ctDNA as a predictor of outcome after curative resection for locally advanced rectal cancer: systematic review and meta-analysis.

AIM: To assess the efficacy of ctDNA measurement at different time intervals in predicting response and prognosis in patients diagnosed with locally advanced rectal cancer (LARC) who underwent neoadjuvant treatment prior to curative resection. METHOD: English language randomized controlled trials and observational studies, published from 1946 to January 2024, comparing outcomes between ctDNA-positive and ctDNA-negative patients with LARC undergoing neoadjuvant treatment prior to curative surgical resection were included in the search. The search included Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and the Cochrane Database of Systematic Reviews (CDSR). RESULTS: Data for 1022 patients were analysed. Patients with positive ctDNA in the preoperative period had more than five times the risk of developing distant metastasis (RR [95% CI] 5.03 [3.31-7.65], p < 0.001), while those with positive ctDNA in the postoperative period had more than six times the risk (RR [95% CI] 6.17 [2.38-15.95], p < 0.001). There was no significant relationship between ctDNA status at baseline, pre-, or postoperative periods and achievement of pCR (RR [95% CI] 1.21 [0.86-1.7], 1.82 [0.94-3.55], 1.48 [0.78-2.82], p = 0.27, 0.08, and 0.23, respectively). However, patients with positive ctDNA in the pre- and postoperative periods had more than 13 and 12 times the risk of overall disease relapse after curative-intent treatment (RR [95% CI] 13.55 [7.12-25.81], 12.14 [3.19-46.14], p < 0.001), respectively. CONCLUSION: ctDNA could potentially guide treatment and follow-up in LARC, predicting high-risk patients for disease relapse, allowing individualized surveillance and treatment strategies. Prospective studies are needed for standardization.

US Liver Transplant Outcomes After Normothermic Regional Perfusion vs Standard Super Rapid Recovery.

Importance: Normothermic regional perfusion (NRP) is an emerging recovery modality for transplantable allografts from controlled donation after circulatory death (cDCD) donors. In the US, only 11.4% of liver recipients who are transplanted from a deceased donor receive a cDCD liver. NRP has the potential to safely expand the US donor pool with improved transplant outcomes as compared with standard super rapid recovery (SRR). Objective: To assess outcomes of US liver transplants using controlled donation after circulatory death livers recovered with normothermic regional perfusion vs standard super rapid recovery. Design, Setting, and Participants: This was a retrospective, observational cohort study comparing liver transplant outcomes from cDCD donors recovered by NRP vs SRR. Outcomes of cDCD liver transplant from January 2017 to May 2023 were collated from 17 US transplant centers and included livers recovered by SRR and NRP (thoracoabdominal NRP [TA-NRP] and abdominal NRP [A-NRP]). Seven transplant centers used NRP, allowing for liver allografts to be transplanted at 17 centers; 10 centers imported livers recovered via NRP from other centers. Exposures: cDCD livers were recovered by either NRP or SRR. Main Outcomes and Measures: The primary outcome was ischemic cholangiopathy (IC). Secondary end points included primary nonfunction (PNF), early allograft dysfunction (EAD), biliary anastomotic strictures, posttransplant length of stay (LOS), and patient and graft survival. Results: A total of 242 cDCD livers were included in this study: 136 recovered by SRR and 106 recovered by NRP (TA-NRP, 79 and A-NRP, 27). Median (IQR) NRP and SRR donor age was 30.5 (22-44) years and 36 (27-49) years, respectively. Median (IQR) posttransplant LOS was significantly shorter in the NRP cohort (7 [5-11] days vs 10 [7-16] days; P < .001). PNF occurred only in the SRR allografts group (n = 2). EAD was more common in the SRR cohort (123 of 136 [56.1%] vs 77 of 106 [36.4%]; P = .007). Biliary anastomotic strictures were increased 2.8-fold in SRR recipients (7 of 105 [6.7%] vs 30 of 134 [22.4%]; P = .001). Only SRR recipients had IC (0 vs 12 of 133 [9.0%]; P = .002); IC-free survival by Kaplan-Meier was significantly improved in NRP recipients. Patient and graft survival were comparable between cohorts. Conclusion and Relevance: There was comparable patient and graft survival in liver transplant recipients of cDCD donors recovered by NRP vs SRR, with reduced rates of IC, biliary complications, and EAD in NRP recipients. The feasibility of A-NRP and TA-NRP implementation across multiple US transplant centers supports increasing adoption of NRP to improve organ use, access to transplant, and risk of wait-list mortality.

