Effects of neoadjuvant chemotherapy vs chemoradiotherapy in the treatment of esophageal adenocarcinoma: A systematic review and meta-analysis.

BACKGROUND: Neoadjuvant therapy is an essential modality for reducing the clinical stage of esophageal cancer; however, the superiority of neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) is unclear. Therefore, a discussion of these two modalities is necessary. AIM: To investigate the benefits and complications of neoadjuvant modalities. METHODS: To address this concern, predefined criteria were established using the PICO protocol. Two independent authors performed comprehensive searches using predetermined keywords. Statistical analyses were performed to identify significant differences between groups. Potential publication bias was visualized using funnel plots. The quality of the data was evaluated using the Risk of Bias Tool 2 (RoB2) and the GRADE approach. RESULTS: Ten articles, including 1928 patients, were included for the analysis. Significant difference was detected in pathological complete response (pCR) [P < 0.001; odds ratio (OR): 0.27; 95%CI: 0.16-0.46], 30-d mortality (P = 0.015; OR: 0.4; 95%CI: 0.22-0.71) favoring the nCRT, and renal failure (P = 0.039; OR: 1.04; 95%CI: 0.66-1.64) favoring the nCT. No significant differences were observed in terms of survival, local or distal recurrence, or other clinical or surgical complications. The result of RoB2 was moderate, and that of the GRADE approach was low or very low in almost all cases. CONCLUSION: Although nCRT may have a higher pCR rate, it does not translate to greater long-term survival. Moreover, nCRT is associated with higher 30-d mortality, although the specific cause for postoperative complications could not be identified. In the case of nCT, toxic side effects are suspected, which can reduce the quality of life. Given the quality of available studies, further randomized trials are required.

Intravitreal Aflibercept for Neovascular Age-Related Macular Degeneration Beyond One Year of Treatment: AZURE, a Randomized Trial of Treat-and-Extend vs. Fixed Dosing.

INTRODUCTION: AZURE was a 76-week, randomized, open-label, parallel-group, phase IIIb noninferiority study comparing the efficacy and safety of intravitreal aflibercept (IVT-AFL) in a treat-and-extend (T&E) regimen with fixed dosing in patients with neovascular age-related macular degeneration (nAMD) previously receiving IVT-AFL for ≥ 1 year. METHODS: Patients were aged ≥ 51 years and had completed ≥ 1 year of IVT-AFL treatment prior to enrollment (IVT-AFL once per month [- 1 or + 2 weeks] for 3 months followed by IVT-AFL every 2 months [6-12 weeks]). Patients were randomly assigned (1:1) to receive IVT-AFL 2 mg in either a T&E (minimum treatment interval of 8 weeks with no upper limit, adjusted according to functional and anatomic outcomes, as assessed by the investigator; n = 168), or a fixed dosing regimen (treatment every 8 weeks [± 3 days]; n = 168). The primary endpoint was best-corrected visual acuity (BCVA) change from baseline to week (W) 52. The key secondary endpoint was the proportion of patients maintaining vision (< 15-letter loss) at W52. RESULTS: The full analysis set comprised 332 patients (T&E: n = 165; fixed dosing: n = 167). Mean BCVA change (baseline to W52) was - 0.3 ± 7.5 vs. - 0.5 ± 8.4 letters (T&E vs. fixed dosing; least-squares mean difference [95% CI]: 0.22 [- 1.51 to 1.96] letters; P < 0.0001 for noninferiority test [5-letter margin]). From baseline to W52, 95.2% (T&E) and 94.0% (fixed dosing) of patients maintained vision. Mean central subfield thickness change from baseline to W52 was - 24 ± 55 (T&E) and - 33 ± 47 (fixed dosing) µm. Last treatment interval to W76 was ≥ 12 weeks for 37.0% of T&E patients. No new safety signals were identified. CONCLUSION: IVT-AFL T&E can achieve similar functional and anatomic outcomes to fixed dosing every 8 weeks over 52 weeks in patients with nAMD who have completed ≥ 1 year of treatment, while reducing treatment burden. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02540954.

