Risk factors for inflammatory and non-inflammatory breast cancer in North Africa.

PURPOSE: Studies of the etiology of inflammatory breast cancer (IBC), a rare but aggressive breast cancer, have been hampered by limited risk factor information. We extend previous studies by evaluating a broader range of risk factors. METHODS: Between 2009 and 2015, we conducted a case-control study of IBC at six centers in Egypt, Tunisia, and Morocco; enrolled were 267 IBC cases and for comparison 274 non-IBC cases and 275 controls, both matched on age and geographic area to the IBC cases. We administered questionnaires and collected anthropometric measurements for all study subjects. We used multiple imputation methods to account for missing values and calculated odds ratios (ORs) and 95% confidence intervals (CIs) using polytomous logistic regression comparing each of the two case groups to the controls, with statistical tests for the difference between the coefficients for the two case groups. RESULTS: After multivariable adjustment, a livebirth within the previous 2 years (OR 4.6; 95% CI 1.8 to 11.7) and diabetes (OR 1.8; 95% CI 1.1 to 3.0) were associated with increased risk of IBC, but not non-IBC (OR 0.9; 95% CI 0.3 to 2.5 and OR 0.9; 95% CI 0.5 to 1.6 for livebirth and diabetes, respectively). A family history of breast cancer, inflammatory-like breast problems, breast trauma, and low socioeconomic status were associated with increased risk of both tumor types. CONCLUSIONS: We identified novel risk factors for IBC and non-IBC, some of which preferentially increased risk of IBC compared to non-IBC. Upon confirmation, these findings could help illuminate the etiology and aid in prevention of this aggressive cancer.

Clinico-pathologic and mammographic characteristics of inflammatory and non-inflammatory breast cancer at six centers in North Africa.

PURPOSE: We describe the clinico-pathologic and mammographic characteristics of inflammatory breast cancer (IBC) and non-IBC cases enrolled in a case-control study. Because IBC is a clinico-pathologic entity with rapid appearance of erythema and other signs, its diagnosis is based on clinical observation and thus, by necessity, subjective. Therefore, we evaluate our cases by photographic review by outside expert clinicians and by degree of adherence to the two most recent definitions of IBC: the international expert panel consensus statement and American Joint Committee on Cancer (AJCC) 8th edition (we used the slightly less restrictive 7th edition definition for our study). METHODS: We enrolled 267 IBC and 274 age- and geographically matched non-IBC cases at 6 sites in Egypt, Tunisia, and Morocco in a case-control study of IBC conducted between 2009 and 2015. We collected clinico-pathologic and mammographic data and standardized medical photographs of the breast. RESULTS: We identified many differences between IBC and non-IBC cases: 54.5% versus 68.8% were estrogen receptor-positive, 39.9% versus 14.8% human epidermal growth factor receptor 2-positive, 91% versus 4% exhibited erythema, 63% versus 97% had a mass, and 57% versus 10% had mammographic evidence of skin thickening. Seventy-six percent of IBC cases adhered to the expert panel consensus statement and 36% to the AJCC definition; 86 percent were confirmed as IBC by either photographic review or adherence to the consensus statement. CONCLUSIONS: We successfully identified distinct groups of IBC and non-IBC cases. The reliability of IBC diagnosis would benefit from expert review of standardized medical photographs and associated clinical information.

Perioperative chemotherapy in locally advanced gastric cancer. A retrospective study about 25 cases.

