Jaber Abbas

Ratio Between Positive Lymph Nodes and Total Excised Axillary Lymph Nodes as an Independent Prognostic Factor for Overall Survival in Patients with Nonmetastatic Lymph Node-Positive Breast Cancer

Background.The status of the axillary lymph nodes in nonmetastatic lymph node-positive breast cancer (BC) patients remains the single most important determinant of overall survival (OS). Although the absolute number of nodes involved with cancer is important for prognosis, the role of the total number of excised nodes has received less emphasis. Thus, several studies have focused on the utility of the axillary lymph node ratio (ALNR) as an independent prognostic indicator of OS. However, most studies suffered from shortcomings, such as including patients who received neoadjuvant therapy or failing to consider the use of adjuvant therapy and tumor receptor status in their analysis.Methods.We conducted a single-center retrospective review of 669 patients with nonmetastatic lymph nodepositive BC. Data collected included patient demographics; breast cancer risk factors; tumor size, histopathological, receptor, and lymph node status; and treatment modalities used. Patients were subdivided into four groups according to ALNR value (<.25, .25–.49, .50–.74, .75–1.00). Study parameters were compared at the univariate and multivariate levels for their effect on OS.Results.On univariate analysis, both the absolute number of positive lymph nodes and the ALNR were significant predictors of OS. On multivariate analysis, only the ALNR remained an independent predictor of OS, with a 2.5-fold increased risk of dying at an ALNR of ≥.25.Conclusions.Our study demonstrates that ALNR is a stronger factor in predicting OS than the absolute number of positive axillary lymph nodes.

Comparative Pharmacokinetics and Metabolic Pathway of Gemcitabine During Intravenous and Intra-arterial Delivery in Unresectable Pancreatic Cancer Patients

AbstractBackground: To study the pharmacokinetics and clinical outcome of gemcitabine (2′-2′-difluoro-deoxcytidine [dFdC]) during intra-arterial versus intravenous delivery in locally advanced and regionally metastatic pancreatic cancer. Patients and methods: Seven patients with unresectable pancreatic cancer received escalating intra-arterial doses of gemcitabine ranging from 800 to 1400 mg/m2, after selective embolisation of all pancreatic blood supply, except for the tumour-feeding arteries. Four patients received intravenous gemcitabine (control). Venous blood samples at different time intervals were taken throughout 270 minutes for pharmacokinetic analyses of gemcitabine and its inactive metabolite 2′-2′-difluorodeoxyuridine (dFdU). Results: Pharmacokinetic data revealed differences in plasma concentrations between intra-arterial and intravenous delivery routes. The plasma concentration-time curve of gemcitabine during and after cessation of intra-arterial pancreatic target administration through the proximal splenic artery showed a profile with an area under the plasma concentration-time curve from 0 to 270 minutes (intra-arterial 29.0 + 0.4 vs intravenous 331.0 + 2.7 ng · min/mL; p < 0.0001) and peak plasma concentration (intra-arterial 1.1 + 0.2 vs intravenous 7.6 + 2.0 ng/mL; p < 0.0001) significantly lower than that for the corresponding systemic intravenous route. A plot of In (% of dose) versus time showed a bi-compartmentalised metabolic model for intravenous administration of gemcitabine, one indicating rapid conversion of gemcitabine to dFdU, and another at a significantly lower affinity resulting in no conversion. Hence, this could be the main reason why dFdU was not detected in the systemic circulation during pancreatic intra-arterial target delivery. Furthermore, during intravenous administration a pseudo first-order rate constant (≈0.20 min-1) for in vivo conversion of gemcitabine to dFdU was estimated, indicating a rapid cellular deamination which was not shown in the intra-arterial route. Clinically, one patient had a partial response and six patients had a stable disease after intra-arterial administration of gemcitabine. The median time to disease progression was 4 months and the median overall survival was 5 months. One patient survived for 26 months. No grade III or IV toxicity was documented. Conclusion: Intra-arterial administration of gemcitabine has a major advantage related to reduced toxicity as increasing the dose through this administration route will eventually result in pancreatic cellular drug target delivery prior to systemic availability. Despite the low number of patients recruited, the clinical results are encouraging and this approach should be tested in a randomised study.

