Inflammatory breast cancer: As surgical oncologists, what can we do?

Breast cancer surgery is the primary treatment for early-stage breast cancer. However, inflammatory breast cancer (IBC), with its specific presentation characterized by skin invasion, is unfit for primary surgery. According to the different guidelines, the management of IBC is trimodal with the coordination of oncologists, surgeons, and radiation therapists. Advances in breast cancer imaging and the development of more targeted therapies make new challenges for this aggressive cancer. This chapter aims to provide an update on the role of surgery in IBC. Radical surgery is still considered the standard surgical treatment in IBC. Some authors suggest a conservative surgery in patients with a clinical response to chemotherapy without affecting survival. For lymph node surgery, the sentinel lymph node biopsy (SLNB) is not feasible in IBC patients, according to the existing studies. However, prospective studies on SLNB are needed to verify its reliability after chemotherapy for a specific group of patients. In the metastatic IBC, surgery can be considered if there is a good response after chemotherapy or for uncontrolled symptoms. Existing studies showed that surgery may impact survival for these patients. Prospective studies are mandatory to optimize IBC management, considering factors such as tumor's molecular profile.

Identification of Eleven Novel BRCA Mutations in Tunisia: Impact on the Clinical Management of BRCA Related Cancers.

BACKGROUND: Breast cancer is the world's most common cancer among women. It is becoming an increasingly urgent problem in low- and middle-income countries (LMICs) where a large fraction of women is diagnosed with advanced-stage disease and have no access to treatment or basic palliative care. About 5-10% of all breast cancers can be attributed to hereditary genetic components and up to 25% of familial cases are due to mutations in BRCA1/2 genes. Since their discovery in 1994 and 1995, as few as 18 mutations have been identified in BRCA genes in the Tunisian population. The aim of this study is to identify additional BRCA mutations, to estimate their contribution to the hereditary breast and ovarian cancers in Tunisia and to investigate the clinicopathological signatures associated with BRCA mutations. METHODS: A total of 354 patients diagnosed with breast and ovarian cancers, including 5 male breast cancer cases, have been investigated for BRCA1/2 mutations using traditional and/or next generation sequencing technologies. Clinicopathological signatures associated with BRCA mutations have also been investigated. RESULTS: In the current study, 16 distinct mutations were detected: 10 in BRCA1 and 6 in BRCA2, of which 11 are described for the first time in Tunisia including 3 variations that have not been reported previously in public databases namely BRCA1_c.915T>A; BRCA2_c.-227-?_7805+? and BRCA2_c.249delG. Early age at onset, family history of ovarian cancer and high tumor grade were significantly associated with BRCA status. BRCA1 carriers were more likely to be triple negative breast cancer compared to BRCA2 carriers. A relatively high frequency of contralateral breast cancer and ovarian cancer occurrence was observed among BRCA carriers and was more frequent in patients carrying BRCA1 mutations. CONCLUSION: Our study provides new insights into breast and ovarian cancer genetic landscape in the under-represented North African populations. The prevalence assessment of novel and recurrent BRCA1/2 pathogenic mutations will enhance the use of personalized treatment and precise screening strategies by both affected and unaffected North African cancer cases.

Tumors of low malignant potential a single institution experience.

BACKGROUND: The tumors of low malignant potential are an independent group of the ovarian epithelial tumors. They represents 10-20% of all ovarian epithelial tumors. Our aim through this study to determine how to treat this disease in the most suitable way. METHODS: A retrospective study involving 73 patients diagnosed with TLMP and treated at our Institute between September 1975 and June 2010. RESULTS: The median age was 49 years. In 33% of the cases, the patients were younger than 40 years. Our study included 38 mucinous tumors, 30 serous and 5 mixed. The tumors were stage I in 69% of the cases, stage II in 11% and stage III in 20%. All patients had surgery as a primary treatment. The surgery was radical in 77% of the cases. Five patients had an adjuvant chemotherapy. After a mean follow up of 10 years, we reported 7 cases of local relapses. The prognostic factors for a disease free survival were: the stage of the tumor and the presence of invasive implants. The overall survival at 5 and 10 years was respectively of 96.9% and 92.8%. The prognostic factors for overall survival were: the age, the stage, the existence of a residual tumor, the presence of pseudomyxoma or peritoneal implants. After having a conservative surgery two patients achieved full term pregnancies. CONCLUSION: Randomized studies are required to back-up our findings and give a higher grade of recommendation to the actual standard of care.

