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PubMed1995

Delay in diagnostic biopsies in suspected cancer.

The number type and results of test done before biopsy were analyzed in patients with gastrointestinal, and lung cancers, adenocarcinoma of unknown primary site and lymphomas in an attempt to investigate the degree and type of delays in performing a diagnostic biopsy. In the 181 patients evaluated a 9 to 14 days delay diagnostic before a biopsy was done and was consistent across the four malignancies studied. In 59% delay be attributed to continued, frequently low yield, noninvasive tests.

Adenocarcinoma↗
PubMed1996

Paclitaxel via 1-hour infusion: clinical experience.

In phase II trials, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) can be safely administered via a 1-hour infusion. One-hour infusions of paclitaxel also have been administered safely in combination with many other cytotoxic regimens, including cisplatin/etoposide/radiation, carboplatin/etoposide (with or without radiation), mitoxantrone/5-fluorouracil/leucovorin, carboplatin, and carboplatin/5-fluorouracil. Notable activity has been seen in patients with several neoplasms, including stages III/IV non-small cell lung cancer, small cell lung cancer, advanced breast cancer, carcinoma of unknown primary site, urothelial carcinomas, and other advanced squamous cell carcinomas. Further study will determine whether these or similar combinations represent improved therapeutic alternatives.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Melanoma of unknown primary: experience at Massachusetts General Hospital and Dana-Farber Cancer Institute.

Melanoma may present metastatically without an identifiable primary lesion. To further characterize the epidemiology of melanoma of unknown primary (MUP), we report our experience with a cohort of MUP patients. We retrospectively reviewed patients seen at the Massachusetts General Hospital (MGH) and the Dana-Farber Cancer Institute (DFCI) between 1986 and 1996 with follow-up to 2002. Data were analysed using log-rank and proportional hazards analyses, with death from any cause as the main outcome measure. Of the 2485 melanoma patients seen, 65 (2.6%) had MUP; 41 patients were male [63.1%; 95% confidence interval (CI), 50.2%, 74.7%]. The median age at diagnosis was 54.1 years (interquartile range, 39.4-67.1 years). Thirty patients had lymph node metastases, 12 cutaneous or subcutaneous metastases and 23 visceral metastases. Of the 62 patients (95.4%) with at least some follow-up, there were 42 deaths from any cause. Patients with lymph node metastases survived significantly longer than patients with other metastases [5-year survival 38.7% (95% CI, 18.1%, 59.1%) vs. 13.9% (95% CI, 4.4%, 28.6%); P<0.01]. After adjusting for stage and age at diagnosis, there was some evidence that men survived longer than women [hazard ratio (HR)=0.55; 95% CI, 0.28, 1.09]. Survival did not differ amongst patients with different types of non-lymph node metastases. The 5-year survival rates in this cohort did not differ from those of historical controls with known primaries. The demographic and survival characteristics of this MUP cohort mirrored those found in previous studies. More studies of MUP patients, as well as a standardized definition of MUP, may shed light on the pathogenesis and prognosis of MUP.

Adult↗
PubMedDate not supplied

Correlation of lymph node metastases and expression of matrix metalloproteinase-7 in patients with gastric cancer.

