Neoadjuvant chemotherapy for stage II-III breast cancer: a single-center experience.

INTRODUCTION: We conducted this study to reflect a single-center experience with the use of neoadjuvant systemic chemotherapy (NAC) for the management of women with operable breast cancer. METHODS: We conducted a retrospective chart review on all women presenting with operable, stage II-III, breast cancer and were scheduled for NAC at Suez Canal University Hospital. The primary outcome of this study was to estimate the proportion of patients with breast cancer who become eligible for breast-conserving surgery (BCS) after (NAC). RESULTS: A total of 147 patients were included. Before the initiation of chemotherapy, only 66 (44.9%) patients were indicated for (BCS). A total of 40 (49.4%) new patients, out of the 81 patients who were ineligible before chemotherapy, became eligible for BCS after NAC (95% CI 39.3-61.9%). On the other hand, 8 (12.1%) patients became ineligible for BCS after NAC, out of 66 patients who were initially eligible. Out of the 98 eligible patients for BCS after chemotherapy, 72 (73.5%) patients underwent the surgery, and the remaining 26 (26.5%) patients chose modified radical mastectomy (MRM). A total of 55 out of 72 (76.4%) patients achieved pathological complete response (pCR). One woman (0.1%) experienced relapse in the 3rd year of follow-up and three women (2%) experienced relapse in the 5th year of follow-up. We found a statistically significant relationship between patients who became eligible for breast-conserving surgery and both age and estrogen receptor negativity (p = 0.001 and 0.007, respectively). CONCLUSION: NAC can play a crucial role in increasing the rate of eligibility for BCS among women with operable, stage II-III, breast cancer.

Synthesis, biological evaluation and in silico molecular docking of novel 1-hydroxy-naphthyl substituted heterocycles.

The versatile precursor 2-acetyl-4-allyl-1-hydroxy naphthalene was synthesized efficiently via Claisen rearrangement 2-acetyl-1-allyloxynaphthalene. The Claisen-Schmidt condensation of latter precursor afforded the corresponding chalcones which were exploited to synthesize a series of potential heterocycles such as pyrazoline, isoxazoline, benzocoumarin and benzoflavone. The synthesized products showed potent antioxidant and antimicrobial activities. Chalcone 3c, naphthyl pyrazoline 6b and hydroxycoumarin 13 exhibited the highest activity as antioxidants. Their binding mode showed specialized recognition of hydroxycoumarin 13 with the triad key amino acids at the active site of the oxidoreductase enzyme (PDB code 1DXO). 1-Hydroxynaphth-2-yl pyrazoline (6b) revealed the highest efficacy against both Gram positive and negative bacterial species. In silico molecular docking of pyrazoline 6b endorsed its proper binding at the active site of the 2EX6 enzyme which explains its potent antibacterial activity in comparison with standard ampicillin.

Enantioselective organocatalytic oxidation of ketimine.

C3-Symmetric chiral trisimidazolines with m-chloroperbenzoic acid promoted the organocatalytic oxidation of N-sulfonyl ketimine. The present imidazoline catalysis produced oxaziridines bearing a tetrasubstituted carbon stereogenic center in high yields with up to 87% ee.

Silver-Catalyzed Asymmetric Desymmetrization of Cyclohexadienones via Van Leusen Pyrrole Synthesis.

A catalytic asymmetric desymmetrization of cyclohexadienones was accomplished via Van Leusen pyrrole synthesis in the presence of a chiral silver catalyst. The ready access to chiral-fused pyrrole derivatives is attributed to the identification of a suitable isocyanomethyl sulfone surrogate, NasMIC. The current Ag(I)-chiral phosphino-carboamide ligand system can be extended to the kinetic resolution of racemic cyclohexadienones, capitalizing on the differentiated reactivity of chiral quaternary complexes from AgSbF6, chiral ligand (L*), cyclohexadienone, and NasMIC.

Synthesis of novel naphthalene-heterocycle hybrids with potent antitumor, anti-inflammatory and antituberculosis activities.

