancers and 1 unknown primary. A greater than or equal to 70% cell kill was seen in 2 samples with cisplatin, 3 with spiroplatin and carboplatin, and 6 with iproplatin. There was only partial cross-resistance between cisplatin and its analogs. Among 57 paired comparisons of cisplatin with spiroplatin, 2 showed drug sensitivity to cisplatin alone, 6 to spiroplatin alone, and 6 to both. The same sort of observation was made with carboplatin. The lack of cross-resistance between cisplatin and iproplatin was particularly striking: among 53 pairs, 6 were sensitive to cisplatin alone, 8 to iproplatin alone, and 2 to both. About 20% of the samples that were resistant to cisplatin were sensitive to iproplatin. Our data show hints of activity in breast and ovarian cancers with all analogs and suggest that they will achieve clinical antitumor activity similar to that they will achieve clinical antitumor activity similar to that of cisplatin. The in vitro evidence of incomplete cross-resistance between cisplatin and its analogs should be investigated further.

Carboplatin↗

Surgery and postoperative radiotherapy in the management of extensive cancer of the cervical lymph nodes from an unknown primary.

Over a 14-year period, from 1971 to 1985, there were 15 patients referred to the Princess Margaret Hospital in Toronto for postoperative radiotherapy to the cervical lymph nodes following radical neck surgery for metastatic cancer. An intensive investigation failed to yield a primary site in any patient. All of the patients had extensive neck disease with significant indications for postoperative radiotherapy (massive neck nodes, invasion of extra nodal structures or fixation to unresectable adjacent structures). Of this highly selected group of patients with advanced neck disease: 4/15 (27%) died within one year of uncontrolled local disease, a further 2/15 (13%) died within four years of metastatic/recurrent disease, 6/15 (33%) died of intercurrent disease and 3/15 (20%) were alive with at least four years follow-up. Although all patients presented with advanced disease, survival and significant palliation was possible in this select group of patients.

Adult↗

Gemcitabine in the second-line therapy of patients with carcinoma of unknown primary site: a phase II trial of the Minnie Pearl Cancer Research Network.

The purpose of this study was to evaluate the activity of single-agent gemcitabine in previously treated patients with carcinoma of unknown primary site. Between January 1997 and October 1998, 39 patients were enrolled in this multicenter Phase II trial performed in the Minnie Pearl Cancer Research Network. Twenty-seven patients (69%) had adenocarcinoma or poorly differentiated adenocarcinoma; 35 patients (90%) had previously received treatment with chemotherapy regimens containing both a platinum agent and a taxane. Only 21% of patients had ever responded to previous therapy. Gemcitabine 1000 mg/m2 was administered intravenously on days 1, 8, and 15 of each 28-day course. Three of 36 evaluable patients (8%) had partial responses, and 9 patients (25%) had minor responses or stable disease with improved symptoms. The median time to progression for patients with partial responses or stable disease/improved symptoms was 5 months. Treatment was well tolerated, with uncommon grade 3 or 4 toxicity. Gemcitabine produced a low objective response rate in this refractory patient population, although approximately one-third of patients experienced symptomatic improvement. Treatment with gemcitabine was well tolerated. Because gemcitabine has activity against a variety of adenocarcinomas, further evaluation of this agent as part of first-line therapy for patients with carcinoma of unknown primary site is appropriate.

Adenocarcinoma↗

Phase II trial of paclitaxel, carboplatin, and etoposide in advanced poorly differentiated neuroendocrine carcinoma: a Minnie Pearl Cancer Research Network Study.

PURPOSE: To evaluate the efficacy of chemotherapy with paclitaxel, carboplatin, and etoposide in advanced adult poorly differentiated neuroendocrine carcinomas. PATIENTS AND METHODS: Patients eligible for this multicenter, phase II trial had metastatic poorly differentiated neuroendocrine carcinoma and had received no previous treatment. Patients with a variety of known primary sites (excepting small-cell lung cancer) and patients with unknown primary site were eligible. Patients received four courses of chemotherapy with paclitaxel, carboplatin, and etoposide, administered at 3-week intervals. After completing four courses of treatment, patients with objective response or stable disease received three courses (24 weeks) of weekly paclitaxel. RESULTS: Seventy-eight patients were treated; 62% had unknown primary site. Forty-one patients (53%) had major responses (complete response rate, 15%), and five patients remain disease free from 18 to 66 months after therapy. Response rates were similar regardless of histology (small-cell v poorly differentiated carcinoma) or primary site. The median, 2-year, and 3-year survivals for the entire group were 14.5 months, 33%, and 24%, respectively. Myelosuppression was the major toxicity, as has been reported previously with this regimen. CONCLUSION: This prospective phase II trial provides additional evidence that this family of relatively uncommon carcinomas is initially chemosensitive, with a high overall response rate to combination chemotherapy and a minority of complete responses. The three-drug regimen evaluated in this trial is moderately toxic, and has no obvious efficacy advantages when compared with standard platinum/etoposide regimens. Treatment for advanced poorly differentiated neuroendocrine carcinoma should parallel treatments used for small-cell lung cancer.

Adult↗

Pattern of head and neck cancers among Nigerians in Lagos.

Three hundred and eight-one cases of head and neck cancers were studied over a 10 year period (1988 - 1998) at the Lagos University Teaching Hospital, Lagos. The aim was to assess the various sites of primary lesion, gender and age distribution and histopathological types. The International Classification of Diagnosis Oncology's (ICDO) 9TH version was used to categorize sites of primary lesion. A yearly incidence of 38 cases was noted with an overall male preponderance. Forty-five percent of the patients with head and neck cancers were in their forth and fifth decades of life. The nasopharynx was the commonest site of primary lesion (16.8%) followed by the nose, paranasal sinuses and middle ear (ICDO - 160) with 13.6%. Laryngeal cancer ranked third accounting for 12.1% of the cases. Other common sites of primary lesion were: the skin (9.2%), the salivary glands (7.6%), the mandible (7.3%) and the thyroid gland (7.3%). Metastatic cancer in the neck with unknown primary lesion was seen in 2.9% of the patients. Cancers associated with heavy tobacco use e.g. laryngeal cancers, lip and tongue cancers showed a very high male predilection with M:F ratios of 10.5:1, 8:1 and 6:1 respectively. 91% of the head and neck cancers were of epithelial tissue origin while sarcomas accounted for only 6.6% of the cases. The results show that head and neck cancers affect Nigerians especially males at the prime of their working life. The devastating psychosocial effects on the individual, the family and the society are enormous. Emphasis on cancer prevention is recommended.

Adult↗