Contraction velocity influence the magnitude and etiology of neuromuscular fatigue during repeated maximal contractions.

This study aimed to compare the magnitude and etiology of neuromuscular fatigue during maximal repeated contractions performed in two contraction modes (concentric vs isometric) and at two contraction velocities (30/s vs 240°/s). Eleven lower limb-trained males performed 20 sets of maximal contractions at three different angular velocities: 0°/s (KE0), 30/s (KE30), and 240°/s (KE240). Cumulated work, number of contraction, duty cycle, and contraction time were controlled. Torque, superimposed and resting twitches, as well as gas exchange, were analyzed. Increasing contraction velocity was associated with greater maximal voluntary torque loss (KE0: -9.8 ± 3.9%; KE30: -16.4 ± 8.5%; KE240: -32.6 ± 6.3%; P < 0.05). Interestingly, the torque decrease was similar for a given cumulated work. Compared with KE0, KE240 generated a greater evoked torque loss (Db100: -24.3 ± 5.3% vs -5.9 ± 6.9%; P < 0.001), a higher O2 consumption (23.7 ± 6.4 mL/min/kg vs 15.7 ± 3.8 mL/min/kg; P < 0.001), but a lower voluntary activation (VA) loss (-4.3 ± 1.6% vs -11.2 ± 4.9%; P < 0.001). The neuromuscular perturbations were intermediate for KE30 (Db100: -10.0 ± 6.8%; VA: -7.2 ± 2.8%). Although the amount of mechanical work cumulated strongly determined the magnitude of torque decrease, the contraction velocity and mode influenced the origin of the neuromuscular fatigue. The metabolic stress and peripheral fatigue increased but reduction of VA is attenuated when the contraction velocity increased from 0°/s to 240°/s.

Investigation of cartilage degradation in patients with spinal cord injury by CTX-II.

STUDY DESIGN: Clinical cross-sectional study. OBJECTIVES: To investigate the cartilage degradation by turnover of C-telopeptide fragments of collagen type-II (CTX-II), a molecule specific for articular cartilage in spinal cord injured patients with respect to clinical functional status. SETTING: Physical Medicine and Rehabilitation Clinics, hospital settings. METHODS: In 68 patients with spinal cord injury (SCI) level and severity of lesion, duration of disease, American Spinal Injury Association Impairment Scale (AIS), motor and sensory score, presence of spasticity, functional ambulation score (FAS) and duration of daily ambulation were evaluated. Cartilage degradation was demonstrated by urinary CTX-II (uCTX-II) measured by enzyme-linked immunosorbent assay. T test, analysis of variance and Pearson correlation analysis were used for statistical calculations. RESULTS: uCTX-II level was significantly higher in patients with AIS grade A, non-functional ambulators or in patients who did not ambulate at all (P<0.05). Although AIS grade, lower extremity motor score, FAS score and duration of daily ambulation were found to be correlated (P<0.05) with uCTX-II, duration of disease, level of neurological lesion, presence of spasticity were not. CONCLUSION: This is the first study providing evidence that cartilage degradation is associated with elevated uCTX-II levels in non-ambulating or non-functional ambulating SCI patients. AIS grade A, FAS zero score and no time for daily ambulation were found to cause significant differences in CTX-II level. It may be important to initiate therapeutic programs as soon as possible after SCI to prevent cartilage atrophy.

Cancer-related fatigue and depression: a monocentric, prospective, cross-sectional study in advanced solid tumors.