Assessment of olfactory recovery after COVID-19: cross-sectional study.

OBJECTIVE: This study aimed to evaluate recovery patterns of olfactory dysfunction among recovered COVID-19 patients, both subjective and objective, and correlate this recovery to the severity of the disease. METHODS: The study recruited 200 patients and assigned them to two equal groups, one of them was a control group. The olfactory function of the study group was assessed via subjective and objective methods at baseline and then monthly for three months, with changes in smell function reported at each visit. These patients underwent chemosensory testing using the Sniffin' Sticks test and completed the validated Arabic version of the Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS). RESULTS: Olfactory dysfunction occurred on the first day of COVID-19 symptoms in 37% of participants. Subjective reports suggested smell recovery in 55% after 3 months, but Sniffin' Sticks showed only 1% with normal function, indicating persistent deficits in others. This study revealed smell recovery for 93% of participants (median 14 days), with most (58%) recovering within 2 weeks. No significant links were found between demographics, COVID-smell loss timing, and recovery speed. CONCLUSION: Three months after COVID-19, many patients perceive smell recovery, but objective tests reveal shockingly high rates of persistent dysfunction. Further follow-up with objective tests is vital to assess the true burden and potential long-term effects of smell loss.

Dermoscopy aids in lesion selection for microbiological and histopathological assessment of mycetoma.

Mycetoma, a chronic granulomatous infection of the skin and the subcutaneous tissue, is characterized by discharge of exudate containing grains. This report illustrates the importance of dermoscopy in selecting lesions for both microbiological and histopathological assessment, which are considered the gold standard of diagnosis in mycetoma.

Intra-oral Drainage of Submandibular Abscess: A Minimally Invasive Technique. A Prospective Study.

PURPOSE: To evaluate the efficacy of intraoral drainage of isolated submandibular space abscess as a minimally invasive surgical technique compared to the standard trans-cervical approach. PATIENTS AND METHODS: This prospective study included 40 subjects with isolated submandibular space abscesses. They were randomly divided into 2 equal groups: trans-cervical surgical drainage (group A) and intra-oral surgical drainage (group B). The included data were demographics, repeated surgery requirement, postsurgical hospitalization duration, formation of scar, and complications. RESULTS: Intraoral drainage (Group B) reduced the mean operative time by 15.25 min (P < 0.001) compared with trans-cervical incision (Group A). No considerable difference was found between the 2 groups in regarding hospitalization postoperatively. No weakness in marginal mandibular nerve was found in both groups. Three patients only have a cervical scar in a group (B) who required external drainage due to recollection. No recurrence was detected in a group (A). CONCLUSION: The current study demonstrated that isolated submandibular abscesses can be successfully managed with an intraoral drainage modality, and it is a better option than the trans-cervical approach regarding better cosmetic outcome and shorter operative time.

Exception Policy Change Increased the Simultaneous Kidney-Liver Transplant Probability of Polycystic Disease in the Centers With High Median MELD at Transplantation.

