[en] I have read with great interest khafagy et all s article in ENC1 2012:24:91-6 This small series needs explanations for following questions: 1- Thirteen cases with N₀ have been operated by a complete axillary dissection. Would it be better to undertake sentinel lymph node biopsy (SLNB) in these cases? 2- The patients with periareolar tumor localization (half of the patients) underwent needlessly a pedicled flap operation instead of an advancement flap or simple rotation flap. They are simple and therefore less time-consuming onco plastic procedures. They do not require whole nippleareola complex excision. Therefore, advancement flaps or periareolar mastopexy [1] were more reasonable. 3- Ten patients with N₂ represent locally advanced cancer of breast (Stage III). They should be treated by primary chemotherapy instead of surgery first. It needs explanation. 4- Four cases with N₊ have not been given adjuvant chemotherapy. It should be explained. 5- The rates of good cosmetic results were the same for both patients and doctors. But in the literature, the rates of health professionals are nearly always lower than patients [2], It needs explanation. 6- The condition of contralateral breasts has not been presented. Is not there some cases requiring contralateral mastoplasty, reduction or any other cosmetic procedure? Kind regards.

[en] (1)Thirteen cases with N₀ have been operated by a complete axillary dissection. Would it be better to undertake sentinel lymph node biopsy (SLNB) in these cases? Answer: Our treatment guidelines do not include SLNB, although it is very much acceptable, but our breast cancer patients are not candidates for such technique. However, previous studies at NCI found an incidence of LN metastasis in T1 tumors of about 70%. (2) The patients with periareolar tumor localization (half of the patients) underwent needlessly a pedicled flap operation instead of an advancement flap or simple rotation flap. They are simple and therefore less time-consuming oncoplastic procedures. They do not require whole mpple areola complex. Therefore, advancement flaps or periareolar mastopexy (1) was more reasonable. Answer: We believe that the proposed technique (advancement flaps) will result in nipple areola complex shift and bad cosmetic outcome, that is why our described technique, although the number of cases is limited, will allow for centralization of the NAC and better cosmcsis. (3) Ten patients with N2 represent locally advanced cancer of breast (Stage III). They should be treated primarily by systemic therapy instead of surgery first. It needs explanation. Answer: Now, in our treatment protocols, patients with advanced disease, or nodal disease would receive CT primarily N2 regarding the number of lymph nodes. (4) Four cases with N+ have not been given adjuvant chemotherapy. It should be explained. Answer: They refused to receive CT. (5) The rates of good cosmetic results were the same for both patients and doctors. But in the literature, the rates of health professionals are nearly always lower than patients (2) . It needs explanation. Answer: We do not think it needs explanation. This is a subjective way for analysis of cosmetic appearance. Moreover, according to the literature, patient expectations usually lead to a lower acceptance than surgeons. (6) The condition of contralateral breasts has not been presented. Is not there some cases requiring contralateral mastoplasty, reduction or any other cosmetic procedure? Answer: Yes, some of them needed contralateral symmetrization which was performed after the end of the study, but these complementary procedures were not included in the study. On the other hand, other patients refused this symmetrization procedure.

[en] Background: Small intestinal cancers (SICs) are very rare all over the world and little is known about them in Egypt. Methods: This a retrospective study. Between 2000 and 2002. 30 cases with SICs were identified in the Gharbiah population based cancer registry (GPBCR); 17 cases of whom were treated at Tanta Cancer Center (TCC). Results: The median age was 51 years with female predominance. The duodenum was the commonest site (43%) followed by the ileum then the jejunum. Adenocarcinoma (AC), carcinoids, gastrointestinal stromal tumors (GISTs), lymphoma and sarcoma represented 50%, 10%, 17%, 13% and 10% respectively. Abdominal pain was the commonest symptom and localized disease was the commonest presentation. Surgery, chemotherapy and radiotherapy were employed in 65%, 35% and 0% of patients, respectively. The median overall survival and progression free survival (OS, PFS) were 18 and 15 months (95% Cl: 10.4-25.6 and 3.6-26.4), respectively. AC had inferior OS and PFS to other histologies (p = 0.08 and 0.12, respectively). Also, duodenum subsite was inferior in OS and PFS to other sites (p = 0.25 and 0.35, respectively). Conclusions: SICs in Gharbiah, Egypt are characterized by predominance of female gender and adenocarcinoma histology. One year survival is 64% with a poor outcome for adenocarcinoma and duodenal subsite.