Multitarget-directed drugs (hybrid drugs) constitute an efficient avenue for the treatment of multifactorial diseases. In this work, novel naphthalene hybrids with different heterocyclic scaffolds such as nicotinonitrile, pyran, pyranopyrazole, pyrazole, pyrazolopyridine, and azepine were efficiently synthesized via tandem reactions of 3-formyl-4H-benzo[h]chromen-4-one 1 with different nucleophilic reagents. Analysis of these hybrids using PASS online software indicated different predicted biological activities such as anticancer, antimicrobial, antiviral, antiprotozoal, anti-inflammatory, etc. By focusing on antitumor, anti-inflammatory, and antituberculosis activities, many compounds revealed remarkable activities. While 3c, 3e, and 3h were more potent than doxorubicin in the case of HepG-2 cell lines, 3a-e, 3i, 6, 8, 10, 11, and 12b were more potent in the case of MCF-7. Moreover, compounds 3c, 3h, 8, 10, 3d, and 12b manifested superior activity and COX-2 selectivity to the reference anti-inflammatory Celecoxib. Regarding antituberculosis activity, 3c, 3d, and 3i were found to be the most promising with MIC less than 1 µg mL-1. The molecular docking studies showed strong polar and hydrophobic interactions with the novel naphthalene-heterocycle hybrids that were compatible with experimental evaluations to a great extent.

Early fractional carbon dioxide laser intervention for postsurgical scars in skin of color.

BACKGROUND: Fractional CO2 laser is one of the most effective treatment options used to resurface scars. OBJECTIVE: To evaluate the efficacy and safety of early treatment of postsurgical scar by fractional ablative CO2 laser. METHODS: A total of 27 Egyptian patients with recent postoperative scars were enrolled in this study. Three sessions of fractional CO2 laser with a 1-month interval were started 4 weeks after surgery. Vancouver Scar Scale (VSS) was used as an assessment tool at 1 and 3 months after the final treatment. Patients reported their satisfaction using a subjective 4-point scale. RESULTS: Results demonstrated a statistically significant overall average improvement of the VSS (5.33±1.33) before compared with (2.55±1.06) 3 months after the last laser treatment (P≤0.001). Among the individual parameters in the VSS, the most significant improvements were found in pigmentation, height, and pliability. Patient's subjective satisfaction scores showed a significant greater degree of satisfaction after laser treatment. CONCLUSION: Fractional ablative CO2 laser is an effective and safe treatment modality for surgical scars in the early postsurgical period.

Unorthodox synthesis, biological activity and DFT studies of novel and multifunctionalized naphthoxocine derivatives.

A new promising protocol has been developed for the synthesis of scarce oxocine derivatives 3a-e and 6 through addition of amine-based nucleophiles such as hydroxylamine hydrochloride, primary amine and hydrazide to chromonylidene benzothiazol-2-ylacetonitrile 2 in refluxing dioxane under metal free reaction conditions in moderate to good yields. Other nitrogen nucleophiles such as piperidine, hydrazine and thiosemicarbazide failed to afford the corresponding oxocinols, and instead pyridine derivatives 7, 8 and 10 were obtained exclusively. Predictive study for the biological activities using PASS (prediction of activity spectra for biologically active substances) online software showed optimistic activities for oxocinols 3a-e in the treatment of cancer, influenza A and microbial infections. Additionally, DFT studies of oxocine derivatives 3a-e and 6 indicated the presence of required thermodynamics parameters for the application in dye-sensitized solar cells (DSSCs).

McKissock's Reduction Mammaplasty Revisited: A Case Series Study with 12-months Follow-up.