BACKGROUND: In 2019, Organ Procurement and Transplantation Network/United Network for Organ Sharing changed the exception policy for liver allocation to the median model for end-stage liver disease at transplantation (MMaT). This study evaluated the effects of this change on-waitlist outcomes of simultaneous liver-kidney transplantation (SLKT) for patients with polycystic liver-kidney disease (PLKD). METHODS: Using the Organ Procurement and Transplantation Network/United Network for Organ Sharing registry, 317 patients with PLKD listed for SLKT between January 2016 and December 2021 were evaluated. Waitlist outcomes were compared between prepolicy (Era 1) and postpolicy (Era 2) eras. RESULTS: One-year transplant probability was significantly higher in Era 2 than in Era 1 (55.7% versus 37.9%; P  = 0.001), and the positive effect on transplant probability of Era 2 was significant after risk adjustment (adjusted hazard ratio, 1.76; 95% confidence interval, 1.22-2.54; P  = 0.002 [ref. Era 1]), whereas waitlist mortality was comparable. Transplant centers were separated into the high and low MMaT groups with a score of 29 (median MMaT) and transplant probability in each group between eras was compared. In the high MMaT transplant centers, the 1-y transplant probability was significantly higher in Era 2 (27.5% versus 52.4%; P  = 0.003). The positive effect remained significant in the high MMaT center group (adjusted hazard ratio, 2.79; 95% confidence interval, 1.43-5.46; P  = 0.003 [ref. Era 1]) but not in the low MMaT center group. Although there was a difference between center groups in Era 1 ( P  = 0.006), it became comparable in Era 2 ( P  = 0.54). CONCLUSIONS: The new policy increased 1-y SLKT probability in patients with PKLD and successfully reduced the disparities based on center location.

Acetylated oligopeptide and N-acetylcysteine protect against iron overload-induced dentate gyrus hippocampal degeneration through upregulation of Nestin and Nrf2/HO-1 and downregulation of MMP-9/TIMP-1 and GFAP.

Iron accumulation in the brain causes oxidative stress, blood-brain barrier (BBB) breakdown, and neurodegeneration. We examined the preventive effects of acetylated oligopeptides (AOP) from whey protein on iron-induced hippocampal damage compared to N-acetyl cysteine (NAC). This 5-week study used 40 male albino rats. At the start, all rats received 150 mg/kg/day of oral NAC for a week. The 40 animals were then randomly divided into four groups: Group I (control) received a normal diet; Group II (iron overload) received 60 mg/kg/day intraperitoneal iron dextran 5 days a week for 4 weeks; Group III (NAC group) received 150 mg/kg/day NAC and iron dextran; and Group IV (AOP group) received 150 mg/kg/day AOP and iron dextran. Enzyme-linked immunosorbent assay, spectrophotometry, and qRT-PCR were used to measure MMP-9, tissue inhibitor metalloproteinase-1 (TIMP-1), MDA, reduced glutathione (GSH) levels, and nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) gene expression. Histopathological and immunohistochemical detection of nestin, claudin, caspase, and GFAP was also done. MMP-9, TIMP-1, MDA, caspase, and GFAP rose in the iron overload group, while GSH, Nrf2, HO-1, nestin, and claudin decreased. The NAC and AOP administrations improved iron overload-induced biochemical and histological alterations. We found that AOP and NAC can protect the brain hippocampus from iron overload, improve BBB disruption, and provide neuroprotection with mostly no significant difference from healthy controls.

Pharmacogenetic study of phosphatase and tensin homolog polymorphism (rs701848) in childhood epilepsy: relation to circulating Wnt signaling.

