Predictors of pneumothorax after CT-guided transthoracic needle lung biopsy: the role of quantitative CT.

AIM: To evaluate the association of quantitative computed tomography (CT) measures of emphysema with the occurrence of pneumothorax after CT-guided needle lung biopsy (NLB) accounting for other risk factors. MATERIALS AND METHODS: One hundred and sixty-three CT-guided NLBs performed between 2008 and 2013 with available complete chest CT within 30 days were reviewed for the occurrence of post-procedure pneumothorax. Percent emphysema was determined quantitatively as the percentage of lung voxels below -950 HU on chest CT images using automated software. Multivariable regression was used to assess the association of percent emphysema volume with the occurrence of post-procedure pneumothorax. The association of percent emphysema volume with the pneumothorax size and need for chest tube placement after NLB was also explored. RESULTS: Percent emphysema was significantly associated with the incidence of post-NLB pneumothorax (OR=1.10 95% confidence interval: 1.01-1.15; p=0.03) adjusting for lower-lobe lesion location, needle path length, lesion size, number of passes, and pleural needle trajectory angle. Percent emphysema was not associated with the size of the pneumothorax, nor the need for chest tube placement after NLB. CONCLUSION: Percent emphysema determined quantitatively from chest CT is a significant predictor of post-NLB pneumothorax.

Primary pure squamous cell carcinoma of the breast: a case report and review of the literature.

Pure primary squamous cell carcinoma (SCC) of the breast is a rare condition. The exact histogenesis of this malignancy is unclear. The rarity of the condition makes it difficult to draw firm conclusions on the course of the disease and the overall prognosis. We report a case of pure primary SCC of the breast occurring in a 62-year-old woman and presenting as an enlarged breast lesion with bleeding. We also review the literature for all cases of pure primary SCC.

P53-dependent upregulation of neutral sphingomyelinase-2: role in doxorubicin-induced growth arrest.

Neutral sphingomyelinase-2 (nSMase2) is a ceramide-generating enzyme that has been implicated in growth arrest, apoptosis and exosome secretion. Although previous studies have reported transcriptional upregulation of nSMase2 in response to daunorubicin, through Sp1 and Sp3 transcription factors, the role of the DNA damage pathway in regulating nSMase2 remains unclear. In this study, we show that doxorubicin induces a dose-dependent induction of nSMase2 mRNA and protein with concomitant increases in nSMase activity and ceramide levels. Upregulation of nSMase2 was dependent on ATR, Chk1 and p53, thus placing it downstream of the DNA damage pathway. Moreover, overexpression of p53 was sufficient to transcriptionally induce nSMase2, without the need for DNA damage. DNA-binding mutants as well as acetylation mutants of p53 were unable to induce nSMase2, suggesting a role of nSMase2 in growth arrest. Moreover, knockdown of nSMase2 prevented doxorubicin-induced growth arrest. Finally, p53-induced nSMase2 upregulation appears to occur via a novel transcription start site upstream of exon 3. These results identify nSMase2 as a novel p53 target gene, regulated by the DNA damage pathway to induce cell growth arrest.

Effects of CYP2B6 genetic polymorphisms in patients receiving cyclophosphamide combination chemotherapy for breast cancer.

PURPOSE: The purpose of this study was to measure the frequency of three CYP2B6 [CYP2B6*4 (rs2279343), CYP2B6*5 (rs3211371) and CYP2B6*9 (rs3745274)] alleles in patients with breast cancer receiving cyclophosphamide (CP) therapy and test whether these variants are predictors of CP-associated toxicity and efficacy. METHODS: A total of 145 female breast cancer patients admitted to the American University of Beirut Medical Center for breast cancer-related therapy were included. Chart review was performed for collection of toxicity data. A time-to-event analysis was performed with a subset of 38 patients. RESULTS: The minor allele frequencies of CYP2B6*9, CYP2B6*4 and CYP2B6*5 were 0.27, 0.29 and 0.07, respectively. CYP2B6 *5/*6, *6/*9 or *6/*6 haplotypes were associated with a significantly shorter time to recurrence of the disease. There were no significant associations with myelo-toxicity. CONCLUSIONS: This is the first report on the pharmacogenetic profile of patients with breast cancer and the therapeutic and myelo-toxic behavior of CP in women from an Arab Middle Eastern country. Our results show that genotyping for these CYP2B6 alleles does not help in personalizing therapy from a toxicity perspective, and the association of shorter survival in these subjects with homozygous variants is interesting yet insufficient to justify routine genotyping prior to therapy, or to consider using a higher CP dose. Larger future studies or meta-analyses will be needed to further clarify the potential implication of these genetic polymorphisms.

