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Intraspinal extradural primitive neuroectodermal tumours (PNET) represent a rare entity that almost always carry a poor prognosis. A recent literature research revealed only four cases reported in adults. The tumours have mainly thoracic and lumbar location. We report the only case with cervical location and with the longest survival. Urgent laminectomy was performed resulting in a rapid pain relief for the patient. The patient was followed up with craniospinal irradiation and several cycles of chemotherapy. The patient died due to dissemination of the disease 31 months after the diagnosis. Intraspinal PNET tumours have a rapidly progressive course, and there is no current consensus on the optimal therapeutic approach.

Abstract Perivascular epithelioid cell tumor (PEComa) is an extremely rare neoplasm that appears to arise most commonly at visceral (especially gastrointestinal and uterine), retroperitoneal, and abdominopelvic sites. Malignant PEComas exist but are very rare. These tumors represent a family of mesenchymal neoplasms, mechanistically linked through activation of the mTOR signaling pathway. Metastatic PEComa is a rare form of sarcoma for which no effective therapy has been described previously and that has a uniformly fatal outcome. Although there is no known effective therapy, the molecular pathophysiology of aberrant mTOR signaling provides a scientific rationale to target this pathway therapeutically. The difficulty in determining optimal therapy, owing to the sparse literature available, led us to present this case. On this basis, we report a case of metastatic retroperitoneal PEComa treated with an oral mTOR inhibitor, with everolimus achieving significant clinical response.

Abstract Introduction Chromophobe renal cell carcinoma is universally accepted as a distinct subtype of renal cell carcinoma. There are conflicting reports on prognosis, and few data on response to treatment exist. Currently, we do not have any effective treatment for the metastatic disease apart from surgical procedures. Current strategies are based on results obtained in the context of clear cell-type renal cell carcinoma. Separate trials for rare histologies seem unfeasible and are unlikely to be performed. For these cases, clinical observations are an important part for advancing therapeutic insight. In recent years, novel tyrosine kinase inhibitors have been shown to have significant clinical benefit in advanced renal cell carcinoma. Case presentation We present the case of a 43-year-old Caucasian man with advanced chromophobe renal cell carcinoma treated with the tyrosine kinase inhibitor sunitinib and subsequently with sorafenib and the mammalian target of the rapamycin inhibitor everolimus, achieving a prolonged response and significant clinical benefit. We report an unexpectedly high efficacy of everolimus as a third-line treatment in a patient with metastatic chromophobe renal cell carcinoma. Conclusions Up to now, no published data from randomized clinical studies have addressed the question of efficacy of everolimus as a third-line treatment after failure of tyrosine kinase inhibitors. To the best of our knowledge, this case is the first report of chromophobe renal cell carcinoma treated successfully with sequential tyrosine kinase and mammalian target of rapamycin inhibitor therapy. Notably, the time on treatment with sunitinib exceeded four years. The case presented here implies that everolimus could be a viable option for patients with metastatic chromophobe renal cell carcinoma.

Abstract Background Renal cell carcinoma (RCC) represents approximately 3% of all adult cancers and is more common in males. Systemic treatment for RCC has improved following the introduction of tyrosine kinase inhibitors, such as sunitinib. The molecular targets of sunitinib are receptor tyrosine kinases (RTKs). Moreover, sunitinib has an additional anti-angiogenic effect through its inhibition of the vascular endothelial growth factor receptor activation. Case presentation We present a case of intra-abdominal abscess formation mimicking disease progression, in a patient with metastatic renal cell carcinoma during sunitinib treatment. Conclusion In the advancing era of molecular therapy of solid tumours, sunitinib has demonstrated significant efficacy in the post-cytokine setting treatment of metastatic renal cancer. Concurrently, however, increasing evidence has emerged to indicate that this class of drugs exert profound immunomodulatory effects on T cells and play major roles in immune tumor surveillance.

Abstract Background Adrenal cortex oncocytic carcinoma (AOC) represents an exceptional pathological entity, since only 22 cases have been documented in the literature so far. Case presentation Our case concerns a 54-year-old man with past medical history of right adrenal excision with partial hepatectomy, due to an adrenocortical carcinoma. The patient was admitted in our hospital to undergo surgical resection of a left lung mass newly detected on chest Computed Tomography scan. The histological and immunohistochemical study revealed a metastatic AOC. Although the patient was given mitotane orally in adjuvant basis, he experienced relapse with multiple metastases in the thorax twice in the next year and was treated with consecutive resections. Two and a half years later, a right hip joint metastasis was found and concurrent chemoradiation was given. Finally, approximately five years post disease onset, the patient died due to massive metastatic disease. A thorough review of AOC and particularly all diagnostic difficulties are extensively stated. Conclusion Histological classification of adrenocortical oncocytic tumours has been so far a matter of debate. There is no officially established histological scoring system regarding these rare neoplasms and therefore many diagnostic difficulties occur for pathologists.