BACKGROUND: Cancer-related fatigue (CRF) is common in patients with advanced solid tumors and several risk factors are described. The possible role of depression is reported by clinicians despite the association with CRF being unclear. MATERIAL AND METHODS: In this monocentric, cross-sectional, prospective study we recruited patients with advanced solid tumors who were hospitalized at Fondazione IRCCS Istituto Nazionale dei Tumori of Milan. The primary objective was to assess the correlation between CRF and depression. Secondary objectives were the estimation of CRF and depression prevalence and the identification of associated clinical risk factors. CRF and depression were evaluated through the Functional Assessment of Cancer Therapy-Fatigue subscale and the Zung Self Depression Scale (ZSDS) questionnaires. The Cochran-Armitage trend test was used to demonstrate the primary hypothesis. Univariate and multivariate logistic regression models were used to investigate the impact of clinical variables. RESULTS: A total of 136 patients were enrolled. The primary analysis found a linear correlation (P < 0.0001) between CRF and depression. The prevalence of CRF and of moderate to severe depressive symptoms was 43.5% and 29.2%, respectively. In univariate analysis, patients with poor Eastern Cooperative Oncology Group performance status (ECOG PS), anemia, distress, pain, and receiving oncological treatment were at a significantly higher risk for CRF, whereas poor ECOG PS, pain, and distress were risk factors for depression. In multivariate analysis, high levels of ZSDS were confirmed to be correlated to CRF: odds ratio of 3.86 [95% confidence interval (CI) 0.98-15.20) and 11.20 (95% CI 2.35-53.36) for ZSDS of 50-59 and 60-100, respectively (P value for trend 0.002). Moreover, the ECOG PS score was confirmed to be significantly associated with CRF (OR 7.20; 95% CI 1.73-29.96; P = 0.007). CONCLUSIONS: Our data suggest a strong correlation between CRF and depression in patients with advanced solid tumors. Further investigations are needed to better understand this relationship and if depressive disorder therapeutic strategies could also impact on CRF.

Ultrasonographic and biochemical evaluation of visceral obesity in obese women with non-alcoholic fatty liver disease.

OBJECTIVE: Identification of specific origin of lipid accumulation in the liver of patients with non-alcoholic fatty liver disease (NAFLD) is the most important step in preventing this condition. Because liver steatosis, in the obese patients without any systemic disease, can be graded easily by ultrasonography (US), we aimed to demonstrate the degree of liver steatosis and abdominal fat distribution by US, furthermore evaluate biochemical, anthropometrical measurements, and define the possible relationship between these parameters in obese women with different grades of liver steatosis. METHODS: In this controlled clinical study, according to US evaluation of liver steatosis, the patients were divided into four groups: control (no steatosis), mild, moderate and severe steatosis groups. Demographic, biochemical and anthropometric measurements were done. Insulin resistance was determined by using homeostasis model assessment (HOMA-IR). Liver steatosis and abdominal fat distributions were evaluated by US. RESULTS: The subcutaneous and preperitoneal fat layer measurements did not show any significant difference between the groups. The visceral fat layer thickness was significantly higher in severe liver steatosis group compared to the control and steatosis groups. The highest serum fasting insulin, uric acid levels and HOMA-IR index were observed in the severe liver steatosis group. Visceral fat thickness was positively correlated with serum UA levels and HOMA-IR CONCLUSIONS: This study suggests that visceral adipose tissue, HOMA-IR and serum uric acid levels are the main determinants of NAFLD in obese patients.

Behavior of borderline tumors with particular interest to persistence, recurrence, and progression to invasive carcinoma: a prospective study.

PURPOSE: Borderline tumors account for 10% to 20% of epithelial ovarian tumors, and their prognosis is outstanding; nevertheless, a mortality of up to 20% has been reported, particularly in earlier reports. There is a lack of information about the actual mortality and the rate of progression into invasive carcinoma in large and prospectively accrued populations. PATIENTS AND METHODS: All women with borderline ovarian tumors undergoing primary surgery in our department or referred within 3 months from surgery performed elsewhere from 1982 to 1997 were prospectively accrued and observed. RESULTS: We studied 339 women (83.4% stage I, 7.9% stage II, and 8.5% stage III). The median age at diagnosis was 39 years. A total of 150 women underwent radical surgery, and 189 underwent fertility-sparing surgery. After surgery, 13 women had macroscopic residual disease. With a median follow-up of 70 months, 317 women are alive with no clinical disease (eight with documented subclinical persistence of implants), three are alive with clinical disease, two died of disease, 10 died of other reasons, and seven women have been lost to follow-up. The recurrence of disease was higher after fertility-sparing surgery (35 of 189 cases) than after radical surgery (seven of 150 cases); nevertheless, all but one woman with recurrence of borderline tumor or progression to carcinoma after conservative surgery were salvaged. We observed seven progressions (2.0%) into invasive carcinoma, five in serous tumors (2.4%), and two in mucinous tumors (1.6%). The disease-free survival is 99.6% in stage I patients, 95.8% in stage II, and 89% in stage III. CONCLUSION: The survival of patients with borderline tumors is higher than previously described in some retrospective studies. Conservative surgery is safe and may be proposed to several patients with early and disseminated disease after thorough discussion of all therapeutic options. Progression to carcinoma is approximately 2% and may be observed in both mucinous and serous tumors.