A Preliminary Study Indicating Improvement in the Median Survival Time of Glioblastoma Multiforme Patients by the Application of Deuterium Depletion in Combination with Conventional Therapy.

Glioblastoma multiforme (GBM) and malignant gliomas are the most common primary malignant brain tumors. Temozolomide (TMZ) chemotherapy plus radiation therapy (RT), admi-mistered after debulking surgery, increased the median survival time (MST) from 12.1 months with RT alone merely to 14.6 months, respectively. In this study, the actions of deuterium-depleted water (DDW) on the survival of GBM patients who also received conventional therapies was investigated. Without changing the conventional treatment, the daily fluid intake of the patients was wholly replaced with DDW in 1.5-2 L per day volume to reduce the D concentration in their bodies. The primary endpoint was the MST. The 55 patients involved in this study, who received conventional treatment and consumed DDW, showed a longer MST (30 months) compared to the historical control (12.1-14.6 months). There was a massive difference between the two genders in the calculated MST values; it was 25 months in the male subgroup (n = 33) and 42 months in the female subgroup (n = 22), respectively. The MST was 27 months without TMZ treatment (38 patients) and 42 months in the TMZ-treated group (17 patients), respectively. For the selected 31 patients, who consumed DDW in the correct way in addition to their conventional treatments, their MST was calculated as 30 months. Within this group, the 20 subjects who had relapsed before DDW treatment had 30 months of MST, but in those 10 subjects who were in remission when DDW treatment started, their MST was 47 months. In the subgroup of patients who began their DDW treatment parallel with radiotherapy, their MST was again 47 months, and it was 25 months when their DDW treatment was started at 8 weeks or later after the completion of radiotherapy. Altogether, these survival times were substantially prolonged compared to the prospective clinical data of patients with primary GBM. Consequently, if conventional therapies are supplemented with D depletion, better survival can be achieved in the advanced stage of GBM than with the known targeted or combination therapies. Application of DDW is recommended in all stages of the disease before surgery and in parallel with radiotherapy, and repeated DDW courses are advised when remission has been achieved.

Faster recovery and bowel movement after early oral feeding compared to late oral feeding after upper GI tumor resections: a meta-analysis.

Background: There were more than 1 million new cases of stomach cancer concerning oesophageal cancer, there were more than 600,000 new cases of oesophageal cancer in 2020. After a successful resection in these cases, the role of early oral feeding (EOF) was questionable, due to the possibility of fatal anastomosis leakage. It is still debated whether EOF is more advantageous compared to late oral feeding. Our study aimed to compare the effect of early postoperative oral feeding and late oral feeding after upper gastrointestinal resections due to malignancy. Methods: Two authors performed an extensive search and selection of articles independently to identify randomized control trials (RCT) of the question of interest. Statistical analyses were performed including mean difference, odds ratio with 95% confidence intervals, statistical heterogeneity, and statistical publication bias, to identify potential significant differences. The Risk of Bias and the quality of evidence were estimated. Results: We identified 6 relevant RCTs, which included 703 patients. The appearance of the first gas (MD = -1.16; p = 0.009), first defecation (MD = -0.91; p < 0.001), and the length of hospitalization (MD = -1.92; p = 0.008) favored the EOF group. Numerous binary outcomes were defined, but significant difference was not verified in the case of anastomosis insufficiency (p = 0.98), pneumonia (p = 0.88), wound infection (p = 0.48), bleeding (p = 0.52), rehospitalization (p = 0.23), rehospitalization to the intensive care unit (ICU) (p = 0.46), gastrointestinal paresis (p = 0.66), ascites (p = 0.45). Conclusion: Early postoperative oral feeding, compared to late oral feeding has no risk of several possible postoperative morbidities after upper GI surgeries, but has several advantageous effects on a patient's recovery. Systematic Review Registration: identifier, CRD 42022302594.

[Robotic-assisted laparoscopic Heller-Dor's cardiomyotomy and fundoplication for achalasia]. / Achalasia miatt végzett robotasszisztált laparoszkópos cardiomyotomia és fundoplicatio (Heller­Dor-mutét).

