The New Era of Total Neoadjuvant FLOT Therapy for Locally Advanced, Resectable Gastric Cancer: A Propensity-Matched Comparison With Standard Perioperative Therapy.

BACKGROUND: The FLOT 4-AIO trial established the docetaxel-based regimen's superiority over epirubicin-based triplet therapy in terms of survival rates and acceptable toxicity for locally advanced resectable gastric (LARGC). Yet, fewer than half of the patients achieved completion of eight prescribed FLOT cycles. We proposed that administering all FLOT cycles in the form of total neoadjuvant therapy may improve completion rates and downstaging. This study contrasted total neoadjuvant therapy (FLOT x8) with standard neoadjuvant therapy (FLOT 4+4) for patients LARGC adenocarcinoma who underwent curative resection with routine D2 lymphadenectomy, focusing on histopathological outcomes, toxicity, and survival outcomes. METHODS: We reviewed patients with histologically confirmed advanced clinical stage cT2 or higher, nodal positive stage (cN+), or both, with resectable gastric tumors and no distant metastases (January 2017 to July 2023). We divided patients into two groups, FLOT 4+4 and FLOT x8; FLOT 4+4 patients underwent four preoperative and four postoperative bi-weekly cycles of docetaxel, oxaliplatin, leucovorin, and fluorouracil, while FLOT x8 patients received all eight cycles preoperatively after a gradual practice change starting from January 2020. Propensity score matching adjusted for age, clinical stage, tumor location, and histology. RESULTS: Of the 77 patients in the FLOT x8 group, 37 were propensity-matched to an equal number in the FLOT 4+4 group. Demographics, duration of surgery, and hospital stay showed no significant differences between the groups. The FLOT x8 group exhibited a significantly higher all-cycle completion rate at 89.1% compared to FLOT 4+4's 67.6% (p < 0.01). Both groups demonstrated comparable hematological and non-hematological toxicity rates, Clavien-Dindo ≥ 3 complications, and CAP tumor regression grades. The mean number of harvested lymph nodes was 42.5 and 41.2 in the FLOT 4+4 and FLOT x8 groups, respectively. Similar rates of disease-free survival and overall survival were noted in both groups, despite a trend toward a higher pathological complete response rate, albeit not statistically significant (8.1% vs. 18.9%, p = 0.29), in the FLOT x8 group at a median follow-up of 36 months. CONCLUSION: Total neoadjuvant therapy with the FLOT x8 protocol corresponds to higher treatment completion rates, a safety profile similar to standard perioperative therapy, and a twofold increase in complete pathological response. Further research on long-term oncological outcomes is needed to confirm the effectiveness of total neoadjuvant therapy.

Reducing dehydration-induced readmissions post-colorectal surgery: the impact of a prevention bundle.

INTRODUCTION: Ileostomy, frequently created after colorectal resections, hinders the physiologic function of the colon and can lead to dehydration and acute kidney injury due to high stoma outputs. This study aimed to evaluate the effectiveness of preventive measures on ileostomy-induced dehydration and related readmissions in a high-volume unit. METHODS: In this prospective cohort study at a high-volume colorectal surgery department in Turkiye, the Prospective Ileostomy-induced Dehydration Prevention Bundle Project (PIDBP) was assessed from March 2021 to March 2022. The study enrolled patients undergoing colorectal surgery with ileostomy and involved comprehensive inpatient stoma care, education, and a structured post-discharge follow-up. The follow-up included the "Hydration follow-up scale" to monitor ileostomy output and related complications. The primary outcome was the readmission rate due to dehydration-related complications. The patients receiving the bundle intervention were compared with patients treated in the preceding year, focusing on the effectiveness of interventions such as dietary adjustments, fluid therapy, and pharmacological management. RESULTS: In the study, 104 patients were analyzed, divided into 54 pre-bundle and 50 bundle group patients, with no significant differences in patient characteristics. While the overall readmission rate due to dehydration was 12.5%, a significant reduction in dehydration-related readmissions was observed in the bundle group compared to the pre-bundle group (2% vs. 22%, p = 0.002). Univariate analysis identified high stoma output (> 800 ml/24 h) (p < 0.001), chronic renal failure (CRF) (p = 0.01), postoperative ileus (p = 0.03), higher ASA status (p = 0.04), extended hospital stays (p = 0.03), and small bowel resections (especially in J-pouch patients) (p < 0.001) as significant predictors of readmission. Multivariate analysis revealed that the mean ileostomy output before discharge was the sole significant predictor of dehydration-related readmission (OR 1.01), with an optimal cutoff of 877.5 ml/day identified with an area under the curve (AUC) of 0.947, demonstrating high sensitivity (92.3%) and specificity (86.8%) in predicting readmission risk. CONCLUSION: The Prospective Ileostomy-induced Dehydration Prevention Bundle Project significantly reduced readmission rates after colorectal surgery.