Cancer in Lebanon: an epidemiological review of the American University of Beirut Medical Center Tumor Registry (1983-1994).

PURPOSE: Cancers recorded in the Tumor Registry at the American University of Beirut Medical Center (AUBMC), the largest tertiary care center, in Lebanon were reviewed. METHODS: Results were compared with those from the same center 30 years ago and current data from western Asia. RESULTS: Between 1983 and 1994, 9364 cases were recorded, averaging 780 cases per year, representing more than one-third of the national case-load. Cases were almost equally distributed between males and females. Average age of females was significantly younger (48.7 years) than that of males (52.2 years). Among males, the five most frequently reported cancers were of the lung, bladder, larynx, lymphoma, and leukemia. Among females, the four most frequently reported cancers were of the breast, cervix uteri, lymphoma, and brain, with leukemia and corpus uteri ranking equally as fifth. Over the past 30 years, the frequency of colorectal cancer decreased and that of lung cancer increased in both sexes. Oral cancer decreased dramatically among males. Digestive system cancers in this series were less frequent than in cumulative data from western Asia area. CONCLUSIONS: Cancer dynamics changed little since the 1950s, except regard to cancers related to smoking and diet. Diet differences may explain the lower frequencies of digestive cancers in Lebanon as compared with elsewhere in western Asia. The potential impact of cancer prevention and early detection on highly prevalent cancer types such as lung, larynx, breast, and cervix was highlighted.

Pressure ulcer accelerated healing with local injections of granulocyte macrophage-colony stimulating factor.

This is the first report of granulocyte macrophage-colony stimulating factor (GM-CSF) inducing accelerated healing of a sacral pressure ulcer in a bedridden patient with bilateral hemiplegia. GM-CSF was diluted and injected locally around and into the ulcer bed every 2-3 days for 2 weeks, then weekly for 4 weeks until complete healing occurred. A new firm granulation tissue was noted within a few days. The ulcer showed 85% healing within 2 weeks and 100% by 2 months. Healing started from the periphery and from within the ulcer bed at sites of GM-CSF injections. It was slower at areas where there was complete necrosis and detachment of skin from underlying tissue. The ulcer remained closed until the patient's sudden death 9 months later. A biopsy of granulation tissue showed inflammatory cells and reactive fibroblasts. The potential role of GM-CSF and growth factors in pressure ulcer therapy and wound healing are discussed.

Prolonged chlorpromazine infusion as antiemetic in patients on daily cisplatin infusion. A pilot study.

Continuous chlorpromazine infusion 120 mg/m2/24 h was administered for a period of 84-110 h to 24 consecutive patients with various advanced solid malignancies receiving concomitantly a 3-day infusion of cisplatin. The latter was given at a dose of 40 mg/m2/day over 6 h every day, in combination with either doxorubicin and cyclophosphamide or 5-fluorouracil infusion or vinblastine and bleomycin. This novel approach of using prolonged continuous chlorpromazine infusion as antiemetic therapy proved quite safe with no incidence of extrapyramidal toxicity, hepatotoxicity, or agranulocytosis. Only one episode of convulsions occurred, promptly reversed. Also, antiemesis was demonstrated in 66% of patients receiving such highly emetogenic chemotherapy. Blood levels of chlorpromazine did not correlate with antiemetic efficacy.

Combination cisplatin-vinorelbine for relapsed and chemotherapy-pretreated metastatic breast cancer.