INTRODUCTION: The outcomes of surgical interventions for achalasia treatment improved with the advent of minimally invasive surgery. Robotic-assisted Heller-Dor's (RAHD) procedure established over the last years, provides important advantages to surgeons, such as binocular three-dimensional vision and improvement of fine motor control. METHOD: Between October and December of 2022, first in Hungary, 3 patients (37-year-old man, 55- and 72-year-old women) underwent RAHD procedure for achalasia at the Clinical Centre of the University of Pécs using the da Vinci Xi system. RESULTS: RAHD procedure was feasible without any particular problems and the postoperative course of all three patients was uneventful. The operation times were 198, 204 and 238 minutes, including 23, 19 and 14 minutes for the setup time of the robot. By the last patient, due to an accompanying hiatal hernia, an additional hiatal reconstruction was also performed. In the first 2 cases, the patients were discharged on the 4th postoperative day, while in the last case, with the additional hiatal reconstruction, the patient was emitted on the 6th postoperative day. DISCUSSION: There are several published studies about RAHD cardiomyotomy. The general conclusion is that, in experienced hands, RAHD procedure is easy to perform, ensures a meticulous esophageal and gastric myotomy, allowing to visualize and divide each muscle fiber with a significantly lower rate of mucosal perforations. However, by RAHD procedure, the overall costs are higher, including a longer operation time during the learning curve. At the same time, the avoidance of mucosal lacerations and their possible consequences has to be weighed against the higher overall costs. CONCLUSION: Laparoscopic cardiomyotomy is the first standard upper-gastrointestinal operation where a clear advantage of the use of a surgical robot has been proven. Thus, wherever this equipment is available, it should be preferred for this procedure. Orv Hetil. 2023; 164(14): 542-547.

Seven-year outcomes following intensive anti-vascular endothelial growth factor therapy in patients with exudative age-related macular degeneration.

BACKGROUND: Anti-vascular endothelial growth factor (VEGF) therapy is currently the most effective therapy of exudative age-related macular degeneration (AMD). The aim of this study was to assess long-term benefits of intensive aflibercept and ranibizumab anti-VEGF therapy in patients with exudative AMD. METHODS: Two clinical trial sites recruited their original subjects for a re-evaluation 7 years after the baseline visit of the phase-3 Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration (VIEW 2) trial. Forty-seven eyes of 47 patients with AMD originally treated with ranibizumab (14 eyes) or aflibercept (33 eyes) were included. RESULTS: Mean number of injections was 17.8 ± 3.0 during participation in the VIEW 2 trial. Fourteen of 47 (30%) eyes were given additional injections with a mean number of 5.7 ± 4.5 after the trial. At a mean follow-up time of 82 ± 5 months best corrected visual acuity (BCVA) remained stable or improved (≤ 10 letters lost) in 55% of patients in the entire study population, in 43% in the ranibizumab group and in 60% in the aflibercept group. In both groups combined mean BCVA was 54 ± 13 letters at baseline, 65 ± 17 letters at the end of the intensive phase and 45 ± 25 letters at the end of follow-up. There was no statistically significant difference in BCVA between the two groups at baseline (p = 0.88) and at the end of follow-up (p = 0.40). Macular atrophy was observed in 96% of eyes, average area was 7.22 ± 6.31 mm2 with no statistically significant difference between groups (p = 0.47). Correlation between BCVA at end-of-follow-up and the area of atrophy was significant (p < 0.001). At the end of follow-up, fluid was detected in 7 of 47 eyes (15%) indicating disease activity. CONCLUSION: Long-term efficacy of aflibercept and ranibizumab was largely consistent. Following a two-year intensive therapy with as-needed regimen, BCVA was maintained or improved in almost half of the patients and in the ranibizumab group and more than half of the patients in the aflibercept group with very few injections. In a remarkable proportion of eyes, BCVA declined severely which underlines the need for long-term follow-ups and may indicate a more prolonged intensive therapy. TRIAL REGISTRATIONS: VIEW 2 study: ClinicalTrials.gov ID: NCT00637377, date of registration: March 18, 2008. Long-term follow-up: IRB nr.: SE RKEB 168/2022, ClinicalTrials.gov ID: NCT05678517, date of registration: December 28, 2022, retrospectively registered.