Purpose: Colon cancer is one of the most common malignancies. Various prognostic markers have been proposed and individualized treatment strategies have been adapted according to tumor molecular and genetic characteristics. The purpose of the present study was to retrospectively analyze a possible association between the expression of COX- 2 and EGFR and clinical and histopathological factors of patients undergoing colon surgery in a Greek population., Methods: Data from our department's prospectively collected database were retrieved for a total of 100 consecutive colectomies that were performed in our department. We examined patient age, sex, tumor stage and location of the tumor. Histological data were also retrieved concerning major tumor diameter, histological grade and immunohistochemical expression of cyclooxygenase (COX)-2 and epithermal growth factor receptor (EGFR)., Results: There was no difference between tumors of different differentiation in the expression of EGFR (p=0.146), while there was statistically significant difference in the expression of COX-2 between these groups (p=0.001). There was no difference between these patients in the expression of EGFR (p=0.136), while a statistically significant difference was found in the expression of COX-2 between the same patient groups (p<0.005)., Conclusion: These data are quite important in order to certify that colorectal cancer molecular and genetic diversity between different study populations is not a confounding factor in the application and clinical implementation of trending individualized decision making in oncological treatments.

Purpose: Local thermal ablation may extend the scope of palliative therapy in patients with colorectal liver metastasis. We performed a retrospective, case-controlled study to compare patients with colorectal liver metastases that were treated with percutaneous radiofrequency (RF) or microwave (MW) thermal ablation, against the control group of chemotherapy alone., Methods: We described baseline demographics, ablation sessions, procedure duration and related complications. We compared outcomes of percutaneous thermal ablation versus chemotherapy alone (controls) in patients with colorectal liver metastasis. The control group assigned (non-ablated patients) had similar demographics and prior treatment profile when compared to ablated patients. Progression-free survival (PFS) and overall survival (OS) were estimated for the two groups., Results: Twenty-eight cases with 57 baseline hepatic lesions (median age 68 years; male to female ratio 2:1) were evaluated and compared with 48 controls. A total of 55 sessions (52 RF, 3 MW) were performed among the cases, with minimal procedural time (median 8 min), zero mortality and no severe complications (3 cases of local hepatic hematoma not requiring hospitalization). Ablated patients had prolonged median PFS (19.4 months) and OS (27.5 months) when compared against controls (14.0 and 21.4 months, respectively). After adjusting for hepatic involvement, PFS estimates were comparable and OS was better for the ablated group. One and 2-year survival estimates were 0.96 and 0.79 for thermal ablation patients compared with 0.82 and 0.52 for controls (p=0.05 and p=0.07, respectively)., Conclusion: Percutaneous thermal ablation may delay progression and death in colorectal cancer patients with metastatic liver disease.

Aim: To evaluate the effect of chemotherapy to the acute toxicity of a hypofractionated radiotherapy (HFRT) schedule for breast cancer., Methods: We retrospectively analyzed 116 breast cancer patients with T1, 2N0Mx. The patients received 3-D conformal radiotherapy with a total physical dose of 50.54 Gy or 53.2 Gy in 19 or 20 fractions according to stage, over 23-24 d. The last three to four fractions were delivered as a sequential tumor boost. All patients were monitored for acute skin toxicity according to the European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group criteria. The maximum monitored value was taken as the final grading score. Multivariate analysis was performed for the contribution of age, chemotherapy and 19 vs 20 fractions to the radiation acute skin toxicity., Results: The acute radiation induced skin toxicity was as following: grade I 27.6%, grade II 7.8% and grade III 2.6%. No significant correlation was noted between toxicity grading and chemotherapy (P = 0.154, χ(2) test). The mean values of acute toxicity score in terms of chemotherapy or not, were 0.64 and 0.46 respectively (P = 0.109, Mann Whitney test). No significant correlation was also noted between acute skin toxicity and radiotherapy fractions (P = 0.47, χ(2) test). According to univariate analysis, only chemotherapy contributed significantly to the development of acute skin toxicity but with a critical value of P = 0.05. However, in multivariate analysis, chemotherapy lost its statistical significance. None of the patients during the 2-years of follow-up presented any locoregional relapse., Conclusion: There is no clear evidence that chemotherapy has an impact to acute skin toxicity after an HFRT schedule. A randomized trial is needed for definite conclusions.

Male breast cancer is a very rare disease with an incidence of about 0.5-1% comparing with the one of female breast cancer but relatively little is known about its cause. Treatment strategies for breast cancer in males are derived from studies performed among females. The probable reasons behind the frequent, late diagnoses presented at stages III or IV might be the lack of awareness. The rarity of the disease precludes large prospective randomized clinical trials. This study reviews male breast cancer and its risk factors, recommendations for diagnosis and the management of patients with male breast cancer.

Purpose: The standard therapeutic approach to epidermoid anal canal cancer consists of combined radiation therapy and chemotherapy. Although disease control has been reported to have excellent results, as many as 40% of patients will develop locoregional disease progression. The treatment of choice for patients with persistent (PD) or recurrent disease (RD) is salvage abdominoperineal resection (APR). The purpose of this study was to review our experience with salvage surgery in this group of patients., Methods: The medical records of all patients with epidermoid anal canal cancer treated from 1997 to 2010 in our department were retrospectively reviewed. Nine patients who presented with persistent or locally recurrent anal canal cancer were subjected to salvage APR. Before surgery, all of the patients had received chemoradiation therapy (CRT)., Results: There were 9 patients (7 women, 2 men) with a median age of 59 years (range 40-79). Six patients underwent radical salvage APR for persistent disease and 3 patients for recurrent disease. There were no deaths attributable to operation. The median follow-up time was 31.75 months (range 3-108) after salvage surgery. Two patients died of disease progression, with a median survival time of 24 months (range 12-36). At the time of last follow-up, 6 patients were alive without evidence of recurrent disease, and one patient was lost to follow-up. The median follow-up time for survivors was 34.3 months (range 3-108)., Conclusion: Long-term survival can be achieved in the majority of patients who undergo radical salvage APR after failed CRT for epidermoid carcinoma of the anal canal.