Neurotoxicity and ototoxicity of cisplatin plus paclitaxel in comparison to cisplatin plus cyclophosphamide in patients with epithelial ovarian cancer.

PURPOSE: To compare the neurotoxicity and ototoxicity of combination cisplatin plus paclitaxel versus cisplatin plus cyclophosphamide using extensive clinical and instrumental evaluation. PATIENTS AND METHODS: Forty-six of 51 consecutive patients affected by-epithelial ovarian cancer seen in our institution between October 1994 and August 1995 entered the study. After randomization, they were assigned to receive cisplatin 75 mg/m2 every 3 weeks associated with cyclophosphamide 750 mg/m2 (CC group, n = 22) or paclitaxel 175 mg/m2 over a 3-hour infusion (CP group, n = 24). Treatment was repeated six times in 43 patients and nine times in 25. Before treatment and after three, six, and nine courses of chemotherapy, patients underwent clinical and instrumental neurologic and otologic examinations. RESULTS: Mild sensory impairment was evident even after only three courses of both treatments and signs and symptoms were more severe at the end of treatment. On clinical grounds only, it was possible to demonstrate after six and nine courses a difference between CC and CP treatment, due to the involvement in some CP patients of pain and thermal sensory modalities. However, the overall severity of the neuropathy was similar. Audiometric parameters demonstrated a more negative outcome after treatment in CC compared with CP patients. However, the different severity of the involvement was closely correlated to this initial difference in audiologic performance. CONCLUSION: Up to nine courses of chemotherapy, the CC and CP schedules are similar in terms of severity of neurotoxicity and ototoxicity when patients are evaluated during and immediately after treatment. With the doses used in our study, these toxicities are not dose-limiting. Our results suggest that most of the toxic effects observed during the treatment were due to cisplatin.

Mycobacterium tuberculosis complex DNA does not exist in atheromatous plaques.

The possible potential role of several infectious agents in atherosclerosis has been shown. Several infectious agents DNA in atheromatous plaques have been displayed by PCR. In patients with atheromas antibody levels against Hsp65 were higher. Vaccination of mice with recombinant Hsp65 and Hsp65-rich M. tuberculosis resulted in formation of atheromatous plaques. We attempted to detect M. tuberculosis DNA in atherosclerotic plaque samples by PCR. In endarterectomy tissue samples obtained from patients during coronary artery bypass graft surgery DNA was prepared by proteinase-K digestion, phenol/chloroform extraction and ethanol precipitation. After amplification with M.tuberculosis complex IS6110 region specific primers, the products were analyzed on electrophoresis. M. tuberculosis DNA was negative in all tissue samples. More data on etiological studies with mycobacteriaceae will be yield information on atherosclerosis pathogenesis.

Assessment of human papilloma viral load of archival cervical intraepithelial neoplasia by real-time polymerase chain reaction in a Turkish population.

The purpose of this study was to determine the existence, and viral load of human papilloma virus (HPV) subtypes 16 and 18 in paraffinized cervical intraepithelial neoplasia (CIN) samples by real-time polymerase chain reaction (RT-PCR). Overall 94 women were included. Of these patients 47 (50%) had CIN I, 27 (28.8%) had CIN II, and 20 (21.2%) had CIN III. HPV positivity for these three groups were 4.2%, 14.8% and 45%, respectively. HPV positivity in CIN III patients was significantly higher than CIN I (OR = 18.41, 95% CI 3.00-145.73; p < 0.001), and CIN II patients (OR = 4.70, 95% CI 1.00-23.76; p = 0.05). The difference between CIN I and II was not significant (p = 0.18). Viral loads were 10(2), and 10(4) copy/ml for two CIN I patients; 10(2), 10(3), and 10(5) for three CIN II patients; and 10(2), 10(3), 10(4), 10(4), 10(5), 10(5), and 10(6) copy/ml for eight patients with CIN III. Viral load of the remaining one patient could not be assessed. No significant variance was noted among the groups with respect to viral load (p = 0.73). RT-PCR had important advantages of detecting, typing, and quantifying at the same time. Although HPV positivity was increased significantly by the degree of lesions, this relation was not observed for viral load.