[en] To the editor Kassem et al. [1] described a novel mutational deletion [del 1178 (A)] in the 30 untranslated region of NPM1 gene detected in a heterozygous form in seven de novo acute myeloid leukemia (AML) patients of their study population. The described nucleotide deletion is an NPM1 gene polymorphism recorded in db SNP database (rs34351976; g28027: Genbank accession number NG₀16018.1) (http://www.ncbi.nlm.nih.gov/projects/SNP/) and was described previously by Do hner et al. [2] and Chou et al. [3]. This variant accounted for 60-70% of AML patients with normal karyotype [2]. The putative deletion was also identified in healthy volunteers and persisted at complete remission and also at relapse of AML patients [3]. This deletion had no effect on the predicted amino acid sequence and is not in linkage disequilibrium with any previously identified NPM1 mutations [2,3]. Analysis of RNA folding at the region surrounding the rs34351976 in the presence or absence of the deletion using Mfold analysis software (http://www.mfold.rna.albany.edu) revealed no RNA folding change that may alter RNA splicing and subsequently gene expression. Furthermore, splicing motifs analysis using Human Splicing Finder software version 2.4.1 showed that the presence of the deletion does not abolish any recognition site of exonic or intronic enhancers or silencer motifs. In general, it seems that the impact of NMP1 polymorphisms on the molecular pathogenesis of AML is not clear yet and needs further investigation. Kassem et al. [1] describes the molecular aspect of de novo AML in the Egyptian population. The previously known NPM1 mutations mentioned in their study are less frequent compared to the figures recorded worldwide. Moreover, the authors wondered whether the NPM1 variants identified in their patients may confer a better outcome of AML. According to the previously mentioned data, one can speculate that the presence of NPM1 gene polymorphism (rs34351976) should not be mistaken as being a diagnostic or prognostic marker of de novo AML. Although NPM1 mutation detection is important in the diagnostic work-up of AML patients with normal karyotype, physicians should be more cautious while interpreting the data of NPM1 gene sequencing. In addition, the relation of NPM1 polymorphism to de novo AML etiology necessitates further clarification.

[en] Purpose: To compare volumetric-modulated arc therapy (VMAT) with 3D-conformal radiation therapy (3D-CRT) mediastinal irradiation for stage I–II supra-diaphragmatic Hodgkin’s Lymphoma (HL). Patients and methods: Eleven patients were planned for RT after 4–6 cycles of ABVD chemotherapy: conventional 3D-CRT (AP/PA) and VMAT plans were conformed to the same PTV. Objective was to choose the best PTV coverage plan with the least OAR dose. The 2 plans were compared for: PTV coverage, mean dose and V5,V20 lung , mean dose and V30 heart , V5, V10, V15 breast (female patients), and the integral body dose. Results: Both techniques achieved adequate PTV coverage. Mean lung and heart dose was consistently lower in VMAT plans. The lung V20 dose was acceptable for VMAT, but exceeded the tolerance threshold in 6 cases with 3DCRT plans. A mean difference of 15.9% for both lungs V20 favored VMAT plans; average MLD difference was 2.3 Gy less for VMAT plans. Similarly, lower maximum and mean heart doses with a 3.3 Gy dose reduction and a 9.4% difference in V30 favored VMAT plans. Mean V5 lung/female breast and integral dose were invariably higher in VMAT plans because of the low-dose spread.