Aims and Background: c-kit (CD117) is a transmembrane tyrosine kinase that acts as a type III receptor for mast cell growth factor. In recent years, the role of c-kit in the development of preinvasive and invasive breast carcinomas has been investigated. The aim of our study was to detect c-kit expression in the entire spectrum of common benign and malignant breast lesions in correlation with a well-studied myoepithelial or stem-cell like marker (p63)., Methods and Study Design: We evaluated 270 cases of benign and malignant breast lesions including fibrocystic disease, fibroadenoma, sclerosing adenosis, atypical ductal hyperplasia, ductal/lobular carcinoma in situ, and ductal/lobular/mixed type carcinoma. C-kit staining was evaluated in the cytoplasm/cell membrane in epithelial and myoepithelial cells and p63 in the nuclei of myoepithelial cells., Results: c-kit was highly expressed (85.3%) in benign lesions (fibrocystic disease, sclerosing adenosis, fibroadenoma), and p63 expression was 95.5% in the aforementioned lesions. c-kit distribution in preinvasive and invasive lesions was as follows: ductal/lobular carcinoma in-situ, 43%/35%; ductal/lobular carcinoma, 36%/39%; and mixed type carcinoma, 20%. c-kit was highly expressed in myofibroblast/fibroblast cells only in grade III ductal/lobular carcinomas. c-kit was totally absent in stromal cells in benign lesions and in situ carcinomas whereas expression was weak in grade I and II carcinomas., Conclusions: Combined overexpression of c-kit and p63 is indicative of benign breast lesions. In contrast, there is reduced expression of c-kit in in situ and invasive breast carcinomas, with simultaneous overexpression in the stromal cells. This suggests that c-kit may play a role in breast cancer progression.

Unlabelled: In human epidermal growth factor 2 (HER-2)-positive advanced breast cancer, taxanes plus trastuzumab are among the most widely applied options in the first-line setting. The addition of capecitabine to docetaxel significantly improves overall survival in anthracycline-pretreated metastatic breast cancer. We evaluated the efficacy and tolerability of trastuzumab plus capecitabine and docetaxel regimen as first-line therapy., Patients and Methods: HER-2-positive patients who had received adjuvant anthracyclines received docetaxel at 75 mg/m(2) on day 1 and capecitabine 950 mg/m(2)/day, days 1-14, every 3 weeks until disease progression or unacceptable toxicity. Trastuzumab was administered at a dose of 6 mg/kg every 3 weeks. Time to progression (TTP) was defined as the primary end point., Results: Twenty-nine patients were evaluable (median age 52, range 34-70 years). The regimen achieved objective responses in 11 patients (38%), including complete response in three (10.3%) and partial response in eight (27.5%). The median overall survival time was 25.5 months, and the median progression-free survival time was 7.8 months. The safety profile of the combination was favorable and predictable, with a low incidence of grade 3/4 adverse events. The most common adverse events were hand-foot syndrome, and gastrointestinal toxicities. Severe myelosuppression was rare and cardiac toxicity did not occur., Conclusion: These data confirm that the combination of trastuzumab plus capecitabine and docetaxel is highly active in patients with HER-2-overexpressing anthracycline-pretreated breast cancer, offering a significant survival benefit and is well tolerated.

Background: Renal cell carcinoma (RCC) represents approximately 3% of all adult cancers and is more common in males. Systemic treatment for RCC has improved following the introduction of tyrosine kinase inhibitors, such as sunitinib. The molecular targets of sunitinib are receptor tyrosine kinases (RTKs). Moreover, sunitinib has an additional anti-angiogenic effect through its inhibition of the vascular endothelial growth factor receptor activation., Case Presentation: We present a case of intra-abdominal abscess formation mimicking disease progression, in a patient with metastatic renal cell carcinoma during sunitinib treatment., Conclusion: In the advancing era of molecular therapy of solid tumours, sunitinib has demonstrated significant efficacy in the post-cytokine setting treatment of metastatic renal cancer. Concurrently, however, increasing evidence has emerged to indicate that this class of drugs exert profound immunomodulatory effects on T cells and play major roles in immune tumor surveillance.

Purpose: The purpose of this study was to determine the efficacy and toxicity of uracil/tegafur (UFT) plus oral leucovorin (LV) and mitomycin C as salvage chemotherapy for heavily pretreated patients with metastatic colorectal cancer., Methods: A total of 44 patients were treated with i.v. mitomycin C (6 mg/m(2) on day 1) and oral UFT (350 mg/m(2)) plus LV (90 mg), both divided in 3 daily doses from day 1 to day 14 every 3 weeks. All patients had failed prior first-line and second- line treatment with oxaliplatin, bevacizumab, irinotecan, cetuximab and 5-fluorouracil (5-FU). Forty -three patients were evaluable for the response., Results: The overall response rate (intent-to-treat) was 9.3% and disease stabilization was achieved in 25.7% of the patients. Median time to progression (TTP) was 5 months (range 2-13) and median overall survival (OS) 7.5 months (range 4-16). Fatigue and myelosuppression were the most frequent side effects. The most common nonhematological toxicities consisted of mild and reversible nausea and diarrhea. Severe symptoms were only occasionally seen., Conclusion: These data show that the combination of mitomycin C/UFT/LV provides an acceptable and safe therapeutic option in extensively pretreated metastatic colorectal cancer.