The purpose of this study was to evaluate the combination of cisplatin and vinorelbine (PVn) for relapsed and chemotherapy-pretreated metastatic breast cancer. Twenty-three patients with metastatic breast cancer and prior chemotherapy were entered in a phase II study between June 1993 and December 1994. Eleven patients were premenopausal and 12 were postmenopausal. Follow-up data up to June 1997 are presented. All patients received cisplatin at a dose of 90 mg/m2 divided over 3 days as 30 mg/m2 infused over 4 hours. Intravenous vinorelbine 25 mg/m2 was given on days 1 and 8 or 15 according to patients' blood counts. Cycles were given every 3 to 4 weeks. An overall response rate of 61% (16/23 patients) was observed. Complete remission was obtained in six patients (26%) and partial remission was obtained in nine patients (35%). The duration of response ranged from 3 to 9 months, with an average of 4 months. Stable disease was noted in 29.1% and progressive disease in 8.3%. Overall survival at 12 months was 50%, and at 36 months it was 8%. Five of 12 patients (42%) who had prior doxorubicin therapy responded well to cisplatin-vinorelbine. Of those 12, seven were refractory and progressive on a doxorubicin-containing regimen, one had complete remission, and four had partial remission. Hematologic toxicity was acceptable. Treatment was delayed because of neutropenia in nine cycles (9.2%) and grade 2 leukopenia occurred in 54% of cycles. Febrile neutropenia occurred in seven cycles (7.1%), and five cycles were complicated by documented sepsis (5.1%). No treatment-related mortality occurred. Thrombocytopenia (grade 3) was seen in 27% of cycles, with no patient having a platelet count below 50,000 or bleeding episodes. Other toxicities were not major or dose-limiting. In conclusion, the combination of cisplatin and vinorelbine produced good responses: 61% response rate (16 of 23 patients) in relapsed, refractory, and heavily pretreated metastatic breast cancer, with 50% survival at 1 year, 12% at 2 years, and 8% at 3 years. In addition, a response rate of 42% (5 of 12 patients) was seen in patients resistant to anthracyclines.

Tamoxifen and ovarian cysts: a prospective study.

PURPOSE: To prospectively follow a group of women with breast cancer on tamoxifen for the development of ovarian cysts. METHODS: 72 women were followed every 6 months with pelvic examination and vaginal ultrasound. Chi square and Student's t-test were used for statistical analysis. RESULTS: The duration of treatment was 31.5+/-20 months. The mean age was 51.2+/-9.8 years. 55.6% were post-menopausal. Out of 72 women, 18 (25%) developed ovarian cysts. The mean age of women who developed ovarian cysts was significantly lower than in those who did not (47.0+/-7.0 and 52.5+/-10.2 years, respectively, P=0.03), however, the mean duration of treatment was not significantly different (33.3+/-17.4 and 29.3+/-20 months, respectively, P=0.45). Out of 32, 14 (43.8%) pre-menopausal and out of 40, 4 (10%) post-menopausal women developed ovarian cysts (P=0.003). They developed the cysts after an average duration of 33.3+/-18 and 50.7+/-6.2 months, respectively (P=0.7). The average diameter of the cysts was 2.8+/-1.2 cm. All cysts were simple except for one pre-menopausal women. All the cysts in post-menopausal women resolved spontaneously. One pre-menopausal patient had a multi-loculated cyst, was operated and had a serious cystadenoma. In nine patients, the cysts resolved spontaneously and in three after discontinuation of tamoxifen, and one patient was lost to follow-up. All cysts were asymptomatic. CONCLUSION: Ovarian cysts frequently develop in women with breast cancer on tamoxifen. The majority of the cysts resolve spontaneously, therefore an expectant management with follow-up ultrasonography is recommended.

Prolonged intake of chlorambucil for ovarian cancer.

The use of alkylating agents has been reported to be a cause of secondary leukemia particularly in patients surviving for 2 years or more after treatment of ovarian carcinoma. The risk of developing leukemia is possibly related to the duration of treatment and the total dose of alkylating agents administered. We report a patient with epithelial ovarian carcinoma who received chlorambucil for 130 consecutive months with no clinical or laboratory evidence of leukemia.

Idiopathic thrombocytopenic purpura and ovarian cancer.

The association of ovarian carcinoma with idiopathic thrombocytopenic purpura (ITP) is rare. There have been different case reports indicating an association between solid tumors and ITP. We report a case of a 47-year-old woman diagnosed with ovarian cancer who presented with abdominal distention and thrombocytopenia. Her clinical course and the mechanisms of thrombocytopenia are discussed.