[Hemolytic uremic syndrome]. / La sindrome emolitico uremica.

Hemolytic uremic syndrome (HUS) is a disease characterized by non immune hemolytic anemia, low platelet count and renal impairment. In children, the disease is most commonly triggered by Shiga-like toxin (Stx)-producing Escherichia coli (Stx-E. Coli): however, renal function recovers in up to 70% of patients. Plasma infusion or exchange reduces mortality and the risk of end-stage renal disease (ESRD) in adult patients. Non-Shiga toxin-associated HUS (non-Stx-HUS), accounting for only 5-10% of all disease cases, can be sporadic or familial. Collectively, non-Stx-HUS forms have a poor outcome. Up to 50% of cases progress to ESRD or have irreversible brain damage, and 25% can die during the acute phase of the disease. Genetic studies have recently documented that the familial form is associated with genetic abnormalities of complement regulatory proteins, and evidence is now emerging that similar genetic alterations can predispose to sporadic cases of non-Stx-HUS as well. Mutations of genes encoding for factor H, a glycoprotein that plays an important role in the regulation of the alternative pathway of complement and for MCP, a widely expressed transmembrane glycoprotein with an inhibitory role of activated C3, are reported in familial HUS. These mutations are more likely to predispose rather than to cause the disease directly.

Circulating adhesion molecules and arterial stiffness.

AIM: VCAM-1 and ICAM-1 are two important members of the immunoglobulin gene superfamily of adhesion molecules, and their potential role as biomarkers of diagnosis, severity and prognosis of cardiovascular disease has been investigated in a number of clinical studies. The aim of the present study was to determine the relationship between circulating ICAM-1 and VCAM-1 levels and aortic stiffness in patients referred for echocardiographic examination. METHODS: Aortic distensibility was determined by echocardiography using systolic and diastolic aortic diameters in 63 consecutive patients referred for echocardiography. Venous samples were collected in the morning after a 12-hour overnight fast, and serum concentrations of ICAM-1 and VCAM-1 were measured using commercial enzyme immunoassay kits. RESULTS: Data of a total of 63 participants (mean age 55.6 ± 10.5 years, 31 male) were included in the study. Circulating levels of adhesion molecules were VCAM-1: 12.604 ± 3.904 ng/ml and ICAM-1: 45.417 ± 31.429 ng/ml. We were unable to demonstrate any correlation between indices of aortic stiffness and VCAM-1 and ICAM-1 levels. CONCLUSION: The role of soluble adhesion molecules in cardiovascular disease has not been fully established and clinical studies show inconsistent results. Our results indicate that levels of circulating adhesion molecules cannot be used as markers of aortic stiffness in patients.

Multiple myeloma and severe renal failure: a clinicopathologic study of outcome and prognosis in 34 patients.

Renal failure (RF) occurring in the course of multiple myeloma is often judged irreversible and generally considered an ominous complication. The aim of the present study was to re-evaluate the outcome, triggering conditions and prognostic factors of severe RF in a series of 34 patients, 33 to 90 years old. RF was totally reversible in 7 patients and partially reversible in 9 although 6 of them had to be temporarily dialyzed. However, the improvement in renal function was often very slow as indicated by an average recovery time of 115 days. The high rate of RF reversibility was associated with markedly lengthened survival. Review of triggering events confirmed the leading role of dehydration and hypercalcemia, but further suggested that intake of nonsteroidal anti-inflammatory drugs and renal infection might play a part in the development of RF. Systematic statistical analysis of potential prognostic factors showed that the outcome was significantly more severe in females, but age, myeloma characteristics including tumor mass, calcemia, and triggering events had no predictive value. The most reliable prognostic indicators were provided by analysis of kidney biopsy performed in 30 patients. Complete recovery from RF was observed only in the absence of global tubular atrophy and interstitial damage. In contrast, cast-induced tubular obstruction detected by the presence of Tamm-Horsfall protein in urinary space of glomeruli did not seem to influence the outcome of RF. Finally, we analyzed the prognostic value of immunochemical properties of light chains (LC). Lambda LC were unexpectedly detected in 2 of 3 patients, as compared to a ratio of 1 to 3 in the population of normal and monoclonal Ig, but LC type did not correlate with the course of RF. Isoelectric points of LC measured in 32 patients were dispersed from 5.2 to 8.9 and bore only weak prognostic significance. These results underline the value of kidney biopsy and justify aggressive treatment including dialysis and chemotherapy.