[Complications of esophageal reconstruction]. / A nyelocsopótlás szövodményei.

Esophageal cancer is the most common cause of esophageal resections. Esophageal replacement is still a significant challenge for surgeons, because complications can be expected in over 50% and death also occurs between 4-7%. Complications can be divided into early and late categories and into general and specific complications. From a surgical point of view, early and late specific complications are the most important aspects. Between 1993 and 2012, 540 esophageal resections were performed due to malignant tumors at the Department of Surgery, Medical Center of the University of Pécs. Stomach was used for replacement in 445 cases, colon in 38 cases, and jejunum in 57 cases. The anastomosis with stomach replacement was located to the neck in 275 cases and to the thorax in 170 cases. The colon was pulled up to the neck in each case. There were 29 cases of free jejunal replacements located to the neck, and 28 cases with a Roux-loop reconstruction located to the thorax. In the case of gastric replacement, anastomotic insufficiency developed in 55 cases, graft necrosis occurred in 8 cases, and early anastomosis stricture developed in 30 cases. These numbers are 3 conduit necrosis and 2 strictures in cases of colonic replacements. There was one anastomosis failure in the case of a thoracic jejunum replacement. Also one conduit necrosis was observed in the free jejunal neck transplantation group. Among late special complications, dysphagia is the most important, the causes of which were found in the order of frequency: anastomotic stricture, conduit obstruction, peptic and ischemic stricture, foreign body, local recurrence, functional causes, new malignant tumor in the esophageal remnant after resection and malignant tumor emerging in the replaced organ. Causes may overlap each other, and their treatment may be conservative, endoscopic or surgical. Surgical treatment is usually the last option to restore the ability to swallow and can present a significant challenge even to experienced centers. Orv Hetil. 2023; 164(7): 243-252.

Female Sexual Dysfunction in Association with Sexual History, Sexual Abuse and Satisfaction: A Cross-Sectional Study in Hungary.

Female sexual dysfunction (FSD) has a negative impact on women's quality of life, self-esteem, and physical health. The aim of the present study was to explore the prevalence and the factors associated with FSD using an online questionnaire. A cross-sectional survey was conducted among young adults (18-35 years old) in Hungary using the DSM-5 criteria. The participants (n = 5942) were divided into three major groups: FSD (20.3%), an intermediate group (43.9%), and a control group (35.6%). Most of the women showing FSD were affected with female orgasmic disorder (9.2%) and genito-pelvic pain/penetration disorder (4.6%), while female sexual interest/arousal disorder was found in altogether 100 women (1.7%); 4.8% of women were affected by more than one definite disorder. The occurrence of female sexual dysfunction was related to the women's previous sexual history (first sexual experience, sexual education, early encounter with pornographic content, and sexual abuse), their self-satisfaction (with their own body, genitalia, and sexual attraction), and their sexual orientation. Sexual dysfunction showed a strong association with abuse, sexually transmitted diseases, and self-esteem. The present study identified the relationship between sexual dysfunctions and other health conditions, which can be the basis for some form of screening and early assistance programs for FSD.

Dysphagia After Esophageal Replacement and Its Treatment.

Dysphagia occurs temporarily or permanently following esophageal replacement in at least half of the cases. Swallowing disorder, in addition to severe decline in the quality of life, can lead to a deterioration of the general condition, which may lead to death if left untreated. For this reason, their early detection and treatment are a matter of importance. Between 1993 and 2012, 540 esophageal resections were performed due to malignant tumors at the Department of Surgery, Medical Center of the University of Pécs. Stomach was used for replacement in 445 cases, colon in 38 cases, and jejunum in 57 cases. The anastomosis with a stomach replacement was located to the neck in 275 cases and to the thorax in 170 cases. The colon was pulled up to the neck in each case. There were 29 cases of free jejunal replacements located to the neck and 28 cases with a Roux loop reconstruction located to the thorax. Based on the literature data and own experience, the following were found to be the causes of dysphagia in the order of frequency: anastomotic stenosis, conduit obstruction, peptic and ischemic stricture, foreign body, local recurrence, functional causes, new malignant tumor in the esophageal remnant, and malignant tumor in the organ used for replacement. Causes may overlap each other, and their treatment may be conservative or surgical. The causes of many dysphagic complications might be prevented by improving the anastomosis technique, by better preservation the blood supply of the substitute organ, by consistently applying a functional approach, and by regular follow-up.

