Treatment Of Distant Metastases Research Articles

Pitfalls in the Staging of Cancer of Thyroid

Thyroid cancer includes several neoplasms originating from the thyroid gland-from indolent and curable histologies of differentiated thyroid carcinoma to aggressive anaplastic thyroid carcinoma. Differentiation of thyroid nodules is problematic on CT and MR imaging unless there is evidence of extrathyroidal extension. Evaluation of regional lymph nodes is often performed clinically or with ultrasound. The retropharyngeal and mediastinal lymph nodes are better evaluated by CT and MR imaging. Nuclear scintigraphy is useful for staging and treatment of distant metastasis in differentiated thyroid carcinoma. PET may have a role in aggressive cancers. Accurate staging affects surgical management and subsequent therapy.

Potential Use of Recombinant Human Thyrotropin in the Treatment of Distant Metastases in Patients with Differentiated Thyroid Cancer

In order to effectively treat differentiated thyroid cancer (DTC) with radioiodine (RAI) it is necessary to raise serum TSH levels either endogenously by thyroid hormone withdrawal (THW) or exogenously by administration of recombinant human TSH (rhTSH). The goal of this review is to present current data on the relative efficacy and side effects profile of rhTSH-aided versus THW-aided RAI therapy for the treatment of patients with distant metastases of DTC. We have searched the PubMed database for articles including the keywords "rhTSH", "thyroid cancer", and "distant metastases" published between January 1, 1996 and January 7, 2012. As references, we used clinical case series, case reports, review articles, and practical guidelines. Exogenous stimulation of TSH is associated with better quality of life because it obviates signs and symptoms of hypothyroidism resulting from endogenous TSH stimulation. The rate of neurological complications after rhTSH and THW-aided RAI therapy for brain and spine metastases is similar. The rate of leukopenia, thrombocytopenia, xerostomia, and pulmonary fibrosis is similar after preparation for RAI treatment with rhTSH and THW. There is currently a controversy regarding RAI uptake in metastatic lesions after preparation with rhTSH versus THW, with some studies suggesting equal and some superior uptake after preparation with THW. Analysis of available retrospective studies comparing survival rates, progression free survival, and biochemical and structural response to a dosimetrically-determined dose of RAI shows similar efficacy after preparation for therapy with rhTSH and THW. The rhTSH stimulation is not presently approved by the FDA as a method of preparation for adjunctive therapy with RAI in patients with metastatic DTC. Data on rhTSH compassionate use suggest that rhTSH stimulation is as equally effective as THW as a method of preparation for dosimetry-based RAI treatment in patients with RAI-avid metastatic DTC.

Assessment of advances of outcome quality in colon carcinoma at a single center

SUMMARY Background: Measuring outcome quality in colon carcinoma is important for efficient quality management. Patients & methods: Four complementary methods of survival analysis have been applied to compare the survival of patients with curatively resected colon carcinoma in two time periods: 1978–1994 (n = 979) and 1995–2005 (n = 639). Results: The 5-year survival rates of both cohorts varied widely depending on the applied analysis method with various improvements in the survival rates. The most evident progress was found in cancer-related survival of pathological stage III and IV disease. Conclusion: High-quality, complete follow-up data facilitate a complex analysis of survival. Advances in surgical technique and treatment of distant metastases, both in a multidisciplinary setting when appropriate, may be important reasons for improved survival in colon carcinoma.

Moderne Pharmakotherapie des malignen Melanoms

The incidence of malignant melanoma continues to rise steadily and is one of the 10 most frequent solid tumors in Germany. Cure rates in early clinical stages are high. However, in case of distant metastasis treatment is palliative by operative, radiological und chemo(immuno)therapeutical means. All therapeutic interventions have until now not shown any clear influence on overall survival. The increasing knowledge of tumor biology, tumor immunology, the pathophysiological mechanisms of the tumor stroma and of molecular-biological understanding of melanoma have led the way to an individual treatment approach. Targeted therapy of melanoma has achieved impressive clinical response in clinical studies and has risen expectations for improving medical care for melanoma-patients in the near future.