OBJECTIVE: The present study aimed at evaluating the potential contribution of Phosphatase and Tensin Homolog (PTEN) and its gene polymorphism (PTEN rs701848 T/C) in relation to Wingless/integrase-1 (Wnt) signaling in childhood epilepsy and the impact of antiepileptic medications on their serum levels. METHODS: This study included 100 children with epilepsy (50 pharmacoresistant and 50 pharmacoresponsive) and 50 matched controls. All subjects had their genotypes for the PTEN rs701848T/C polymorphism assessed using TaqManTM assays and real-time PCR. By using the sandwich ELISA technique, the blood concentrations of PTEN and Wnt3a were measured. RESULTS: Serum Wnt3a levels in epileptic patients were significantly higher than in the control group, p < 0.001. Children with epilepsy who received oxcarbazepine had considerably lower serum Wnt3a levels than those who didn't, p < 0.001.With an AUC of 0.71, the cutoff value for diagnosing epilepsy as serum Wnt3a > 6.2 ng/mL has a sensitivity of 55% and a specificity of 80%. When compared to controls, epileptic children had considerably more (TT) genotype and less (TC and CC) genotypes, p < 0.05 for all. Epileptic children had significantly higher (T) allele frequency than controls, p = 0.006 with OR (95%CI) = 1.962(1.206-3.192). Pharmacoresistant epileptic children had significantly higher (TT) genotype compared to pharmacoresponsive type (p = 0.020). CONCLUSION: We originally found a strong association between PTEN rs701848 T/C and childhood epilepsy, in particular pharmacoresistant type. Serum Wnt3a levels increased in epilepsy, but were not significantly different between different alleles of PTEN. In pharmaco-responsive children Wnt3a levels differed significantly between the different PTEN genotypes. Antiepileptics may affect Wnt3a levels.

Antiapoptotic and chemotaxis-stimulating effects of poly (D, L-lactide-co-glycolide)-chitosan and whey proteins against aflatoxicosis-induced splenic and thymic atrophy.

BACKGROUND: Aflatoxin B (AFB) induces toxicological effects on the liver and immune organs. The whey proteins can modulate the immune response during aflatoxicosis. Our work evaluates the novel polylactic acid-glycolic acid-chitosan-encapsulated bovine and camel whey proteins against AFB-induced thymic and splenic atrophy in rats. METHODS AND RESULTS: Seventy adult male Wister albino rats were divided into a control healthy group (G1) and six AFB1-intoxicated groups (G2-G7). One of the following supplements: distilled water, camel whey proteins (CWP), bovine whey proteins, poly (D, L-lactide-co-glycolide) (PLGA)- chitosan-loaded with camel whey protein microparticles (CMP), PLGA-chitosan loaded with bovine whey protein microparticles (BMP), and PLGA-chitosan nanoparticles were administered as prophylactic supplements to AFB1-intoxicated groups. The AFB-treated group showed significantly higher hepatic levels of oxidative stress and lower levels of antioxidants. In the aflatoxicated group, atrophy of the splenic lymphatic nodules and disfigurement in the organisation with an apparent decrease in the thickness of the cortex in the thymus were observed, as well as a decrease in splenic and thymic CD4+T and CD8+T lymphocytes. Moreover, CXCL12 levels were downregulated, whereas tumour necrosis factor-alpha, nuclear factor kappa B, and cleaved caspase-3 levels were upregulated. CWP, BMP, and CMP supplements markedly decreased oxidative stress, inflammation, and apoptosis, as well as significantly raised CXCL12, CD4+T, and CD8+T cells. CONCLUSIONS: The CWP, BMP, and CMP supplements rescue the liver and immune tissues from the toxic effects of AFB through their antioxidant, antiapoptotic, anti-inflammatory, and chemotaxis-enhancing roles.

Incidence of Post Total Laryngectomy Hypothyroidism: Effects of Thyroid Gland Surgery and Post-Operative Radiotherapy.

To record the incidence of hypothyroidism in patients after total laryngectomy, whether with or without postoperative radiation therapy and to analyze the effect of hemithyroidectomy for the development of hypothyroidism. A retrospective study included patients who underwent total laryngectomy (with or without hemithyroidectomy) between 2018 and 2021 for laryngeal carcinoma and/or received postoperative radiotherapy. Thirty-six (45%) of the 80 enrolled patients developed hypothyroidism after a median follow-up of 16 months. In this study, adjuvant radiation and central neck dissection were found to be significantly linked with developing post-operative hypothyroidism (p values: 0.001, 0.007, respectively). The incidence of hypothyroidism in patients treated for laryngeal carcinoma is high, especially after combination treatment of surgery and radiotherapy.

Assessment of the Safety and Effectiveness of Colorectal Robotic-Assisted Surgery: The First 50 Consecutive Cases at a Single Centre.