Aim: This study's aim is to evaluate the effectiveness of using an internal stent when fashioning a duct-to-mucosa pancreatojejunostomy on preventing pancreatic fistula formation, as well as on the overall outcome for patients undergoing pancreaticoduodenectomy., Materials and Methods: Between January 2000 and December 2008, 82 consecutive patients underwent pancreaticoduodenectomy and duct-to-mucosa pancreaticojejunostomy in an isolated jejunal loop, either with or without the aid of an internal stent. The allocation of the patients into group A (n = 41, stented anastomosis) and group B (n = 1, unstented anastomosis) was performed in a strictly alternating way. No statistically significant differences were identified between the two groups regarding age, sex, operative time, intraoperative pathological findings, and comorbidities. The two groups were compared regarding the rate of pancreatic fistula formation, postoperative complications, and hospital stay., Results: In group A, pancreatic fistula formation rate was 4.9%; overall morbidity reached 30%; and hospital stay duration was 13 +/-4 days. In group B, pancreatic fistula formation rate was 2.4%; overall morbidity was 26%; and hospital stay duration extended to 14 +/- 5. According to Clavien's classification, the severity of surgical complications was designated as follows: for group A, 56% of the complications were allocated as grade I, 38% grade II, 4% grade III, 2.5% grade IV, and 0% grade V. The relative values for group B were 53%, 42%, 3%, 2%, and 0%, respectively. In six group A patients (14.7%), the internal stent was found stuck in the pancreatic stump, causing severe back pain requiring analgesic treatment with opioids for four of them. In group B, four patients (9.7%) complained of mild back pain, none of which required regular treatment. No mortalities were recorded in both groups. No statistically significant differences were found between the two groups regarding fistula formation and severity of complications., Conclusions: Internal stenting of a duct-to-mucosa pancreatojejunostomy does not diminish the rate of pancreatic fistula formation or alter overall patient's outcome.

Purpose: The relationship between breast cancer and thyroid diseases is controversial. Conflicting results have been reported in the literature. The incidence of autoimmune and non-autoimmune thyroid diseases were investigated in patients with breast cancer who had received prior therapy as compared with age-matched control individuals without breast or thyroid disease., Patients and Methods: Clinical and ultrasound evaluation of the thyroid gland, and determination of serum thyroid hormones and autoantibody levels were performed in 143 breast cancer patients and 128 healthy control individuals. Patients were classified into subgroups according to estrogen receptor (ER) and progesterone receptor (PR) status and type of oncological treatment., Results: The mean values for serum antibodies against thyroid peroxidase (anti-TPO) were 9 IU/ml and 25 IU/ml for antithyroglobulin antibodies (anti-TGB) in breast cancer patients, and 9.5 IU/ml and 23.5 IU/ml, respectively, in the control group (p>0.05. The difference between breast cancer patients and the control group in the incidence of autoimmune and non-autoimmune thyroid diseases was not statistically significant. No significant differences between the groups according to both menopausal status and ER status were seen (p= 0.67). Also, no significant influence of hormonal therapy with tamoxifen and chemotherapy on serum levels of thyroid stimulating hormone (TSH), free thyroxin (fT4), TPO and TGB autoantibodies was proved., Conclusion: This study demonstrated a similar incidence of thyroid enlargement and the same frequency of thyroid disturbances in patients with breast cancer and controls. No relationship was found among ER and PR status, and the presence of serum thyroid autoantibodies. Although we have been unable to demonstrate any impact of breast cancer therapy on thyroid function tests, more prolonged studies with larger number of patients may be required to demonstrate significant trends.

Capecitabine has been developed as a prodrug of FU, with the goal of improving tolerability and intratumor drug concentration through tumor-specific conversion to the active drug. The purpose of this article is to review the available information on capecitabine with respect to clinical efficacy for tumors of the digestive tract, adverse-effect profile, documented drug interactions, dosage and administration, and future directions of ongoing research. Relevant English-language literature was identified through searches of NCI, PubMed, ASCO.org and ESMO, ECCO meetings proceedings.

Background: Adrenal cortex oncocytic carcinoma (AOC) represents an exceptional pathological entity, since only 22 cases have been documented in the literature so far., Case Presentation: Our case concerns a 54-year-old man with past medical history of right adrenal excision with partial hepatectomy, due to an adrenocortical carcinoma. The patient was admitted in our hospital to undergo surgical resection of a left lung mass newly detected on chest Computed Tomography scan. The histological and immunohistochemical study revealed a metastatic AOC. Although the patient was given mitotane orally in adjuvant basis, he experienced relapse with multiple metastases in the thorax twice in the next year and was treated with consecutive resections. Two and a half years later, a right hip joint metastasis was found and concurrent chemoradiation was given. Finally, approximately five years post disease onset, the patient died due to massive metastatic disease. A thorough review of AOC and particularly all diagnostic difficulties are extensively stated., Conclusion: Histological classification of adrenocortical oncocytic tumours has been so far a matter of debate. There is no officially established histological scoring system regarding these rare neoplasms and therefore many diagnostic difficulties occur for pathologists.