Claudin expression profiles in Epstein-Barr virus-associated nasopharyngeal carcinoma

Claudins are a family of proteins that are structural and functional components of tight junctions and have crucial roles in the maintenance of cellular arrangement, adhesion and paracellular transport. Recent studies have shown that changes and/or loss of claudin expression plays an important role in tumorigenesis and tumor progression, and altered expression of claudins has been reported in various human carcinomas. Non-keratinizing nasopharyngeal carcinoma (NPC) is a common Epstein-Barr virus (EBV)-associated carcinoma with characteristic clinicopathological features. The aim of this study was to investigate claudin expression profiles in EBV-associated non-keratinizing NPC. We analyzed expressions of claudin-1, -2, -3, and -4 in 18 cases of EBV-associated non-keratinizing NPC by immunohistochemical methods. Claudin-1 was expressed in all 18 cases, but claudin-2 was not expressed in any of the 18 cases. Claudin-3 expression was variable, with 8 of the 18 cases (45%) showing no immunoreactivity for claudin-3. Claudin-4 displayed positive immunoreactivity in all cases, even in claudin-3-negative cases. Claudin-3 and -4 are receptors for cytotoxic Clostridium perfringens enterotoxin (CPE) and CPE has emerged as a potential therapeutic target for malignant tumors expressing claudin-3 and/or -4, because CPE specifically and rapidly lyses cells expressing these proteins. Clinically, treatment of distant metastases is a serious problem in EBV-associated non-keratinizing NPC, because frequently there is lymph node involvement and distant metastasis before detection of the primary tumor. Therefore, CPE therapy may be a potential therapeutic target for EBV-associated non-keratinizing NPC, since our results clearly showed claudin-3 and/or -4 expression in all cases studied.

Cervical cancer therapy: current, future and anti-angiogensis targeted treatment

While the incidence of cervical cancer has declined significantly in the USA, ethnic disparities remain in terms of increased mortality and morbidity. Furthermore, this disease continues to be a significant burden on developing countries, with cervical cancer currently ranked as the second most common cause of cancer-related morbidity and the third most common cause of mortality worldwide. Treatment of cervical cancer has typically been viewed as surgical with possible adjuvant therapy versus initial radiotherapy and platinum-based chemotherapy. Prognosis and therapy for patients with recurrent disease is dependent upon the site of recurrence and ability to pursue curative therapy. This article will review the management of cervical cancer, including studies that have evaluated the treatment of distant metastasis or recurrent disease, as well as discussing the importance of angiogenesis and the use of therapies targeted against this phenomenon.

Management of primary and metastasized melanoma in Germany in the time period 1976–2005: an analysis of the Central Malignant Melanoma Registry of the German Dermatological Society

This study analysed the changes of excision margins in correlation with tumour thickness as recorded over the last three decades in Germany. The study also evaluated surgical management in different geographical regions and treatment options for metastasized melanoma. A total of 42 625 patients with invasive primary cutaneous melanoma, recorded by the German Central Malignant Melanoma Registry between 1976 and 2005 were included. Multiple linear regression analysis was used to investigate time trends of excision margins adjusted for tumour thickness. Excision margins of 5.0 cm were widely used in the late 1970s but since then have been replaced by smaller margins that are dependent on tumour thickness. In the case of primary melanoma, one-step surgery dominated until 1985 and was mostly replaced by two-step excisions since the early 1990s. In eastern Germany, one-step management remained common until the late 1990s. During the last three decades loco-regional metastases were predominantly treated by surgery (up to 80%), whereas systemic therapy decreased. The primary treatment of distant metastases has consistently been systemic chemotherapy. This descriptive retrospective study revealed a significant decrease in excision margins to a maximum of 2.00 cm. A significant trend towards two-step excisions in primary cutaneous melanoma was observed throughout Germany. Management of metastasized melanoma showed a tendency towards surgical procedures in limited disease and an ongoing trend to systemic treatment in advanced disease.