BACKGROUND: Colorectal robotic-assisted-surgery (RAS) is a novel technology with scarce real-world evidence. The aim of this retrospective review was to ascertain the safety and effectiveness of colorectal RAS. METHODS: The da Vinci® Xi™ robot system (Intuitive Surgical, Inc., Sunnyvale, CA, USA) was used to perform the first 50 colorectal resections in our centre. Outcomes regarding safety and efficacy were analysed and learning curves (LC) were plotted using RStudio. RESULTS: The median patient age and BMI were 65 years (IQR, 50.25-76.5) and 28.3kg/m2 (IQR, 25.2-30.7), respectively, and 27 patients were female. Malignancy (66%) followed by rectal prolapse (18%) was the most frequent diagnosis, and all malignant tumours were completely resected. High anterior resection was the most frequently performed operation (36%). The median operative time was 256.5 minutes (IQR, 202.2-332.8). Twenty-seven patients had anastomosis (54%), a stoma was formed in 7 (14%) and 7 anastomoses required defunctioning loop ileostomy (14%). Two unexpected intra-operative events occurred, and neither required conversion to an open procedure. Thirty-eight complications occurred in 21 patients, and most were minor by the Clavien-Dindo classification: CD 1 (17, 44.7%) or 2 (11, 28.9%). Moreover, 5 patients developed an anastomotic leak (14.7%), 5 developed infections (10%), 2 required transfusions (4%) and 3 needed re-operation (6%). There was no 30-day mortality and the readmission rate was 8%. The median length of stay in hospital was 6 days (IQR,4-8). All resections, except for low anterior resections, resulted in a significantly longer stay compared to rectopexies. Finally, projections from LCs indicated that outcome optimization can be achieved after experience with 33-39 cases. CONCLUSIONS: Colorectal RAS in our centre was both safe and effective. In the initial 50 cases, there was no 30-day mortality and no need for conversion to an open surgery. The readmission and complication (>CD 2) rates were 8% and 20%, respectively.

Clinical and Prognostic Biomarker Value of Blood-Circulating Inflammatory Cytokines in Hepatocellular Carcinoma.

INTRODUCTION: Circulating inflammatory cytokines play critical roles in tumor-associated inflammation and immune responses. Recent data have suggested that several interleukins (ILs) mediate carcinogenesis in hepatocellular carcinoma (HCC). However, the predictive and prognostic value of circulating ILs is yet to be validated. Our study aimed to evaluate the association of the serum ILs with overall survival (OS) and clinicopathologic features in a large cohort of HCC patients. METHODS: We prospectively collected data and serum samples from 767 HCC patients treated at the University of Texas MD Anderson Cancer Center between 2001 and 2014, with a median follow-up of 67.4 months (95% confidence interval [CI]: 52.5, 83.3). Biomarker association with OS was evaluated by the log-rank method. RESULTS: The median OS in this cohort was 14.2 months (95% CI: 12, 16.1 months). Clinicopathologic features were more advanced, and OS was significantly inferior in patients with high circulating levels of IL1-R1, IL-6, IL-8, IL-10, IL-15, IL-16, and IL-18. CONCLUSION: Our study shows that several serum IL levels are valid prognostic biomarker candidates and potential targets for therapy in HCC.

Chromatographic reversed HPLC and TLC-densitometry methods for simultaneous determination of serdexmethylphenidate and dexmethylphenidate in presence of their degradation products-with computational assessment.