BACKGROUND: Perioperative chemotherapy containing 5FU, Cisplatin ± Docetaxel is one of the most active regimens in advanced gastric cancer. OBJECTIVE: To report epidemiological and clinical profile and therapeutic results of perioperative chemotherapy in locally advanced gastric cancer in Tunisia. METHODS: Our retrospective study concerned patients with histologically confirmed advanced gastric cancer treated at the institute Salah Azaiez of Tunis. They received 2-3 cycles / 3 weeks of neoadjuvant chemotherapy based on FP (5FU and Cisplatin) or TPF (Docetaxel-Cisplatin-5FU). RESULTS: From 2010 to 2012, 25 patients with a median age of 60 years and 7.3 sex-ratio received neoadjuvant chemotherapy. Protocols used were TFP in 20 and FP in 5 patients, 17 patients receiving more than 2 cycles. Side effects were represented by mucositis grade 3 in 2 patients, neutropenia grade ¾ in 3 patients and renal failure in 5 patients. After neoadjuvant chemotherapy, we observed 40% of partial response and 20% of stable disease. Six patients (24%) underwent surgery, curative in 4 (R0 in 3 cases) by total gastrectomy and D2 lymphadenectomy and palliative in 2 cases due to peritoneal carcinomatosis. With a median follow up of 16 months, median overall survival was 16 months (2-21 months). CONCLUSION: Probably due to the very bulky and advanced stages of our gastric cancer cases, neoadjuvant chemotherapy using FP±T showed no benefit in the treatment of locally advanced gastric cancer in Tunisian patients.

Adherence to guidelines in curative treatment of venous thromboembolism in cancer patients: Insights from a retrospective Tunisian study.

AIM: To describe the management and treatment practices of venous thromboembolism (VTE) in cancer patients, assess compliance with the 2023 European Society for Medical Oncology recommendations, and identify factors that may limit or influence their application. METHODS: We conducted, in a Tunisian center, a retrospective study that included patients treated for cancer or hematologic malignancies and diagnosed with deep vein thrombosis (DVT) and/or pulmonary embolism between January 1, 2022, and August 1, 2023. RESULTS: The study involved 90 patients. DVTs were significantly predominant (81.1%). VTE mostly occurred within 3 months of the cancer diagnosis (41.1%). All patients received anticoagulant treatment. The most frequently prescribed class of anticoagulants was direct oral anticoagulants (42.2%), followed by low molecular weight heparin (36.7%), and finally vitamin K antagonists (21.1%). Financial constraints and/or refusal of social security to provide the treatment were the main cause for changes in the anticoagulant therapy (16.7%). Deaths (25.5%) and repermeabilization of the initially thrombosed venous network on imaging (11.1%) were the two primary reasons for treatment discontinuation. Bleeding complication was the cause of treatment modification or discontinuation in 7.7% and 5.5% of patients, respectively. Overall, guidelines were fully followed in 49 patients (54.4%) concerning the choice of pharmacological class, dose and duration of treatment. Financial constraints experienced by patients were significantly and independently associated with lower adherence to recommendations (p = 0.032). CONCLUSION: Adherence to guidelines is insufficient. Measures must be implemented to enhance the management of VTE and to develop strategies for improving access to anticoagulants.

Carcinoma of unknown primary: retrospective study of 437 patients treated at Salah Azaiez Institute.

BACKGROUND: Carcinoma of unknown primary (CUP) origin is defined as histologically confirmed metastatic carcinoma in the absence of a detectable primary site at the time of making therapeutic decision. AIM: To report epidemiological, clinical, histopathological, therapeutic, and prognostic features of CUP's patients collected at the Salah Azaiez institute (SAI). METHODS: We reviewed retrospectively the files of 437 CUP-patients in SAI between January 1994 and December 2006. We analyzed their epidemiological, clinical, histological and therapeutic features and classify patients in favourable and unfavourable subsets. Statistical analysis was performed with R software. Survival curves were made with the method of Kaplan-Meier. RESULTS: We collected 437 patients with a median age of 60 years and a sex-ratio of 1.8. CUP are metastatic to lymph nodes (56.5%), bones (29.7%) and liver (28%). 33% of patients had a unique site of metastases. Adenocarcinoma represented 50.5% of cases while 10.5% are classified in the favourable subgroup. 141 out 437 patients received palliative chemotherapy, 83% of them by cisplatin-based regimens obtaining 13% (58 patients) of objective response. Median survival was 7 months. 24 out 58 patients (41%) relapsed. Poor prognostic factors for survival were: multiple metastases (p=0.00033), >3 sites (p=0.03), undifferentiated carcinoma and adenocarcinoma (p>0.0001), liver metastases (p=0.0137), bone (p=0.00653) and adrenal gland (p=0.0334) metastatic sites. Patients who underwent chemotherapy (p>0.001) and who received cisplatbased regimen had better survival (p=0.01). CONCLUSION: Our retrospective study done in the context of a minimal and biological work-up confirmed the difficulty to find the primary in CUP.