1418 POSTER Post-operative radioiodine therapy in children – an effective tool for decreasing locoregional recurrence and treatment of distant metastases in differentiated thyroid cancer

1418 POSTER Post-operative radioiodine therapy in children – an effective tool for decreasing locoregional recurrence and treatment of distant metastases in differentiated thyroid cancer

Assessment of surgical treatment for distant metastasis from completely resected non-small cell lung cancer

原発性非小細胞肺癌完全切除例の遠隔転移巣に対する外科治療後の予後をretrospectiveに検討した．対象は1998～2003年の期間に原発巣切除と同時あるいは異時性に一臓器のみに認められた数個以内の初遠隔転移巣とした．症例は35例．転移部位は脳，肺，副腎，胸壁がそれぞれ17，10，6，2例，原発巣病理病期（同時転移は考慮せず）はI，II，III期がそれぞれ16，14，5例であった．転移巣術後の2年生存率は全体で68.0％（中間生存期間43.1ヵ月），原発巣病理病期別ではI，II，III期がそれぞれ86.5，53.0，60.0％であった．pN因子別比較ではpN0，pN1-2がそれぞれ82.9，50.3％と有意にpN0症例が予後良好であった．単発あるいは少数個の遠隔転移巣に対する外科治療の有効性はリンパ節転移を認めない原発肺癌早期症例において存在し，その予後の向上に寄与する可能性が示唆された．

Survival patterns in hormone treated advanced breast cancer.

This study investigates a series of factors, all recordable by the time of presentation of distant metastases from primary breast cancer and relates these to survival after the initiation of endocrine therapies. One hundred and ninety-one patients have received endocrine therapy as initial treatment for distant metastases. In all patients both the histological grade and oestrogen receptor (ER) status of primary tumour tissue; the lymph node stage and menopausal status at mastectomy and the disease-free interval and sites of initial metastases are available for analysis. Four of these factors have been found to contribute independently towards prolonged survival after the initiation of treatment: tumour grade, ER status, disease-free interval and sites of metastases. Employing a multivariate analysis incorporating these four factors, three groups of patients have been identified with survivals of 67, 37 and 0 per cent at 18 months on therapy. These three groups of patients contain 37, 41 and 22 per cent of the patient population respectively.

頭頚部原発神経内分泌小細胞癌の２例

This report described two patients with small cell neuroendocrine carcinoma of the larynx (patient 1) and maxillary sinus (patient 2). Immunohistological examination was helpful for the diagnosis. Both patients had lymph node metastasis of the bilateral neck, but at the start of their treatment distant metastasis was not detected by conventional clinical examinations including systemic imaging examinations (computed tomography, magnetic resonance imaging, and radioisotope imaging). Patients responded to systemic chemotherapy with or without radiotherapy. Surgical treatment for the resultant primary tumor and lymph node metastasis was effective. However, after initial treatment, distant metastasis appeared in the brain (patient 1) and in the liver (patient 2). They died 16 months (patient 1) and 7 months (patient 2) after their initial diagnoses. Although chemoradiotherapy and surgical treatment was effective for the regional tumor, the treatment of distant metastasis was crucial for acquiring the long term survival.

Pulmonary Metastasis 12 Years After Resection of Thymoma with Microscopic Capsule Invasion

We report on a 50-year-old female who developed pulmonary metastasis 12 years following the resection of a thymoma with microscopic capsular invasion. The patient was found to have a mediastinal mass at the age of 18 years; however, she refused to undergo surgery. At the age of 38 years, the patient underwent surgery for resection of the tumor; it was diagnosed as a macroscopically encapsulated thymoma with microscopic capsular invasion. Multiple pulmonary metastases occurred 12 years following the resection of the tumor; all the metastatic masses were resected. Although the patient suffered from myasthenia gravis 4 months following the resection of pulmonary metastases, she remains free of myasthenia gravis with no recurrence of tumor at 2 years post-surgery. Long-term follow-up is essential for the detection of recurrence after resection of a thymoma with microscopic capsular invasion, and surgery could be the best treatment for distant metastasis in case of resectable lesions.

Survival benefit of KRN7000 immune therapy in combination with TNP470 in hamster liver metastasis model of pancreatic cancer

Pancreatic cancer is a solid malignancy with the poor prognosis largely due to frequent and lethal liver metastases. The combination of immunotherapy and anti-angiogenesis therapy might be a hopeful strategy for the treatment of distant metastases. The benefits of the combination therapy by an immune stimulator alpha-galactosylceramide (KRN7000) and an angiogenesis inhibitor AGM-1470 (TNP470) were evaluated on the hamster highly aggressive liver metastasis model using the syngeneic pancreatic cancer cell line HPD-NR. KRN7000 immediately activated hepatic mono-nuclear cells to produce IFN-gamma in vitro. Intraportal injection of KRN7000 exhibited a dense accumulation of CD4-CD8- natural killer T cells, around the liver metastases in vivo. KRN7000 treatment significantly inhibited the growth of liver metastases, and importantly, significant survival prolongation was confirmed when TNP470 treatment was added to it. Furthermore, cytotoxic T lymphocytes were induced at the sites of a few residual metastases in the liver of a long-term survivor. Thus, the combination of KRN7000 and TNP470 showed a high effectiveness for the treatment of liver metastases of pancreatic cancer.