De-epithelialized dermal barrier for a safe immediate prosthetic breast reconstruction post circumvertical skin sparing/reducing mastectomy (SSM/SRM)

BackgroundSkin-sparing mastectomy (SSM) and skin-reducing mastectomy (SRM) with immediate breast reconstruction (IBR) is oncologically safe and has become increasingly popular as an effective treatment for patients with early stage breast cancer requiring mastectomy. Cosmetic appearance following IBR depends largely on the location of the skin incision, the quantity of breast skin left as well as the pocket for prosthetic placement, whether submuscular, subcutaneous, or both. SRM with Le Jour pattern skin excision has already been described in conjunction with autogenous tissue reconstruction. This technique is not recommended for implant-based IBR because any compromise of skin viability can result in exposure of the implant or expander.MethodsWe propose SRM with a circumvertical skin excision pattern and IBR comprising a de-epithelialized dermal barrier to reinforce the vertical suture line. We performed this technique on 10 breast cancer patients.ResultsEight patients underwent SSM with IBR using textured anatomical cohesive gel implants. One patient had Becker tear drop implants for both breasts (right SSM with IBR, and delayed left breast reconstruction); and the last patient had completion mastectomies with IBR using Becker tear drop implants. None of the patients developed complications.ConclusionThis technique is reliable and safe for implant-based IBR, ensuring minimal scarring and pleasing aesthetic results.Level of Evidence: Level IV, therapeutic study.

BRCA1 and BRCA2 Mutations in Ethnic Lebanese Arab Women With High Hereditary Risk Breast Cancer

PURPOSE Breast cancer is the most common malignancy among women in Lebanon and in Arab countries, with 50% of cases presenting before the age of 50 years. METHODS Between 2009 and 2012, 250 Lebanese women with breast cancer who were considered to be at high risk of carrying BRCA1 or BRCA2 mutations because of presentation at young age and/or positive family history (FH) of breast or ovarian cancer were recruited. Clinical data were analyzed statistically. Coding exons and intron-exon boundaries of BRCA1 and BRCA2 were sequenced from peripheral blood DNA. All patients were tested for BRCA1 rearrangements using multiplex ligation-dependent probe amplification (MLPA). BRCA2 MLPA was done in selected cases. RESULTS Overall, 14 of 250 patients (5.6%) carried a deleterious BRCA mutation (7 BRCA1, 7 BRCA2) and 31 (12.4%) carried a variant of uncertain significance. Eight of 74 patients (10.8%) aged ≤40 years with positive FH and only 1 of 74 patients (1.4%) aged ≤40 years without FH had a mutated BRCA. Four of 75 patients (5.3%) aged 41-50 years with FH had a deleterious mutation. Only 1 of 27 patients aged >50 years at diagnosis had a BRCA mutation. All seven patients with BRCA1 mutations had grade 3 infiltrating ductal carcinoma and triple-negative breast cancer. Nine BRCA1 and 17 BRCA2 common haplotypes were observed. CONCLUSION Prevalence of deleterious BRCA mutations is lower than expected and does not support the hypothesis that BRCA mutations alone cause the observed high percentage of breast cancer in young women of Lebanese and Arab descent. Studies to search for other genetic mutations are recommended.

Barreira cutânea para reconstrução mamária com prótese

BACKGROUND: Immediate breast reconstruction with silicone implant after subcutaneous mastectomy became a valid option among doctors and patients based on the simplicity of the surgical maneuvers, shorter surgical period, minimal scarring and immediate aesthetic results. Submuscular implants also have been advocated despite its more aggressive surgical procedures. Both also may bring secondary already described diversifications problems. An in attempt to reduce this kind of problems, in this article, a modification of the circumvertical mastopexy, reduction mammoplasty pattern for mastectomy and immediate breast implant reconstruction is described. METHODS: The skin between the medial and lateral vertical skin incision lines is de-epithelialized, providing a dermal barrier over the prosthesis to reinforce the vertical suture line. CONCLUSIONS: The technique ensures a safe reconstruction with gratifying aesthetic results.

A clinical phase II study of cisplatinum and vinorelbine (PVn) in advanced breast carcinoma (ABC).

Objectives:The effectiveness of cisplatinum and vinorelbine (PVn) as a salvage regimen in patients with metastatic breast cancer was reported in previous studies. This report is a pilot study assessing the antitumor efficacy and safety of this regimen as first line therapy for advanced breast cancer patients. Methods:Thirty-five patients were enrolled: 22 with metastatic breast carcinoma and 13 with locally advanced breast carcinoma (stage III). A total of 4 cycles of PVn were planned. After the 4th cycle, patients with metastatic breast cancer received vinorelbine biweekly until disease progression or for a total of 12 cycles, whereas those with locally advanced breast cancer who showed complete or partial response underwent curative surgery. Results:The overall response rate of our whole population was 74.29%. For the metastatic breast cancer group, the overall response rate was 64%, with a median survival of 19 months (range 2–36). For the locally advanced breast cancer group, the overall response rate was 92.3% with a median time to disease progression of 26 months (range 25–27). Toxicity was acceptable, and no treatment-related mortality was encountered. Conclusions:PVn is effective as first line treatment of advanced breast cancer with overall response rate of 64% in metastatic breast cancer and 92.3% in locally advanced breast cancer, and acceptable toxicity.