Intraocular neutralizing antibodies against aflibercept in patients with age related macular degeneration.

PURPOSE: To detect immunoglobulins in aqueous humour of AMD patients after repeated administration of intravitreal aflibercept. PATIENTS AND METHODS: Twenty-one patients (age: 77.85 ± 9.21 years) previously treated with intravitreal aflibercept due to wet type age-related macular degeneration (AMD group) and 18 age-matched control subjects (age: 69.75 ± 12.67 years) were included in this study. Patients in the AMD group received a mean of 5 intravitreal injections (min: 1 max: 17) prior to the cataract surgery. Samples of aqueous humour (50 µl) were obtained by anterior chamber paracentesis as the first step of routine cataract surgery. The IgG content of the samples was analysed by an in-house developed ELISA system. RESULTS: A significant increase in nonspecific IgG levels in the AMD group was detected compared to the control group (13.37 ± 6.65 vs. 9.44 ± 6.55 µg/ml; p = 0.03). In 11 patients, intraocular anti-aflibercept immunoglobulins could be detected (0.05 ± 0.01 µg/ml) which was significantly higher than the limit of detection for anti-aflibercept (0.04 µg/ml; p = 0.001). No correlation was found between the number of injections or the type of CNV and the aqueous level of anti-aflibercept (r = 0.02; p = 0.95). CONCLUSION: According to our results, penetration of non-specific systemic antibodies through the impaired blood-retinal barrier is higher in patients with neovascular AMD than in subjects with an intact structural barrier. Evaluation of neutralizing antibodies to anti-VEGF agents in the aqueous humour can lead us to understanding tachyphylaxis and changes in intraocular immune mechanisms due to AMD.

Biosimilar SB11 versus reference ranibizumab in neovascular age-related macular degeneration: 1-year phase III randomised clinical trial outcomes.

BACKGROUND/AIMS: To provide longer-term data on efficacy, safety, immunogenicity and pharmacokinetics (PK) of ranibizumab biosimilar SB11 compared with the reference ranibizumab (RBZ) in patients with neovascular age-related macular degeneration (nAMD). METHODS: Setting: Multicentre. Design: Randomised, double-masked, parallel-group, phase III equivalence study. Patient population: ≥50 years old participants with nAMD (n=705), one 'study eye'. INTERVENTION: 1:1 randomisation to monthly intravitreal injection of 0.5 mg SB11 or RBZ. Main outcome measures: Visual efficacy endpoints, safety, immunogenicity and PK up to 52 weeks. RESULTS: Baseline and disease characteristics were comparable between treatment groups. Of 705 randomised participants (SB11: n=351; RBZ: n=354), 634 participants (89.9%; SB11: n=307; RBZ: n=327) completed the study until week 52. Previously reported equivalence in primary efficacy remained stable up to week 52 and were comparable between SB11 and RBZ. The adjusted treatment difference between SB11 and RBZ in full analysis set at week 52 of change from baseline in best-corrected visual acuity was -0.6 letters (90% CI -2.1 to 0.9) and of change from baseline in central subfield thickness was -14.9 µm (95% CI -25.3 to -4.5). The incidence of ocular treatment-emergent adverse events (TEAEs) (SB11: 32.0% vs RBZ: 29.7%) and serious ocular TEAE (SB11: 2.9% vs RBZ: 2.3%) appeared comparable between treatment groups, and no new safety concerns were observed. The PK and immunogenicity profiles were comparable, with a 4.2% and 5.5% cumulative incidence of antidrug antibodies up to week 52 for SB11 and RBZ, respectively. CONCLUSIONS: Longer-term results of this study further support the biosimilarity established between SB11 and RBZ.