Two Chromatographic methods have been established and optimized for simultaneous determination of serdexmethylphenidate (SER.DMP) and dexmethylphenidate (DMP) in the presence of their degradation products. The first method is a reversed phase high performance liquid chromatography with diode array detection (HPLC-DAD). Isocratic separation was carried out on Waters X-bridge Shield RP18 column (150×3.9×5 µm particle size) using a mixture of 5 mM phosphate buffer (pH 5.5): acetonitrile (40:60, v/v) as a mobile phase, flow rate 1 mL/min and detection at 220 nm. The second method is a thin-layer chromatography (TLC)-densitometry method using methanol: chloroform (70:30, v/v) as a mobile phase and UV scanning at 220 nm. In HPLC method, the linearity range of SER.DMP was (2.5-25 µg/mL); with LOD (0.051 µg/mL) and LOQ (0.165 µg/mL) while for DMP was (2.5-25 µg/mL); with LOD and LOQ of (0.098 µg/mL) and (0.186 µg/mL), respectively. For TLC method the sensitivity range of SER.DMP was (5-25 µg/mL), LOD was (0.184 µg/spot), while LOQ was (0.202 µg/ spot) whereas for DMP the sensitivity range was (5-25 µg/mL) with LOD of (0.115 µg/ spot) and LOQ of (0.237 µg/ spot), respectively. SER.DMP was found to be equally labile to acidic and alkaline hydrolysis, whereas DMP was sensitive to acidic hydrolysis only. Both drugs were successfully determined in presence of acidic and basic degradants by the two developed methods (stability indicating assay method). Chromatographic separation of the degradation products was carried out on TLC aluminum silica plates 60 F254, as a stationary phase, using methanol: dichloroethane: acetonitrile (60:20:20 v/v), as a mobile phase. The degradation pathway was confirmed using TLC, IR, 1H-NMR and mass spectroscopy; moreover, the separation power was correlated to the computational results by applying molecular dynamic simulation. The developed methods were validated according to the International Conference on Harmonization (ICH) guidelines demonstrating good accuracy and precision. They were successfully applied for quantitation of SER.DMP and DMP in pure and capsule forms. The results were statistically compared with those obtained by the reported method in terms of accuracy, precision and robustness, and no significant difference was found.

Chronomodulated Administration of Chemotherapy in Advanced Colorectal Cancer: A Systematic Review and Meta-Analysis.

In this systematic review, the efficacy and safety of chronomodulated chemotherapy, defined as the delivery of chemotherapy timed according to the human circadian rhythm, were assessed and compared to continuous infusion chemotherapy for patients with advanced colorectal cancer. Electronic English-language studies published until October 2020 were searched. Randomised controlled trials (RCTs) comparing chronomodulated chemotherapy with non-chronomodulated (conventional) chemotherapy for the management of advanced colorectal cancer were included. The main outcomes were the objective response rate (ORR) and system-specific and overall toxicity related to chemotherapy. Electronic databases including Ovid Medline, Ovid Embase, Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Review were searched. In total, seven RCTs including 1,137 patients were analysed. Males represented 684 (60%) of the study population. The median age was 60.5 (range = 47.2-64) years. There was no significant difference between chronomodulated and conventional chemotherapy in ORR (risk ratio (RR) = 1.15; 95% confidence interval (CI) = 0.87-1.53). Similarly, there was no significant difference in gastrointestinal toxicity under the random effect model (RR = 1.02; 95% CI = 0.68-1.51). No significant difference was found regarding neurological and skin toxicities (RR = 0.64, 95% CI = 0.32-1.270 and RR = 2.11, 95% CI = 0.33-13.32, respectively). However, patients who received chronomodulated chemotherapy had less haematological toxicity (RR = 0.36, 95% CI = 0.27-0.48). In conclusion, there was no overall difference in ORR or haematologic toxicity between chronomodulated and non-chronomodulated chemotherapy used for patients with advanced colorectal cancer. Chronomodulated chemotherapy can be considered in patients at high risk of haematological toxicities.

Acetylated Oligopeptide and N-acetyl cysteine Protected Against Oxidative Stress, Inflammation, Testicular-Blood Barrier Damage, and Testicular Cell Death in Iron-Overload Rat Model.