BACKGROUND: Reduction mammaplasty is 1 of the highly challenging yet demanded plastic surgeries worldwide. Different techniques have been described, and their modifications are always evolving to achieve better aesthetic results. The objective of the current study was to explore the efficiency and safety of bipedicled McKissock's technique with 3 newly added modifications as a reliable procedure for reduction mammaplasty. METHODS: The study was conducted in Royal Hospital, Cairo, Egypt, during the period from January 2015 to October 2016. It included 25 female patients undergoing reduction mammaplasty. All patients were evaluated by detailed history, careful physical examination, and photographed pre- and postoperatively. The new modifications included surgical undermining and thinning of the bipedicle for volume reduction and contour enhancement. The second modification was a dermal suspension of the lower pole for parenchymal support and longer breast shape stability. The third change was an S-shaped folding of the upper pole of the pedicle during nipple-areolar complex (NAC) transposition. After the operation, all subjects were followed up for 12 months to assess the outcomes of the procedure. RESULTS: Twenty-five female patients were included in the analysis of this study. The age of the patients ranged from 22 to 49 years with a mean age of 36.2 (7.3) years. The mean body mass index was 30.5 ± 4.3 kg/m2 with a minimum of 24 and a maximum of 38. The average time of operation was 4 hours. The resected tissue was 630-980 g. The optimal aesthetic appearance of the breasts was achieved at 6-9 months postoperatively and marinated to 12 months. The maintenance of improvement was measured by the distance between the mid-clavicular point and 12 O'clock point of the NAC (12'NAC). It varied between 28 and 43 cm preoperatively (mean ± SD, 34.12 ± 4.19 cm), and between 19 and 22 cm postoperatively (mean ± SD, 20.70 ± 1.03 cm; P < 0.001). The average percentage reduction in mid-clavicular point-NAC distance was 38.7% ± 6.2% with a minimum reduction of 27.6% and a maximum 48.8%. Moreover, the nipple to inframammary crease distance varied between 16 and 20 cm preoperatively (mean ± SD, 16.08 ± 1.66 cm), and between 8 and 10 cm postoperatively (mean ± SD, 8.04 ± 0.79 cm; P < 0.001). The patients were very satisfied in most of the cases (20 cases), satisfied in 3 cases, and 2 cases were unsatisfied as they wanted slightly smaller breasts. No complications detected in 18 cases (72%), superficial wound dehiscence at the T-junction in 3 (12%), and seroma in 1 (4%). Two cases (8%) demanded smaller breasts and 1 case (4%) needed a surgical revision of widened scars after 11 months. The major drawbacks were NAC sensitivity alteration and the inability to lactate. CONCLUSION: We can conclude that our modifications for the McKissock's technique with its maintained aesthetic shape in those patients are a reliable option that can be considered, as it is a simple, efficient, and satisfactory method that can improve the results of reduction mammaplasty operations.

A Randomized Comparison Between Staple-Line Oversewing Versus No Reinforcement During Laparoscopic Vertical Sleeve Gastrectomy.

BACKGROUND: Varieties of intraoperative methods such as oversewing of staple lines or other reinforcement products are used for preventing the laparoscopic vertical sleeve gastrectomy (LSG) complications. The aim of this study is to evaluate the complication rates of the gastric stapling alone versus stapling with oversewing invagination of the staple line in the LSG. METHODS: This is a single-center randomized study, Patients were randomized to two groups, 200 patients underwent LSG without reinforcement of the staple line and 200 patients underwent LSG with oversewing of the staple line. All patients were followed up for 1 year. The data collected prospectively for statistical analysis included demographics, BMI, preoperative comorbidities, operative time, complications, and hospital stay. RESULTS: The overall mean operative age was 33.7 ± 9.4 years and mean BMI was 42.4 ± 4.3 kg/m2. Patient baseline characteristics (age, gender, weight, and BMI) and comorbidities were generally a nonsignificant different between the treatment arms. Surgical time was shorter in patients of the nonreinforced group (44.3 ± vs 51.3 ± 4.3 min; p < 0.01) with lower %EWL (73 ± 13.8 vs 80.7 ± 13.6%, p < 0.01). One patient in the nonreinforced group was complicated by gastric leak. The staple-line bleeding rate was significantly lower in patients underwent oversewing of the staple line during LSG (p < 0.05). CONCLUSION: Oversewing of the staple line during LSG is a nonexpansive and easy method to decrease the incidence and severity of the postoperative bleeding. However, it is time-consuming and should be performed by experienced surgeons to avoid the complications which may occur secondary to the seroserotomy suturing.

Immunotherapeutic Strategies for Gastric Carcinoma: A Review of Preclinical and Clinical Recent Development.

Gastric carcinoma (GC) is the 2nd most common cause of cancer-related death. Despite advances in conventional treatment and surgical interventions, a high percentage of GC patients still have poor survival. Recently, immunotherapy has become a promising approach to treat GC. Here, we present preclinical and clinical studies encouraging the use of vaccination, adoptive T-cell therapy (ACT), and immune checkpoint inhibitors, such as programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). The ongoing immunotherapy clinical trials have shown promising results in safety and tolerability even in late-stage GC patients. Moreover, we highlight that the combination of ACT with chemotherapy could be the best choice to treat GC.

Outcomes of Omega Loop Gastric Bypass, 6-Years Experience of 1520 Cases.

