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IntroductionImmunotherapy by blocking immune checkpoints programmed death/ligand (PD1/PDL1) and cytotoxic T-lymphocyte-associated protein 4(CTLA4) has emerged as new therapeutic targets in cancer. However, their efficacy has been limited due to resistance. A new- checkpoint V-domain Ig-containing suppressor of T cell activation (VISTA) has appeared, but the use of its inhibition effect in combination with antibodies targeting PDL1/PD1and CTLA4 has not been reported in ovarian cancer.MethodsIn this study, we investigated the expressions of VISTA, CTLA4, and PDL1 using immunohistochemistry (IHC)on 135 Formalin-Fixed Paraffin-Embedded (FFPE)tissue samples of High-grade serous carcinoma (HGSOC). VISTA, CTLA4, PDL1, PD1, CD8, CD4, and FOXP3 mRNA extracted from 429 patients with ovarian cancer in the Cancer Genome Atlas (TCGA) database was included as a validation cohort. Correlations between these checkpoints, tumor-infiltrating- lymphocytes (TILs), and survival were analyzed.Results and discussionCTLA4 was detectable in 87.3% of samples, VISTA in 64.7%, PD1 in 56.7%, and PDL1 in 48.1%. PDL1 was the only tested protein associated with an advanced stage (p=0.05). VISTA was associated with PDL1, PD1, and CTLA4 expressions (p=0.005, p=0.001, p=0.008, respectively), consistent with mRNA level analysis from the TCGA database. Univariate analyses showed only VISTA expression (p=0.04) correlated with overall survival (OS). Multivariate analyses showed that VISTA expression (p=0.01) and the coexpression of VISTA+/CTLA4+/PD1+ (p=0.05) were associated with better OS independently of the clinicopathological features. Kaplan-Meier analysis showed that the coexpression of the VISTA+/CTLA4+/PDL1+ and VISTA+/CTLA4+/PD1+ checkpoints on tumor cells (TCs)were associated with OS (p=0.02 and p

Abstract A cell-free DNA (cfDNA) assay would be a promising approach to early cancer diagnosis, especially for patients with dense tissues. Consistent cfDNA signatures have been observed for many carcinogens. Recently, investigations of cfDNA as a reliable early detection bioassay have presented a powerful opportunity for detecting dense tissue screening complications early. We performed a prospective study to evaluate the potential of characterizing cfDNA as a central element in the early detection of dense tissue breast cancer (BC). Plasma samples were collected from 32 consenting subjects with dense tissue and positive mammograms, 20 with positive biopsies and 12 with negative biopsies. After screening and before biopsy, cfDNA was extracted, and whole-genome next-generation sequencing (NGS) was performed on all samples. Copy number alteration (CNA) and single nucleotide polymorphism (SNP)/insertion/deletion (Indel) analyses were performed to characterize cfDNA. In the positive-positive subjects (cases), a total of 5 CNAs overlapped with 5 previously reported BC-related oncogenes (KSR2, MAP2K4, MSI2, CANT1 and MSI2). In addition, 1 SNP was detected in KMT2C, a BC oncogene, and 9 others were detected in or near 10 genes (SERAC1, DAGLB, MACF1, NVL, FBXW4, FANK1, KCTD4, CAVIN1; ATP6V0A1 and ZBTB20-AS1) previously associated with non-BC cancers. For the positive–negative subjects (screening), 3 CNAs were detected in BC genes (ACVR2A, CUL3 and PIK3R1), and 5 SNPs were identified in 6 non-BC cancer genes (SNIP1, TBC1D10B, PANK1, PRKCA and RUNX2; SUPT3H). This study presents evidence of the potential of using cfDNA somatic variants as dense tissue BC biomarkers from a noninvasive liquid bioassay for early cancer detection.

