Risk Factors of Poor Outcomes After Colorectal Cancer Surgery for Patients With Severe Comorbidities.

BACKGROUND/AIM: An increasing number of patients with complicated systemic comorbidity can undergo colorectal cancer (CRC) surgery. Such patients have a high risk of developing poor postoperative outcomes. This study aimed to identify preoperative factors, including nutritional and sarcopenia statuses, leading to poor postoperative outcomes in patients with severe systemic comorbidities. PATIENTS AND METHODS: This study included 114 patients who underwent radical CRC resections and had American Society of Anesthesiologists Physical Statuses ≥3. We retrospectively analyzed the relationships between clinical factors, postoperative complications (within 28 days postoperatively and Clavien-Dindo classification grade ≥2), length of hospital stay, discharge destination, and overall survival (OS). RESULTS: The median patient age was 74.5 years (range=41.0-93.0 years). Thirty-six patients had postoperative complications (31.6%), and the risk factors in the multivariate analyses were rectal cancer and preoperative nutritional disorders with Prognostic Nutritional Index ≤40. In patients with nutritional disorders, the postoperative hospital stay was longer, and a higher (but not statistically significant) percentage were not discharged home. Moreover, the independent factors for OS identified in the multivariate analyses were body mass index (BMI) and hemodialysis. CONCLUSION: In patients with CRC and severe systemic comorbidities, those with Prognostic Nutritional Index ≤40 have a high risk of developing postoperative complications, leading to a prolonged postoperative hospital stay and possibly preventing discharge home. Additionally, among these patients, OS was poor in those with low BMI or preoperative hemodialysis.

A Mature Tertiary Lymphoid Structure with a Ki-67-Positive Proliferating Germinal Center Is Associated with a Good Prognosis and High Intratumoral Immune Cell Infiltration in Advanced Colorectal Cancer.

Tertiary lymphoid structures (TLSs) are complex lymphocyte clusters that arise in non-lymphoid tissues due to inflammation or cancer. A mature TLS with proliferating germinal centers is associated with a favorable prognosis in various cancers. However, the effect of TLS maturity on advanced colorectal cancer (CRC) remains unexplored. We analyzed the significance of TLS maturity and tumor Ki-67 expression in surgically resected tumors from 78 patients with pathological T4 CRC. Mature TLS was defined as the organized infiltration of T and B cells with Ki-67-positive proliferating germinal centers. We analyzed the relationship between TLS maturity and intratumoral immune cell infiltration. Mature TLS with germinal center Ki-67 expression was associated with microsatellite instability and improved survival; however, high tumor Ki-67 expression was associated with poor survival in the same cohort. Multivariate analysis identified the absence of mature TLS as an independent predictor of poor post-recurrence overall survival. Intratumoral infiltration of T lymphocytes and macrophages was significantly elevated in tumors with mature TLS compared to those lacking it. High Ki-67 levels and absent mature TLS were identified as poor prognostic factors in advanced CRC. Mature TLS could serve as a promising marker for patients at high-risk of CRC.

The Gustave Roussy Immune score is a powerful biomarker for predicting therapeutic resistance to chemotherapy in gastric cancer patients.

PURPOSE: It is highly important to be able to predict the therapeutic efficacy of chemotherapy on patients with unresectable advanced or recurrent gastric cancer (GC). The Gustave Roussy Immune Score (GRIm-s) is a predictor of therapeutic sensitivity to chemotherapy and immune checkpoint inhibitors (ICIs) in other cancers. The present study aimed to analyze the association of the GRIm-s with the therapeutic sensitivity of first-line chemotherapy in GC patients. METHODS: We included 156 patients receiving primary chemotherapy treatment for unresectable or advanced recurrent GC between January 2012 and December 2021 at our institution. We evaluated the correlation between the GRIm-s and therapeutic sensitivities to chemotherapy. The GRIm-s was assessed before the start of first-line chemotherapy. RESULTS: Among the 156 patients, 138 (88.5%) and 18 (11.5%) were classified in the low- and high-risk groups, respectively. The GRIm-s high-risk group was significantly older (p = 0.013), had more advanced unresectable cancer (p = 0.0098), and was significantly less likely to progress to second-line chemotherapy (p = 0.014). The overall survival rate (OS) (p = 0.039) and the progression free survival rate (PFS) (p = 0.017) were significantly worse in the GRIm-s high-risk group. The high GRIm-s was an independent prognostic factor for poor survival in multivariate analysis (p = 0.0094). CONCLUSIONS: Focusing on the GRIm-s before first-line chemotherapy initiation for unresectable advanced or postoperative recurrent GC was useful in predicting the therapeutic resistance to chemotherapy, transition to second-line chemotherapy, and poor prognosis.

Poorly cohesive gastric cancer with increased epithelial­mesenchymal transition is associated with a poor prognosis.

