An insight into the diagnostic and prognostic value of HOX A13's expression in non-muscle invasive bladder cancer.

BACKGROUND: Several studies have interrogated the molecular pathways and their interacting genes underlying bladder cancer (BCa) tumorigenesis, yet, the role of homeobox genes is still poorly understood. Specifically, HOXA13, which plays an important role as a major actor in the urogenital tract's development. METHODS: Immunohistochemical (IHC) staining was performed to inspect the differential expression of HOXA13 protein in non-muscle-invasive bladder cancer (NMIBC) and non-tumoral tissues. A semiquantitative scoring system was adopted to evaluate the IHC labeling. Correlation to clinical parameters was performed by descriptive statistics. Overall survival was estimated by the Kaplan-Meier method and Cox regression model. The functional HOX A13 protein association networks (PPI) were obtained using String 11.0 database. RESULTS: HOX A13 exhibited cytoplasmic and nuclear staining. Its expression levels were lower in high-grade NMIBC (HG NMIBC) compared to low-grade ones (LG NMIBC). The expression of HOX A13 was correlated to tumor grade (LG/HG) (p = 0.036) and stage (TA/T1) (p = 0.036). Nevertheless, its expression was not correlated to clinical parameters and was not able to predict the overall survival of patients with HG NMIBC. Finally, PPI analysis revealed that HOX A13 seems to be a part of a molecular network holding mainly PBX1, MEIS, ALDH1A2, HOX A10, and HOX A11. CONCLUSION: The deregulation of HOX A13 is not associated with the prognosis of BCa. It seems to be rather implicated in the early initiation of urothelial tumorigenesis and thus may serve as a diagnostic marker in patients with NMIBC. Further experimentations on larger validation sets are mandatory.

Clinical and pathological characteristics, treatment outcome and prognostic factors in adult rhabdomyosarcoma: a monocentric retrospective study.

Rhabdomyosarcoma (RMS) is rare in adults. Our study is the first in Tunisia to report outcomes of adult RMS. We retrospectively analyzed clinical data of adult RMS patients. We collected data regarding clinical characteristics, treatment outcome and prognostic factors. Survival was assessed using the Kaplan Meier method. Forty-seven patients were included. Median age was 39. Twenty-five patients were young adults (53%). Sex ratio (M/F) was 1.9. RMS was localized in 33 patients (70%) and metastatic in 14 patients (30%). Extremities were the most frequent tumor site (40%) followed by trunk (23%). Median tumor size was 9 cm. Pleomorphic RMS was the major subtype (36%). Twenty seven of 33 patients with localized RMS underwent surgery (82%). Relapse free survival (RFS) was 38%. Young adults had a significantly worse RFS than adults aged ≥40 (p = 0.045). Surgery was associated with a significantly better RFS (p = 0.023). Five year overall survival (OS) was 35% and 27% in localized and metastatic RMS respectively. RMS localized in the extremities had significantly poorer OS (p = 0.041), same as non-operated patients (p = 0.025). OS for metastatic RMS was significantly worse after surgery of the primary tumor (p = 0.002). In multivariate analysis, surgery (HR = 0.108; 95%CI (0.023-0.519); p = 0.005) and non-extremity localization (HR = 0.238; 95%CI (0.075-0.751); p = 0.014) were independent prognostic factors for OS in localized RMS. Adults with RMS have poor 5 year OS. Surgery and non-extremity localization were independent prognostic factors for OS in localized RMS.

Polymorphisms in NQO1 and MPO genes and risk for bladder cancer in Tunisian population.