A hydatic cyst of the appendix mimicking a uterine lateral mass: a case report.

BACKGROUND: Hydatic cyst is a zoonotic disease caused by Echinococcus granulosus. It is a public health problem in Tunisia and remains endemic. It occurs in intra-abdominal organs in 10-15% of the cases, particularly in the liver representing the most common affected organ. The aim of the case is to highlight the scarcity of this appendicle origin and to consider it among the differential diagnosis of any intra-abdominal cystic lesion. CASE PRESENTATION: A 45-year-old Tunisian woman, with no past medical history, was admitted for a pelvic cystic mass. The clinical manifestation as well as the imaging findings were toward a lateral uterine mass. Our patient underwent appendectomy and resection of the mass. The patient had no recurrence at 2 years of follow-up. CONCLUSIONS: An extrahepatic hydatid cyst should be recognized among the differential diagnosis of any intra-abdominal cystic lesion. Treatment should be based on surgical excision. Due to the risk of recurrence, a close follow-up is mandatory.

Fertility-sparing surgery in advanced stage malignant ovarian germ cell tumor: a case report.

BACKGROUND: Malignant ovarian germ cell tumor is a rare type of disease, which generally has a good prognosis due to the high chemosensitivity of this type of tumor. Fertility preservation is an important issue because malignant ovarian germ cell tumor commonly affects young women. Although conservation is the standard for early stage, it becomes more debatable as the disease progresses to more advanced stages. AIM: Report the case of a patient with an International Federation of Gynecology and Obstetrics Stage IIIc malignant ovarian germ cell tumor, who had conservative surgery and chemotherapy with a good fertility outcome. CASE PRESENTATION: A 23-year-old North African woman with a left malignant ovarian germ cell tumor stage IIIc was treated by left adnexectomy and omentectomy followed by chemotherapy. A 15-year follow-up showed no signs of relapse, and she completed three full-term natural pregnancies. CONCLUSIONS: Malignant ovarian germ cell tumor is a rare ovarian tumor with a good prognosis. It is usually associated with a good fertility outcome in early stages. However, due to the rarity of the disease in advanced stages, the fertility outcome for this group of patients is not clear. This lack of data surrounding advanced stages points to the need for a meta-analysis of all published cases.

Identifying accessible prognostic factors for breast cancer relapse: a case-study on 405 histologically confirmed node-negative patients.

BACKGROUND: Histologically, node-negative breast cancer generally have a good prognosis. However, 10 to 30% of the cases present local relapses or metastasis. This group of people has high chances of remission if detected early. The aim of this study is to identify financial affordability for developing countries to adjust treatment. METHODS: We selected 405 patients with histologically confirmed node-negative breast cancer in our institution between January 2001 and December 2003. Patients with metastasis were excluded. The statistical analysis was conducted using SPSS ver. 18 (SPSS, Inc., Chicago, Illinois). RESULTS: The medial age was 51 years old. The medial tumor size was 35.4 mm. Clinically, 67.2% of the patients were staged cT2 and 63.2%, cN1i. Breast conservation was achieved in 41% of cases. In the histologic examination, the medial size was 30 mm. Grade III tumors were found in 50.1% of patients and positive hormonal receptors in 53.4%. The mean number of lymph nodes was 14. Eight patients had neoadjuvant chemotherapy. Adjuvant locoregional radiation and adjuvant chemotherapy were prescribed respectively in 70.6 and 64.4% of cases. 59.7% had adjuvant hormonal therapy. The follow-up showed 17.7% cases of relapse either locally or in a metastatic way in a mean time of 57.4 months. The disease-free survival at 5 years was 82.1%, and the overall survival for the same period was 91.5%. The histologic tumor size and the grade and number of lymph node dissected were shown to be influencing the disease-free survival. Radiation therapy and hormone therapy showed improved disease-free survival and overall survival. CONCLUSION: Our study found interesting results that may help personalize the treatment especially for patient living in underdeveloped countries, but further studies are needed to evaluate those and more accessible prognostic factors for a more accessible healthcare.

[Cutaneous melanoma: about 200 cases]. / Mélanome cutané: A propos de 200 cas.

