The vertical rectus myocutaneous flap (VRAM) is a relatively simple and reliable technique for perineal wound reconstruction after abdominoperineal resection.

Background: Laparoscopic gastrectomy has been used as a superior alternative to open gastrectomy for the treatment of early gastric cancer. However, the application of laparoscopic D2 lymphadenectomy remains controversial. This study aimed to evaluate the feasibility and outcomes of laparoscopic gastrectomy with D2 lymphadenectomy for gastric cancer. Results: Between May 2016 and May 2018, twenty-five consecutive patients with gastric cancer underwent laparoscopic D2 gastrectomy: eighteen patients (72%) underwent distal gastrectomy, four patients (16%) underwent total gastrectomy, and three patients (12%) underwent proximal gastrectomy. The median number of lymph nodes retrieved was 18 (5-35). A positive proximal margin was detected in 2 patients (8%). The median operative time and amount of blood loss were 240 min (200-330) and 250 ml (200-450), respectively. Conversion to an open procedure was performed in seven patients (28%). The median hospital stay period was 8 days (6-30), and the median time to start oral fluids was 4 days (3-30). Postoperative complications were detected in 4 patients (16%). There were two cases of mortality (8%) in the postoperative period, and two patients required reoperation (8%). Conclusions: Laparoscopic gastrectomy with D2 lymphadenectomy can be carried out safely and in accordance with oncologic principles.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide and the second cause of cancer related mortality. Treatment options for patients with metastatic CRC (mCRC) expanded during the last two decades, with introduction of new chemotherapeutic and targeted agents. Egypt is a lower middle-income country; Egyptian health care system is fragmented with wide diversity in drug availability and reimbursement policies across different health care providing facilities. We report the results of consensus recommendations for treatment of patients with metastatic colorectal cancer developed by Egyptian Foundation of Medical Sciences (EFMS), aiming to harmonize clinical practice through structured expert consensus-based recommendations consistent with the national status. EFMS recommendations could be utilized in other countries with similar economic status. Methods: EFMS recommendations were developed using a modified Delphi process, with three rounds of voting till the final recommendations were approved. A non-systematic review of literature was conducted before generating the provisional statements. Content experts were asked to vote on some recommendations in two different resource groups (restricted resources and non-restricted resources). External review board of experts from a low income and lower-middle countries voted on the applicability of EFMS recommendations in their countries. Results:The current recommendations highlighted the discrepancy in health care between restricted and non-restricted resources with expected survival loss and quality of life deterioration. Access to targeted agents in first line is very limited in governmental institutions, and no access to agents approved for third line in patients who failed oxaliplatin and irinotecan containing regimens for patients treated in restricted resource settings. Conclusion: Management of mCRC in developing countries is a challenge. The currently available resource-stratified guidelines developed by international cancer societies represent a valuable decision-making tool, adaptation to national status in each country based on healthcare system status is required.

This study aims at identifying common pathogenic somatic mutations at different stages of colorectal carcinogenesis in Egyptian patients. Our cohort included colonoscopic biopsies collected from 120 patients: 20 biopsies from patients with inflammatory bowel disease, 38 from colonic polyp patients, and 62 from patients with colorectal cancer. On top of this, the cohort included 20 biopsies from patients with non-specific mild to moderated colitis. Targeted DNA sequencing using a customized gene panel of 96 colorectal related genes running on the Ion Torrent NGS technology was used to process the samples. Our results revealed that 69% of all cases harbored at least one somatic mutation. Fifty-seven genes were found to carry 232 somatic non-synonymous variants. The most frequently pathogenic somatic mutations were localized in TP53, APC, KRAS, and PIK3CA. In total, 16 somatic mutations were detected in the CRC group and in either the IBD or CP group. In addition, our data showed that 51% of total somatic variants were CRC-specific variants. The average number of CRC-specific variants per sample is 2.4. The top genes carrying CRC-specific mutations are APC, TP53, PIK3CA, FBXW7, ATM, and SMAD4. It seems obvious that TP53 and APC genes were the most affected genes with somatic mutations in all groups. Of interest, 85% and 28% of the APC and TP53 deleterious somatic mutations were located in Exon 14 and Exon 3, respectively. Besides, 37% and 28% of the total somatic mutations identified in APC and TP53 were CRC-specific variants, respectively. Moreover, we identified that, in 29 somatic mutations in 21 genes, their association with CRC patients was unprecedented. Ten detected variants were likely to be novel: six in PIK3CA and four variants in FBXW7. The detected P53, Wnt/βcatenin, Angiogenesis, EGFR, TGF-β and Interleukin signaling pathways were the most altered pathways in 22%, 16%, 12%, 10%, 9% and 9% of the CRC patients, respectively. These results would contribute to a better understanding of the colorectal cancer and in introducing personalized therapies for Egyptian CRC patients.