Introduction: Any alteration in nutritional status can compromise the progression of breast cancer, as well as the tolerance and efficacy of chemotherapy. The aims of our study were to assess the nutritional status of breast cancer patients treated with chemotherapy and to identify nutritional factors that may exacerbate chemo-induced digestive toxicity. Methods: This descriptive cross-sectional study was conducted within the medical oncology department of the National Institute of Salah Azaiez. A Mediterranean Diet Score (MDS) was used to evaluate the level of adherence to the Mediterranean Diet. Nutritional status was assessed using 2 methods; body composition evaluation utilising the TANITA BC 601 impedance metre and High authority of health (HAS) criteria of malnutrition. Digestive effects were assessed with World Health Organization (WHO) grades ranging from 0 to 4. High grades 3 and 4 signified toxic grades. Results: We enrolled 107 adult women diagnosed with breast cancer undergoing the same chemotherapy protocol. The participants had an average age of 52.56 ± 9.75 years and an average BMI of 29.85 ± 5.72 kg/m2 with 78.5% classified as overweight. Malnutrition was observed in 41% of patients, while sarcopenia was present in 12%. Chemotherapy-related adverse effects were predominantly constipation (80%), diarrhea (73%), nausea (70%) and vomiting (63.4%) with one-third experiencing high-grade toxicity. Strong adherence to Mediterranean Diet was observed in 48.6% of cases and higher MDS scores were inversely correlated with the severity of nausea (P =.01) and constipation (P =.02). Malnutrition was significantly associated with all digestive toxicities except with constipation. Sarcopenia was associated only with vomiting (P =.005). Conclusion: There is a relationship between nutritional status and digestive toxicity, justifying early nutritional treatment to improve the tolerance and efficacy of chemotherapy. [ABSTRACT FROM AUTHOR]

Objective:This study was designed to investigate treatment satisfaction in patients and Health Care Professionals (HCP) and to evaluate the safety and tolerability of subcutaneous (SC) trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (eBC).Materials and Methods:Two-hundred and twenty-three patients with eBC were screened, of whom 173 patients met the eligibility criteria and received at least one dose of SC trastuzumab. The primary efficacy endpoint was to assess patient satisfaction via a questionnaire.Results:The majority of patients (n = 166, 97.6%) reported satisfaction with the SC route. Patients and HCPs stated that SC trastuzumab was easy to use (93.5% and 62.5%, respectively) compared to the intravenous (IV) route and all HCPs (n = 16) expressed satisfaction with the SC route. Progression, disease recurrence or death was reported in 24 patients (13.8%) by two years of follow up. Four-year disease-free survival (DFS) and overall survival (OS) rates were 84.2% (±3.1) and 90.5% (±4.7), respectively. A total of 1299 adverse events (AEs) were recorded over 4-years follow-up, nearly 97% of which were judged non-serious. The most common AEs were arthralgia (n = 54, 4.2%), flu-like symptoms (n = 41, 3.2%) and nausea (n = 39, 3.0%). Fifty-four cardiac events, including left ventricular dysfunction, left ventricular failure and cardiotoxicity, were reported. Ejection fraction (EF) decrease [median decrease 3.5% (0.12–19.0)] was reported in 5.4% of cases. SC trastuzumab treatment was interrupted due to decreased EF in two cases.Conclusion:SC trastuzumab was widely acceptable to both patients and HCPs. The safety and tolerability of SC trastuzumab was consistent with the known safety profile of SC and IV administration.