Pixantrone (BBR2778) reduces the severity of experimental allergic encephalomyelitis.

Pixantrone is less cardiotoxic and is similarly effective to mitoxantrone (MTX) as an antineoplastic drug. In our study, pixantrone reduced the severity of acute and decreased the relapse rate of chronic relapsing experimental allergic encephalomyelitis (EAE) in rats. A marked and long-lasting decrease in CD3+, CD4+, CD8+ and CD45RA+ blood cells and reduced anti-MBP titers were observed with both pixantrone and MTX. In vitro mitogen- and antigen-induced T-cell proliferation tests of human and rodents cells evidenced that pixantrone was effective at concentrations which can be effectively obtained after i.v. administration in humans. Cardiotoxicity was present only in MTX-treated rats. The effectiveness and the favorable safety profile makes pixantrone a most promising immunosuppressant agent for clinical use in multiple sclerosis (MS).

Is platelet phospholipid-dependent thrombin generation altered by acute myocardial infarction or aspirin?

The ability of unactivated and calcium ionophore activated platelets to support thrombin generation in defibrinated plasma was measured by a chromogenic substrate assay in the absence of clot formation. Platelet phospholipid-dependent thrombin generation (Platelet-TG) could be measured using platelets isolated from blood collected into either sodium citrate or EDTA as anticoagulant. Measurements were stable in samples kept at room temperature for 24 hours after venesection. There was no significant difference in either the unactivated or activated platelet-TG with platelets collected into either anticoagulant (mean difference 10.12 nmol/min unactivated and 10.60 nmol/min activated). There was no correlation between unactivated and activated platelet-TG and patient age. Platelet-TG was 179 (153-237) nmol/min (median and inter quartile range) for unactivated and 489 (462-508) nmol/min for activated platelets from healthy volunteer subjects (median age 31, range 20-40 years). Platelet-TG was the same in subjects from a population-based cohort study (median age 58, range 45-70 years [162 (142-193) nmol/min and 527 (490-551) nmol/min, unactivated and activated platelets respectively] as compared to patients admitted with acute myocardial infarction (median age 68, range 36-85 years [179 (146-200) nmol/min and 473 (440-517) nmol/min unactivated and activated platelets respectively] (p = 0.497 for comparison between unactivated platelet-TGs and p = 0.487 for comparison between activated platelet-TGs in the two groups). Aspirin inhibited platelet aggregation but did not affect platelet-TG using either unactivated or activated platelets exposed to aspirin in vitro; or in vivo, using platelets obtained from individuals after ingestion of aspirin. In conclusion these results show that for measurement of platelet-TG, blood samples can be anticoagulated with EDTA as well as sodium citrate for up to 24 hours after venesection and that this measurement is not affected by subject age, aspirin treatment or the acute stage of myocardial infarction.

Clinical relevance of retroperitoneal involvement from epithelial ovarian tumors of borderline malignancy.

Rota SM, Zanetta G, Ieda N, Rossi R, Chiari S, Perego P, Mangioni C. Clinical relevance of retroperitoneal involvement from epithelial ovarian tumors of borderline malignancy. Ovarian tumors of borderline malignancy have an outstanding prognosis. The need for aggressive surgical staging is questionable and the need for retroperitoneal node sampling is debated. From 1982 to 1996, 81 women underwent surgical staging including retroperitoneal sampling. Three patients (3.7%) with serous tumor had microscopic nodal involvement. Retroperitoneal metastases were found in two intraperitoneal stage I tumors and in one stage IIIA tumor. Positive nodes were found in 1/31 (3.2%) women undergoing sampling of para-aortic nodes and in 2/69 (2.8%) women undergoing sampling of pelvic nodes. With a median follow-up of 79 months we observed five recurrences, but none involved the retroperitoneum. The three patients with positive nodes remain alive without disease. Among 236 patients with diagnosis of borderline tumor but without sampling of the nodes, we observed one retroperitoneal recurrence (0.4%) in a serous tumor. There are no indications for retroperitoneal sampling of mucinous borderline tumors. For serous tumors this procedure should only be performed as a part of prospective trials. The clinical relevance of retroperitoneal involvement in borderline tumors appears minimal and does not justify routine aggressive surgery.