Unlabelled: Capecitabine, an oral 5-fluorouracil (5-FU) prodrug, is increasingly replacing intravenous i.v. 5-FU/leucovorin in colorectal cancer treatment. THE AIM of this study was to evaluate efficacy and safety of the combination chemotherapy of irinotecan plus capecitabine (XELIRI), in patients with advanced colorectal adenocarcinoma., Patients and Methods: Forty patients received first-line chemotherapy with capecitabine (1.000 mg/m2 twice daily) on days 1-14 and irinotecan (240 mg/m2) on day 1 of a 21-day cycle. Baseline characteristics: 24 men, 16 women; median age 64.5 years. Most common metastatic sites were the liver (55%), lymph nodes (45%), lung (22.5%) and bones (17.5%)., Results: There were 12 partial responses (30%), 11 cases of stable disease (27.5%), and 17 cases of disease progression (42.5%). The median survival was 16 months (range, 6-26 months) and median progression-free survival was 7 months (range, 3-14 months). Frequently encountered therapy-related events were leukopenia and gastrointestinal side effects including diarrhea., Conclusion: XELIRI is a well-tolerated regimen, with an activity comparable to, but more convenient than, irinotecan-5-FU i.v. combinations in patients with previously untreated advanced colorectal cancer.

Uridine diphospho-glucuronosyltransferase 1 (UGT1A1) is involved in estradiol glucuronidation, which may play a central role in the etiology of breast cancer. A common insertion/deletion polymorphism in the TATAA-box of the promoter region of UGT1A1 results in decreased initiation of transcription, and has been associated with breast cancer risk in different ethnic groups. In the present study, the role of the above genetic variation at the UGT1A1 locus in breast cancer susceptibility was investigated in a homogeneous population. Our case-control study included 136 women with breast cancer and 186 healthy female controls of Greek origin. The polymorphism A(TA)nTAA in the promoter region of UGT1A1 gene was studied using the Fragment Analysis Software of an automated DNA sequencer and three genotypes (homozygous 7/7, heterozygous 6/7, and normal homozygous 6/6) were identified. No significant associations were observed between the 7/7 genotype and breast cancer risk, indicating that further studies in Caucasian women are needed to elucidate the role of UGT1A1 polymorphism in breast cancer risk.

Aim: To compare the safety and efficacy of simultaneous versus two stage resection of primary colorectal tumors and liver metastases., Methods: From January 1996 to May 2004, 103 colorectal tumor patients presented with synchronous liver metastases. Twenty five underwent simultaneous colorectal and liver surgery and 78 underwent liver surgery 1-3 mo after primary colorectal tumor resection. Data were retrospectively analyzed to assess and compare the morbidity and mortality between the surgical strategies. The two groups were comparable regarding the age and sex distribution, the types of liver resection and stage of primary tumors, as well as the number and size of liver metastases., Results: In two-stage procedures more transfusions were required (4 +/- 1.5 vs 2 +/- 1.8, pRBCs, P < 0.05). Chest infection was increased after the two-stage approach (26% vs 17%, P < 0.05). The two-stage procedure was also associated with longer hospitalization (20 +/- 8 vs 12 +/- 6 d, P < 0.05). Five year survival in both groups was similar (28% vs 31%). No hospital mortality occurred in our series., Conclusion: Synchronous colorectal liver metastases can be safely treated simultaneously with the primary tumor. Liver resection should be prioritized over colon resection. It is advisable that complex liver resections with marginal liver residual volume should be dealt with at a later stage.

Aim: To assess progression-free survival (PFS) and overall survival (OS) in patients with advanced epithelial ovarian cancer receiving the combination of cisplatin (75 mg/m(2) i.v.) and cyclophosphamide (700 mg/m(2) i.v.) (CP), or the combination of paclitaxel (175 mg/m2) followed by cisplatin (75 mg/m2) (TP)., Patients and Methods: One hundred and twenty patients were randomized to receive six cycles of one of the treatments every 3 weeks. If measurable, complete response (CR) or partial response (PR) was determined., Results: There was a significant difference (p<0.05) in the frequency of response (CR +PR) rates between treatment groups, in favor of paclitaxel containing regimen. The median PFS was 9 months for patients in the CP group and 12 months for patients in the TP group (log-rank p=0.215). The median OS were 24 months and 20 months in TP and CP arms, respectively (log-rank p=0.350). Neutropenia and alopecia were more severe with paclitaxel-containing regimen., Conclusion: Although OS and PFS were similar in two arms, TP regimen yielded superior response rates relative to CP, with an acceptable toxicity profile. Therefore, the TP regimen remains the preferred initial treatment option.

Background: Gemcitabine is an active agent in pancreatic cancer, showing clinical synergy with 5-fluorouracil (5-FU). The aim of the study was to evaluate the safety and efficacy of the combination of gemcitabine and 5-FU in patients with advanced adenocarcinoma of the pancreas., Patients and Methods: Forty-two patients (median age, 62 years), with advanced or metastatic pancreatic adenocarcinoma, were enrolled in the study. The combination of gemcitabine (1000 mg/m2) and 5-FU (600 mg/m2) was administered on days 1, 8 and 15 and repeated every 28 days., Results: A total of 168 cycles (median 4 cycles per patient) were administered. Partial responses were observed in 6 patients (14.2%) and stable disease in 11 (26.2%). The overall clinical benefit was 40.4%. Symptom relief and improvement of performance status were observed in 18 (42.8%) patients. The median time to progression, median duration of response and the median overall survival, were 6, 7 and 13 months, respectively. The most common grade 3 to 4 toxicities were neutropenia, anaemia and diarrhoea., Conclusion: The combination of gemcitabine and 5-FU is an active regimen for the treatment of advanced pancreatic cancer with an acceptable toxicity profile.