Immunotherapy by blocking immune checkpoint regulators has emerged as a new targeted therapy for some cancers. Among them V-domain Ig suppressor of Tcell activation (VISTA) which is identified as a novel checkpoint regulator in ovarian cancer. This study aimed to investigate the VISTA role in Epithelial ovarian cancer (EOC), and its relationship with tumor-infiltrating lymphocytes (TILs) markers and its prognostic value. The expression of VISTA, CD3, CD8, CD4, FOXP3, and CD56 was assessed in 168 EOC tissue microarrays (TMA) by immunohistochemistry (IHC). In addition, associations between VISTA, TILs, clinicopathological variables, and overall survival (OS) were analyzed. VISTA expression in IGRov1 cells, as well as in PBMC of EOC patient, was evaluated by western blot. VISTA expression was detected in 64,28% of tissues, among which 42.3% were positive for tumor cells (TCs), and 47,9% were positive for immune cells (ICs). In univariate analysis, VISTA expression was significantly associated with a high density of TILs:CD3+ (p = 0,001), CD4+ (p = 0,002) and CD8+ (p≤0,001), in ICs but not in TCs. In terms of OS, multivariate analysis showed a significant association between the high density of CD8+ TILs and VISTA positive staining in ICs (p = 0,044), but not in TCs (p = 0,108). Kaplan-Meier curves demonstrated no correlation between VISTA expression and prolonged OS in both ICs (p = 0,841) and TCs (p = 0,090). Classification of EOC tumor microenvironment based on VISTA and CD8+TILs expression, demonstrated four immune subtypes: VISTA+/CD8+, VISTA+/CD8-, VISTA-/CD8+ and VISTA-/CD8-. The dual positive VISTA+/CD8+ subtype was significantly associated with prolonged OS in both TCs and ICs (p = 0,012 and p≤0,01, respectively), whereas patients with VISTA+/CD8- had the worst OS. Our results showed that VISTA is highly expressed in the IGRov1 cell line and LT-CD8 from a patient with EOC. Our results highlighted the association of VISTA expression and CD8+ TILs in EOC, with prolonged OS in patients with VISTA+/CD8+ and proposed VISTA as a potential immunotherapeutic target in EOC.

Abstract Background Colorectal cancer (CRC) is the third most diagnosed malignancy worldwide. The global burden is expected to increase along with ongoing westernized behaviors and lifestyle. The etiology of CRC remains elusive and most likely combines environmental and genetic factors. The Kv2.1 potassium channel encoded by KCNB1 plays a collection of roles in malignancy of cancer and may be a key factor of CRC susceptibility. Our study provides baseline association between Tunisian CRC and interactions between KCNB1 variants and lifestyle factors. Methods A case-control study involving 300 CRC patients, and 300 controls was conducted Patients were carefully phenotyped and followed till the end of study. KCNB1 genotyping was confirmed by Sanger sequencing. Bivariate and multivariable logistic regression analyses were used to assess the clinical status, lifestyle and study polymorphisms association with CRC. Results We noted significant gender association with CRC occurrence. Moreover, CRC risk increases with high meat and fat consumption, alcohol use and physical activity (PA). Carriage of rs1051296 A/G and both rs11468831 ins/del and del/del genotypes (p

Abstract The gastric location of EBVMCU is extremely rare. The pathology examination and immunochemistry are mandatory for the diagnosis. It is essential that physicians be aware of this new entity to accurately diagnose and handle this disease.

Abstract Cutaneous metastases are rare and represent a sign of poor prognosis. They are a sign of widespread disease. Breast cancer is the most common neoplasm leading to their appearance. Palliative care is the treatment of choice.

Abstract Clear cell sarcoma of the esophagus is very rare. The etiology of this neoplasm remains unknown. Confirmed diagnosis requires histopathology with immunochemistry and molecular study. CCS typically shows highly aggressive behavior with a high rate of local recurrence, metastases, and death from disease.

Objectives: Colorectal cancer (CRC) is a serious gastrointestinal disease. Cancer cells can survive in a microenvironment that includes distinct immune cells, various immune checkpoints including HLA-G, and different immune effectors such as interleukin-6 (IL-6), TNF-alpha (TNF-α), and interferon-gamma (IFN-γ). Thus, the objective of this study was to investigate HLA-G involvement in CRC as a prognostic factor in the Tunisian population, both in its soluble form (sHLA-G) and in its form linked to extracellular vesicles (HLA-GEV). Additionally, we examined its association to the secretion of cytokines. Methods: Fifty Tunisian patients, diagnosed with CRC, matched with ninety-eight healthy blood donors (HD) were enrolled in this study. Levels of sHLA-G, HLA-GEV, IL-6, TNF-α, and IFN-γ were dosed in plasma samples using specific ELISA. For the functional assay, we assessed sHLA-G effects on the production of cytokines by stimulated T lymphocytes. We measured the concentration of IL-6, TNF-α, and IFN-γ produced by activated T lymphocytes pre-stimulated by plasma sHLA-G and HLA-GEV. Results: Our case-control analysis showed high concentration of both sHLA-G (8.8 [0–63] ng/ml vs. 2.1 [0–63] ng/ml, p