BACKGROUND/AIMS: Matrix metalloproteinase-7 (MMP-7) is thought to play an important role in the progression of cancer invasion. However, the expression of MMP-7 in primary and nodal lesions of gastric cancer is unknown. METHODOLOGY: Expression of MMP-7 protein in primary and nodal lesions of human gastric cancer was evaluated by immunohistochemistry. Expression of MMP-7 mRNA in the sentinel node, i.e. the first lymph node in the lymphatic basin to receive metastases from the primary tumor, was evaluated by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Among primary lesions, 73 (48%) of 153 tumors were strongly positive for MMP-7. Strong positivity rates in the primary lesion were associated with deep invasion of the gastric wall, nodal metastases, and infiltration of vessels or lymphatics. Five-year survival rates were 43.8% in patients with strongly positive tumors and 75.0% in patients with weakly positive tumors. Among nodal metastases, 53 (76%) of 70 lesions were strongly positive for MMP-7, which was significantly higher than the strong positivity rate for primary lesions. Strong positivity rates in metastatic lesions were significantly higher when metastatic lymph nodes were present in group 2 or more. All of six patients with peritoneal dissemination in the absence of gastric serosal invasion had nodal metastases strongly positive for MMP-7. Five-year survival rates were 17.5% in patients with strongly positive nodal metastases and 68.6% in patients with weakly positive nodal metastases. RT-PCR demonstrated MMP-7 expression in sentinel nodes of 3 cases of 30. All 3 cases had metastases not only in the sentinel node but also in non-sentinel nodes. However, in 27 cases, including 24 without metastases and 3 with metastases in the sentinel nodes only, expression of MMP-7 in the sentinel nodes was not observed. CONCLUSIONS: MMP-7 may contribute to the invasion of both primary and nodal lesions in patients with gastric cancer. The MMP-7 expression is a useful prognostic factor, and evaluating the expression in sentinel node may help surgeons determine what level of lymph node dissection should be performed.

Humans↗
PubMed2003

[Lymphatic metastasis in the neck from unknown primary. Analysis of treatment results and prognostic factors].

The aim of this study is to analyze the results of treatment results and prognostic factors related to clinical and treatment characteristics in patients with neck lymph nodes metastases from the unknown primary site. 90 patients with pathology proven cancer metastases in the neck lymph nodes from the unknown primary site were treated between 1984-1998. Most of them (58 patients--63%) had advanced disease in lymph nodes N3. The rest had stage N2abc before initial treatment. 40 patients underwent combined treatment--surgery and definitive radiotherapy. 3 patients had induction chemotherapy followed by resection and radiotherapy. 30 patients received radiotherapy alone or radiotherapy and chemotherapy. In 7 cases chemotherapy after surgical resection were used. Curves of overall survival were estimated using Kaplan-Meier method. Analysis of the prognostic factors was performed using Cox's multivariate proportional risk model. 5 years overall survival probability was 24%. In the group of patients who underwent surgery and radiotherapy probability of 5 years overall survival was 43%. In patients who received radiotherapy alone or radiotherapy and chemotherapy probability of 5 year overall survival was 2%. Multivariate analysis showed significant influence of the performance status (PS--WHO scale), sex and stage N3 on overall survival. The patients with PS 0-1 had better prognosis comparing with PS 2-3 (p < 0.001). Male had worse prognosis then female (p = 0.05). N3 stage reduced overall survival in comparison to N2abc (p = 0.06). In the analysis of disease free survival N3-stage was the only independent factor concerning with poor outcome (p = 0.03). Patients who had surgery followed by radiotherapy had better prognosis. Poor performance status, sex-male and N3 stage were identified as the important factors influencing overall survival. N3-stage was an independent factor influencing disease free survival.

Adult↗
PubMed2003

Second primary cancers in patients with laryngeal cancer: a population-based study.

BACKGROUND: Literature regarding incidence of site-specific second cancers after laryngeal cancer is limited. Risk factors associated with second primaries are unknown. METHODS: Second primaries after laryngeal cancer in the SEER database (1973-1996) were analyzed for incidence, relative risk compared with the general population, and potential risk factors, including radiotherapy. Information on chemotherapy and tobacco smoking was not available in the SEER database. RESULTS: Of 20,074 laryngeal cancer patients surviving at least 3 months, 3533 (17.6%) developed second cancers. The cumulative risk of developing a second cancer was 26% at 10 years and 47% at 20 years. Compared with age-adjusted, gender, and tumor-specific rates in the general population, laryngeal cancer patients had higher risks of second cancers overall (observed-to-expected ratio [O/E] = 1.68, 95% confidence interval [CI] = 1.58-1.79), head-and-neck (4.81 [4.31-5.58]), esophageal (3.99 [3.29-4.83]), and lung (3.56 [3.34-3.79]) cancer. Advanced age at initial diagnosis was associated with increased risks of second cancers (p = 0.0001). Radiotherapy was associated with increased risk of second cancers overall (relative risk [RR] = 1.10 [1.02-1.18], p = 0.012), especially second cancers of the lung (RR = 1.18, [1.05-1.33], p = 0.006) and possibly second cancers of the head and neck (RR = 1.26, [0.99-1.60], p = 0.061). Radiotherapy was associated with a 68% excess risk (RR = 1.68, [1.16-2.43], p = 0.007) of developing a second head-and-neck cancer in patients who survived more than 5 years. Second primary was associated with a poor survival (p = 0.0001). CONCLUSIONS: Second cancers after laryngeal cancer are common, especially for long-term survivors. Radiotherapy was associated with a small increased risk of developing second cancers overall and long-term risk of head-and-neck cancers. This data should be interpreted with caution in light of the lack of information on chemotherapy and tobacco smoking in the SEER database. Prevention and early detection are indicated.