Gut microbiota, an emergent target to shape the efficiency of cancer therapy.

It is now well-acknowledged that microbiota has a profound influence on both human health and illness. The gut microbiota has recently come to light as a crucial element that influences cancer through a variety of mechanisms. The connections between the microbiome and cancer therapy are further highlighted by a number of preclinical and clinical evidence, suggesting that these complicated interactions may vary by cancer type, treatment, or even by tumor stage. The paradoxical relationship between gut microbiota and cancer therapies is that in some cancers, the gut microbiota may be necessary to maintain therapeutic efficacy, whereas, in other cancers, gut microbiota depletion significantly increases efficacy. Actually, mounting research has shown that the gut microbiota plays a crucial role in regulating the host immune response and boosting the efficacy of anticancer medications like chemotherapy and immunotherapy. Therefore, gut microbiota modulation, which aims to restore gut microbial balance, is a viable technique for cancer prevention and therapy given the expanding understanding of how the gut microbiome regulates treatment response and contributes to carcinogenesis. This review will provide an outline of the gut microbiota's role in health and disease, along with a summary of the most recent research on how it may influence the effectiveness of various anticancer medicines and affect the growth of cancer. This study will next cover the newly developed microbiota-targeting strategies including prebiotics, probiotics, and fecal microbiota transplantation (FMT) to enhance anticancer therapy effectiveness, given its significance.

Functional characterization of MLH1 missense variants unveils mechanisms of pathogenicity and clarifies role in cancer.

Lynch syndrome is a heritable condition caused by a heterozygous germline inactivating mutation of the DNA mismatch repair (MMR) genes, most commonly the MLH1 gene. However, one third of the identified alterations are missense variants, for which the clinical significance is unclear in many cases. We have identified three MLH1 missense alterations (p.(Glu736Lys), p.(Pro640Thr) and p.(Leu73Pro)) in six individuals from large Tunisian families. For none of these alterations, a classification of pathogenicity was available, consequently diagnosis, predictive testing and targeted surveillance in affected families was impossible. We therefore performed functional laboratory testing using a system testing stability as well as catalytic activity that includes clinically validated reference variants. Both p.(Leu73Pro) and p.(Pro640Thr) were found to be non-functional due to severe defects in protein stability and catalytic activity. In contrast, p.(Glu736Lys) was comparable to the wildtype protein and therefore considered a neutral substitution. Analysis of residue conservation and of the structural roles of the substituted residues corroborated these findings. In conjunction with the available clinical data, two variants fulfil classification criteria for class 4 "likely pathogenic". The findings of this work clarify the mechanism of pathogenicity of two unclear MLH1 variants and enables predictive testing and targeted surveillance in members of carrier families worldwide.

Rituximab-induced interstitial lung disease: case report and literature review.

Rituximab, a chimeric monoclonal antibody against CD20, very rarely causes lung toxicity. Toxicity may present as interstitial lung disease, alveolar hemorrhage and adult respiratory distress syndrome. Sixteen cases of rituximab-induced interstitial lung disease (R-ILD) have been reported. With this case and a review of all other cases reported in the literature, we will try to identify the features of R-ILD, its treatment and why the early diagnosis of this complication is important.

[Predictive factors of maintain of employment and return to work after cancer]. / Facteurs prédictifs de maintien en emploi et de retour au travail après un cancer.