AIM: To analyze the clinical and pathological aspects of cutaneous melanoma and to determine the prognostic factors. METHODS: This is a retrospective study about 200 cases of cutaneous melanoma collected in Salah Azaiz Institute over a period of 36 years (1969-2005). RESULTS: The mean age was 55.4 years, with a slight female predominance. The tumour was developed on a pre-existent lesion in 31.5% of cases. The average delay of consultation was 18 months. The mean tumor size was 37 mm (10-180 mm). The ulcero exophytic appearance represented 45% of the cases. The tumor was metastatic in 19.5 % of cases. Hands and feet represented 53% of the tumour localizations. The treatment was curative in 71% of cases and palliative in 13% of cases. The lymph node dissection was performed in 59% of the patients. Histologically, nodular melanoma and Grade V of Clark represented 43.5 and 35% of the cases, respectively. The mean tumoral thickness was 14 mm. Chemotherapy, immunotherapy and radiotherapy were performed in 5.5%, 3.5% and 5.5% of cases respectively. The lymph node recurrences were noted in 43.6% of the patients treated with curative intent. The mean recurrence free survival was 76 months. Tumour size > 2 cm, the localization on the leg, Clark level invasion IV and the involvement of the tumour margin were significant prognostic factors for the recurrence free survival. The prognostic factors for the metastasis free survival were: tumour size, tumour localization, type of resection and finally the lymph node dissection. The 5-year overall survival was 28.5% and was influenced significantly by the tumour size, tumour localization, type of resection, involvement of the tumour margins, Clark grade, tumour thickness and finally the lymph node involvement. CONCLUSION: The dismal prognosis can be improved by early diagnosis and especially the prevention based on the photo protection and surveillance of patients at high risk.

Borderline tumors of the ovary.

BACKGROUND: Borderline tumors of the ovary (BOT) were described for the first time by Taylor in 1929. These lesions have a more favorable outcome than do other ovarian cancers. Their prognosis and treatment are still subject of discussion since they occurred more often in young women where the sparing fertility surgery is always considered primarily. AIM: Evaluate the management of patients with borderline ovarian tumors. METHODS: A retrospective study was conducted in 40 patients with borderline ovarian tumors treated between January 1, 1991 and December 31, 2004. RESULTS: Median follow-up was 43 months, mean age was 44 years. Initial surgery was conservative in 17 patients and radical in 23 cases. Six patients had residual disease. Serous, mucinous and mixte tumors were observed in 18, 21 and 1 cases respectively. Staging was I, II, III in 26, 5, and 9 cases respectively with two pseudomyxomas. Adjuvant Chemotherapy was given in 3 patients. There was a recurrence in 13 patients and seven died. The 5-year overall survival rate was 78 %. Prognostic factors with an impact on survival rate were age, stage of the disease, histological subtype and residual tumor. Factors with a negative impact on recurrence were age, type of surgery and residual disease. With Cox multivariate analysis, residual tumor is an independent factor for overall survival, on the other hand age and type of surgery were significant for recurrence free survival. CONCLUSION: Careful staging followed by complete and radical surgery is mandatory. Unilateral salpingo-oophorectomy with omentectomy and multiple peritoneal biopsies and washing could be indicated in patients with child bearing age. Radical surgery after pregnancy is advised.

Results of second-look laparotomy in advanced ovarian cancer: one single center experience.

Objective. The goal of the study was to analyse the results of 85 cases of second-look laparotomy (SLL) and explore the influence of this procedure on survival. Patients and Methods. We reviewed retrospectively 85 cases of SLL collected and treated in our institute between 1994 and 2003. Results. Complete pathologic response (CPR) was 25.8%, microscopic disease (Rmicro) was 38.8%, and macroscopic disease (Rmacro) was 35.4%. In patients with negative SLL results, disease recurrence was diagnosed in 41%. The 3- and 5-year overall survival rates for the entire population were 91% and 87%, respectively. The 3- and 5-year disease-free survivals were, respectively, 76.3% and 58.5% in negative SLL versus 55.7% and 16% in positive SLL. The difference between the group of patients with complete response (76%) and the patients with residual microscopic disease (72%) was not significant. The tumoral residuum after initial surgery was the only prognostic factor influencing significantly the disease-free survival. On Cox regression model analysis, only initial tumoral residuum (P = 0.04) and tumoral residuum after SLL (P = 0.02) were independent prognostic factors for survival. Conclusions. The most important advantage of SLL is the early detection of recurrence and thus the early administration of consolidation treatment resulting in a better prognosis.