Short duration neoadjuvant chemotherapy followed by radiotherapy for advanced carcinoma of the cervix: results and prognostic variables.

PURPOSE: The value of neoadjuvant chemotherapy in squamous cell carcinomas of the cervix has not been proven. It has been suggested that the potential benefit of this therapy on local and occult metastatic disease could be offset by delaying effective radiation therapy and selection of more aggressive tumor clones. This report examines the potential impact of short duration neoadjuvant chemotherapy on the response and outcome of advanced carcinoma of the cervix. MATERIALS AND METHODS: Between 1993 and 1997, 37 patients with advanced squamous cell carcinoma of the cervix (FIGO Stages IIB to IV) were enrolled in a prospective nonrandomized study using short duration neoadjuvant chemotherapy. Median age was 57 years (range: 34-70). Twenty-one patients (57%) had Stage IIB disease, one (3%) had Stage IIIA, 11 (30%) Stage IIIB, and four (11%) had Stage IV disease. The average tumor diameter at presentation assessed by physical examination and by CT scan measurements was 5.3 + 1.9 cm and 5.3 + 1.4 cm, respectively. Patients received three cycles of chemotherapy consisting of cisplatin 50 mg/m2 and vincristine 1 mg/m2 for 1 dose and bleomycin 25 mg/m2 daily for three days. Cycles were repeated every ten days. All patients started definitive radiotherapy within a week from the end of chemotherapy. Radiation therapy consisted of whole pelvis radiotherapy followed by 1-3 sessions of low dose rate brachytherapy. RESULTS: Response to neoadjuvant chemotherapy was as follows: seven patients (19%) had minor or no response, one patient had progressive disease, and 28 (76%) had more than 50% tumor reduction; 14 of them (38%) had no clinical evidence of residual tumor. Chemotherapy was discontinued in one patient after the second cycle because of significant changes in pulmonary function tests (PFT), and one patient developed a grade 4 urinary complication after radiotherapy. Median follow-up time for the whole group was 24 months (range: 1-67). Five-year actuarial rates of local control and disease-free survival were 47 and 42%, respectively. At three years, 20 patients (54%) were alive or had died without evidence of disease, and 17 (46%) had succumbed to their disease, with a median time to recurrence of 25 months. Stage and response to neoadjuvant chemotherapy had significant impact on survival, while age. tumor size, and menopausal status did not influence survival. CONCLUSIONS: Our data indicate that short duration chemotherapy followed by definitive radiotherapy is well tolerated and feasible. However, despite a high rate of objective response (76%), and improved survival for responders, there was no obvious long-term survival benefit for the entire group.

Case report: endometrial cancer implanting in the laparotomy scar.

A 58-year-old woman underwent abdominal hysterectomy and bilateral salpingo-oophorectomy for stage Ib, grade 2 endometrial adenocarcinoma followed by external pelvic irradiation. Five years later she presented with a 7 cm solitary infraumbilical incisional tumor recurrence that was resected. Histology of the tumor implant was similar to that of the primary cancer. The patient was then started on progestin therapy with no evidence of recurrence for four years. To our knowledge this is the fourth reported case of endometrial cancer implanting in an abdominal scar.

Papillary serous carcinoma of the ovary following prolonged tamoxifen treatment.

We present a patient with breast cancer who developed papillary serous adenocarcinoma of the ovary after 13 years of tamoxifen use. The possible association is explored and the literature is reviewed.

The relation between erythropoietin, hematocrit and hemoglobin in breast cancer patients on non-nephrotoxic chemotherapy.

Serum erythropoietin (EPO), hematocrit and hemoglobin levels were determined in 17 female patients with stage II breast cancer before, during and at the conclusion of non-nephrotoxic chemotherapy. Serum EPO levels were determined using the ELISA technique. No irradiation was given to any patient. The hemoglobin and hematocrit levels remained stable. However, a statistically significant increase in EPO was noted (p<0.05). The possible factors involved in this increase are reviewed, however the exact mechanism remains to be elucidated.