Aim: This study aimed to sequence custom 96 genes of tumor suppressor genes and oncogenes frequently associated with colorectal cancer (CRC) to identify the frequency of the detected genetic mutations in the disease progression of CRC patients and to develop personalized therapy in those somatic mutation carriers. Material and methods: Biopsy samples were collected from Egyptian patients classified into inflammatory bowel disease (IBD) (n=20), colonic polyp (CP) (n=38) and CRC (n=60) patients as well as subjects with chronic non-specific colitis served as a control group (n=20). The libraries were performed using Qiaseq UMI-based targeted panel and sequenced via Ion proton sequencer. The detected genetic variants with an average coverage of 500x were annotated against Cosmic and dbSNP and Clinvar databases. Results: Analysis revealed that 52 genes harbor 128, 47 genes harbor 111, 40 genes harbor 71 and 39 genes harbor 66 somatic variants were detected in the CRC, CP, IBD and control groups; respectively. ARID1A (c.5548dupG (5%)), ATM (c.2572T>C (10%)), AXIN2 (c.1975C>T (5%)), FLCN (c.1285dupC (8%)), KRAS (c.35G>T (8%)), MSH6 (c.3261dupC (5%)), SLC9A9 (c.1765A>G (10%)), TP53 (c.1024C>T (5%)) were found to be the highly frequently detected pathogenic CRC specific variants. We also identified 29 genes harbor 43 common variants. The highly frequently common detected variants were ACVR2A (c.1310delA), ATM (c.5557G>A), BRCA1 (c.3548A>G, c.2612C>T), BRCA2 (c.1114A>C), IGF2 (c.677delG), KIT (c.1621A>C), MLH1 (c.655A>G), MLK4 (c.2223G>T, c.2182G>A), PIK3CA (c.1173A>G), PTPN12 (c.964G>A), RET (c.2071G>A), TP53 (c.121delG, c.215C>G) Conclusion: Our data showed that our Egyptian genetic makeup is different from other population. Also, the identified somatic mutations are crucial for understanding cancer predisposition and developing personalized therapies for the Egyptian colorectal cancer patients. Citation Format: Amira Salah El-Din Youssef, Ahmed Moustafa, Ahmed Osama Touny, Zeinab K. Hassan, Mohammed Mohey Eldin, Mai M. Lotfy, Auhood Nassar, ola sayed, Abdel-Rahman N. Zekri. Somatic mutation profiling of colorectal cancer by targeted next generation sequencing [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3616.

Background: Colorectal cancer (CRC) incidence is progressively increasing in Egypt. Unfortunately, there is inadequate knowledge of the acquired somatic mutations in Egyptian CRC patients which limit our understanding of its progression. To the best of our knowledge, our study is the first to sequence multiple-gene panel to identify the somatic mutation pattern associated with CRC disease progression in a cohort of Egyptian patients. Custom 72 genes, which are frequently associated with CRC, were sequenced using Qiaseq UMI-based targeted DNA panel in 120 fresh tissues classified into; inflammatory bowel disease (IBD; n=20), colonic polyp (CP; n=38) and CRC (n=62) as well as 20 biopsies with non-specific colitis served as a control group (n=20). Results: Using Ingenuity Variant Analysis (IVA), we revealed that APC, TP53 & ATM genes harbored the highly frequent CRC-specific somatic mutations (15, 11 & 6, respectively). We also identified common somatic mutations (predictors) that were associated with disease progression from colitis to CRC; APC (c.1742delA (65%)), TP53 (c.121delG (58%), c.215C>G (52%)), ATM (c.640delT (16%)), IGF2 (c.677delG (56%)), RET (c.2071G>A (37%)), ACVR2A (c.1310delA (26%)), PIK3CA (c.1173A>G (16%)) & KIT (c.1621A>C (13%)). Furthermore, pathway analysis using Ingenuity Pathway Analysis (IPA) showed that Wnt/βcatenin, ATM signaling, RTK-RAS and TGF-β were the most altered pathways in the CRC group (73%. 72%, 40% & 36%, respectively).Conclusion: In this data set, we shed the light on the most frequent somatic mutations and the most altered pathways that are crucial for understanding colorectal cancer predisposition and developing personalized therapies for the Egyptian CRC patients.