Reliability and validity of the Turkish version of the New Cleveland Clinic Colorectal Cancer Quality of Life Questionnaire.

PURPOSE: This study aims to adapt and validate the Cleveland Clinic Colorectal Cancer Quality of Life Questionnaire (CCF-CaQL) in Turkish, addressing the significant need for reliable, language-specific QoL measures for colorectal cancer (CRC) in Turkiye. This effort fills a critical gap in CRC patient care, enhancing both patient-provider communication and disease-specific QoL assessment. METHODS: The CCF-CaQL was translated into Turkish, verified for accuracy, and reviewed for clarity and relevance. Eligible patients who underwent colorectal surgery for cancer between July 2021 and July 2022 from six hospitals completed the CCF-CaQL and SF-36 questionnaires. For analysis, confirmatory factor analysis using Smart PLS 4 and descriptive statistics were employed. The questionnaire's reliability and validity were assessed using Cronbach alpha, composite reliability, and the heterotrait-monotrait (HTMT) ratio, along with multicollinearity checks and factor loadings. Nonparametric resampling was used for precise error and confidence interval calculations, and the Spearman coefficient and split-half method were applied for reliability testing. RESULTS: In the study involving 244 colorectal cancer patients, confirmatory factor analysis of the CCF-CaQL indicated effective item performance, with one item removed due to lower factor loading. The questionnaire exhibited high internal consistency, evidenced by a Cronbach alpha value of 0.909. Convergent validity was strong, with all average variance extracted (AVE) values exceeding 0.4. Discriminant validity was confirmed with HTMT coefficients below 0.9, and no significant multicollinearity issues were observed (VIF values < 10). Parallel testing with the SF-36 scale demonstrated moderate to very strong correlations, affirming the CCF-CaQL's comparability in measuring quality of life. CONCLUSION: The Turkish version of the CCF-CaQL was validated for assessing quality of life in colorectal cancer patients. This validation confirms its reliability and cultural appropriateness for use in Turkiye. The disease-specific nature of the CCF-CaQL makes it a useful tool in clinical and research settings, enhancing patient care by accurately monitoring treatment effects and interventions in the Turkish colorectal cancer patient population.

Multimodal assessment after total neoadjuvant therapy versus standard neoadjuvant chemoradiotherapy in locally advanced rectal cancer accurately predicts complete responders.

PURPOSE: This study aimed to compare local regrowth rates after total neoadjuvant therapy (TNT) versus standard neoadjuvant chemoradiotherapy (SNCRT) in locally advanced rectal cancer (LARC) patients that were strictly selected and assessed with a multimodal approach. Secondary outcomes were 4-year disease-free (DFS) and overall survival (OS) rates. METHODS: Locally advanced rectal cancer patients without distant metastases treated at Koç Healthcare Group between January 2014 and January 2021 were included. Patients were assessed for complete response with a combination of digital rectal exam, endoscopy, and magnetic resonance imaging with a dedicated rectum protocol. The systemic evaluation was performed with an upper abdomen MRI using intravenous hepatobiliary contrast agent and a thorax CT. RESULTS: Of the 270 patients with LARC, 182 fulfilled the inclusion criteria. Ninety-seven (53.3%) underwent TNT, while 85 (46.7%) underwent SNCRT. A cumulative combination of pathological and sustained clinical complete response was significantly higher in the TNT group than in the SNCRT (45.4% vs. 20.0%, p < 0.0001). After a median follow-up of 48 months, seven patients in the W&W group had regrowth [TNT: 4 (10.8%) vs. SNCRT: 3 (23.1%), p = 0.357]. Based on pathological examination, complete/near complete mesorectum rates (p = 1.000) and circumferential resection margin positivity rates (p = 1.000) were similar between the groups. The 4-year DFS and OS rates were comparable. The patients with clinical or pathological complete response had significantly longer overall survival (p = 0.017) regardless of the type of neoadjuvant treatment. CONCLUSIONS: Multimodal assessment after TNT effectively detects complete responders, resulting in low local recurrence and increased cumulative complete response rates. However, these outcomes did not translate into a survival advantage.

The role of tissue inhibitor of metalloproteinases in the aetiology of inguinal and incisional hernias.

