Study of anxiety-depressive disorders among doctors at "Salah Azaïez" Cancer Institute in Tunis.

INTRODUCTION: Oncologists are often confronted with patients at the end of their lives who are suffering. This can lead to anxiety and depressive disorders (ADD), affecting the quality of the doctors's quality of life. AIM: To compare the level of ADD among doctors practicing at Salah Azaiez Institute (SAI) in Tunis with doctors who do not treat cancer patients, while identifying any factors associated with these disorders. METHODS: We conducted a comparative and analytical study of 141 physicians:53 oncologists practicing at the Salah Institut Azaiez and 91 at other hospital structures (Charles Nicolle's Hospital and Rabta's Hospital), matched by age and gender for a period of 2 months, started from 02 May to 30 June 2022. RESULTS: Our research showed that SAI's doctors were significantly more exposed to anxiety disorders (p= 0.016) compared with other doctors (47.2% vs. 37.5%), without being more exposed to depressive disorders. SAI's doctors reported more associated stress factors, notably exposure to body image-distorting tumors (p<0.001), exposure to the suffering of loved ones (p=0.006), lack of human resources (p=0.017), perceived unsuitability of premises (p=0.001) and overwork (p=0.013). These doctors consumed more alcohol (p=0.04). In addition, 58.5% of SAI's doctors felt that their profession significantly affected their quality of life, compared to 45% of doctors in other hospitals (p=0.04). CONCLUSIONS: All the doctors questioned, "all specialties combined", showed varying rates of anxiety and depressive disorders. However, anxiety disorders were significantly higher among SAI's doctors, for whom stress factors had a greater impact.

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.

Clinico-Epidemiological Profile, Prognostic Factors and Treatment Outcome of Refractory Hodgkin Lymphoma.

Approximately 5-10% of patients with Hodgkin lymphoma are refractory to initial treatment. The aim of our study was to assess the clinico-epidemiological profile, prognostic factors and treatment outcome. A retrospective study was conducted over a period of 12 years between June 2006 and January 2018 at the oncology department of Salah Azaïz Institute. Thirty-one patients were included. The median age was 27 years with a female predominance (sex ratio = 0.93).The majority had an advanced stage (61%). IGEV regimen was the most commonly used salvage chemotherapy (n = 14). Age above 30 years was predictive of treatment failure after salvage therapy (p = 0.003). IGEV regimen showed better results than ICE protocol in terms of response to salvage therapy (p = 0.048). Seven patients had salvage radiotherapy. Four patients had autologous stem cell transplant. Progressive disease (n = 12) was the main cause of non-eligibility of autologous stem cell tansplant. Overall survival and progression free survival at 3 years were 50% and 5% respectively. The prognostic factors influencing the overall survival were age above 30 years (p = 0.001), advanced Ann Arbor stage before progression (p = 0.02), advanced Ann Arbor stage of refractory Hodgkin lymphoma (p = 0.001), histological subtype (p = 0.001), CD20 expression (p = 0.027) and non-response to salvage therapy (p = 0.004). The prognostic factor influencing progression free survival was the non-response to salvage therapy (p = 0.045). The prognosis of refractory Hodgkin lymphoma remains poor. The current standard secondary treatment consists of combination therapy, usually followed by autologous stem cell transplantat. Innovative therapies are needed to improve the prognosis of refractory Hodgkin lymphoma. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-021-01463-4.

Patterns of complementary and alternative medicine use among Tunisian cancer patients.

INTRODUCTION: The use of complementary and alternative medicine (CAM) among cancer patients is prevalent worldwide as cancer patient are perpetually seeking for a way to improve their quality of life and to cure their disease. Unfortunately, the majority ignore the danger that can resort when they use CAM currently with conventional therapies. The purpose of this study is to assess prevalence and predictors of CAM use in cancer patients. METHODS: Cross-sectional study using a questionnaire administered to cancer patients, who were attending Salah Azaiz institute, Tunis, Tunisia. The study took place from September to December 2018. RESULTS: In 222 cancer patients, the overall prevalence of CAM use was 40.54%. On univariate analysis, patients who had university education level were less likely to use CAM (p = 0.05). Based on multivariate analysis, CAM users had more likely metastatic tumor (p = 0.047; OR = 1.913).It is reported that the majority of the population used herbal medicine. The most common herbal products consuming by patients, included Ephedra foeminea (51.8%), Annona muricata (12%) and Curcuma longa L. (10.84%).The main source of information was entourage (family, friends, hospital entourage) (74.44%).The majority of CAM users (61.11%) reported to consume CAM currently with conventional therapies. CONCLUSION: This survey revealed a high prevalence of CAM use. The most common type of CAM use is herbal products. Some of the used herbal products are known to interact with conventional anticancer medication. This emphasizes the importance of patients disclosure of CAM use to health professionals in order to avoid herb-medications interactions.