Multiple organs, including the testes, are damaged by iron overload. It has been shown that N-acetyl cysteine (NAC) influences oxidative stress in iron overload. The present study aimed to evaluate the roles of acetylated peptide (AOP) and NAC in the inhibition of iron-overload induced-testicular damage. At the beginning of the experiment, NAC (150 mg /kg) was given for a week to all 40 rats. Then, four groups were formed by dividing the animals (10 rats/group). Group I included healthy control rats. Group II (iron overload) was given intraperitoneal iron dextran (60 mg/kg/day) 5 days a week for 4 weeks. Group III (NAC) was given NAC orally at a dose of 150 mg/kg/day for 4 weeks in addition to iron dextran. Group IV (AOP) was given AOP orally at a dose of 150 mg/kg/day for 4 weeks besides iron dextran. When the experiment time was over, testosterone serum level, testicular B cell lymphoma-2 (BCL-2) and protein kinase B (PKB) protein levels, nuclear factor kappa-B (NF-κB), and Beclin1 mRNA expression levels, and malondialdehyde (MDA), and reduced glutathione (GSH) were determined by ELISA, quantitative reverse transcription-PCR, and chemical methods. Finally, histopathological examinations and immunohistochemical detection of claudin-1 and CD68 were performed. The iron overload group exhibited decreased testosterone, BCL-2, PKB, claudin-1, and GSH and increased MDA, NF-κB, Beclin1, and CD68, while both NAC and AOP treatments protected against the biochemical and histopathological disturbances occurring in the iron overload model. We concluded that NAC and AOP can protect against testes damage by iron overload via their antioxidant, anti-inflammatory, antiapoptotic, and ant-autophagic properties. The NAC and AOP may be used as preventative measures against iron overload-induced testicular damage.

Cytotoxic n-Hexane Fraction of the Egyptian Pteris vittata Functions as Anti-breast Cancer Through Coordinated Actions on Apoptotic and Autophagic Pathways.

We investigated the possible anticancer mechanisms of Pteris vittata [PV] n-hexane extract on MCF-7 [breast cancer cell line]. Cultured cell lines were treated with various concentrations of this extract ± Baf-A1 [autophagic inhibitor]. Cells' viability, apoptotic markers [caspase-7, Bax, and Bcl-2], autophagic markers [light chain 3 [LC-3] and P62/SQSTM1]], and the tumor suppressor P53 and its mRNA were checked by their corresponding methods. Treated cell lines showed significant concentration and time-dependent reductions in cell viability in response to PV-n-hexane extract and also exhibited a concomitant induction of apoptosis [increased chromatin condensation, nuclear fragmentation, and pro-apoptotic Bax, and cleaved caspase-7 levels while decreased Bcl-2 levels] and autophagy [increased autophagosomes vacuoles, and LC3B II levels while decreased P62/SQSTM1 levels]. Moreover, PV-n-hexane extract-treated cells showed significant increases in the P53 and its mRNA levels. The addition of Baf-A1 reversed the PV-n-hexane extract autophagic effects and increased apoptotic cell percentage with a much increase in the cleaved caspase-7 and P53 protein and its mRNA levels. We concluded that the PV-n-hexane extract exhibits cytotoxic effects on the MCF-7 cell line with significant reductions in cell viability and concomitant autophagy and apoptosis induction. Inhibition of autophagy in the PV-treated MCF-7 cells enhances apoptosis via a p35-dependent pathway.

Suggested Guidelines for the Treatment of Mycosis Fungoides in Countries with Limited Resources.