Topical treatment of diabetic macular edema using dexamethasone ophthalmic suspension: A randomized, double-masked, vehicle-controlled study.

PURPOSE: To evaluate topical dexamethasone ophthalmic suspension OCS-01 (Oculis SA, Lausanne, Switzerland) in diabetic macular edema (DME). METHODS: This was a multicenter, double-masked, parallel-group, randomized, Phase 2 study. Patients aged 18-85 years with DME of <3 years duration, ETDRS central subfield thickness ≥ 310 µm by SD-OCT, and ETDRS letter score ≤ 73 and ≥ 24 in the study eye were randomized 2:1 to OCS-01 or matching vehicle, 1 drop 3 times/day for 12 weeks. Efficacy was evaluated as change from baseline to Week 12 of ETDRS letter score and central macular thickness (CMT). The primary analysis used a linear model with baseline ETDRS letters as a covariate, and missing data imputed using multiple imputation pattern mixture model techniques. Active treatment was considered superior to vehicle if the one-sided p-value was <0.15 and the difference in mean change from baseline in ETDRS letters was >0. RESULTS: Mean CMT showed a greater decrease from baseline with OCS-01 (N = 99) than vehicle (N = 45) at Week 12 (-53.6 vs -16.8 µm, p = 0.0115), with significant differences favouring OCS-01 from Weeks 2 to 12. OCS-01 was well-tolerated, and increased intraocular pressure was the most common adverse event. Mean change in ETDRS letter score from baseline to Week 12 met the p was +2.6 letters with topical OCS-01 and 1 letter with vehicle (p = 0.125). In a post-hoc analysis, there was a greater difference in patients with baseline BCVA ≤65 letters, the OCS-01 group improved 3.8 letters compared with 0.9 letters with vehicle. CONCLUSION: Topical OCS-01 was significantly more effective than vehicle in improving central macular thickness in patients with DME. Visual improvement was better in eyes with lower baseline vision.

Endoluminal Suture-technique for the Stomach Closure of an Experimental Model.

BACKGROUND/AIM: In the modern minimally invasive era, diagnostic and therapeutic endoscopic interventions are one of the most emerging fields. For the new operational techniques, it is a major aim to develop reliable instruments, such as suturing devices for flexible endoscopes. The aim of this study was to assess the feasibility of a safe and reproducible suturing technique with an endoluminal suturing device. MATERIALS AND METHODS: The evaluation of the technique was performed in twenty explanted special prepared porcine stomachs. Three different techniques were compared, single stitches, figure-of-eight, or Z-pattern and running sutures in terms of suturing time and bursting pressure. After verification of the reliability of the method, a 3 cm long full thickness incision on the stomach was closed with the endoscopic suturing device in four surviving animals. RESULTS: In our ex vivo studies, we have shown that the figure of 8 or Z- technique is the most optimal for stomach closure without considerable time-cost, thus this technique was chosen as the standard method for the in vivo study. The endoscopic stomach wall suturing was successful in all four cases, the postoperative period was uneventful and ended on the tenth postoperative day with autopsy. CONCLUSION: With the applied suturing device, the endoscopic suturing of the stomach is safe and reproducible, thus a human application may also be justified.

Atrophy of retinal vessels in neovascular age-related macular degeneration following long-term treatment with 20 intravitreal anti-VEGF injections.