Epidemiological and anatomopathological profile of breast cancer in the region of North-West of Tunisia.

INTRODUCTION: Breast cancer is a common and serious disease. It represents the first cause of mortality and morbidity from cancer of Tunisian women and worldwide. AIM: To analyze the clinico-pathological and evolutionary characteristics of the patients followed at the carcinology's pole in the region of the North-West of Tunisia. METHODS: We conducted a retrospective descriptive study of 114 patients, who were diagnosed with non metastatic breast cancers over a 6-year period, from January 2011 to December 2016. RESULTS: Among the 289 patients treated in the medical carcinology department of the Jendouba regional hospital for invasive breast carcinoma over a period of 6 years, 114 patients had localized breast carcinoma, they were the subject of our study. The average age was 51 years. Nonspecific invasive cancer was the most frequent histological type (95.6%). The mean histological size was 29.3 mm. SBR grade II was most prevalent. Histological lymph node involvement was observed in 50.9%. Lymphovascular invasion was detected in 23.9% of cases and perineural sheaths was detected in 21.9% of cases. The most common molecular subtype was Luminal B. After discussion in a multidisciplinary concertation meeting, the patients received locoregional treatment: surgery, radiotherapy and systemic treatment: chemotherapy, endocrine hormone therapy. After a median follow-up of 45 months, OS and PFS at 5 years were 85.6% and 79.2% respectively. CONCLUSION: In the region of the North-West of Tunisia, breast cancer is characterized by its occurrence at a young age, the importance of tumor size, the importance of lymph node involvement, the frequency of inflammatory breast carcinoma and especially by the predominance of the molecular groups Luminal B and HER2 neu.

Western influenced lifestyle and Kv2.1 association as predicted biomarkers for Tunisian colorectal cancer.

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 < 0.001) were significantly associated with CRC risk. Analysis according to gender reveals correlation of rs1051295 A/G, rs11468831 non ins/ins (p = 0.01) with CRC susceptibility regardless of patients' gender while rs3331 T/C (p = 0.012) was associated with females. Stratification study according to malignancy site; Rectal Cancer (RC) and Colon Cancer (CC), reveals increasing RC risk by gender and high meat and fat consumption, alcohol use and PA. However, additional association with high brine consumption was noted for CC. The rs1051295 A/G (p = 0.01) was associated with RC risk. Increased CC risk was associated with carriage of rs1051295 A/G, rs11168831 (del/del) and (ins/del) genotypes. CONCLUSION: The risk of CRC increases with modifiable factors by Western influences on Tunisian lifestyle such as alcohol use, high fat consumption and possibly inadequate intake of vegetables. In addition, KCNB1 polymorphisms also markedly influence CRC susceptibility. Our study establishes key elements of a baseline characterization of clinical state, Western influenced lifestyle and KCNB1 variants associated with Tunisian CRC.

KCNB1 gene polymorphisms and related indel as predictor biomarkers of treatment response for colorectal cancer - toward a personalized medicine.

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 < 0.001). Stratification of colorectal cancer patients' response according to tumor localization and TNM stages reveals negative association of rs3331 Major allele to treatment response among the patients with advanced cancer stages (subgroup G2). The presence of rs3331 (homozygous minor) C/C genotype was positively associated with decline in carcino-embryonic antigen (p = 0.043) and CA19-9 (p = 0.014) serum levels. On the other hand, the presence of rs1051295 (homozygous minor) A/A genotype was correlated with marked decline in CA19-9 serum levels. KCNB1 haplotype did not reveal any association between haplotypes and treatment response. The results obtained suggest that gender-specific strategies for screening treatment and prevention protocols as well as KCNB1 variants may constitute an effective model for ongoing personalization medicine.

Identification of novel advanced glycation end products receptor gene variants associated with colorectal cancer in Tunisians: A case-control study.

