Cemil Burak Kulle

Neoadjuvant treatment (NAT) has been increasingly used for locally advanced gastric cancer considering the potential for systemic dissemination and inoperability of the disease. This study aimed to evaluate the effects of NAT on the early postoperative complications and pathological outcomes in patients undergoing surgery for gastric cancer. We included patients with gastric cancer who underwent surgery at a tertiary care center between January 2014 and December 2021. The patients were divided into NAT receiving (Group I) and non-receiving (Group II) groups. Demographic data, clinical characteristics, intraoperative and postoperative complications, and pathological findings were retrospectively analyzed and compared between the 2 groups. Among the 186 patients, 27% (n = 51) were in group I and 73% (n = 135) were in group II. The 2 groups were comparable in terms of their demographic characteristics. There were no significant differences in surgery time (P = .932), intraoperative complication rates (P = .993), postoperative complications (Clavien–Dindo grade ≥ III) (P = .549), or anastomotic leakage rates (P > .05) between the groups. Both groups had a similar median number of total harvested lymph nodes (n = 28, P = .917), metastatic lymph nodes (n = 6, P = .509), and R0 resection rates (94% vs 95, 6% P = .707). Subgroup analysis revealed no significant difference in early postoperative complication rates between patients receiving chemotherapy and chemoradiotherapy (P = .330). Neoadjuvant treatment did not appear to increase the risk of early postoperative complications or affect the extent of lymphadenectomy in patients who underwent curative surgery for gastric cancer. These findings support the surgical safety and feasibility of NAT, particularly in multidisciplinary settings. A longer follow-up is required to assess the impact on survival outcomes and long-term complications.

Cytoreductive Surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are techniques developed for curative treatment of peritoneal carcinomatosis (PC). Studies have shown that CRS + HIPEC provides a survival advantage in PC, and long-term survival can be achieved in selected cases. This study aimed to evaluate CRS + HIPEC cases performed for curative purposes and to examine the prognostic factors. PC patients who underwent CRS + HIPEC with curative intent between January 2011 and September 2022 were included. Demographic, clinical, and pathological findings, procedure-specific parameters, complications, mortality, progression-free survival (PFS), and overall survival (OS) were analyzed. Optimal cytoreduction was achieved in 70% of the patients. The median PFS for the entire series was 9.2 months, while the median OS was 20.5 months, with a 3-year OS rate of 36%. Appendiceal origin, cytoreduction score, absence of lymph node metastasis, and absence of complications were factors associated with a positive impact on both PFS and OS. In multivariate analysis, cytoreduction score emerged as the sole independent factor influencing both PFS and OS. Considering the results in our series, cases of PC in which complete cytoreduction can be achieved should be evaluated for CRS + HIPEC.

Background Abdominoperineal resection (APR) is the standard treatment for locally advanced distal rectal cancer (LADRC) following neoadjuvant treatment when sphincter-preserving procedures are inapplicable. However, complications such as perineal site infection, perineal hernia and postoperative ileus remain ongoing challenges. We aimed to compare the rate of postoperative ileus due to pelvic incarceration in APR patients with/without pelvic inlet closure. Methods LADRC patients, who underwent APR with/without pelvic inlet closure between January 2016 and September 2022 at a comprehensive cancer center were analyzed retrospectively. After laparoscopic APR, the pelvic inlet was closed with a bladder peritoneal flap. A U-shaped peritoneal flap, up to approximately 15 × 20 cm in size, was peeled off from the dome of the bladder with its base at the posterosuperior part of the bladder. Results Of the 80 patients included in the analysis, 27 (34%) underwent laparoscopic APR with pelvic inlet closure and 53 (66%) had no pelvic inlet closure. There was no significant difference in age, mean body mass index and American Society of Anesthesiologists score among both groups. Patients with a pelvic inlet closure had a significantly lower postoperative ileus rate because of incarceration [0 vs. 17%, n = 9/53; (P = 0.03)] and a shorter hospital stay [6.74 ± 4.21 vs. 9.00 ± 5.99 days; P = 0.03]. The rate of perineal surgical site infection (SSI) [5/27 (18.5%) vs. 14/53 (26.4%); P = 0.61) was lower in the laparoscopic APR with pelvic inlet closure group, but this was not significant. Conclusion Pelvic inlet closure using a bladder peritoneal flap following APR is a safe and feasible procedure associated with reduced postoperative ileus due to pelvic incarceration rates, emergent surgical interventions due to pelvic incarceration and shorter hospital stay.