BACKGROUND: NAD (P) H: quinone oxidoreductase (1) (NQO1-HGNC: 2874) and myeloperoxidase (MPO-HGNC: 7218) are two enzymes involved in phase II of the xenobiotic metabolism pathway. METHODS: In this study, a case-control analysis was conducted to investigate the relationship between genetic variations in the NQO1 (C609T, rs1800566; IVS1-27 C >G, rs689452) and MPO (G463A, rs2333227) genes and the risk for bladder cancer among Tunisian population. RESULTS: We have found that the MPO 463GA genotype was associated with a decreased risk of developing bladder cancer (p = 0.049; OR = 0.696; 95% CI 0.484-0.999). In contrast, we have found that the NQO1 609CT genotype could increase the risk of bladder cancer patients (p = 0.0039; OR = 1.454; 95% CI = 1.017-2.078). Moreover, patients with "NQO1 609 CT/IVS1-27 CG" genotype show a 2.180-fold increasing risk for developing bladder cancer in comparison to the control group with wild genotype. This OR is estimated at 5.6-fold in smokers patients with "NQO1 609 CT/IVS1-27 CG" genotype. Lastly, study findings suggest that the NQO1 IVS-27 *CG genotype (rs689452) is associated with a risk of progression to muscle invasive bladder cancer. CONCLUSION: Our study suggests that environmental risk factors in association to NQO1 genotypes (NQO1 609 CT/IVS1-27 CG) play an important role in the development of bladder cancer in Tunisian population.

The diagnostic applicability of A-type Lamin in non-muscle invasive bladder cancer.

PURPOSE: Lamin A is a major component of the nuclear lamina maintaining nuclear integrity, regulation of gene expression, cell proliferation, and apoptosis. Its deregulation in cancer has been recently reported to be associated with its prognosis. However, its clinical significance in non-muscle invasive bladder cancer (NMIBC) remains to be defined. MATERIAL/METHODS: Immunohistochemical staining and RT-qPCR were performed to screen the expression patterns of Lamin A/C protein and Lamin A mRNA respectively in 58 high and low grade NMIBC specimens. RESULTS: Lamin A/C protein was expressed only in the nucleus and less exhibited in NMIBC tissues compared to non-tumoral ones. On the other side, Lamin A mRNA was up-regulated in NMIBC compared to controls. Nevertheless, both expression patterns (protein and mRNA) were not correlated to clinical prognosis factors and were not able to predict the overall survival of patients with high-grade NMIBC. CONCLUSIONS: The deregulation of A-type Lamin is not associated with the prognosis of NMIBC, but it could serve as a diagnostic biomarker distinguishing NMIBC patients from healthy subjects suggesting its involvement as an initiator event of tumorigenesis in our cohort.

An Acute Jejunojejunal Intussusception Revealing a Metastatic Combined Lung Cancer.

Intussusception is a relatively common disease in pediatric age but it is uncommon in adults. We report a case of a 49-year-old male who presented with an acute jejunojejunal intussusception revealed by abdominal pain and vomiting. He underwent an en bloc resection, and pathological findings concluded to a metastasis of a pulmonary combined small cell carcinoma and adenocarcinoma. A subsequent CT scan revealed the primitive mass of the right lung with no evidence of secondary localization. The biopsy was difficult to perform. The patient underwent a pneumonectomy with lymph node dissection confirming the same diagnosis. He made a good recovery from the surgery, and a postoperative chemotherapy was administrated, and he is in remission until this date.

Granulosa Cell Tumor of the Ovary: A Retrospective Study of 31 Cases and a Review of the Literature.

BACKGROUND: Adult granulosa cell tumors (AGCTs) are the most common sex cord-stromal tumors. Unlike epithelial ovarian tumors, they occur in young women and are usually detected at an early stage. The aim of this study was to report the clinical and pathological characteristics of AGCT patients and to identify the prognostic factors. METHODS: All cases of AGCTs, treated at Salah Azaïz Institute between 1995 and 2010, were retrospectively included. Kaplan-Meier's statistical method was used to assess the relapse-free survival and the overall survival. RESULTS: The final cohort included 31 patients with AGCT. The mean age was 53 years (35-73 years). Patients mainly presented with abdominal mass and/or pain (61%, n = 19). Mean tumor size was 20 cm. The majority of patients had a stage I disease (61%, n = 19). Two among 3 patients with stage IV disease had liver metastasis. Mitotic index was low in 45% of cases (n = 14). Surgical treatment was optimal in almost all cases (90%, n = 28). The median follow-up time was 14 years (1-184 months). Ten patients relapsed (32%) with a median RFS of 8.4 years (6.8-9.9 years). Mean overall survival was 13 years (11-15 years). Stage I disease and low-to-intermediate mitotic index were associated with a better prognosis in univariate analysis (resp., p = 0.05 and p = 0.02) but were not independent prognostic factors. CONCLUSION: GCTs have a long natural history with common late relapses. Hence, long active follow-up is recommended. In Tunisian patients, hepatic metastases were more frequent than occidental series. The prognosis remains good and initial staging at diagnosis is an important prognostic factor.