A central role for advanced glycation end products (AGE) and their receptor (RAGE) in the pathogenesis of multiple cancer types, including colorectal cancer (CRC) was reported. We investigated the association between CRC and rs2853807, rs77170610, rs184003, rs1035798, rs2070600, rs1800684, rs1800624, and rs1800625 RAGE gene (AGER) polymorphic variants. Study subjects comprised 293 CRC patients [186 colon cancer (CC) and 107 rectal cancer (RC)] patients), and 264 age-, gender-, BMI-, and ethnicity-matched controls. Minor allele frequency (MAF) of rs77170610 and rs1800625 were significantly lower, while MAF of rs1035798 was significantly higher in CRC patients compared to control subjects, which was associated with reduced and increased risk of CRC, respectively; MAF of the remaining variants was comparable between CRC patients and controls. Significant difference in the distribution of rs2853807 and rs77170610 genotypes was seen between CRC patients and controls, with both variants associated with decreased risk of CRC. Comparison of the distribution of minor allele-carrying genotypes in CC and RC patient subgroups revealed lack of significant difference in the distribution of these genotypes between the patient subgroups. In view of the lack of LD between rs2853807 and rs77170610 with other variants, six-locus (rs184003, rs1035798, rs2070600, rs1800684, rs1800624, rs1800625) haplotypes were constructed. Haplotype analysis did not identify any specific 6-locus AGER haplotype associated with CRC. In conclusion, AGER gene rs2853807 and rs77170610 variants rs77170610 are associated with altered risk of CRC in Tunisians, but with no discrimination between CC and RC types.

Clear cell sarcoma of the esophagus: A rare location.

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.

Toxicity, risk factors and management of cisplatin-induced toxicity: A prospective study.

BACKGROUND AND PROPOSE: Cisplatin is a cytotoxic drug that triggers several toxicities. However, nephrotoxicity and ototoxicity remain major clinical limitations. The aim of our study was to evaluate the incidence of chemotherapy toxicity induced by cisplatin and to analyze the influence of risk factors in the Tunisian population. METHODS: We performed a prospective descriptive study in a period of four months. Patients were eligible if they had pathologically confirmed malignancies and treated with cisplatin-regimen chemotherapy. Nephrotoxicity and digestive toxicity were graded according to the World Health Organization toxicity scale and ototoxicity was scored clinically according to the Common Terminology Criteria for Adverse Events (CTCAE). Multivariate logistic regression analysis was performed to evaluate the influence of clinical variables on cisplatin-induced toxicity. RESULTS: A total of 150 patients were included. Forty-four percent of patients developed cisplatin-regimen toxicity: 15% developed cisplatin-induced nephrotoxicity, 9% cisplatin-induced ototoxicity and 27% digestive toxicity. In the multivariate analysis, age >65 years (OR= 6.129, p = 0.010), metastatic cancer (OR = 0.171, p = 0.007) and cumulative dose (OR= 1.004 mg/m2; p = 0.042) were strong predisposing factors for CDDP-induced nephrotoxicity. The cumulative dose was an independent prognostic indicator for digestive toxicity (OR = 0.997, p = 0.002). CONCLUSION: In our study, age >65 years and metastatic cancer were risk factors for cisplatin-induced nephrotoxicities. We also found the correlation between cumulative dose and nephrotoxicity or digestive toxicity.

Interleukin-17A polymorphisms predict the response and development of tolerance to FOLFOX chemotherapy in colorectal cancer treatment.

Polymorphic variants in IL-17A gene were differentially associated with colorectal cancer (CRC) susceptibility but their link with response and toxicity to CRC treatment have not yet been evaluated. We investigated association between seven IL-17A variants with the response and toxicity to CRC treatment in 294 patients with CRC. IL-17A genotyping was done by real-time PCR. MAF of rs3748067 was significantly higher in CRC cases resistant to FOLFOX treatment (R+) than non resistant (R-). Significantly higher rs3804513 MAF was noted in R+ versus R- colon cancer (CC). Higher rs2275913 and rs10484879, and reduced rs3804513 MAF were seen in rectal cancer (RC) tolerant to FOLFOX (T+) compared to (T-) patients. Strong association of rs3819025, rs3804513, and rs7747909 was found with tolerance to RC treatment. rs3748067 was associated with FOLFOX tolerance in CC but not RC. Significant higher frequency of AGGCAGG and GAGCAGG haplotypes was seen among R + CC, thus assigning non-favorable nature to these haplotypes. Higher and lower frequencies of GAGTAAG and AGGCTGA haplotypes, respectively, were observed in T + RC, thereby assigning FOLFOX-tolerant and non-tolerant nature to these haplotypes. The obtained results suggest that IL-17A variants and haplotypes may be a target for future management of CRC treatment.

Gestational trophoblastic neoplasia: experience at Salah Azaiez Institute.

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 were 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.

Common matrix metalloproteinase-2 gene variants and altered susceptibility to breast cancer and associated features in Tunisian women.