Biochemical failure as a determinant of distant metastasis and death in prostate cancer treated with radiotherapy

Purpose Biochemical failure (BF), defined by a rising prostate-specific antigen (PSA) profile, is an early surrogate of treatment failure. However, little evidence is available to show that BF is associated with death for patents with prostate cancer treated with radiotherapy. We examined the relationship between BF and death from prostate cancer. Methods and materials A total of 942 patients were treated between 1987 and 1998 with external beam radiotherapy who had sufficient PSA determinations in follow-up for the analyses described. The median radiation dose was 72 Gy, median PSA was 9.9 ng/mL, and median follow-up was 73 months. The American Society for Therapeutic Radiology and Oncology consensus definition was used to define BF. Kaplan-Meier calculations were from the start of radiotherapy. Cox proportional hazards regression multivariate analyses were used to investigate the association of BF (time-dependent variable) and other factors to distant metastasis (DM), cause-specific death (CSD), and overall death (OD). The year of treatment was included in some of the multivariate analyses to correct for potential unknown factors that may have occurred during the years of the study, such as stage migration. Results BF was observed in 316 patients (34%), and 66 (7%) experienced DM, 32 (3%) died of prostate cancer, and 230 (24%) died overall during the study period. The Kaplan-Meier 5-year rate estimates from the start of treatment for BF, DM, CSD, and OD were 38%, 6%, 3%, and 13%, respectively. All patients with DM had BF. In multivariate analyses, BF was associated with DM and CSD, but not OD. The inclusion of the year of treatment did not alter these relationships. Conclusion BF, as a time-dependent covariate, was the strongest determinant of DM and was also very significantly related to CSD. The inclusion of the year of treatment had little effect on these associations. Longer follow-up is needed to determine conclusively the relationship of BF to OD.

The Treatment of Distant Metastases in Head and Neck Cancer – Present and Future

At the present time the occurrence of distant metastases in patients with head and neck squamous cell carcinoma means that lifespan is measured in months. In most instances treatment is purely palliative. Isolated lung metastasis can be successfully removed with long-term disease control in selected patients. Radiotherapy can be useful for palliation of bone metastases and occasionally lung or brain metastases. Chemotherapy does not have a major impact at the present time except for the treatment of metastases from nasopharyngeal cancer. Palliative symptomatic care, along with appropriate pain control, is essential since pain management is very important in these patients. A significant change in the survival of patients with head and neck cancer is only likely to occur by the development of new approaches to treatment. Blocking tumor angiogenesis and treatment based on genetic abnormalities or cell surface receptors offer the two strategies that are most likely to be successful.

A clinical study on the cervical lymph node metastasis of maxillary sinus carcinoma

Objective: to improve the management of maxillary sinus carcinoma, we retrospectively investigated the significance of cervical lymph node metastasis in our treated cases and discussed how to deal with the cervical lymph node metastasis as a prognostic factor. Methods: medical records of 118 patients with maxillary sinus carcinoma diagnosed and treated in our institute from 1982 to 1997 were retrospectively reviewed. Tumors were staged according to UICC classification 1987. The cumulative survival was analyzed by the Kaplan–Meier method. Generally, the patients had undergone preoperative radiotherapy and surgery. We examined the cervical lymph node metastasis detected at the first examination and the subsequent cervical lymph node metastasis in relation to the prognoses. Results: the incidence of cervical lymph node metastasis at the initial diagnosis was 7.9% ( n=9), and that of secondary cervical lymph node metastasis without recurrence at the primary site after the first treatment was 8.3% ( n=9). In most cases, we observed metastasis to the lymph nodes in the submandibular region and in the jugular chain. The result of treatment of cervical lymph node metastasis was grave. Among the patients with cervical lymph node metastasis detected at the first examination, four patients developed local recurrence and three patients developed distant metastasis. On the other hand, among those with secondary cervical metastasis, three patients developed neck recurrence and three patients developed distant metastasis, but no local recurrence. Conclusions: in the cervical metastasis of maxillary sinus carcinoma, it is important to treat the primary lesion completely. In addition to it, we should control cervical metastasis and careful neck dissection is required. For the patients with cervical lymph node metastasis, it is necessary to consider the further treatment of distant metastasis.