Aims and Background: The understanding of hormonal therapies in postmenopausal women with metastatic breast cancer has advanced greatly in the past several decades. With the introduction of orally active, potent and selective third-generation aromatase inhibitors (anastrozole, letrozole and exemestane), approaches to the treatment of hormone-sensitive advanced breast cancer are undergoing reevaluation. For treatment of advanced or metastatic disease that has progressed on tamoxifen, all three agents are active. The purpose of the study was to assess the antitumor efficacy and tolerance of exemestane administered as third-line hormonal therapy to postmenopausal women with metastatic breast cancer refractory to letrozole and anastrozole., Study Design: Sixty postmenopausal women with stage IV hormone receptor-positive carcinoma of the breast were enrolled in the study. All patients had received two prior hormonal manipulations and had measurable or assessable disease. All adverse events were monitored., Results: Objective tumor response was achieved in 12 (20%) patients (95% CI, 9.6-30.4). The overall clinical benefit was 38.3% (95% CI, 21.2-49.3), and the median duration of objective tumor response was 20 months (range, 9-26). The median time to death was 17.4 months (95% CI, 16.14-18.66)., Conclusions: Exemestane represents an active and well-tolerated treatment option in pretreated patients with advanced breast cancer who have received standard first- and second line hormonal therapies. By extending the sequence of hormonal therapy, disease progression and the need for chemotherapy may be significantly delayed.

Purpose: To evaluate the activity and toxicity of gemcitabine and vinorelbine in patients with metastatic breast cancer (MBC), previously treated with anthracyclines alone or with taxanes., Patients and Methods: A total of 86 pretreated patients with MBC (median age 62 years), entered the study. Thirty-six patients had been pretreated with anthracyclines and 8 were resistant. The combination of gemcitabine (1000 mg/m2) and vinorelbine (25 mg/m2) was administered on days 1 and 8 every 3 weeks, for a total of 6 cycles., Results: A total of 344 cycles of chemotherapy were administered (median 4 cycles per patient). Partial responses were observed in 31 patients (36.0%; 95% CI: 23-56). The median duration of response was 7 months (range 3-11 months) and the median overall survival was 14 months (range 6-21). The scheme was well tolerated., Conclusion: The combination of vinorelbine and gemcitabine is an active scheme in pretreated MBC, demonstrating an acceptable toxicity profile, and may well represent a valuable therapeutic choice after anthracycline/taxane regimens.

Purpose: The purpose of this study was to investigate in a randomized way the clinical benefit of addition of intracavitary hyperthermia (ICHT) to a conventional chemoradiotherapy schedule in patients with T2-T3N0M0 anal cancer., Methods and Materials: Patients were randomly assigned to undergo chemotherapy with 5-fluorouracil (5-FU) and mitomycin-C combined with radiotherapy with (arm A: 24 patients) or without ICHT (arm B: 25 patients). A microwave applicator operating at 433 MHz inserted into the anal-rectal cavity was used for ICHT. Patients in both arms received 1000 mg/m2 per day of 5-FU on days 1-4 and days 28-31 plus 15 mg/m mitomycin-C on day 1. Radiotherapy was administered with a dose of 41.4 Gy (1.8 Gy per fraction) plus a booster dose of 14 Gy (2 Gy per fraction)., Results: One patient from group A developed severe mucositis, whereas no severe morbidity was noted in the rest of the patients in both groups. The incidence of lower-intestine acute reactions was higher in the ICHT arm. After a 5-year follow up in the hyperthermia arm, 23 of 24 patients (95.8%) preserved their anorectal function and avoided permanent colostomy, whereas in the second arm, 17 of 25 (68.0%) had sphincter preservation. Local recurrence-free survival time was significantly higher in the ICHT arm (P = 0.0107, log rank test), whereas no significant difference in overall survival was noted., Conclusion: The addition of ICHT to the chemoradiotherapy schedule of anal cancer seems to offer a new effective and safe therapeutic modality. The preservation of anorectal function seems to be the significant clinical benefit of adjuvant ICHT.

A liver tumor (2.5x3 cm) with malignant features on computed tomography (CT) and magnetic resonance imaging (MRI) was detected in a 69-year-old man with hepatitis B virus (HBV)-associated cirrhosis. On exploratory laparotomy a mass at the right diaphragmatic dome adherent to the liver segment VIII was found. En-block resection of this segment and the part at diaphragm hosting the tumor was carried out. On histology the tumor was a diaphragmatic hyaline plaque while in the resected liver no tumor was found.