Analysis of Variance↗
PubMed2000

Unsuspected metastases presenting as solitary soft tissue lesions: a fourteen-year review.

OBJECTIVE: To describe a series of patients with no known primary malignancy who presented with a solitary unsuspected soft tissue metastasis masquerading as a soft tissue sarcoma, and secondarily to describe the imaging appearance of these lesions. DESIGN: Records of two academic hospitals with active orthopedic oncology services were reviewed for patients meeting the above criteria. Clinical charts were examined, and the imaging appearance of the soft tissue lesions retrospectively reviewed. PATIENTS: Of 1421 patients examined for soft tissue lesions, 11 were found who met the above criteria. RESULTS: Of the 11 patients whose initial presentation was a solitary soft tissue metastasis, eight were found to have a primary lung cancer, two were diagnosed with adenocarcinoma of unknown primary, and adenocarcinoma of the colon was discovered in the remaining patient. CONCLUSIONS: The clinical presentation of a solitary soft tissue metastasis without a known primary malignancy is a rare occurrence, with an incidence of approximately 0.8%. Lung cancer is the primary neoplasm in a high percentage of these cases.

Adenocarcinoma↗
PubMed1977

Mechanism of feminization in primary liver cancer.

Primary liver cancer occasionally presents with feminization. The mechanism is unknown. We studied a young man with primary liver cancer associated with feminization that disappeared after removal of the tumor. Before operation, the serum estrone level was markedly (1113 pg per milliliter) and estradiol and estriol levels were slightly elevated. Human placental lactogen was also increased (0.52 microng per milliliter). Luteinizing hormone, follicle-stimulating hormone and prolactin levels were normal, and testosterone reduced. Beta subunits of human chorionic gonadotropin were not detected in the serum. In vitro assay of tumor tissue showed estrogenic activity and high levels of these subunits. With a reversed isotope dilution technic with crystallization to constant specific activity, we showed the tumor tissue to convert dehydroepiandrosterone sulfate and dehydroepiandrosterone to estrone and estradiol. Production of beta subunits of chorionic gonadotropin and raised serum levels of placental lactogen provided further evidence that the tumor was functioning as trophoblastic tissue.

Adult↗
PubMedDate not supplied

[Origin and distribution of brain metastases].

INTRODUCTION: Malignant neoplasmas account for 20% of overall mortality in developed countries, and are the second leading cause of death. According to the World Health Organization central nervous system tumors account for 4% of all tumors and brain tumors cause 0.2-2.4% of all hospital deaths. By their origin, brain tumors are classified into primary and secondary tumors or metastases. The aims of this study were to examine the number of metastases, their origin and distribution and to compare the prevalence of primary and secondary brain tumors during the same period. MATERIAL AND METHODS: A retrospective cohort study included 63 adults (40 males and 23 females) with diagnosed brain tumors treated during 2001 and 2002 at the Department of Neurology in Novi Sad. Tumors were diagnosed by computed tomography and magnetic resonance imaging. RESULTS: Secondary tumors were also diagnosed, but without statistical significance (2 = 0.38; p > 0.05) and metastases were significantly more frequent among men (2 = 14.22; p < 0.01). Supratentorial metastases were significantly more frequent than tumors in other localizations (2 = 23.6; p < 0.01). Multiple metastases were estimated in 56% of patients and solitary tumors in 44%, without statistical significance (2 = 0.48; p > 0.05). In most cases metastases originated from primary lung cancers and tumors of unknown origin. CONCLUSIONS: During the studied period more secondary than primary tumors have been diagnosed and more multiple than solitary metastases. They were more frequent in men with supratentorial distribution as most frequent. Lung cancer proved to be their most common source.