Cutaneous leiomyosarcoma on the trunk: An unusual presentation with an aggressive course - Case report and review of literature.

Primary cutaneous leiomyosarcoma (PCL) are soft-tissue sarcoma, arising in the dermis, with or without extension into the subcutis. They are thought to have an indolent course compared to their subcutaneous counterparts, they may recur but rarely metastases. We report the case of a patient with a PCL arising in the anterior trunk wall who developed pulmonary, bone and retroperitoneal metastases 6 years after wide surgical excision of the primary tumor.

Potential predictive factors for pathologic complete response after the neoadjuvant treatment of rectal adenocarcinoma: a single center experience.

OBJECTIVE: : To assess the response rate of patients with rectal adenocarcinoma to neoadjuvant therapy and to identify the predictors of histological regression after neoadjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). METHODS: : This study recruited 64 patients. The patients had resectable cancer of the lower and the middle rectum (T3/T4 and/or N+) without distant metastasis and received neoadjuvant RT or CCRT followed by radical surgery with total mesorectal excision (TME) between January 2006 and December 2011. The patients were classified into non-response (NR), partial response (PR), and pathologic complete response (pCR) based on the Dworak tumor regression grading system. RESULTS: : The median age of patients was 57 years (ranging from 22 to 85). A total of 24 patients were treated with neoadjuvant CCRT, whereas 40 patients were treated with RT alone. Abdominoperineal resection (APR) was performed on 29 patients (45%). Anterior resection with TME was performed on 34 patients (53%). One patient had local resection. Histologically, 12 (19%), 24 (73%), and 28 (44%) patients exhibited pCR, PR, and NR, respectively. Univariate analysis revealed that the predictors of tumor regression were as follows: the absence of lymph node involvement from initial imaging (cN0) (P=0.021); normal initial carcinoembryonic antigen (CEA) level (P=0.01); hemoglobin level ≥12 g/dl (P=0.009); CCRT (P=0.021); and tumor downstaging in imaging (P=0.001). Multivariate analysis showed that the main predictors of pCR were CT combined with neoadjuvant RT, cN0 stage, and tumor regression on imaging. CONCLUSIONS: : Identifying the predictors of pCR following neoadjuvant therapy aids the selection of responsive patients for non-aggressive surgical treatment and possible surveillance.

Squamous cell carcinoma of the gallbladder.

Gallbladder cancer is the most common malignant tumor of the biliary tract. The majority of cases are adenocarcinoma (AC). Pure squamous cell carcinoma (SCC) of gallbladder accounts only 3% of the malignant neoplasm of this organ. Many patients are at advanced stage when diagnosed and have bad therapeutic efficacy. At present, radical surgery is the only chance to gain long-term survival for patients with early-stage gallbladder cancers. Recent reports have shown a benefit of adjuvant chemoradiation in this type of tumor. At present, no therapy is defined for unresectable cancer of the gallbladder, especially for SCC.

[Aromatases inhibitors for breast cancer in menopausal patients]. / Les inhibiteurs de l'aromatase dans le traitement adjuvant du cancer du sein de la femme ménopausée.

AIMS: To analyze the litterature data concerning the results of the main international randomized trials of adjuvant Aromarase Inhibitors (AI) in adjuvant setting for early breast cancer and the impact on daily practice in the management of breast cancer. METHODS: We selected through a litterature review 30 publications concerned the topic of AI RESULTS: They concerned the large ATAC, BIG, MA17 and IES concerning anastrozole, letrozole and exemestane . AI have been compared to tamoxifen in upfront of swich intents and showed a superiority to reduce, mortality rate, controlateral breast cancer risk, a better tolerance profile compared to tamoxifen and a sigificant benefit in term of disease-free survival. These results made a revolution in the adjuvant BC treatment, leading to the systematic use of upfront AI in menopaused patients. CONCLUSION: Adjuvant hormonotherapy in menopaused patients is now based on AI and proved its superiority to tamoxifen in term of distant, controlateral risks reduction and disease-free survival, less for overall survival.