Purpose: To assess whether disodium pamidronate (DP) once started should be given life-long in women with lytic bone metastases., Patients and Methods: One hundred and three women with breast cancer who had at least one osteolytic lesion received 180 mg of DP as a 2-h intravenous infusion given every 4 weeks for a life-time, following local radiotherapy. After six cycles, 26 out of 103 patients (25%) refused to continue their bisphosphonate-treatment. Thus two groups were constituted: non-stop (group A) and premature discontinued (group B). The new skeletal complication free survival (NSCFS) was the primary endpoint verified during extramural review. Performance status, pain-score and biochemical markers were secondary endpoints., Results: Generally DP was well tolerated. At 36 months, the proportion of patients having had any skeletal complication was 54.5 and 84.6% in group A and B, respectively. The median time of NSCFS was apparently longer for group A. In group A, the pain score and the ECOG status were significantly lower, while the overall survival appeared to be longer. Multivariate analysis revealed age, nodal status and interruption of treatment as prognostic factors to NSCFS, with relative risk 1.05, 2.3 and 1.5 respectively., Conclusion: Data concerning the suspension of new skeletal complications, as well as the apparent improvement of overall survival, pain score and ECOG status, suggest that the pamidronate-treatment should not be stopped once started. These results should be confirmed in a randomised trial.

Thirty patients with local relapses after radical mastectomy and radiotherapy and undergoing infusion of liposomal doxorubicin (40 mg/m(2) monthly for 6 months) were randomized to receive re-irradiation. Radiotherapy was with either 17 fractions of 1.8 Gy, 5 days a week (N=15, group A) or 4 Gy plus two fractions of 3 Gy the 1st week and six fractions of 3 Gy given every second day (N=15, group B). Eight patients from group A (53.3%) and nine patients (60%) from group B demonstrating a clinically complete response (P=0.9). Grade I/II acute skin toxicity was monitored in 26.6% of patients in group A versus 73.3% in group B. The radiation schedule of group A seems superior for grade I/II acute (P=0.027) and late (P=0.015) skin toxicity. The linear quadratic model enabled the prediction of tumor response as well as normal skin reactions.

Background: The aim of this study was to determine whether the efficacy of the combination of 5-fluorouracil (5-FU), leucovorin (LV) and radiation therapy (RT) could be improved by the addition of interferon-alpha2b (IFN-alpha) in patients who have had a 'curative' resection, for rectal adenocarcinoma (Dukes' B2/C; T3 N0, T4 N0, N1-3)., Patients and Methods: A total of 207 eligible patients with a performance status of 0 or 1 were randomized postoperatively between days 21 and 70 to one of the two treatment groups: group A, LV 20 mg/m2 i.v. bolus and 5-FU 425 mg/m2 i.v. days 1-5 and 29-33, LV 20 mg/m2 and 5-FU 400 mg/m2 days 57-60 and 85-88, LV 20 mg/m2 and 5-FU 380 mg/m2 days 1-5 and 29-33 with the second day 1 occurring 28 days after the completion of RT (45 Gy); group B, LV, 5-FU and RT as in group A, and IFN-alpha 5 x 10(6) IU s.c. three times during each week chemotherapy is given., Results: 104 patients were randomized into group A and 103 into group B. There was no statistically significant difference in either disease-free survival or overall survival between the two groups. Toxicity was also the same, except for the flu-like syndrome associated with the IFN-alpha administration., Conclusions: There was no difference in efficacy between the two combinations. Toxicity was greater with the LV + 5-FU + IFN-alpha regimen because of the flu-like syndrome.

We conducted a phase III study in patients with advanced colorectal carcinoma (ACC). The total number of patients randomized from October 1993 until July 1998 was 192, whereas therapy was started on 179 and 158 (82.3%) have been evaluable. The treatment schedules consisted of weekly bolus administration for 6 weeks of 5-fluorouracil (5-FU), 600 mg/m2 (arm I) versus 5-FU (500 mg/m2) intravenous bolus and interferon-alpha, 5 MU subcutaneously, three times a week (arm II) versus leucovorin 200 mg/m2 in 2-hour infusion and 5-FU 500 mg/m2 intravenous bolus at the midtime of leucovorin infusion (arm III) followed by a 2-week rest period. Treatment was continued for six cycles or until progression. This study failed to show any superiority of the modulated 5-FU versus single administration of 5-FU. There were no significant differences between the three arms in the overall response rate (10.3% versus 11.3% versus 12.9%, p = 0.95), the time to tumor progression (median, 3.9 versus 3.8 versus 6.0 months, p = 0.59), or survival duration (median, 14.7 versus 12.4 versus 16.3 months, p = 0.71). The incidence of severe (grades III and IV) toxicity was significantly higher in patients in arm II and III (24.5% and 18.6%) versus arm I (6.0%) (p = 0.01). Because modulated 5-FU failed to show superiority versus 5-FU, new agents and new strategies are needed for the treatment of advanced colorectal carcinoma.

Aims and Background: Trials of adjuvant systemic therapy in high risk patients with Dukes' B2 and C colon cancer utilizing 5-fluorouracil-based regimens have been ongoing since the 1960s. The aim of this study was to compare the combination of 5-FU and leucovorin with the combination of 5-FU and alfa-2b interferon (IFN) in patients who had undergone "curative" resection foronocarcinoma., Study Design: A total of 322 patients with histologically proven adenocarcinoma of the colon, Dukes' stage B2 and C, were entered in the study. They were randomized to A) leucovorin 20 mg/m2 rapid intravenous injection and 5-FU 425 mg/m2 IV days 1-5 every 28 days for six cycles or B) 5-FU 600 mg/m2 24-hour infusion for five days, then 600 mg/m2 IV once a week and IFN 5 MU subcutaneously three times a week for six months., Results: There was no statistically significant difference in either disease-free survival or overall survival. Toxicity was the same in the two groups with the exception of flu-like syndrome, which was universal in IFN-treated patients., Conclusions: There was no difference in disease-free survival or overall survival between the two combinations in any patient subset. Toxicity was greater with the 5-FU+IFN combination because of the flu-like syndrome. These data do not support the use of IFN in combination with 5-FU as systemic adjuvant therapy for patients with locally advanced colon carcinoma.