A role for matrix metalloproteinase polymorphisms in breast cancer development and progression was proposed, but with inconclusive results. We assessed the relation of matrix metalloproteinase-2 variants with breast cancer and related phenotypes in Tunisians. This case-control retrospective study involved 430 women with breast cancer and 498 healthy controls. Genotyping of matrix metalloproteinase-2 rs243866, rs243865, rs243864, and rs2285053 was analyzed by allelic exclusion. The minor allele frequency of rs2285053 was significantly lower in women with breast cancer cases as compared to control women; minor allele frequencies of the remaining single-nucleotide polymorphisms were similar between cases and control women. The distribution of rs243865 and rs2285053 genotypes was significantly different between breast cancer patients and control subjects. This persisted when key covariates were controlled for. None of the matrix metalloproteinase-2 variants were associated with estrogen receptor positivity, progesterone receptor positivity, or with double estrogen receptor-progesterone receptor positivity in breast cancer patients. Matrix metalloproteinase-2 rs243866, rs243865, and rs243864 were positively associated with menstrual irregularity and histological type, while rs243866 and rs2285053 were negatively associated with menarche and nodal status. In addition, rs2285053 was negatively associated with triple negativity, tumor size, distance metastasis, molecular type, and chemotherapy. Haploview analysis revealed high linkage disequilibrium between matrix metalloproteinase-2 variants. Four-locus Haploview analysis identified haplotypes GCTT and GTTC to be negatively associated with breast cancer, which remained statistically after controlling for key covariates. Matrix metalloproteinase-2 alleles and genotypes, along with four-locus haplotypes, are related to reduced susceptibility to breast cancer in Tunisian women, suggesting a protective effect.

Target therapy for metastatic breast cancer.

Breast cancer is the first cancer in women worldwide. Since the previous estimates of WHO in 2008, incidence is increasing and it is estimated that 30% of women will develop immediately a metastatic form. However, advances in molecular biology and the discovery of new therapies have extended significantly the survival of patients and improved the quality of life of patients with metastatic breast cancer. The study of gene expression and protein profile has resulted in a finer classification of breast cancer and adapt the treatment of patients according to their molecular profiles. The purpose of our work is to describe the different targeted therapies used in the MBC and their action's mechanism   referring to various therapeutic trials described in the literature.

[Synchronous pulmonary and lachrymal glands involvement by MALT lymphoma]. / Atteinte synchrone pulmonaire et des glandes lacrymales par un lymphome de type MALT.

Primary lung lymphomas are rare tumors representing less than 1% of malignant tumors of the lung. The most frequent form is the mucosa-associated lymphoid tissue (MALT). Ocular involvement is also rare and it is mostly located in the lachrymal glands. We report the case of a patient with pulmonary MALT lymphoma associated with synchronous involvement of the lachrymal glands. This study illustrates the nonspecific clinical, radiological and evolutionary features of this disease.

[Tunisian National Protocol for Adult Hodgkin's Lymphoma Treatment: Results of a therapeutic regimen adapted to the 2-cycle CT response, about 444 patients]. / Protocole national Tunisien prospectif de traitement du Lymphome de Hodgkin de l'adulte : résultats d'un schéma thérapeutique adapté à la réponse par tomodensitométrie à 2 cycles, à propos de 444 patients.

OBJECTIVE: In Tunisia, the management of Adult Hodgkin's Lymphoma (HL) has been standardized since 1999. We propose in this study to report the therapeutic results of the national protocol of adult HL treatment (MDH2008). PATIENTS AND METHODS: Our study is prospective multicenter interesting 444 patients followed for HL between July 2008 and June 2013 and treated according to the MDH2008 protocol. The median age of our patients was 30 years. B symptoms were present in 62.8 % of our patients. According to the Ann Arbor classification, our patients were in stages I, II, III and IV in 3 %, 42 %, 26 % and 29 %, respectively. The MDH2008 protocol is based on a strategy adapted to the therapeutic response to 2 cycles of chemotherapy. RESULTS: Response≥75 % to 2 courses of chemotherapy was achieved in 43 % of patients and the response rate at the end of treatment was 92.1 %. Forty-eight patients (11.4 %) had primary failure. In the multi-variant study, bulky mediastinal mass (IMT≥0.35) was an independent predictive factor of primary failure (P: 0.000). Nineteen toxic deaths (4.35 %) were reported. The relapse rate was 7.8 %. Event free survival, relapse-free survival and overall survival at 5years were 75 %, 89 % and 90 %, respectively. Adaptation of the treatment to the 2 cycles response was effective in unfavorable early stages and advanced stages. CONCLUSION: Compared to MDH2002 (second version of Tunisian prospective protocol), the MDH2008 reduced the primary failure rate, the rate of toxic deaths with escalated BEACOPP and the rate of relapse in Tunisian patients.

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.