The treatment options for mycosis fungoides (MF) have been expanding but unfortunately many of the currently used treatment modalities are unavailable in Egypt and other African/Arab countries. In addition, there is a lack of consensus on the treatment of hypopigmented MF (HMF), which is a frequently encountered variant in our population. We aimed to develop regional treatment guidelines based on the international guidelines but modified to encompass the restricted treatment availability and our institutional experience. Special attention was also given to studies conducted on patients with skin phototype (III-IV). Treatment algorithm was formulated at Ain-Shams cutaneous lymphoma clinic through the collaboration of dermatologists, haematologists, and oncologists. Level of evidence is specified for each treatment option. For HMF, phototherapy is recommended as a first line treatment, while low-dose methotrexate is considered a second line. For early classical MF, we recommend Psoralen-ultraviolet A (PUVA), which is a well-tolerated treatment option in dark phenotype. Addition of either retinoic acid receptor (RAR) agonist and/or methotrexate is recommended as a second line. Total skin electron beam (TSEB) is considered a third-line option. For advanced stage, PUVA plus RAR agonist and/or methotrexate is recommended as first line, TSEB or monochemotherapy is considered a second line option. Polychemotherapy is regarded as a final option. All patients with complete response (CR) enter a maintenance and follow-up schedule. We suggest a practical algorithm for the treatment of MF for patients with dark phenotype living in countries with limited resources.

Assessment of Occult Nodal Micrometastases to the Clinically Negative Contralateral Neck in Locally Advanced Supraglottic Squamous Cell Carcinoma.

The aim of this study is  to study the incidence of occult nodal micrometastases (ONM) in the contralateral neck and compare it to the laterality of the primary tumor. Retrospective analysis of the medical records of patients with locally advanced supraglottic squamous cell carcinoma and Clinically negative contralateral neck (cN0-CLN) - who had concurrent total laryngectomy and bilateral neck dissection as their primary treatment at the Otolaryngology Department, Al Kas Al Ainy School of Medicine-Cairo University between 2015 and 2020 - was conducted. Patients were divided into 3 groups according to the extent of the primary tumor. 28 patients met the inclusion criteria. Patients with well-lateralized tumors were 14 (Group A), tumors abutting the midline were 4 (Group B) and tumors significantly involving the contralateral side were 14 (Group C). There was no statistically significant difference in age of patients among the three groups. Eleven patients had cervical lymphadenopathy in the final pathology reports. Seven patients had ONM, all of whom were among group C patients (7/14; 50%). The degree of tumor differentiation was not associated with the presence of ONM. Treatment of the cN0-CLN is justified in locally advance supraglottic carcinoma significantly crossing the midline. The total number of patients with ONM in the cN0-CLN exceeds the threshold for observation, however the authors could not recommend or refute the practice of routine prophylactic treatment of the cN0-CLN as none of the patients-in this study-with well-lateralized tumors or tumors just abutting the midline showed ONM.

Liver Transplantation as a New Standard of Care in Patients With Perihilar Cholangiocarcinoma? Results From an International Benchmark Study.

OBJECTIVE: To define benchmark values for liver transplantation (LT) in patients with perihilar cholangiocarcinoma (PHC) enabling unbiased comparisons. BACKGROUND: Transplantation for PHC is used with reluctance in many centers and even contraindicated in several countries. Although benchmark values for LT are available, there is a lack of specific data on LT performed for PHC. METHODS: PHC patients considered for LT after Mayo-like protocol were analyzed in 17 reference centers in 2 continents over the recent 5-year period (2014-2018). The minimum follow-up was 1 year. Benchmark patients were defined as operated at high-volume centers (≥50 overall LT/year) after neoadjuvant chemoradiotherapy, with a tumor diameter <3 cm, negative lymph nodes, and with the absence of relevant comorbidities. Benchmark cutoff values were derived from the 75th to 25th percentiles of the median values of all benchmark centers. RESULTS: One hundred thirty-four consecutive patients underwent LT after completion of the neoadjuvant treatment. Of those, 89.6% qualified as benchmark cases. Benchmark cutoffs were 90-day mortality ≤5.2%; comprehensive complication index at 1 year of ≤33.7; grade ≥3 complication rates ≤66.7%. These values were better than benchmark values for other indications of LT. Five-year disease-free survival was largely superior compared with a matched group of nodal negative patients undergoing curative liver resection (n=106) (62% vs 32%, P <0.001). CONCLUSION: This multicenter benchmark study demonstrates that LT offers excellent outcomes with superior oncological results in early stage PHC patients, even in candidates for surgery. This provocative observation should lead to a change in available therapeutic algorithms for PHC.