Seroprevalence of rubella virus in Turkish pregnant women.

OBJECTIVES: To assess the immune status of a group of Turkish pregnant women who had never been immunized. METHODS: Between June 1990 and April 1993, the seroprevelance of rubella was determined in the study group of 1351 women. RESULTS: A total of 242 (17.9%) pregnant women were found to be susceptible to rubella infection and the seropositivity rate related to prior infection was 82.1%. CONCLUSIONS: The importance of Rubella IgG determination in Turkish pregnant women is discussed and recommendations for prevention and control of congenital rubella syndrome (CRS) are suggested.

HIV antibody screening in a gynecology and obstetrics clinic Ankara, Turkey.

In 416 pregnant women, admitted to our outpatient obstetric clinic for antenatal care between December 1987 and August 1988, HIV antibody assessments were performed by ELISA technique. No seropositive case was reported.

Limited invasiveness to assess retroperitoneal spread in stage I-II ovarian carcinoma.

OBJECTIVE: To evaluate the incidence of retroperitoneal metastases, survival rate and site of recurrence in early ovarian tumors undergoing limited retroperitoneal surgery. METHOD: Three hundred seventy-three consecutive patients underwent assessment of the retroperitoneum consisting of intraoperative palpation with or without biopsies. RESULTS: Retroperitoneal metastases were detected in 10 stage-I tumors (3.2%) and in 10 stage-II tumors (16%). The risk was inversely related to tumor differentiation. Palpation revealed metastases in 10 cases. During follow-up, none of the borderline tumors (1.9% of stage-I grade-1 node-negative, 2.7% of grade-2 and 7.0% of grade-3 tumors) recurred in the retroperitoneum. In stage II, two recurrences were observed in grade-2 tumors (11%) and one in grade 3 (4.5%). CONCLUSION: Limited retroperitoneal surgery enables satisfactory outcome in early ovarian cancers. Risk of retroperitoneal recurrence is minimal in grade 1 and non-existent in borderline tumors. Less differentiated tumors have low risk but further investigation of the therapeutic role of lymphadenectomy is justified.

Sample adequacy in detecting Chlamydia trachomatis.

OBJECTIVE: Chlamydia trachomatis is an important etiological agent in female genital infection and may result in infertility. In recent years rapid diagnostic methods have become widely used as alternatives to cell culture. Our objective was to evaluate the technique of direct fluorescence assay (DFA) in estimating the presence of C. trachomatis. METHODS: Specimens taken from 40 infertile and 20 fertile women were examined by DFA for the presence of C. trachomatis. RESULTS: Six of forty (15%) infertile women were found to be positive whereas no positive specimens were detected in the control group. When the specimens were grouped into those which were adequate or inadequate, 19 and five specimens, respectively, were adequate in the infertile and healthy groups. If only adequate specimens are included in estimating the presence of Chlamydia, the percentage is 31.6%. CONCLUSIONS: In order to use DFA as a more reliable and rapid diagnostic test of C. trachomatis in female genital infection, false-negativity must be eliminated. Specimens must be collected adequately and concentrated in order to achieve optimal diagnostic success.

[Brain metastases in patients with malignant ovarian epithelial tumors]. / Metastasi cerebrali in pazienti affette da tumore maligno epiteliale ovarico.

From September 1983 to September 1994, 23 patients with Central Nervous System (CNS) metastases from ovarian carcinoma were observed in our institution. The mean age at the time of CNS metastases diagnosis was 59 years, the mean interval between diagnosis of ovarian carcinoma and documentation of the CNS involvement was 35 months. All the patients presented neurological symptoms. One patient had meningeal carcinomatosis; 22 presented parenchymal lesions. Nine patients had a single CNS lesion and 13 had multiple metastatic sites. CNS was the only site of disease in 9 patients, while 8 had concomitant extraperitoneal dissemination. Four patients received hormonal treatment with a mean survival (MS) of 3 months; 14 received radiotherapy alone (MS 5.5 months), 5 underwent surgical resection of solitary lesion followed by radiotherapy (MS 17 months). Number of CNS lesions, extent of the disease at time of CNS metastases and the treatment were the factors which significantly affected survival. The prognosis of these patients appears poor, however, early diagnosis followed by multimodal treatment may result in significant palliation an improve overall survival in a selected group of patients.