Inguinal and incisional hernias are the two most common types of hernias caused by abdominal wall weakness and defects in connective tissue. The structure of the extracellular matrix, mainly collagen and metalloproteinases (MMPs), and their regulators have been studied extensively and found to play a significant role in the pathophysiology of hernias. One of the regulators of MMPs, tissue inhibitor metalloproteinases (TIMPs), bind to MMPs and inhibit its activity significantly shifting the balance towards collagen synthesis rather than degradation. Due to their importance in collagen metabolism, their metabolism might be significant in the aetiology of hernias. Our study used immunohistochemical techniques to investigate the possible effects of TIMP 1 and 2 on the samples taken from the abdominal walls of patients with inguinal and incisional hernias, compared them with control patients, and reviewed the literature. In this study, samples of 90 patients (30 patients from control, inguinal hernia, and incisional hernia groups) were taken and analysed. These samples were stained with TIMP-1 Ab-2 and TIMP2 Ab-5 (Clone 3A4) antibodies and evaluated under ×100 magnification. The degree of staining was classified as (a): No staining (0), (b): Staining less than 10% (I), (c): Staining between 10% and 50% (II), (d): Staining more than 50% (III). Statistical analyses were done. No significant difference was found between groups in terms of patient demographics. Smoking and family history of hernia was not found to be associated with TIMP expression. TIMP1 expression was significantly higher in the incisional and inguinal hernia group than in the control group (P < .05), while the level of TIMP2 was higher in the control group. (P < .05). TIMP1 and TIMP2 levels did not significantly differ between incisional and inguinal hernia groups. We found significantly increased TIMP-1 levels in tissue samples from patients with hernia supporting its suggested role in hernia pathophysiology. Local alterations in MMP and TIMP levels might play a role in the pathogenesis of hernias. Thus detection of TIMP in tissues can be important for clinical use after further validation studies. In the era of molecular medicine, detecting TIMP levels in hernia patients can impact clinical practice.

The use of focused, radioguided parathyroidectomy in geriatric patients with a history of thyroid surgery.

OBJECTIVE: Geriatric patients are often reluctant to undergo parathyroid surgery under general anesthesia because of the major comorbidities. The use of minimally invasive techniques for parathyroid lesions under local anesthesia have been published. Radioguided lesion localization has been known to decrease operative time and reduce the occurrence of positive margins in breast cancer surgery. We hypothesize that it could also be effectively used in focused parathyroid surgery in geriatric patients with in history of thyroid surgery. MATERIALS AND METHODS: Our study group consists of geriatric patients with a history of thyroid surgery who underwent focused parathyroid surgery between February 2017 and October 2019. Group-1 included 18 patients who had parathyroidectomy under radioguidance. Group-2, 22 patients who had surgery without it. Patient demographics, operative time, number of frozen sections and length of hospital stay were analyzed. RESULTS: Analyzed data were similar between groups. The mean age of the patients was 72.56±12.65 years (range: 65-88). The operative times for group-1 and group-2, were 65.42±7.78 and 74.63±15.98 minutes, respectively (P=0.002). All patients were discharged uneventfully on postoperative day-2. CONCLUSION: Radioguidance parathyroidectomy positively affected the operative time and also decreased the need for additional frozen section.

Single-incision robotic adrenalectomy (SIRA): the future of adrenal surgery?

In compliance with the trend toward less invasive techniques, single incision robotic surgeries have become more common and they have been increasingly used for several surgeries including adrenalectomy. Single incision robotic adrenalectomy (SIRA) aims to combine the merits of robotic surgery with previously defined single incision laparoscopic techniques. It has been shown to be safe and feasible, however, there are only few studies on this new technique. Due to scant data on SIRA in the current literature, it remains to be a current challenge in adrenal surgery. In this review, our goal is to present current literature on SIRA and discuss the data regarding perioperative outcomes, patient selection, learning curve, and its limitations.

Impact of the ST101 clone on fatality among patients with colistin-resistant Klebsiella pneumoniae infection.

Objectives: We describe the molecular characteristics of colistin resistance and its impact on patient mortality. Methods: A prospective cohort study was performed in seven different Turkish hospitals. The genotype of each isolate was determined by MLST and repetitive extragenic palindromic PCR (rep-PCR). Alterations in mgrB were detected by sequencing. Upregulation of pmrCAB, phoQ and pmrK was quantified by RT-PCR. mcr-1 and the genes encoding OXA-48, NDM-1 and KPC were amplified by PCR. Results: A total of 115 patients diagnosed with colistin-resistant K. pneumoniae (ColR-Kp) infection were included. Patients were predominantly males (55%) with a median age of 63 (IQR 46-74) and the 30 day mortality rate was 61%. ST101 was the most common ST and accounted for 68 (59%) of the ColR-Kp. The 30 day mortality rate in patients with these isolates was 72%. In ST101, 94% (64/68) of the isolates had an altered mgrB gene, whereas the alteration occurred in 40% (19/47) of non-ST101 isolates. The OXA-48 and NDM-1 carbapenemases were found in 93 (81%) and 22 (19%) of the total 115 isolates, respectively. In multivariate analysis for the prediction of 30 day mortality, ST101 (OR 3.4, CI 1.46-8.15, P = 0.005) and ICU stay (OR 7.4, CI 2.23-29.61, P = 0.002) were found to be significantly associated covariates. Conclusions: Besides ICU stay, ST101 was found to be a significant independent predictor of patient mortality among those infected with ColR-Kp. A significant association was detected between ST101 and OXA-48. ST101 may become a global threat in the dissemination of colistin resistance and the increased morbidity and mortality of K. pneumoniae infection.