Aim: This study aimed to sequence BRCA1 & BRCA2 genes to identify the frequency of the detected genetic mutations in the disease progression of colorectal cancer (CRC) and to estimate colorectal cancer risks in those BRCA mutation carriers. Material and methods: 140 biopsy samples were collected from Egyptian patients categorized into inflammatory bowel disease (IBD) (n=20), colonic polyp (CP) (n=38) and CRC (n=62) patients as well as subjects with chronic colitis served as a control group (n=20). The libraries were performed using Qiaseq UMI-based targeted panel and sequenced via Ion proton sequencer. The detected genetic variants at 500x were annotated against Cosmic, dbSNP, exac all, Polyphen2, Sift and Clinvar databases. Results: Analysis revealed that BRCA1 gene harbored 26, 19, 8 and 11 variants in the CRC, CP, IBD and control groups; respectively. Exon 10 was the most affected exon harbored 7 pathogenic variants in the CRC group. Two out of 7 were the most frequently detected common pathogenic variants associated with disease progression from colitis to CRC (c.1961delA (11%) & c.3214delC (16%). Moreover, 3 common begnin SNP variants were found to be related to ethnicity (c.3548A>G (58%), c.2612C>T (60%), c.4900A>G (69%). Moreover, BRCA2 gene harbored 48, 29, 24 and 18 variants in the CRC, CP, IBD and control groups respectively. Exon 2, 11, 23 were the most affected exons harbored 12 pathogenic variants in the CRC group. Four out of 12 were the most frequently detected common pathogenic variants associated with disease progression from colitis to CRC (c.3860delA (8%), c.5351delA (18%), c.9097delA (24%) & c.36delT (34%). Conclusion: Our data showed that BRCA1 & BRCA2 genes analyzed by Next-Generation Sequencing (NGS) identifies large number of pathogenic and begnin variants that are crucial for understanding CRC predisposition and early detection. Also, developing personalized therapies that efficiently target the individual CRC-specific mutations. Key words: Egyptian Colorectal cancer, BRCA1, BRCA2, pathogenic, begnin, Next Generation Sequencing Citation Format: Amira Salah El-Din Youssef, Ahmed Osama Touny, Zeinab K. Hassan, Mohammed Mohey Eldin, Mai M. Lotfy, Auhood Nassar, Mohamed El-Hadidi, Ali Kishk, ola sayed, Abdel-Rahman N. Zekri. Profiling of BRCA1 & BRCA2 mutations in Egyptian colorectal cancer patients via next generation sequencing [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3615.

Surgery is the primary treatment for resectable gastric cancer. Total/subtotal gastrectomy has been the main surgical procedure for resectable gastric cancer depending on the extent and location of the tumor. Nevertheless, studies have shown that surgery alone is less than satisfactory with cure rates approaching 40% [1] . The optimal surgical principles have not reached consensus with the extent of lymph node dissection being the most controversial aspect in this issue. Adding adjuvant chemo-radiation was suggested as an alternative for extensive therapeutic nodal dissection [2] .The 5-year overall survival for early stage disease is 75% however this drops to ≤ 30% with the presence of positive lymph nodes. The incidence of local recurrence is approximately 60% for cases treated surgically, pattern-of-failure data from clinical, second-look surgery, Abstract Objective: The suboptimal outcome after surgery alone for gastric cancer indicated the necessity of adjuvant treatment for potentially resectable carcinoma of the stomach. In 2001, postoperative adjuvant radiochemotherapy started to be implemented in the NCI, Cairo, Egypt. However, the fear of the acute complication hindered its use as a standard treatment with some staff didn't follow the SWAG's adjuvant protocol. The aim of this report is to verify this issue. Methods: In the period from 1999 to 2009, 320 out of 581 patients with gastric carcinoma, underdid potentially curative surgery. Adjuvant postoperative radiochemotherapy for stage ≥ IIA started since 2001. Radiation (45 Gy, 1.8 Gy/f) was targeted to the tumor bed, anastomosis site, duodenal stump, remnant stomach and regional lymph node together with 4-5 cycles chemotherapy (SWOG protocol). Survival analysis was performed and comparison between survival curves was done to analysis different prognostic factors. Results: The patients' age ranged from 17 to 86 years [mean (54 ± 12.5) years]. About 1/3 of the patients had a diffuse lesion. Adenocarcinoma was the most common pathology (60.4%). High grade pathology constituted 59.1% of the cases. About one fifth of the patients had metastatic disease at presentation. Only 351 (75%) of the patients had potentially curative gastrectomy. The median number of lymph node (LN) dissected was 12 (ranged from 0-45) with a median number of the positive LN of 3.5 (ranged from 0-40). Postoperative mortality was 12%. The median follow up period was 21.9 months (ranged from 3-129.4 months). For the 257 patients who had curative surgery, 164 (62.8%) patients were alive at the end of follow up. During follow up period, 30 patients had loco-regional relapse, and 26 patients had metastasis, and 39 patients had both pattern of failure. The overall survival (OS), loco-regional control (LRC), and metastasis free survival (MFS) rates, at median follow up period of 22 months, were 61.2%, 66.7% and 71%, respectively. At 3 and 5 years the corresponding values were: OS (42% and 28%), LRC (64% and 50.4%) and MFS (56.3% and 49%), respectively. Only stage and degree of nodal involve...