PURPOSE: Sunitinib offers improved efficacy for patients with metastatic renal cell carcinoma (mRCC). To provide better disease management in the Middle East, we studied its use in mRCC in real-life practice in this region. MATERIAL AND METHODS: Patients diagnosed with mRCC and started on sunitinib between 2006 and 2016 from 10 centers in Africa and the Middle East region were studied in this regional, multicenter, observational, retrospective trial to obtain routine clinical practice data on the usage patterns and outcomes of sunitinib in mRCC in real-life practice. RESULTS: A total of 289 patients were enrolled. Median age at diagnosis was 58.7 years. The patient characteristics were as follows: 73.6% of patients were males; 85.8% had clear-cell renal cell carcinoma (RCC); 97.5% had unilateral RCC; 66.3% had metastatic disease at initial diagnosis; 56.3% received previous treatment for RCC, among which 98.7% had undergone surgery; and 15.2% and 31.4% were classified in the favorable and poor-risk groups (expanded Memorial Sloan Kettering Cancer Center criteria), respectively. On treatment initiation, the mean total sunitinib dose was 48.1 mg, and 87.6% of patients were started on a sunitinib dose of 50 mg. The mean duration of sunitinib treatment was 9.6 months. Overall response rate was 20.8%, with a median duration of 8.2 months. Median time to progression was 5.7 months. Median follow-up time was 7.8 months. By months 12 and 24, 34.3% and 11.4% of patients, respectively, were still alive. Seventy-six patients (60.9%) experienced 314 adverse events. Twenty-three patients (8.0%) experienced 28 serious adverse events. Overall, 83 patients (28.7%) discontinued their sunitinib treatment. CONCLUSION: The results are indicative of the general treatment outcomes of patients with mRCC in the Middle East using sunitinib in routine clinical practice. Reported adverse events are similar to those described in the literature but at lower frequencies.

Gestational trophoblastic disease (GTD) develops from abnormal cellular proliferation of trophoblasts following fertilization. It includes benign trophoblastic disease (hydatidiform moles (HM) and the malignant trophoblastic diseases or gestational trophoblastic neoplasia (GTN). The frequency of the GTD in Tunisia is one per 918 deliveries. The aim of this study is to analyze the clinical characteristics, treatment and outcomes of GTD at Salah Azaiez Institute (ISA). Medical records of women diagnosed with GTD at ISA from January 1, 1981 to December 31, 2012 were retrospectively reviewed. FIGO (International Federation of Gynecology and Obstetrics) score was determined retrospectively for patients treated before 2002 One hundred and nine patients with GTN were included. Patients presented with metastases at 43% of cases. The most common metastatic sites was lung (30%) and vagina (13%). 56 (51%) patients had low-risk and 21 (19%) cases had high-risk, the FIGO score was not assessed in 32 cases. After a median follow-up of 46 months, 21 patients were lost to follow-up, 12 patients died, 19 progressed and 8 relapsed. At 10 years, the OS rate was 85% and the PFS rate 79%. OS was significantly influenced by the presence of metastases at presentation (M0 100 % vs. Metastatic 62 %; p < 0.0001), FIGO stage (I-II 100% VS 61% and 65% for stage III and IV; p < 0.001), FIGO score (low-risk 99 % vs. high-risk 78 %; p < 0.001). GTN is a significant source of maternal morbidity with increased risk of mortality from complications if not detected early and treated promptly.