Introduction:: The aim of the study was to develop deep-learning neural networks to guide treatment decisions and for the accurate evaluation of tumor response to neoadjuvant chemoradiotherapy (nCRT) in rectal cancer using magnetic resonance (MR) images. Methods:: Fifty-nine tumors with stage 2 or 3 rectal cancer that received nCRT were retrospectively evaluated. Pathological tumor regression grading was carried out using the Dworak (Dw-TRG) guidelines and served as the ground truth for response predictions. Imaging-based tumor regression grading was performed according to the MERCURY group guidelines from pre-treatment and post-treatment para-axial T2-weighted MR images (MR-TRG). Tumor signal intensity signatures were extracted by segmenting the tumors volumetrically on the images. Normalized histograms of the signatures were used as input to a deep neural network (DNN) housing long short-term memory (LSTM) units. The output of the network was the tumor regression grading prediction, DNN-TRG. Results:: In predicting complete or good response, DNN-TRG demonstrated modest agreement with Dw-TRG (Cohen’s kappa= 0.79) and achieved 84.6% sensitivity, 93.9% specificity, and 89.8% accuracy. MR-TRG revealed 46.2% sensitivity, 100% specificity, and 76.3% accuracy. In predicting a complete response, DNN-TRG showed slight agreement with Dw-TRG (Cohen’s kappa= 0.75) with 71.4% sensitivity, 97.8% specificity, and 91.5% accuracy. MR-TRG provided 42.9% sensitivity, 100% specificity, and 86.4% accuracy. DNN-TRG benefited from higher sensitivity but lower specificity, leading to higher accuracy than MR-TRG in predicting tumor response. Conclusion:: The use of deep LSTM neural networks is a promising approach for evaluating the tumor response to nCRT in rectal cancer.

Background: Over the past few decades, nonoperative management (NOM) has become increasingly prevalent as an effort to preserve organs and improve functional outcomes compared to surgery. Objectives: This study aims to compare the clinical outcomes of patients with locally advanced distal rectal cancer (LADRC) following neoadjuvant treatment with either total mesorectal excision (TME) or NOM. Design: The study was conducted retrospectively. Patients and Methods: The study was conducted at two comprehensive cancer centers between January 1, 2014, and October 31, 2019. The study included all LADRC patients with clinical complete response (cCR) following neoadjuvant treatment, and who agreed to NOM or had a pathology report concluding that they had achieved pathologic complete response (pCR) following TME. Main Outcomes and Measurements: We evaluated patients for the presence of local regrowth or recurrence (LR), distant metastases (DM), and survival. Sample Size: A total of 462 individuals were identified from the database of the centers. Among them, 137 (31.8%) were confirmed to have achieved cCR. Results: Out of 137 patients with cCR, 67 patients were treated with NOM and 70 patients underwent TME, with 69 of them achieving pCR. In terms of baseline characteristics and tumor location, the patients in the NOM group (n = 67) did not differ from those in the pCR group (n = 69) (P > 0.05). Surveillance of the 67 patients in the NOM group revealed that 10 (15%) developed local regrowth and required salvage surgery. As a result of salvage surgery, 65 patients (97%) maintained pelvic control. Although there was no evidence of pelvic recurrence in the pCR group, three patients (4.3%) underwent metastasectomy for DM. In the NOM group, DM was observed in two (20%) out of ten patients after salvage surgery for local regrowth, whereas no DM was detected in NOM patients without local regrowth. In the NOM group, DM was significantly associated with local regrowth compared to those who did not develop pelvic regrowth (20% vs. 0%; P < 0.05). It was observed that the pCR group had improved disease-free survival rates (95.7% vs. 85.1%, P = 0.034); however, there was no difference in the overall survival rates (100% vs. 98.5%, P = 0.248). Conclusion: Compared with the traditional trimodal treatment strategy, NOM is a safe and promising treatment option for selected LADRC patients with an acceptable rate of pelvic control and overall survival. Consequently, close endoscopic and radiologic monitoring is essential to maximize the likelihood of an early detection of recurrence and a successful salvage surgery. Limitations: Due to its retrospective nature, this study has limitations primarily related to data collection from patients’ records and databases after the completion of follow-up. Conflict of Interest: The authors have no conflict of interest to declare.

Circulating nucleic acids (CNAs) are under investigation as a liquid biopsy in cancer as potential non-invasive biomarkers, as stable structure in circulation nucleosomes could be valuable sources for detection of cancer-specific alterations in histone modifications. Our interest is in histone methylation marks with a focus on colorectal cancer, one of the leading cancers respective the incidence and mortality. Our previous work included the analysis of trimethylations of lysine 9 on histone 3 (H3K9me3) and of lysine 20 on histone 4 (H4K20me3) by chromatin immuno- precipitation-related PCR in circulating nucleosomes. Here we asked whether global immunologic measurement of histone marks in circulation could be a suitable approach to show their potential as biomarkers. In addition to H3K9me3 and H4K20me3 we also measured H3K27me3 in plasma samples from CRC patients (n = 63) and cancer free individuals (n = 40) by ELISA-based methylation assays. Our results show that of three marks, the amounts of H3K27me3 (p = 0.04) and H4K20me3 (p < 0.001) were significantly lower in CRC patients than in healthy controls. For H3K9me3 similar amounts were measured in both groups. Areas under the curve (AUC) in receiver operating characteristic (ROC) curves indicating the power of CRC detection were 0.620 for H3K27me3, 0.715 for H4K20me3 and 0.769 for the combination of both markers. In conclusion, findings of this preliminary study reveal the potential of blood-based detection of CRC by quantification of histone methylation marks and the additive effect of the marker combination.