The Neurotoxicity and Pharmacokinetics of Oral Ifosfamide
Pages 13-23
Martin S. Highley, Guido Momerency, Diane Sawyers, Ernst A. De Bruijn, Hans Prenen, Gunther Guetens, Gert De Boeck, Allan T. Van Oosterom, Janine L. Mansi, Peter R. Blake, Tim Mant, Robert A.A. Maes and Peter G. Harper

DOI: http://dx.doi.org/10.6000/1927-7229.2015.04.01.3
Published: 12 February 2015

Abstract: Purpose:Ifosfamide can cause an unexplained encephalopathy. The incidence after intravenous infusion is 10%, but is much higher after oral administration. This study assesses the pharmacokinetics of oral ifosfamide in relation to neurotoxicity.

Patients and Methods:Eleven patients received oral ifosfamide 500 mg twice daily for 14 days, with concurrent oral mesna. The concentrations of ifosfamide, isophosphoramide mustard, 2-dechloroethylifosfamide, 3-dechloroethylifosfamide, carboxyifosfamide, ketoifosfamide, chloroethylamine and 3-oxazolidine-2-one were measured using GC-MS. Patients were evaluated clinically, and also with the EEG, psychometric testing, the national adult reading test, and the mini-mental state examination.

Results:A decrease in the electroencephalogram alpha frequency was observed, with the development of pathological slow wave activity. Psychometric performance was also impaired. Neurotoxicity was progressive during treatment, and the incidence of grade 3 neurotoxicity was 22%. The mean day 14 / day 1 Cmax ratios for 2-dechloroethylifosfamide and 3-dechloroethylifosfamide were 2.73 (± 2.11) and 2.04 (± 1.32) respectively. The metabolite with the lowest ratio was isophosphoramide mustard 1.07 (± 0.39). High chloroethylamine Cmax values were associated with lower alpha frequencies, and increased clinical neurotoxicity.

Conclusion:Oral ifosfamide 500 mg twice daily for 14 days causes unacceptable neurotoxicity. It was not possible to identify one particular metabolite responsible for the neurotoxicity, although the dechloroethyl metabolites and chloroethylamine are implicated.

Adverse Effects of Bevacizumab During Treatment for Metastatic Colorectal Cancer 
Pages 24-29
Kenji Ina, Ryuichi Furuta, Takae Kataoka, Sayaka Sugiura, Satoshi Kayukawa, Takayuki Kanamori, Takaki Kikuchi, Megumi Kabeya, Satoshi Hibi and Shu Yuasa
DOI: http://dx.doi.org/10.6000/1927-7229.2015.04.01.4
Published: 12 February 2015

Abstract: Objective:Bevacizumab has been increasingly used in combination chemotherapy for the treatment of metastatic or recurrent colorectal cancer.The aim of this report is to underline the possible risks associated with bevacizumab use.

Methods:Between July 2005 and March 2013, a total of 130 patients with metastatic colorectal cancer who received oxaliplatin as first-line chemotherapy were divided into 2 groups those treated with bevacizumab (group A) and those without (group B), and compared. The primary endpoint was to clarify the profile of bevacizumab - induced adverse effects. Secondary endpoints examined therapeutic effects, including overall survival (OS).

Results:The incidence of major side effects was almost equivalent, except for bleeding, between the 2 groups. With regard to the therapeutic effects, 1 patient in group A showed complete disappearance of multiple lung metastases without any evidence of recurrence. The median OS was 926 days (95% confidence interval [CI], 756 - 1257) in group A and 534 days (95% CI, 421 – 621) in group B (p < 0.01).

Conclusion:The results demonstrate that bevacizumab prolonged survival in these patients although there was an increased risk of clinically significant bleeding.

Epidemiological and Pathological Aspects of Head and Neck Cancers in Togo 
Pages 30-34
Tchin Darré, Haréfétéguéna Bissa, Komlavi Ehlissou Akloa, Essobozou Pegbessou, Bathokédeou Amana, Aman Alphonse N’guessan, Koffi Amégbor, Essohana Boko and Gado Napo-Koura
DOI: http://dx.doi.org/10.6000/1927-7229.2015.04.01.5
Published: 12 February 2015

Abstract: Purpose:Head and neck cancers are a major public health issue. Its current incidence is unknown in Togo. This study aimed at determining the epidemiological and histological features of head and neck cancers in Togo.

