Results of salvage abdominoperineal resection after failed chemoradiation therapy for epidermoid anal canal carcinoma: Retrospective analysis at a single institution.

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.

Mitomycin C and UFT/leucovorin as salvage treatment in patients with advanced colorectal cancer.

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.

Breast cancer in association with thyroid disorders.

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.

How is sleep quality affected by the psychological and symptom distress of advanced cancer patients?

The aim of this study was to assess the relationship between sleep quality, pain, psychological distress, cognitive status and post-traumatic experience in advanced cancer patients. Participants were 82 advanced cancer patients referred to a palliative care unit for control of pain and other symptoms. A variety of assessment tools were used to examine the prevalence of sleep disturbance, the severity of pain and depression, hopelessness, cognitive function and quality of life. Using the Pittsburgh Sleep Quality Index (PSQI) 96% of patients were 'poor sleepers'. Statistically significant associations were found between PSQI and the SF-12 (Short Form-12) Quality of Life Instrument (MCS, P < 0.0005, PCS, P < 0.0005), depression (Greek Depression Inventory) (P < 0.0005) and hopelessness (Beck Hopelessness Scale) (P = 0.003). Strong associations were also found between PSQI and IES-R (Impact of Event Scale-Revised) (P = 0.004). The strongest predictors of poor sleep quality in this model were MCS (P < 0.0005), PCS (P < 0.0005) and IES-R (P = 0.010). Post-traumatic experience and quality of life seemed to be the strongest predictors of sleep quality in a sample of advanced cancer patients referred for palliative care.

Irinotecan plus capecitabine as first-line chemotherapy in advanced colorectal cancer.

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.

Association of repeat polymorphisms in the estrogen receptors alpha, beta (ESR1, ESR2) and androgen receptor (AR) genes with the occurrence of breast cancer.

Genetic variation in genes involved in estrogen biosynthesis, metabolism and signal transduction have been suggested to play a role in breast cancer. To determine the possible contribution of genetic variation in the ESR1 (ER-alpha), ESR2 (ER-beta) and AR genes in breast cancer risk the -1174(TA)(7-27), c. 1092+3607(CA)(10-26) and c. 172(CAG)(6-40) repeat variants were studied in a case-control study of 79 women with sporadic breast cancer and 155 controls. No significant difference was observed in the frequency distribution of -1174(TA)(7-27) in the ESR1 gene between patients and controls, while a significant difference was observed for repeat polymorphisms c. 1092+3607(CA)(10-26) in the ESR2 gene and c. 172(CAG)(6-40) in the AR gene (p0.0001). A significantly decreased odds ratio (OR) for breast cancer risk was observed in individuals having the LL and the SL genotypes for both the ESR2 (OR=0.010, 95% CI 0.003-0.036, p<0.001; OR=0.013, 95% CI 0.004-0.040, p<0.0001, respectively) and the AR gene (OR=0.040, 95% CI 0.011-0.138, p<0.0001; OR=0.189, 95% CI 0.10-0.359, p<0.0001, respectively), compared to SS genotype. The protective effect of these genotypes remained evident even after adjustment for various risk factors (BMI, age, age at menarche and menopause, family history). In conclusion, an association for breast cancer risk between short (SS) alleles for the repeat variants of the ESR2 and AR genes was found in women of Greek descent.

A phase III randomized study comparing paclitaxel and cisplatin versus cyclophosphamide and cisplatin in patients with advanced ovarian cancer.

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.

A prospective randomized study of irinotecan (CPT-11), leucovorin (LV) and 5-fluorouracil (5FU) versus leucovorin and 5-fluorouracil in patients with advanced colorectal carcinoma.

The purpose of this study was to compare the activity and toxicity of an irinotecan (CPT-11), leucovorin (LV) and 5-fluorouracil (5FU) combination with a standard regimen of 5FU and LV, in patients with advanced colorectal carcinoma. One hundred and sixty patients were randomized; 80 patients (group A) received LV 20 mg/m(2) bolus i.v. and 5FU 425 mg/m(2) bolus i.v. on days 1-5, every 28 days; 80 patients (group B) received CPT-11 80 mg/m(2) (30-90 min i.v. infusion), followed by LV 20 mg/m(2) bolus i.v. and 5FU 425 mg/m(2) bolus i.v. on days 1, 8, 15, 22, 29, and 36, every 8 weeks. The overall response rate was 30% and 47.5% in groups A and B respectively. Progression-free survival was significantly higher in the triple-drug combination arm (median 7.5 vs. 4.5 months; p= 0. 0335). However, overall survival did not differ significantly between the two arms (15 months vs. 14 months for the groups B and A respectively; p=0.3531). The main grade 3 adverse events were diarrhea (19%, in group A vs. 35% in group B; p=0.032) and mucositis (2% vs. 14%; p=0.017). The regimen containing irinotecan showed activity in advanced colorectal cancer. The overall safety data confirm this combination as a well-tolerated treatment.

Localized hyaline plaque of the diaphragmatic peritoneum: report of a rare entity mimicking a hepatic tumor.

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.

Surgical adjuvant therapy of rectal carcinoma: a controlled evaluation of leucovorin, 5-fluorouracil and radiation therapy with or without interferon-alpha2b.

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.

Prognostic significance of tissue DF3 antigen and CA15-3 tumor marker in primary breast cancer.

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.

Chemotherapy in advanced ovarian cancer: four systematic meta-analyses of individual patient data from 37 randomized trials. Advanced Ovarian Cancer Trialists' Group.

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.

Palliative therapy using rhenium-186-HEDP in painful breast osseous metastases.

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.

Ifosfamide and paclitaxel salvage chemotherapy for advanced epithelial ovarian cancer.

OBJECTIVE: To evaluate the efficacy and toxicity of the combination of ifosfamide (1.5 g/m2 i.v. on days 1, 2, 3) and paclitaxel (135 mg/m2 i.v. over 3 hours on day 3) with G-CSF (5 micrograms/kg/d subcutaneously, days 7-11) administered every 3 weeks on an outpatient basis in patients with advanced epithelial ovarian cancer previously treated with platinum-based chemotherapy. PATIENTS AND METHODS: Thirty-five consecutive patients were treated, 12 of whom had previously received two regimens. Twelve of the 35 were defined as platinum-resistant and 23 as potentially platinum-sensitive. RESULTS: Fifteen patients (43%; 95% CI: 26%-61%) achieved objective responses, five of them complete and ten partial. Objective responses occurred in 17% of the platinum-resistant patients and in 57% of those with potentially platinum-sensitive disease. The median duration of response was seven months and the median overall survival 11 months. The treatment was well tolerated and only 15% of the patients developed grade 3 or 4 neutropenia. With the exception of alopecia there were no other grade 3 or 4 toxicities. CONCLUSIONS: The combination of ifosfamide and paclitaxel was well tolerated and showed activity in patients with ovarian cancer who had previously undergone platinum-based chemotherapy.

The smoking-cessation promotion practices of physician smokers in Greece.

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.

Malignant schwannoma of the stomach in a patient with neurofibromatosis.

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.

A randomized phase II trial of aminoglutethimide and hydrocortisone versus combined aminoglutethimide, hydrocortisone and fluoxymesterone in advanced breast cancer.

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.

Extraskeletal Ewing's sarcoma in a pregnant woman: a case report.

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.