The specific monoclonal antibody, DF3, for breast cancer and the corresponding tumor marker CA15-3 were evaluated in 108 patients with primary cancer of the breast. These antigens correlated poorly with the known prognostic parameters. Elevated CA15-3 serum values were associated with the cytoplasmic distribution of the DF3 antigen in the cell. The DF3 distribution pattern and the CA15-3 serum values had prognostic significance for disease-free interval.

The purpose of this systematic study was to provide an up to date and reliable quantitative summary of the relative benefits of various types of chemotherapy (non-platinum vs platinum, single-agent vs combination and carboplatin vs cisplatin) in the treatment of advanced ovarian cancer. Also, to investigate whether well-defined patient subgroups benefit more or less from cisplatin- or carboplatin-based therapy. Meta-analyses were based on updated individual patient data from all available randomized controlled trials (published and unpublished), including 37 trials, 5667 patients and 4664 deaths. The results suggest that platinum-based chemotherapy is better than non-platinum therapy, show a trend in favour of platinum combinations over single-agent platinum, and suggest that cisplatin and carboplatin are equally effective. There is no good evidence that cisplatin is more or less effective than carboplatin in any particular subgroup of patients.

The efficacy and toxicity of treatment with 1400 +/- 100 MBq of Re-186-HEDP were evaluated in women with osseous metastatic breast cancer. The follow-up period was fourteen weeks. The efficacy of treatment was assessed by a) a pain and performance questionnaire that patients were asked to complete daily and b) a CT scan comparison of a randomly preselected osseous lesion before and 30 weeks after Re-186-HEDP i.v. application. The response to treatment was also evaluated by using the Kamofsky Index. Two out of fourteen women (14%) experienced loss of pain, 6 experienced obvious and 2 some improvement. No change was observed in 4 patients. Five patients manifested a flare response to treatment, with increase in pain within the first, 4 to 5 days after Re-186-HEDP administration. Five patients showed a decrease in platelet levels and absolute number of polymorphonuclear blood transfusion; no neurologic side effects were observed. Re-186-HEDP appears to be a useful new radiopharmaceutical for pain palliation induced by osseous metastases due to breast cancer. Compared to Sr-89 chloride efficacy, it provides longer-lasting analgesia, and when needed it can be reinjected with less risk due to its improved physico- and radiochemical properties.

In order to investigate Greek physicians' smoking habits and how these affect their role in promoting smoking cessation, a survey of 148 hospital physicians was undertaken. According to their answers, 44% of the internists and 54% of the surgeons admitted to smoking more than 20 cigarettes per day for at least five years. Major obstacles for quitting were their personalities (70-80%) and stress in hospitals (40%). For those willing to quit, an antismoking policy in their homes (32%) and hospitals (26-29%) could have been of a great help. With respect to smoking cessation, all (100%) of the non-smoking physicians were involved in smoking-cessation counseling or stressing the health hazards of smoking, compared with only 50% of the smoking group (p < 0.001). Moreover, the smokers tended to underestimate the risks of several smoking-related health hazards and did not emphasize them when counseling patients. Major obstacles to advising smoking cessation were lack of counseling time (53-70%) and pessimism regarding the outcomes of their efforts (60%), while 8% of the internists and 14% of the surgeons believed that counseling was not part of their role. The authors conclude that physician smokers need to be encouraged in their efforts to quit by their colleagues and by members of their families. Quitting smoking might help them to develop an optimistic view of success in their cancer-prevention practices.

Extraskeletal Ewing's sarcoma is an unusual form of soft-tissue sarcoma. We report a case of a pregnant woman with a rapidly growing tumour of the left thigh, who went into complete remission with combination chemotherapy. Aggressive therapy is justified in this kind of tumour even in cases with advanced disease.

Fifty postmenopausal women with advanced breast cancer were included in the following randomized phase II trial: 25 patients received aminoglutethimide 1000 mg and hydrocortisone 40 mg daily. Twenty-five patients received aminoglutethimide 1000 mg, hydrocortisone 40 mg and fluoxymesterone 20 mg daily. The two groups of patients were comparable in respect to the most important pretreatment characteristics. The majority of patients in both groups had bone lesions. There was a history of response to tamoxifen in all the cases and 17 patients had positive estrogen and progesterone receptors. The evaluation of response was based on the system adopted by the UICC. In the aminoglutethimide-hydrocortisone group, 16 (64%) patients obtained a partial remission, 3 (12%) remained stable and 6 (24%) had progressive disease. In the combination treatment group, 17 (68%) patients obtained a partial remission, 3 (12%) remained stable and 5 (20%) developed progressive disease. The median duration of partial remission and stabilization of the disease was 9 and 7 months respectively in both groups.

Malignant schwannoma of the stomach is a rare neurogenic tumor. We report a case in a man with neurofibromatosis, who developed liver metastasis 1 year after excision of the tumor and died a few months later despite aggressive chemotherapy.