BACKGROUND: Return-to-work after cancer depends on several factors related to the disease but also other socio-professional factors. The primary aim of this study was to identify socio-demographic, disease related and professional factors influencing the return-to-work process. METHODS: It was a prospective and descriptive study reporting the return-to-work process in 89 cancer patients, in a professional activity age, who had cancer treatment and a follow up in the Oncology department in Tahar Maamouri Teaching Hospital of Nabeul, between September 2015 to December 2019. RESULTS: Our study included 89 patients. Mean age was 45 years±8. The population was predominantly feminine (59 %). They were employees in 45 % of cases. Private professional sectors included 60 % of all patients. An open-ended contract was performed in 87 % of cases. Most frequent primary tumors were breast tumors (45 %) and colon tumors (20 %). Thirty-four patients went back to work after recovery. Seventy-nine percent of them were female patients and 70 % had breast cancer. Predictive factors identified in univariate statistical analysis and correlated to return-to-work were gender (P=0.002), occupation (P<10-3), initial duration off sick (P=0.015), fitting out measures at work (P=0.01), primary tumor origin (P=0.01), disease stage (P=0.037), treatment (P=0.014) and disease outcome after treatment (P=0.024). CONCLUSION: Our study underlined a need to create a pluridisciplinary platform unifying collaborators among oncologists and occupational health professionals in order to enhance professional reintegration process and to hold patient's professional equilibrium after cancer recovery.

Breast cancer screening: a dividing controversy.

AIM: To report the conlcusions of articles and reviews assessing the benefit and harms of breast cancer screening in the world and in Tunisia. METHODS: This is a review of articles searched through specialized medical data bases (Pubmud, Science Direct) using the following key-words: Dépistage / Screening,Cancer du sein/ Breast Cancer, Surdiagnostic/ Overdiagnosis,Mammographie/ Mammography,Controverse/ controversy,Tumeur in Situ/ In Situ Tumour. RESULTS: We reviewed 36 articles published between 2001 and 2018 assessing the benefit of breast cancer screening. The mortality reduction due to breast cancer screening is estimated between 15-30% by the randomized trials. However, overdiagnosis is estimated between 0-50%. CONCLUSION: Breast cancer screening has been useful in the fight against cancer. In the era of innovative and efficient therapies, breast cancer screening remains controversial due to the potential overdiagnosis. However, this concept still need to be defined more precisely and estimated more accuratly.

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.

Primary leiomyosarcoma of thyroid gland: the youngest case.

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.

[Primary small intestinal lymphoma: epidemiological, histological and therapeutic transition in Tunisia]. / Transition épidémiologique, histologique et thérapeutique des lymphomes primitifs du grêle (LPG) en Tunisie.

INTRODUCTION: Primary small intestinal lymphoma (PSIL) is the second Non-Hodgkin lymphoma (NHL) of the digestive tract (after gastric NHL). PURPOSE: To evaluate during the past 28 years the epidemiological, anatomoclinical and therapeutic changes of PSIL in Tunisia through an acquired experience of more than a quarter of a century. METHODS: Our retrospective study included patients with histologically confirmed small intestinal lymphoma from 1981 to 2008 in Tunisia at Salah Azaiz Institute. The cohort of 210 patients was divided into two groups: A group from 1981 to 1992 (152 patients) and B group from 1993 to 2008 (58 patients). We analysed the epidemiological, anatomoclinical, histological, and therapeutic characteristics. RESULTS: We observed a significant decrease in the annual incidence of PSIL but also a significant transition of diffuse immunoproliferative small intestinal disease (IPSID) also known as "Mediterranean" PSIL, which were progressively replaced by "Western" lymphomas. Laparotomy with or without a debulking surgery, largely performed in group A, has disappeared at the cost of a primary chemotherapy (p < 0.001). Five-year actuarial global and relapse free survivals were respectively 60.5 and 57.3%. CONCLUSION: PSIL in Tunisia were subjected to a triple transition: epidemiological, histological and therapeutic.