BACKGROUND: Omega loop gastric bypass (OLGB) has been viewed with skepticism after the failure of the "old Mason loop." During the past 15 years, a growing number of authors worldwide approved that OLGB is a safe and effective procedure, which appears clearly from the operative outcome and long-term follow-up of consecutive cohort studies of patients who underwent OLGB. The aim of this study is to evaluate the outcomes of OLGB at the bariatric center of our university hospital between 2009 and 2015. METHODS: The data of 1520 patients who underwent OLGB from November 2009 to December 2015 at our center were reviewed. Mean age was 37.15 years, mean preoperative BMI was 46.8 ± 6.6 kg/m2, mean preoperative weight was 127.4 ± 25.3 kg, and 62.7% were women. Diabetes mellitus (DM) affected 683 (44.9%) of the 1520 patients, whereas 773 of the 1520 patients (50.9%) presented with hypertension. The mean operative time was 35 min. RESULTS: The 1-year postoperative BMI mean decreased to 29.6 ± 3.1 kg/m2, and at the 3-year follow-up, it was 27.5 ± 3.4 kg/m2. The mean of weight decreased to 81.3 ± 16.7 kg and to 78.9 ± 16.9 kg at the 1-year and the 3-year follow-up, respectively. Mortality rate was 0.1%. Overall complications were 9.3%; 0.8% required reoperations. Early complications were encountered in 50 patients (3.3%), and the late complications rate was (6.1%). CONCLUSIONS: In this study, greater excess weight loss was observed with OLGB which appeared to be a short, simple, low-risk, effective, and durable bariatric procedure.

Outcomes of One Anastomosis Gastric Bypass in 472 Diabetic Patients.

BACKGROUND: The positive impact of Roux-en-Y gastric bypass (RYGB) on metabolic syndrome and glycemic control has been proven in obese patients. One anastomosis gastric bypass (OAGB) is a simple, effective and easy to learn procedure. OAGB provides encouraging results for the treatment of diabetes obese patients, but does it have the ability to be an alternative procedure to RYGB in the treatment of these patients? The aim of this study is to evaluate the outcomes of OAGB on diabetic obese patients at the bariatric centre of our university hospital. By extension, we evaluated the possibility of BMI and the preoperative antidiabetic medication usage to be predictive factors for postoperative diabetes resolution. METHODS: This is a retrospective single-centre study of 472 diabetic patients who underwent OAGB from November 2009 to December 2015. All patients were followed-up for at least 1 year, and up to 3 years, where available. Weight, HbA1c, and anti-diabetic medications were recorded at baseline, 3, 6, 12, 24 and 36 months. RESULTS: A total of 472 patients have been followed-up for 1 year and 361 for 3 years. The mean BMI decreased from 46.8 ± 7.2 to 29.5 ± 2.8 kg/m2 and HbA1c from 9.6 ± 1.3 to 5.7 ± 1.5% at the 12-month follow-up. At the 3-year follow-up, the mean BMI was 32.1 ± 3.3 and HbA1c mean was 5.8 ± 0.9%. Diabetes remission was achieved by 84.1% of patients. CONCLUSIONS: OAGB can be an excellent alternative to RYGB for the treatment of diabetes and obesity. Pre-operative medications may be used to predict postoperative diabetes remission, but not BMI.

Enantioselective synthesis of tetrahydrocyclopenta[b]indole bearing a chiral quaternary carbon center via Pd(ii)-SPRIX-catalyzed C-H activation.

The highly enantioselective cyclization of 3-alkenylindole via C-H activation has been established using Pd(OCOCF3)2 in conjunction with the chiral spiro bis(isoxazoline) ligand (SPRIX). The presence of an N-allyl substituent on the substrate has a strong impact on both reactivity and selectivity, leading to tricyclic indole products (up to 96% ee) with a chiral quaternary carbon center.

Determination of the absolute configuration of compounds bearing chiral quaternary carbon centers using the crystalline sponge method.

Determination of the absolute configuration of chiral tetra-substituted carbon centers is one of the most taxing steps in the enantioselective construction of this structural motif in asymmetric synthesis. Here, we demonstrate that the crystalline sponge method provides an effective way to crystallographically determine the absolute configuration of organic compounds bearing chiral quaternary carbons (including tetra-substituted ones) that are synthesized by recently developed enantioselective catalytic reactions.

Enantio- and Diastereoselective Betti/aza-Michael Sequence: Single Operated Preparation of Chiral 1,3-Disubstituted Isoindolines.

The first enantio- and diastereoselective Betti/intramolecular aza-Michael sequence carried out using a C3-symmetric chiral trisimidazoline organocatalyst is reported. The reaction of phenols and N-tosylimines bearing a Michael acceptor moiety afforded densely functionalized 1,3-disubstituted isoindolines bearing two stereogenic centers as single diastereomers in high yields (≤93%) and excellent enantioselectivities (≤99.9%).