Adolescent↗
PubMed1986

Direct effects of the hypoxic cell sensitizer misonidazole on colony formation in a human tumor cloning assay.

The human tumor cloning assay as described by Hamburger and Salmon was utilized to study the direct antitumor effects of the hypoxic cell sensitizer misonidazole (MISO). Cells from 106 tumor specimens directly obtained from patients were exposed to MISO at clinically achievable drug concentrations (0.5 mM). Of 30 evaluable tumors, seven specimens (23%) showed a less than or equal to 50% decrease of TCFU's. In vitro sensitivity to MISO was noted in human breast cancer, renal cancer, non small-cell lung cancer, and adenocarcinoma of unknown primary site. A dose response relationship was demonstrated in a subset of experiments including 6 patient's tumors and one human breast cancer cell-line. An analysis relating MISO sensitivity or resistance to the results obtained with other, simultaneously tested standard anticancer drugs indicated that tumors exhibiting a less than or equal to 50% decrease of TCFU's in the presence of MISO were also likely to be sensitive to other cytotoxic drugs. In summary, our data suggest that the 'nitroimidazoles' may exert clinically significant direct antitumor effects in individual tumors. The human tumor cloning assay may have potential to evaluate these direct effects of MISO-analogues and other new radiosensitizers currently being tested in clinical trials.

Antineoplastic Agents↗
PubMed1999

Is it reasonable to use faecal occult blood test for colorectal cancer screening?

There is a high prevalence and incidence of colorectal cancer in industrial countries. It is the commonest cancer in women after breast cancer and in men after prostate and lung cancer and one of the most common causes of death from malignant disease. The cause of colorectal cancer is unknown, thus primary-prevention programs could not be elaborated and the only occasion to reduce mortality is the use of screening to detect this cancer early. Faecal occult blood test (FOBT) was chosen for screening. Large population based trials included thousands of inhabitants of the United States and Europe to demonstrate: 1. Screening with FOBT Hemoccult II reduced mortality from colorectal cancer. 2. In the screening group the incidence of advanced stages of colorectal cancer decreased (Dukes' D stage). 3. The ideal balance between sensitivity and specificity revealed HemeSelect (immunodiagnosis of human haemoglobine) and combined test (Hemoccult II Sensa + HemeSelect). These two screening tests for colorectal cancer have not been verified by large population trials. 4. More sensitive guaiac tests decrease their own specificity and also lead to increase rate of expensive colon examinations. 5. The high-risk population for colorectal cancer ought to be submitted to screening. The problem is the detection of this group. 6. Patients' compliance to screening differs in various trials, but the percentage of patients undergoing FOBT evaluation decreases as the number of screenings increases. Therefore faecal occult blood test could be recommended for national programs of the screening for colorectal cancer.

Colorectal Neoplasms↗
PubMed1998

Resection of liver metastases from a noncolorectal primary: indications and results based on 147 monocentric patients.