The relationship between serum levels of erythropoietin (EPO) and insulin-like growth factor-1 (ILGF-1) and hematocrit (HCT) in breast cancer patients receiving non-nephrotoxic chemotherapy.

OBJECTIVE: To evaluate the relationship between the hematocrit (HCT), serum erythropoietin (EPO) and insulin-like growth factor-1 (ILGF-1) levels in breast cancer patients receiving non-nephrotoxic chemotherapy. METHODS: Seventeen patients with stage II breast cancer were included. All received 6 cycles of non-nephrotoxic chemotherapy (cyclophosphamide, 5-fluorouracil and doxorubicin or methotrexate with or without tamoxifen). Insulin-like growth factor-1 and EPO levels were determined before and at the end of therapy. Serum EPO levels were determined by Enzyme linked- immunosorbant assay (ELISA) while those of ILGF- I by radioimmunoassay (RIA). RESULTS: A significant drop in mean HCT from 37.41%+/-0.77% to 35.18%+/-0.70%, associated with a significant decline in ILGF-1 levels from 92.1+/-15.48 ng/ml to 52.75+/-10.5 ng/ml at the end of the treatment was noted. This association became significant when patients receiving tamoxifen were excluded (r=0.69, p=0.02). The mean serum EPO levels increased significantly from 13.64+/-0.55 U/l to 19.44+/-3.18 U/l and correlated negatively with ILGF-1 level (r=-0.46, p=0.05). There was no significant relation between the serum EPO levels and HCT (r=-0.26, p=0.32). CONCLUSION: The current data show that ILGF-1 may play an important role in erythropoiesis and it correlates better than EPO with HCT in breast cancer patients receiving non-nephrotoxic chemotherapy.

Nail toxicity related to taxanes.

A 70-year-old woman with non-small-cell lung cancer developed severe nail toxicity while she was being treated with docetaxel at three-week intervals. Docetaxel is a chemotherapeutic agent of the taxane family. Taxanes are well known to cause nail changes, but mainly when used on a weekly basis.

Cancer in Lebanon: analysis of 10,220 cases from the American University of Beirut Medical Center.

Cancers seen and recorded between 1983 and 1995 in the Hospital Tumor Registry at the American University of Beirut Medical Center (AUBMC), one of the largest primary and tertiary care hospitals in Lebanon, were retrospectively reviewed and analyzed. There was a total of 10,220 cases, excluding 916 skin cancers other than skin melanoma, averaging 786 cases per year. There were 5086 cancer cases in males with the five most common cancers being: lung cancer (915 cases: 17.9%) followed by bladder cancer (503 cases: 9.8%), larynx (438 cases: 8.6%), lymphoma (393 cases: 7.7%) and leukemia (336 cases: 6.6%). As for female cancer cases, a total of 5134 cases were observed with the five most common cancers being: breast cancer (1821 cases), followed by cervical cancer (535 cases), colo-rectal cancer (256 cases: 4.9%), lymphoma (232 cases: 4.5%), and brain cancer (213 cases: 4.1%). The average age for all cancer cases was 50.5 years with a standard deviation (SD) of 18.8 years. The average age of females (48.8 yrs; SD 17.4) was relatively lower than that of males (52.2 yrs; SD 19.9) and the difference was statistically significant. 40.6% of the patients were under the age of 50 years. 49% of breast cancer patients were below 50 years of age. In children less than 15 years of age, there were 555 cases, with leukemia being the commonest (185 cases: 33.3% of childhood cases) followed by brain cancer (112 cases: 20.1%), lymphoma (63 cases: 11.3%), bone cancer (41 cases: 7.3%), soft tissue sarcoma (35 cases: 6.3%) and kidney cancer (28 cases: 5.0%). Lung cancer in males and breast cancer in females are the most common cancers in Lebanon. These cancers are amenable to prevention (cigarette cessation and anti-smoking campaigns for lung cancer) and early detection (screening, regular breast examination and mammography for breast cancer). Our paper emphasizes the importance of addressing those and other issues including bladder cancer and age at diagnosis of breast cancer. It also presents important epidemiological and historical reference data on cancer in Lebanon during the civil war and immediately after it.