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.

Background: Osteosarcoma is the most frequent bone cancer occurring in children and adolescents aged 10–20 years. Several prognostic factors have been identified by studies done at western centers. The aim of our study was to identify the prognostic factors in Tunisian patients in order to improve their management. Methods: We reviewed the data of localized limb osteosarcoma patients treated in Salah Azaïz Institute from January 1980 to December 2018. Patient’s treatment and survival variables were assessed. Patients received a neoadjuvant chemotherapy and underwent surgery in an expert center. They received afterward an adjuvant chemotherapy depending on the tumor necrosis assessed by Huvos. Results: Eighty-five patients were enrolled. Mean duration of follow-up was 30 months (range 1–297 months). Males were 1.6 times more frequent, median age was 17 (from 1 to 62 years). Conventional osteoblastic osteosarcoma was the most frequent histological subtype (77%). Median tumor size was 10 cm. Femoral location was the most frequent (60%). The overall average history of symptoms was 103 days (4 to 423 days). The 5-year overall-survival was 38% and the event free survival 32%. Tumor site, lactate dehydrogenase levels, high methotrexate levels at 24 h, clinical evaluation of the tumor perimeter, surgery type and delay of relapse were found to affect overall survival. Tumor site, Lactate dehydrogenase levels and clinical evaluation of the tumor perimeter affected the progression free survival. Conclusion: Demographic characteristics of Tunisian patients are mainly the same than worldwide. Femoral site, normal level of lactate dehydrogenase, a clinical response during neoadjuvant treatment, an R0 surgery, a delay of relapse over 2 years and Median H24 Methotrexate level superior to 4.4 µmol/l were associated with a better prognosis in our study.

Prostate cancer is the second most frequent among men. Bones and lymph nodes are the most common sites of metastases in advanced prostate cancer. Oral cavity metastases are rare. We report a case of 65-year-old man with a prostate adenocarcinoma revealed by gingival metastasis. We analyze through this observation the clinical, morphological and therapeutic characteristics of this neoplasia.

The KCNB1 gene variants were differentially associated with cancers. However, their association with colorectal cancer has not yet been explored. We investigated the contribution of the KCNB1 gene variants rs3331, rs1051295, and indel (insertion/deletion) rs11468831 Polymorphism as predictors of the treatment response in colorectal cancer patients. A retrospective study, which involved 291 Tunisian colorectal cancer patients (aged 60.0 ± 13.1 years), who were stratified into responder and non-responder groups, according to TNM stages and their responsiveness to chemotherapy based on fluorouracil. KCNB1 genotyping was performed with amplification-refractory mutation system–polymerase chain reaction, and was confirmed by Sanger sequencing. Sex-specific response was found and colorectal cancer females are less likely to achieve a positive response during the chemotherapy strategy, compared to males. Weight and body mass index, tumor size, and tumor localization are considered as predictive factors to treatment responsiveness. Carriage of rs11468831 Ins allele was significantly associated with successful therapy achievement ( p adjusted

Objectives. Desmoid tumor also called aggressive fibromatosis is a rare type of benign tumor. It is a mesenchymal malignancy without metastatic potential. The standard management is resection, but other options including observation may be discussed. Desmoid-type fibromatosis may occur throughout the body, but the abdominal wall is the most common site. The aim of our study was to assess the clinicoepidemiological profile, prognostic factors, and treatment outcome of desmoid tumors. Methods. A monocentric retrospective study was conducted over a period of 19 years between February 2000 and November 2019 at the oncology department of Salah Azaïz Institute. Our study concerns 30 patients with desmoid tumor. All data regarding patients were obtained from the medical record. Results. Thirty patients were included. The median age was 35 years with a female predominance (sex ratio = 0.07). A palpable mass was the most common complaint (n = 27). Median tumor size was 5 cm. The principal site of involvement was the abdominal wall (n = 14). Surgery was performed in 27 patients. The histopathology reports listed 14 (52%) cases with negative margins and 13 (48%) cases with positive margins. Radiation therapy was performed in 2 patients. One patient received tamoxifen. Local recurrence occurred in 11 patients. Two patients died of their desmoid tumor. Abdominal wall tumors have less risk of recurrence compared with other sites (p=0.047). Macroscopic margin involvement (R2) was the only prognostic factor influencing disease-free-survival (p=0.034). Conclusion. Desmoid tumors are aggressive tumors with a tendency for local recurrence. Abdominal wall tumors have less risk of recurrence. Macroscopic margin involvement was the only prognostic factor that affects disease-free-survival.