Skin sparing/skin reducing mastectomy (SSM/SRM) and the concept of oncoplastic breast surgery

INTRODUCTION With the better understanding of breast cancer history and biology, improved diagnostic modalities and the shift towards minimally invasive surgeries, indications for prophylactic mastectomy, skin sparing or skin reducing mastectomies (SSM/SRM) with nipple areolar complex (NAC) preservation coupled with immediate breast reconstruction are gaining popularity. The authors share their experience and conception with mastectomy and immediate alloplastic breast reconstruction with the esthetic circumvertical mammoplasty pattern combined with the dermal barrier buttress flap. MATERIAL AND METHODS The described technique was performed for 28 patients presenting for mastectomy and immediate alloplastic breast reconstruction. With close collaboration between the oncologic and plastic surgeons, mastectomy was performed in all cases with the esthetic circumvertical mammoplasty pattern. To achieve safe excision and optimal reconstruction, the standard incisions could be custom designed to fit oncologic requirements and allow the creation of a dermal barrier flap used as a buttress separating the implant from the suture line. CONCLUSION The circumvertical mastectomy pattern combined with the dermal barrier buttress flap is a versatile option allowing safe reconstruction regardless of the tumor and necessary skin excision location.

Tensioned reverse abdominoplasty for reconstruction of large post-mastectomy defects

1 American University of Beirut Medical Center, Beirut, Lebanon. Conflicts of interest: none. As opções reconstrutivas para defeitos da parede anterior do tórax podem ser desafiadoras especialmente quando o defeito é extenso e sujeito a radioterapia pré-operatória. Apresenta-se caso de paciente com carcinoma ductal invasivo de mama não tratado que realizou radioterapia e quimioterapia incompleta no pré-operatória. O exame patológico revelou carcinoma ductal invasivo de 11,5 cm, grau III, com invasão linfovascular e linfonodos axilares positivos (20/20). Após a mastectomia, defeitos estendidos seguido de longa excisão de pele mediram 25 x 20 cm, sendo esses cobertos imediatamente com retalhos em abdominoplastia reversa tensionada. Trata-se do primeiro caso relatado de excisão larga de mastectomia reconstruída exclusivamente com retalhos avançados em abdominoplastia reversa e alta tensão progressiva de pontos de adesão demostrando que nos pacientes selecionados, a pele abdominal pode ser avançada superiormente com segurança e facilidade para atingir a área superior do tórax e cobrir a área com defeito significante. ■ RESUMO

Synchronous vulvar and breast cancer

Synchronous vulvar and breast cancer is rare. A 44-year-old women presented with a lesion in the right labia majora and right upper quadrant breast lump. After work-up, she underwent radical wide local vulvar excision and modified radical mastectomy with axillary lymph node dissection. The pathology of the vulva revealed moderately-differentiated squamous cell carcinoma and that of the breast infiltrating ductal carcinoma. Only two such cases have been previously reported: one was an elderly patient and the second a young patient with HIV infection. Our patient is a young and healthy woman making her presentation a unique and rare case.

Phyllodes tumors of the breast treated in a tertiary health care center: case series and literature review:

Objective This study was performed to determine the subtypes of phyllodes tumor (PT) in patients at a single tertiary healthcare center in Lebanon and to describe their characteristics along with a review of the literature. Methods This single-institution retrospective cohort study included all cases of PT of the breast treated at the American University of Beirut Medical Center from 1 January 2010 to 31 December 2014. The patients’ demographic data, tumor characteristics, treatment data, and pathology reports were analyzed. Results Thirty patients were enrolled. Their median age was 42 years. In total, 66.7% had benign disease and 22.3% had malignant disease. Twenty-seven patients underwent surgery, four received radiotherapy, and one received systemic chemotherapy after PT progression. Twenty-seven patients had no recurrence at the last follow-up, two had local recurrence, and one had metastatic disease. All three patients with recurrence had an adequate negative surgical margin at the first excision. Conclusion This is the first cohort of patients with PT described in Lebanon and one of few in the Middle East. Our findings provide insight into the epidemiology, treatment modalities, and prognosis of PT in this geographical region.