BACKGROUND: Very few series have reported indications for and results of hepatectomy for isolated unique or multiple liver metastases (LM) from a noncolorectal primary. We performed a prospective analysis of 147 patients submitted to hepatectomy for LM to evaluate the results and indications for this unusual type of treatment. STUDY DESIGN: Of 538 patients submitted to hepatectomy for a malignant tumor between 1984 and 1996, 147 underwent operations for noncolorectal LM. Conventional and unconventional hepatectomy procedures were used with intermittent clamping of the hepatic pedicle, and in some patients with intermittent vascular occlusion of the liver. RESULTS: Postoperative hospital mortality was 2%. The crude 5-year survival was 36%, and survival without progressive disease was 28%. No difference was observed in survival when synchronous and metachronous LM were compared, or when patients with more or fewer than three LM were compared. Five-year survival rates were 20% for 35 breast cancers, 74% for 27 neuroendocrine tumors, 46% for 20 testicular tumors, 18% for 13 sarcomas, and slightly less than 20% for 11 gastric carcinomas, 10 melanomas, and 7 tumors of the gallbladder, according to the primary. Survival exceeded 20% for 6 gynecologic tumors but was disappointing for head and neck cancers, when the primary was unknown, or when the tumor was truly undifferentiated. CONCLUSIONS: Certain guidelines emerge from this series on the indications and uses of adjuvant chemotherapy. Indications for hepatectomy are relatively straightforward for neuroendocrine, testicular, and renal tumors. Hepatectomy for LM from other primaries appears beneficial in certain sarcomas, breast and gynecologic cancers, and perhaps melanoma, for which selection criteria, unfortunately, remain obscure.

Adolescent↗
PubMed2006

Cutaneous metastases of lung cancer.

It is uncommon for a cancer to be diagnosed because of skin metastases. Cutaneous metastases as initial manifestation of internal neoplasias, represent only 0.8% of total cases and implies, in general, a very advanced grade of the disease and short survival. When skin metastases of an unknown primary site appear, lung cancer is the first option to be discarded in case of men, and breast cancer in case of women. Lung cancer spreads to the skin in 2.8-8.7% of the cases, in advanced phases of the disease, although just in 7-23.8% of the cases, cutaneous metastases appear as first manifestation of the primary tumor. Sometimes, a complete examination to discover the tumor reveals no metastases elsewhere.

Adult↗
PubMed2005

Cancer patients' first treatment episode with opioids: a pharmaco-epidemiological perspective.

GOAL: The factors underlying the choice of opioids for cancer patients in primary care are largely unknown. Our aim was to describe cancer patients' first treatment episode with opioids in relation to disease characteristics and clinical course. PATIENTS AND METHODS: During 1997 and 1998, a population-based cohort of 4,006 incident cancer patients from a Danish county was identified. The patients were followed up from diagnosis to death or until 31 December 2003, and data on their use of opioids were obtained from a prescription database. MAIN RESULTS: Eventually, 54% of the cancer patients became incident users of opioids. Opioid treatment was initiated close to the diagnosis date in 20% of the patients. Most incident users (57%) were not terminal when they began using opioids, and 44% survived the first treatment episode. Of those who died, 70% received opioids in their terminal phase. The incidence rates of new opioid users were inversely related to the 5-year cancer survival period. A weak opioid was the first choice in 64% of the non-terminal users and in 43% of the terminal ones. No statistically significant differences in opioid use were found between men and women. CONCLUSIONS: Opioid use in cancer patients was not confined to the terminal course. Treatment with opioids should be viewed as a dynamic condition, with patients shifting between periods of use and non-use. The aggressiveness of the cancer and the presence of metastases were characteristics found to be strong determinants of opioid use.

Aged↗
PubMed1998

[Cancer metastases to the cervical lymph nodes in an unknown primary location of the tumor].

Out of 120 patients hospitalized with the diagnosis of metastases to the cervical lymph nodes and unknown primary location of the tumor, tumors were detected in 29 and lymphosarcoma in 10. In 24 (82.7%) patients the tumor was located in the upper respiratory tract and gastrointestinal tract. Malignant tumors of the naso- and stomatopharynx and vestibular part of the larynx most often metastasize into the lymph nodes. Radiotherapy was administered to all 81 patients with metastases and unknown location of the primary tumor and to 10 patients with lymphosarcoma of the cervical lymph nodes. The protocol of radiotherapy took account of the site of the metastases and probable primary tumor. A radical course provides cure in 15% of cases, as shown by follow-up of at least 2 years.

Adult↗
PubMed1983

Technetium-99m glucoheptonate imaging in lung cancer and benign lung disease: concise communication.