[en] Introduction Lymphoblastic lymphoma (LBL) and acute lymphoblastic leukemia (ALL) are neoplasms of immature B or T-cell precursors. They are considered as a unique biological entity in the 2008 World Health Organization Classification of Hematologic Neoplasm. Both entities are arbitrarily separated by a cut-off point of 20–25% of blast cells in the bone marrow. Treatment of LBL has evolved over time from conventional high-grade NHL schedules to ALL-derived protocols. The aim of this work is to report the clinical characteristics, overall survival (OS), event free survival (EFS), and common chemotherapy toxicities of lymphoblastic lymphoma (LBL) patients during a 5.5 year period. Patients and methods A Retrospective review of patient’s charts diagnosed and treated as LBL during the period between July 2007 and end of December 2012 was done. Patients were treated according to St. Jude Children Research Hospital ALL Total Therapy XV protocol, standard risk arm. Results This study included 77 patients. T-cell LBL patients were 67, while 10 were of B-cell origin. The median age at diagnosis was 9 years (95% CI: 7–10). The majority were males 54/77. Stage III patients were 51, stage IV 13, stage II 11 and stage I 2 patients. Two patients were excluded from analysis as they died before receiving chemotherapy. Complete remission post induction chemotherapy was seen in 22 patients considered early responders, and partial remission in 55 considered late responders. With a median follow up duration of 47 months (95% CI: 38–56), the 4 year overall survival and event free survival were 86.45% (95% CI: 73.78–94.09) and 82.18% (95% CI: 69.25–90.61) respectively. Twelve patients died during the study period; 2 early deaths before starting chemotherapy from dis- ease progression, 2 in CR due to chemotherapy related toxicity and 8 from disease progression. All the relapsed patients were T-cell, had advanced disease at presentation (6 with stage III; 2 with stage IV). Two patients (2.6%) had isolated local, BM, and CNS relapse each, while 1 (1.3%) had both local and CNS relapse. Disease recurrence was local in 3 patients (3.9%), and systemic in 5 (6.4%), while it was early in 6 (7.8%), and late in 2 (2.6%) patients. Median time to disease progression was 20 months (range 5–39 months). All relapsed patients did not survive salvage chemotherapy. The most common chemotherapy toxicities were cerebral venous thrombosis (20%), followed by bone infarcts (10.6%), and avascular necrosis (AVN) of head of femur (9.3%). One patient developed secondary acute myeloid leukemia after 3 years of FU with unfavorable cytogenetic abnormalities.

[en] Introduction: Fractionation plays a pivotal role in determining the effectiveness of radiation and follows the principle of 4 ‘‘R ” of radiobiology. The various altered fractionation schedules used are hyper-fractionation, accelerated fractionation, and hypo fractionation. Methods: We reviewed the landmark articles published in the peer reviewed journals to summarize the beneficial role of altered fractionation in the treatment of head and neck carcinoma. Results: Hyper-fractionation definitely gives very good overall survival benefit for locally advanced head and neck patient’s equivalent to survival benefit to that of concurrent chemoradiotherapy. Adding concomitant chemotherapy to altered fractionation is a logical approach to improve survival in locally advanced head and neck cancer patients, but it may be at a cost of higher toxicity. Mild hypo fractionation may be beneficial in early laryngeal cancers and may help in achieving better local control. Conclusion: Altered fractionation is a very important treatment schema and requires the reinforcement of its use.

[en] Tamoxifen has been the mainstay of breast cancer therapy. Over time, resistance to tamoxifen may develop. The aromatase inhibitors have proven to be a powerful drug for use in hormone-sensitive early breast cancer. The switching strategy was designed to combine the apparent superior efficacy of aromatase inhibitors with tamoxifen favourable effects. Methods: This study was performed on 120 postmenopausal women with histologically confirmed, hormone receptor-positive, operable invasive breast carcinoma who remained free of disease after 2 years of adjuvant tamoxifen therapy. They were randomized to receive either letrozole 2.5 mg/day (60 patients) or to continue 20 mg/day tamoxifen for 5 years (60 patients). Results: The treatment groups were well balanced in terms of age, tumor size, nodal status, oestrogen and progesterone receptor status, and previous surgery. The disease recurred in 10 patients in the group receiving tamoxifen and 3 patients in the same group switched to letrozole. There were 8 deaths in the group receiving tamoxifen and 3 deaths in the group of patients who switched to letrozole. Disease-free survival was higher in the group of patients who switched to letrozole compared to the group of patients who received tamoxifen (p=0.04), while the overall survival was not statistically significantly different in the two groups. Letrozole was associated with a significantly lower rate of vaginal bleeding and thromboembolic events. However, bone fractures and adverse cardiovascular events were more frequent in the arm receiving letrozole than in the arm receiving tamoxifen but these differences were not statistically significant. Conclusion: Switching to letrozole after 2 years of tamoxifen may be better than continuing five years of tamoxifen therapy as regard efficacy and tolerability. Further study is recommended on a larger group of patients to verify this finding