Aim of the study: Several studies implicated altered inflammatory response in the susceptibility to ovarian cancer, and polymorphisms in inflammatory cytokines were shown to play an important role in the development of malignancies, including ovarian cancer (OC). Here we investigated the relationship between polymorphisms in IL-1 (-511C>T), IL-1RN VNTR, TNF- (-308G>A), and TNF RII (-322 VNTR) and OC risk in Tunisian women. Methods and results: Study subjects comprised 62 OC patients and 126 healthy women. Genotyping was done from genomic DNA obtained from blood simple by PCR. Positive association between IL-1RN (-VNTR) A1 allele (p = 0.0069; OR = 2.04; 95% CI:1.17-3.58) and OC risk, while negative association was seen with the A3 allele (P = 0.0034; OR = 0.09; 95% CI: 0.00-0.64), suggesting a protective role by the A3 allele. For IL-1 (-511C>T), homozygous C/C genotype was associated with significantly increased risk of OC (p = 0.0002; OR = 4.14; 95% CI: 1.77-9.76), while heterozygote C/T genotype was linked with reduced risk of OC (p = 0.0033; OR = 0.40; 95% CI: 0.20-0.78). Furthermore, TNF- -308A allele was significantly associated with heightened risk of OC (p = 0.016; OR = 1.70; 95% CI: 1.08-2.69), and homozygote G/G genotype was associated with decreased risk of OC (p = 0.0018; OR = 0.25; 95% CI: 0.09-0.66). In contrast, TNFRII (-322 VNTR) polymorphism was not associated with altered OC risk in the studied group. Conclusions: The significant association between IL-1RN VNTR, IL1- (-511), TNF- (-308) and OC susceptibility in Tunisian women confirms a role for altered inflammatory response in ovarian cancer pathogenesis.

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.

Gestational trophoblastic disease (GTD) develops from abnormal cellular proliferation of trophoblasts following fertilization. It includes benign trophoblastic disease (hydatidiform moles (HM)) and the malignant trophoblastic diseases or gestational trophoblastic neoplasia (GTN). The frequency of the GTD in Tunisia is one per 918 deliveries. The aim of this study is to analyze the clinical characteristics, treatment and outcomes of GTD at Salah Azaiez Institute (ISA). Medical records of women diagnosed with GTD at ISA from January 1st, 1981 to December 31st, 2012 were retrospectively reviewed. FIGO score was determined retrospectively for patients treated before 2002. One hundred and nine patients with GTN were included. Patients presented with metastases at 43% of cases. The most common metastatic sites was lung (30%) and vagina (13%). Fifty six (56 (51%) patients had low-risk and 21 (19%) cases had high-risk, the FIGO score was not assessed in 32 cases. After a median follow-up of 46 months, 21 patients were lost to follow-up, 12 patients died, 19 progressed and 8 relapsed. At 10 years, the OS rate was 85% and the PFS rate 79%. OS was significantly influenced by the presence of metastases at presentation (M0 100 % vs. Metastatic 62 %; p = 0.0001), FIGO stage (I-II 100% VS 61% and 65% for stage III and IV; p = 0.001), FIGO score (low-risk 99 % vs. high-risk 78 %; p =0.001). GTN is a significant source of maternal morbidity with increased risk of mortality from complications if not detected early and treated promptly.