The "reverse" latissimus dorsi flap for large lower lumbar defect.

The latissimus dorsi (LD) flap is one of the most common flaps used in plastic surgery based on its dominant thoracodorsal pedicle as well as free tissue transfer. The "distally based" or "reverse" fashion design has been used to repair myelomeningoceles, congenital diaphragmatic agenesis, or thoracolumbar defects. We present a case of a large lumbar defect after cancer resection covered by a combined tegument solution starring the "reverse" LD flap in its muscular version with a cutaneous gluteal flap. This flap is a safe and reliable way to cover large distal lumbar defect.

[Radiation therapy in extra abdominal desmoid tumours]. / Radiothérapie des tumeurs desmoïdes extra abdominales.

BACKGROUND: Desmoid tumours are rare benign tumours that have local "malignity". They can be locally aggressive by infiltrating adjacent vascular, nervous and bony structures. AIM: To define the role of radiotherapy in the management of desmoid tumours. METHODS: Retrospective study of six extra-abdominal desmoid tumours treated with surgery and radiation therapy. RESULTS: Median age was 26.8 years (16-35 years). The tumor was located in the arm (1 case), in the legs (2 cases) and in the body (3 cases). Median tumoral sizes were 86.6 mm (60-100 mm). Five patients had local recurrence after surgical resection. Radiation therapy included Cobalt 60 in five cases and photons associated to linear acceleration in one case. Total dose was between 54 and 62 Gy. At the end of radiation therapy, tumoral control was obtained in five cases after a median follow-up of 26 months (1-83 months). CONCLUSION: Surgery is the main treatment of desmoids tumours but local recurrence rates remain high even after complete resection. The role of adjuvant radiation therapy is controversial.

Inflammatory breast cancer in Tunisia: epidemiological and clinical trends.

Inflammatory breast cancer (IBC) is characterized by a peculiar geographic distribution in incidence, being described as more common in Tunisia and the region of North Africa. The authors performed a systematic review of published literature on rapidly progressing breast cancer and IBC in Tunisia and analyzed the evolution in epidemiology, clinical presentation, treatment, and therapeutic results. They collected, analyzed, and compared all the indexed Tunisian articles about rapidly progressing breast cancer and IBC since the 1970s opening of the Institut Salah Azaiz Institute in Tunis. In the 1970s, rapidly progressing breast cancer diagnosis was based on the Poussée Evolutive classification (1-3). Since the 1990s, IBC diagnosis has been based on the American Joint Committee on Cancer Poussée Evolutive 3/T4d staging. The authors compared the historical data to the most recent publications in terms of epidemiology, clinical features, treatment, and therapeutic results. The most important historical report of rapidly progressing breast cancer concerned 340 patients, representing 58.5% of a cohort of 581 breast cancer patients collected from 1969 to 1974, including 320 (55.2%) with inflammatory signs, 37(6.5%) with Poussée Evolutive 2, and 283 (48.7%) with Poussée Evolutive 3. Subsequent papers have documented a steady decrease in incidence to the current 5% to 7% T4d/IBC. Since the 1970s, Poussée Evolutive in premenopausal woman has increased from 52.5% to 75%; rural predominance has persisted. The 5-year overall survival reached 28% by the year 2000. The authors' analysis demonstrated a trend of decreasing incidence of IBC diagnoses from 50% to presently <10%, probably related to a combination of factors, including the use of more stringent criteria (Poussée Evolutive 3/T4d) for IBC diagnosis and an improvement in the socioeconomic level of Tunisia.

Endometrial adenocarcinoma in a 27-year-old woman.

BACKGROUND: Endometrial adenocarcinoma usually occurs after menopause, but in 2%-14% of cases, it occurs in young patients (less than 40 years of age) who are eager to preserve their fertility. Its treatment includes hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy, and, in some cases, radiation therapy. AIM: To describe a case of endometrial adenocarcinoma occurring in a young woman and to undertake a literature review of risk factors and therapeutic options proposed for young women wishing to preserve their fertility. CASE: We report a case of endometrial cancer in a 27-year-old woman treated for resistant menorrhagia and cared for in our department as well as in the Salah Azaiez Institute. CONCLUSION: Endometrial adenocarcinoma rarely occurs in young women. In such cases, other therapeutic options can be proposed: progesterone therapy and LH-RH (Luteinzing-Hormone-Releasing-Hormone) agonists therapy in order to preserve fertility in younger patients.