BACKGROUND: The study aimed to evaluate the changes in retinal vascular density in exudative age-related macular degeneration (AMD) after long-term anti-VEGF treatment using optical coherence tomography angiography (OCT-A), and to compare these changes with the vascular density in AMD treated for one year and healthy eyes. METHODS: In our cross-sectional study OCT-A was performed on 60 eyes of 60 patients. Group AMD 20 × consisted of patients receiving long-term (minimum 20 injections) aflibercept therapy (n = 17), and Group AMD one year consisted of patients treated for one year with a treat & extend protocol (n = 25). The vascular density values obtained with OCT-A were compared with an age-matched control group of 18 healthy eyes. We examined the central retinal thickness (CRT), the vascular density of the fovea and parafovea in the superficial and deep retinal plexus, and evaluated the extent of the non-flow area and the foveal avascular zone (FAZ) on a 3 × 3 mm macular region. Kruskal-Wallis test was performed for statistical analysis. RESULTS: In Group AMD 20x, the vascular density of superficial retinal plexus in the fovea (p = 0.0022) and parafovea (p < 0.0001) was significantly lower compared to Group one year and control group. In the deep retinal plexus, vascular density in the fovea (p = 0.0033) was significantly lower in both AMD groups compared to the control group, with no difference in the parafoveal region (p = 0.0774). The extent of non-flow area (p = 0.0003) and FAZ (p = 0.0008) were significantly larger in both AMD groups compared to the control group. There was a significant difference in CRT between those treated for one year and control eyes (p = 0.0036). CONCLUSIONS: In our study, we demonstrated that macular vessel density was lower in the foveal area in the superficial retinal plexus in AMD patients after one year and long-term anti-VEGF treatment. These vascular density changes were absent in the parafoveal and whole areas of the deep retinal plexus. Our results indicate that long-term anti-VEGF treatment reduces the vascular density of the superficial retinal plexus to a greater extent compared to the deep retinal plexus.

Network meta-analysis of randomized controlled trials on esophagectomies in esophageal cancer: The superiority of minimally invasive surgery.

BACKGROUND: Previous meta-analyses, with many limitations, have described the beneficial nature of minimal invasive procedures. AIM: To compare all modalities of esophagectomies to each other from the results of randomized controlled trials (RCTs) in a network meta-analysis (NMA). METHODS: We conducted a systematic search of the MEDLINE, EMBASE, Reference Citation Analysis (https://www.referencecitationanalysis.com/) and CENTRAL databases to identify RCTs according to the following population, intervention, control, outcome (commonly known as PICO): P: Patients with resectable esophageal cancer; I/C: Transthoracic, transhiatal, minimally invasive (thoracolaparoscopic), hybrid, and robot-assisted esophagectomy; O: Survival, total adverse events, adverse events in subgroups, length of hospital stay, and blood loss. We used the Bayesian approach and the random effects model. We presented the geometry of the network, results with probabilistic statements, estimated intervention effects and their 95% confidence interval (CI), and the surface under the cumulative ranking curve to rank the interventions. RESULTS: We included 11 studies in our analysis. We found a significant difference in postoperative pulmonary infection, which favored the minimally invasive intervention compared to transthoracic surgery (risk ratio 0.49; 95%CI: 0.23 to 0.99). The operation time was significantly shorter for the transhiatal approach compared to transthoracic surgery (mean difference -85 min; 95%CI: -150 to -29), hybrid intervention (mean difference -98 min; 95%CI: -190 to -9.4), minimally invasive technique (mean difference -130 min; 95%CI: -210 to -50), and robot-assisted esophagectomy (mean difference -150 min; 95%CI: -240 to -53). Other comparisons did not yield significant differences. CONCLUSION: Based on our results, the implication of minimally invasive esophagectomy should be favored.

The Effect of Trimetazidine on Diathermy-related Thermic Injury of the Rat Liver.