We prospectively studied technetium-99m glucoheptonate (Tc-GHA) uptake in 58 patients with newly diagnosed lung cancer and in 20 patients with pulmonary inflammatory disease or metastatic carcinoma. Fifty-three (91%) primary tumors accumulated Tc-GHA: squamous cell 20/22, adenocarcinoma 7/7, large cell 10/11, and small cell 16/18. Intensity of tumor uptake was greatest in small-cell cancer. Supraclavicular metastases were detected in two patients. Fourteen patients with mediastinal evaluation by Tc-GHA imaging and trispiral tomography underwent mediastinoscopy or thoracotomy. Five of ten patients with negative mediastinum by tomography and Tc-GHA imaging showed metastases by biopsy (false-negative Tc-GHA). Less intense accumulation of Tc-GHA was observed in 18/20 cases of pulmonary inflammatory disease or pulmonary metastases. Although Tc-GHA accumulates by an unknown mechanism in primary lung cancer, we cannot recommend its use in detecting mediastinal spread of lung cancer due to its unacceptably high false-negative rate.

Adenocarcinoma↗
PubMed2000

FDG PET detection of unknown primary tumors.

UNLABELLED: The management of patients presenting with metastases of unknown primary origin remains a clinical challenge despite a large variety of imaging modalities. The aim of this study was to evaluate FDG PET in detecting the sites of primary cancer in these patients. METHODS: Fifty-three patients with metastatic cervical adenopathy (n = 44) or extracervical metastases (n = 9) of unknown primary origin were included after extensive but inconclusive conventional diagnostic work-up. Patients received 370 MBq FDG (10 mCi) intravenously, and whole-body images were acquired at 60 min after injection. Clinical, surgical, and histopathologic findings and complete correlative imaging were used to assess the results. RESULTS: In 27 of 53 patients FDG PET showed focal tracer accumulations corresponding to potential primary tumor sites located in the lungs (n = 12), the palatine tonsil (n = 5), the salivary glands (n = 2), the nasopharynx (n = 1), the oropharynx (n = 3), the maxillary sinus (n = 1), and the larynx (n = 1). Moreover, in 2 patients FDG PET revealed lesions suspected to be tumors in the breast and the ileocolonic area. In 20 (37.8%) of these 53 patients FDG PET was true-positive, identifying the primary tumor in the lungs (n = 10), the head and neck region (n = 8), the breast (n = 1), and the ileocolonic area (n = 1). In 6 of 27 patients FDG PET was false-positive, predominantly identifying suspicious areas in the palatine tonsil (n = 3). One patient denied further diagnostic work-up after PET; thus, positive PET could not be evaluated. In 26 of 53 patients PET did not reveal lesions suspected to be the primary. However, primary tumors were not found in these patients at clinical follow-up. CONCLUSION: FDG PET is a valuable diagnostic tool in patients with cancer of unknown primary because it imaged unknown primary tumors in about one third of all patients investigated. In addition, FDG PET assists in both guiding biopsies for histologic evaluation and selecting the appropriate treatment protocols for these patients.

Adult↗
PubMed1994

[Expression of transforming growth factor beta-3 (TGF-beta-3) on reactive and malignant cells in ascites and pleural effusion].

PATIENTS AND METHOD: The expression of TGF-beta-3 was examined in 64 patients with reactive and malignant effusion by immunocytochemistry. RESULT: In about half of the patients with malignant effusions (especially breast cancer, gastric cancer, and carcinomas of unknown primary) TGF-beta positive tumor cells could be detected. We could show here for the first time that reactive mesothelial cells could also express TGF-beta. Lymphatic cells were negative in all cases. TGF-beta-3 bioactivity could also be detected in the effusions studied. In our group of patients with far advanced cancer, the expression of TGF-beta had no clear-cut clinical or prognostic correlate. However, the expression of TGF-beta on tumor cells should be interpreted as a marker of tumor progression, taking into account the fibrogenic, angiogenic and immunosuppressive properties of TGF-beta. CONCLUSION: Further research is necessary to answer the question if the 3 isoforms of TGF-beta are coordinately expressed and to elucidate the involvement of this cytokine in tumor progression and metastasis.

Adult↗