Materials and Methods: We examined data from patients files recorded in the registers of laboratory of pathology of the university teaching hospital of Lomé. The study concerned data of the patients received from January 1994 to December 2013. We selected only the files whose diagnosis was a cancer. The parameters analyzed were: frequency, age, gender of patients, site, macroscopic and histological type of cancer.

Results: Epidemiological, we collected 5234 cases of cancer of which 309cases ORL cancers, representing 5.1% of all cancer cases. The annual frequency was 15.09 cases. The average age was 45 years ranging from 3 to 87 years and a peak incidence between 41-50 years (20%). Sex ratio of 1.55.

Concerning pathological, the salivary gland cancers were the most prevalent (28.2%) followed by larynx cancers (24%). Four groups histological were observed: Carcinomas 196cases (63.43%), lymphomas 105cases (33.98%), 6 cases sarcomas (1.94%) and 2cases melanomas (0.65%). The squamous carcinoma (40.78%) was the most frequent carcinomas. The high grade non-Hodgkin lymphomas (48,4%) were common with prevalent Burkitt lymphoma.

Conclusion: the head and neck cancers are prevalent in young adults in Togo. The squamous carcinoma is the most common histological type.

Buschke Löwenstein Tumor of the Right Lower Abdominal Wall: Case Report and Review of the Literature 
Pages 35-38
Martin Balog, Ulrich Lang and Günther Winde
DOI: http://dx.doi.org/10.6000/1927-7229.2015.04.01.6
Published: 12 February 2015

Abstract: Buschke-Löwenstein tumor (BLT), known as giant condyloma acuminatum (GCA), is a very rare disease that typically appears as a penile lesion but can although appear in the anogenital region, bladder, vulva, scrotum and sacrococcygeal area as well.

Despite of its histologically benign signs, a high recurrence rate, invasiveness and destructive growth characterizes this rare disease as clinically malignant.

Malignant transformation into verrucous carcinoma (VC) and squamous-cell carcinoma (SCC) have been described as well.

Many treatment modalities inclusive neoadjuvant radio-and chemotherapy and topical treatment have been reported but due to lack of controlled studies no treatment can be recommended.

We present a case of Buschke-Löwenstein tumor involving the right lower abdominal wall of the colostomy region at a 71 years old male.

To our knowledge, we first describe a case report of GCA involving abdominal wall at the colostomy region, successfully treated by wide radical excision and plastic reconstruction.

Comparison of Prostate Specific Antigen and Prostate Specific Antigen Density for Predicting the Degree of Gleason Score of Prostate Cancer 
Pages 39-43
Mehrzad Lotfi, Naghmeh Roshan and Amin Abolhasani Foroughi
DOI: http://dx.doi.org/10.6000/1927-7229.2015.04.01.7
Published: 12 February 2015

Abstract: Introduction: In this study we evaluate the relationship of PSA and PSAD with the degree of Gleason’s score of prostate cancer in transrectal ultrasound guided biopsy specimens.

Methods: From March 2003 to October 2009, 1025 transractal ultrasound guided biopsies were performed in our hospital. PSA was measured by monoclonal antibody method and PSAD was calculated. The Gleason grade of the detected tumors in the biopsy specimens was classified as low, moderate and high grade. Data were analyzed by SPSS software.

Results: 292 patients were diagnosed to have prostate adenocarcinoma. There was an acceptable correlation between PSA (P=0.001) and PSAD of the specimens (P = 0.013) with Gleason grades. PSA level showed a statistically significant difference between the low and high grade groups (P=0.005) and the intermediate and high grade groups (p=0.014). A statistically significant difference of PSAD level was seen only between the low and high grade (P=0.006) groups

Conclusions: PSA and PSAD are both effective diagnostic tools for detection of prostate cancer; PSA level has a valuable role in predicting Gleason pattern higher than 7/10 and it can be the predictor of advanced pathological features but PSAD is effective in prediction of Gleason pattern lower than 5/10.