The treatment of distant metastases in soft tissue sarcoma

This article reviews the current standard approaches to the treatment of metastatic soft tissue sarcoma (STS) and evaluates new chemotherapy agents and novel approaches. A computerized search strategy was used to identify articles examining the role of chemotherapy and surgery in metastatic STS, which were published between January 1992 and December 1998. This search was supplemented by key articles from our files published before 1992. In selecting articles for inclusion in this review, emphasis was placed on randomized data and novel approaches. Only three agents-doxorubicin, ifosfamide, and dacarbazine-have shown significant activity in metastatic STS. Numerous studies have examined the efficacy and toxicity of combining the known active agents in standard doses or in high doses with cytokine support. Promising results, in terms of increased response rates, often have not been reproduced in randomized trials, and there is no convincing evidence of enhanced overall survival. New regimens should be evaluated in randomized trials incorporating quality-of-life endpoints. High-dose chemotherapy with bone marrow/stem cell rescue remains an investigational procedure of uncertain efficacy. Pilot studies have established the feasibility of intraperitoneal chemotherapy, after cytoreductive surgery, in patients with peritoneal sarcomatosis. To date, the efficacy of this approach has not been validated in phase II or III trials. The role of surgery in the treatment of isolated pulmonary metastases is well established. Results of small series raise the possibility that resection of hepatic metastases is beneficial in selected patients. Current chemotherapy options for patients with STS are limited. There is reason to hope that the situation will change with the further development of new agents that have novel and specific mechanisms of action.

当院における胃癌診療の特徴 特に腹膜転移の新診断法と肝転移に対する動注化学療法

(1) 開設後30年間に早期癌とくにm癌が増加し非切除が減少した. 1965-1989年の4,839例を5年ごとの5期に分け年代別治療成績を比較した. 非切除 (676例) と根治度C (563例) では変化がなく, 根治度AとB (3,600例) で約20%の向上を認めた. 成績向上はt2, n (+)(395例) で著しく (約33%), 手術単独群の治療成績の向上によりIII期以降では化学療法の併用効果がみられなくなった.(2) 150例の腹腔洗浄細胞診をPCR法と従来法とで比較した. PCR法で41例が, 従来法で27例が陽性と判定され, 18例で判定が異なった. この18例のうち, 従来法で陽性でもPCR法が陰性であった2例には腹膜転移がなく, 従来法で陰性であってもPCR法が陽性であった16例中5例に腹膜転移を認め, 従来法よりもPCR法の方が腹膜転移とより高い相関を示した.(3) 肝転移例に対する抗癌剤 (5-FU, MMC, ADM) の肝動注の効果を40例で検討した. CR6例を含む奏効率72%を得, 50%生存期間は15か月であった.

Surgical issues in the management of melanoma.

The mainstay of treatment of cutaneous melanoma is surgical excision. Excision of the primary disease, lymph node metastases, and in some instances, distant metastases is the only therapeutic strategy that leads to long-term disease-free survival with rare exceptions. Surgical treatment of melanoma can be divided into therapy of the primary lesion, treatment of the lymph nodes, treatment of distant metastases, and treatment of in-transit disease by regional administration of intravascular chemotherapeutics. The current recommendations for each of these four areas is discussed in this review.

Surgical removal of solitary metastasis of colorectal cancer to the lungs

Despite the wide discussion in the literature about the possibility of surgical treatment of distant metastases of colorectal cancer to various organs, the reports about surgical removal of colorectal cancer metastases to the lungs are still rare. According to literature data, frequency of lung surgeries for malignant tumor metastases of various localizations makes up to 4.6% of surgeries for lung cancer, and the 3-year survival rate is observed in 50% of cases, 5-year - in 38%.