[en] Tumor budding (TB) is showing increasing promise as a colorectal cancer (CRC) prognosticator that is independent of TNM staging. P-Catenin is a component of the Wing-less/Wnt signaling pathway that is bound to membrane-associated E-cadherin and is essential for its correct position and function. Methods: This study was designed to detect TB in 44 resected primary CRC cases and also to compare P-catenin expression in the tumor budding sites (TBS) and in the tumor center. Tumor budding was assessed in both H and E and pankeratin immunostained sections. Agreement between TB scoring using pancytokeratin and H and E was tested. Also, typing of the tumor margin and determination of degree of cytoplasmic pseudo-fragmentation was done. Tumor budding, cytoplasmic pseudo fragments and p-catenin expression were related to known CRC prognosticates. Results: Ten tumors (22.7%) showed low grade (LG) budding and 34 tumors (77.3%) showed high grade (HG) budding. The 34 HG budding tumors were further subdivided into moderate and severe (n = 13, n = 21, respectively) budding cancers. Twenty nine tumors (65.9%) showed LG cytoplasmic pseudo fragments and 15 tumors (34.1 %) showed HG pseudo fragments. Scoring of TB on H and E and pankeratin stained sections revealed moderate agreement (Kappa = .558; p = < .000). A significant relation between TB and cytoplasmic pseudo fragments was observed (p = .009). Both TB and cytoplasmic pseudo fragments did not significantly associate with clinico pathologic parameters. Immunoreactivity of nuclear and cytoplasmic p-catenin was significantly higher at TBS compared to tumor center (p - .005, p = .000, respectively). In opposition, membranous (5-catenin expression was significantly higher in the tumor center than in TBS (p = .001). Although, nuclear (3-catenin accumulation at TBS was noted, yet, it did not relate significantly with both TB and cytoplasmic pseudo fragments around TBS (p = .649; p = .675, respectively). Also, nuclear P-catenin immunoreactivity did not relate significantly with the various clinico pathological variables. Conclusion: Pan keratin immunostaining facilitates typing of CRC invasive margin, and determination of the degree of TB and cytoplasmic pseudo-fragmentation. p-Catenin expression differs significantly between tumor center and TBS in CRC. Cut-offs for TB assessment should be unified and further studies are recommended to allow a better understanding of this process before establishing TB as a prognostic factor beyond the TNM staging in CRC. All rights reserved

[en] The standard treatment for women with endometrial cancer is total abdominal hysterectomy and pelvic lymphadenectomy for surgical staging. Total laparoscopic radical hysterectomy (TLH) is an alternative approach providing surgical and patient related advantages to laparoscopy. Methods: Twenty female patients with early stage endometrial cancer were operated upon by TLH and pelvic lymphadenectomy, aiming to assess the safety and efficacy of TLH. Results: The mean operative time was 296.8 min conversion to laparotomy was done in one patient due to bleeding from the uterine vessels. The mean blood loss was 517.5 cc. The uterus was removed transvaginally in 18 patients (90%) and via a small Pfannenstiel incision in two patients (10%). The mean number of pelvic lymph nodes retrieval was 21.2. Postoperative bleeding occurred in one patient (5%) which necessitated exploration. One patient (5%) suffered a pulmonary embolism. Four patients (20%) developed pyrexia, and one patient (5%) suffered from a chest infection. One patient (5%) had wound infection. The mean hospital stay was 4.5 days (range 3-10). Conclusion: TLH with pelvic lymphadenectomy is a safe and effective approach in the treatment of early endometrial carcinoma.