Breast cancer (BC) is the most common form of cancer among women worldwide. Despite the huge advancements in its treatment, the exact etiology of breast cancer still remains unresolved. There is an increasing interest in the role of the gut microbiome in modulating the anti-cancer therapeutic response. It seems that alteration of the microbiome-derived metabolome potentially promotes carcinogenesis. Taken together, metabolomics has arisen as a fascinating new omics field to screen promising metabolic biomarkers. In this study, fecal metabolite profiling was performed using NMR spectroscopy, to identify potential biomarker candidates that can predict response to neoadjuvant chemotherapy (NAC) for breast cancer. Metabolic profiles of feces from patients (n = 8) following chemotherapy treatment cycles were studied. Interestingly, amino acids were found to be upregulated, while lactate and fumaric acid were downregulated in patients under the second and third cycles compared with patients before treatment. Furthermore, short-chain fatty acids (SCFAs) were significantly differentiated between the studied groups. These results strongly suggest that chemotherapy treatment plays a key role in modulating the fecal metabolomic profile of BC patients. In conclusion, we demonstrate the feasibility of identifying specific fecal metabolic profiles reflecting biochemical changes that occur during the chemotherapy treatment. These data give an interesting insight that may complement and improve clinical tools for BC monitoring.

Primary cutaneous leiomyosarcoma (PCL) is the rarest subtype, 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.

Les lymphomes pulmonaires primitifs sont des tumeurs rares représentant moins de 1% des tumeurs malignes du poumon. La forme la plus fréquente est le lymphome de type Mucosa-Associated Lymphoid Tissue (MALT). L'atteinte oculaire est aussi rare et elle est dans la plupart du temps localisée dans les glandes lacrymales. Nous rapportons l'observation d'un patient ayant présenté un lymphome pulmonaire de type MALT associé à une atteinte synchrone des glandes lacrymales. Cette observation illustre les aspects cliniques, radiologiques et évolutifs de cette entité qui sont peu spécifiques.

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.

Primary leiomyosarcomas of the thyroid gland are extremely rare. We report a case of a 32 year-old women with a multinodular goiter. She underwent total thyroidectomy. The tumor histology showed spindle-shaped cells that expressed desmine, caldesmone and smooth muscle actine but were negative cytokeratins.

IL23/IL17 pathway plays an important role in the development of inflammatory bowel diseases (IBD). In general, the genes encoding the cytokines are genetically polymorphic and polymorphisms in genes IL23R and IL17 have been proved to be associated with its susceptibility to inflammatory diseases as well as cancer including colorectal cancer. Moreover, it has been shown that these interleukins are involved in anti-tumor or pro-tumor effects of various cancers. Previously, we showed that there is a significant association between IL17A, IL17F and IL23R polymorphisms as well as the occurrence of colorectal cancer and the clinical features of the disease. The purpose of the present work is to investigate an association between IL17A, IL17F and IL23R polymorphisms in 102 Tunisian patients with colorectal cancer treatment. The association was analyzed by statistical tools. We found that patients with mutated genotypes of IL17A G197A SNP could be a risk factor for the inefficiency of chemotherapy and radiotherapy. Unlike IL17F variant, patients with wild type genotypes require surgery and adjuvant chemotherapy. On the one hand, we found no evidence that supports a significant association between IL23R polymorphism and the combined genotypes of these three genes and the colorectal cancer treatment. On the other hand, we showed that there is an important interaction between IL17A/IL17F polymorphisms and the stage of the disease as well as its treatment. Finally, patients with IL17F wild type genotype highlighted that there is a valid longer OS without all treatments and with radiotherapy and a neoadjuvant chemotherapy. In contrast, we observed that there are no relationships between IL17A, IL23R and the survival of these patients neither with nor without the treatment. Our results suggest that polymorphisms in IL17A and IL17F genes may be a predictive source of colorectal cancer therapy type. Therefore, IL17F may serve as an independent prognostic factor for overall survival in patients with colorectal cancer.