BACKGROUND/AIM: Owing to new oncotherapy modalities, the importance of an R0 resection decreased in the last decade; however, liver metastasis of colorectal cancer significantly decreases survival. Furthermore, to prevent cardiovascular disease, more and more patients are treated with anti-ischemic drugs, which may influence oncologic treatments in such patients. This study aimed to examine the effect of Trimetazidine on liver surface injury after spray diathermy. MATERIALS AND METHODS: We performed standard liver resections with resection-margin spray coagulation in 36 rats on both liver lobes. In all procedures, a Pringle maneuver was performed on the right lobe, while on the left lobe, no vessel occlusion was applied. Half of the animals were on Trimetazidine therapy. In 12 animals, histologic samples were taken immediately after operation, while 12 animals were terminated 1 week later, and the remaining 12 animals 3 weeks later. After standard HE staining, histologic analysis was performed. RESULTS: When diathermy was used, a coagulation zone appeared. Destruction was slightly wider in case of Trimetazidine therapy (745.75 vs. 680.04 µm). In cases of 1-week-surviving animals, a necrotic zone was observed under the coagulated tissue, and a fibrotic zone appeared after 3 weeks. In TMZ medicated animals, the destruction zone was significantly thinner (645.08 vs. 893.76 µm; p<0.001) and the necrosis zone showed the same difference (2,430.05 vs. 3,238.45 µm; p<0.001). CONCLUSION: Administration of Trimetazidine can reduce the extent of thermic necrosis. Furthermore, a great effort should be applied to achieve R0 resection in patients on anti-ischemic therapy.

Results in Antireflux Surgery, an Analysis of Case-Controlled Cohorts versus Multicenter Studies and Meta-Analyses.

Introduction: With the advent of minimally invasive techniques, laparoscopic Nissen fundoplication and Toupet partial fundoplication have been very successful in the management of GERD. In the past 10 years, a number of very attractive new technologies have entered the market around therapeutic GERD-management such as Transoral Incisionless Gastroplication, other endoscopic plication techniques, and the implantation of the magnetic sphincter augmentation (MSA). These new technologies are excessively promoted by the respective companies, propagating their techniques as causing fewer side effects. The purpose of this paper is an overview on the successrates of these differently used techniques and technologies and, in addition, different study-designs. Methods: A literature review was performed searching for publications on laparoscopic fundoplication (LF), Transoral Incisionless Fundoplication (TIF), and laparoscopic MSA. The reported classified were separated according to their design into (group 1) large case-controlled series or comparative studies (n 100 cases) from high-volume centers and into (group 2) trials between different technologies of antireflux procedures, multicenter-studies, and meta-analyses of GERD-trials. Results: In total, 4030 abstract were screened according to the selected key words. Following the section criteria, 19 publications were selected and analyzed. Regarding group 1 and LF (selected studies 2565 patients), the morbidity ranged from 2.0-4.8 % of cases. With a follow-up time of 36-222 months most of these patients were followed 5 years. In group 2, more than 150 studies and several multicenter-registries were summarized in these 9 selected publications. The overall follow-up periods were substantially shorter with a range of 7-48 months. Conclusions: It can be concluded that special efforts in patient management in high volume centers and a vast experience may substantially contribute to excellent results for several antireflux techniques, which may reach a level of quality above results of registries and meta-analyses.

Changes in surgical principles as a result of modern, effective, perioperative treatments / A sebészeti elvek változása a modern, hatékony, perioperatív onkológiai kezelések következményeként

Oncology has evolved to a great extent over the last quarter of century. The significant success is multifactorial, including primary and secondary prevention, the development of diagnostics, new methods of chemo-and radiotherapy, and the integration of basic research results into practice. From the point of view of surgery, the establishing and widespread practical application of the principles of preoperative oncotherapy played a major role in this development. Between 1997 and 2005, 44 patients with gastric cancer and 102 patients with borderline resectable or irresectable esophageal cancer received perioperative treatment at the Department of Surgery of the University of Pecs. The response rate was above 50% in both groups and complete pathological remission was achieved in 3 patients with gastric cancer and 17 patients with esophageal cancer. Based on our own experience and literature data, the development of seven new principles in surgical oncology were observed as the result of a very successful preoperative oncologic treatment. The desired free resection margin was reduced to the millimeter dimension in many cancer cases. Thus so-called organ-preserving procedures were made possible. Regarding the prognosis, the stage after the treatment became determinant. Complete histopathological remission could also be achievable in patients with oligometastases. In the case of a complete remission, the watch and wait tactics emerged as an option. Along the preoperative treatment of resectable colorectal liver metastases, there is no need to strive for complete remission. The treatment order of the primary tumor and its metastases can be reversed. Based on the improving results of oncology treatments, a reduction in surgical activity in the treatment of cancer patients is expected.