The present study examined the surgical outcome and prognosis of patients with poorly cohesive carcinoma (PCC), and characterized the molecular pathological factors, epithelial-mesenchymal transition (EMT) and interstitial signals of the disease. A total of 281 patients who underwent gastric cancer (GC) surgery between April 2015 and August 2020 were included. Furthermore, tissue samples from another 197 patients with GC who underwent surgery between 1999 and 2003 were assessed using a tissue microarray. Preoperatively treated cases and endoscopic submucosal dissection cases were excluded, and multiple blocks containing the invasion region were collected for tissue microarray. For tissue microarray analysis, the clinicopathological factors of protein wnt3a (wnt3a), leucine-rich repeat-containing G-protein coupled receptor 5, transforming growth factor-ß-induced, phosphorylated serine/threonine-protein kinase mTOR and E-cadherin expression were collected as EMT markers. The results of the surgical case evaluation and tissue microarray indicated that PCC was more common in younger patients and women, as the ratio of women to men was higher in the PCC group compared with that in the non-PCC group. However, none of the results revealed that the prognosis was worse in all patients with PCC compared with the non-PCC group. Furthermore, in the tissue microarray study, PCC samples exhibited significantly decreased expression of the cell adhesion molecule E-cadherin, suggesting enhanced EMT, which activates wnt3a signaling. PCC with increased EMT was significantly associated with a poor prognosis.

Importance of duodenal stump reinforcement to prevent stump leakage after gastrectomy: a large-scale multicenter retrospective study (KSCC DELICATE study).

BACKGROUND: The significance of reinforcement of the duodenal stump with seromuscular sutures and the effectiveness of reinforced staplers in preventing duodenal stump leakage remain unclear. We aimed to explore the importance of duodenal stump reinforcement and determine the optimal reinforcement method for preventing duodenal stump leakage. METHODS: This retrospective cohort study was conducted between January 1, 2012 and December 31, 2021, with data analyzed between December 1, 2022 and September 30, 2023. This multicenter study across 57 institutes in Japan included 16,475 patients with gastric cancer who underwent radical gastrectomies. Elective open or minimally invasive (laparoscopic or robotic) gastrectomy was performed in patients with gastric cancer. RESULTS: Duodenal stump leakage occurred in 153 (0.93%) of 16,475 patients. The proportions of males, patients aged ≥ 75 years, and ≥ pN1 were higher in patients with duodenal stump leakage than in those without duodenal stump leakage. The incidence of duodenal stump leakage was significantly lower in the group treated with reinforcement by seromuscular sutures or using reinforced stapler than in the group without reinforcement (0.72% vs. 1.19%, p = 0.002). Duodenal stump leakage incidence was also significantly lower in high-volume institutions than in low-volume institutions (0.70% vs. 1.65%, p = 0.047). The rate of duodenal stump leakage-related mortality was 7.8% (12/153). In the multivariate analysis, preoperative asthma and duodenal invasion were identified as independent preoperative risk factors for duodenal stump leakage-related mortality. CONCLUSIONS: The duodenal stump should be reinforced to prevent duodenal stump leakage after radical gastrectomy in patients with gastric cancer.

Risks and Outcomes of Early Dose Reduction in Adjuvant CAPOX Therapy for Colorectal Cancer.

BACKGROUND/AIM: Adjuvant capecitabine and oxaliplatin (CAPOX) therapy is standard strategy for colorectal cancer with risk of recurrence. Early dose reduction (EDR) of CAPOX therapy is commonly used in real-world practice. However, there is limited evidence regarding the effectiveness of CAPOX for patients who had EDR. Therefore, this study aimed to clarify the risks of EDR and its effect on long-term outcomes and body composition factors. PATIENTS AND METHODS: Patients who received CAPOX therapy after radical surgery for colorectal cancer between June 2013 and December 2021 were included. EDR was defined as dose reduction within four courses of CAPOX therapy. Body composition factors were measured for 1 year following surgery to determine the EDR effects. RESULTS: Eighty-four patients were included; 35 (42%) of them had EDR. The multivariate analysis revealed that underweight [odds ratio (OR)=4.95, 95% confidence interval (CI)=1.13-21.7, p=0.03] was a risk factor for EDR. Relapse-free survival (RFS) was significantly better in the non-EDR group (p=0.01). The 5-year RFS rates for the non-EDR and EDR groups were 88.7% and 65.4%, respectively. The multivariate analysis revealed that age >65 years [hazard ratio (HR)=3.97; 95% CI=1.16-13.62, p=0.03] and EDR (HR=7.62; 95% CI=1.71-33.91, p=0.005) were associated with poorer RFS. The 1-year body composition analysis revealed decreases in all factors in the EDR group. CONCLUSION: Preoperative underweight status was associated with EDR, which resulted in decreased RFS and body composition factors when compared with the non-EDR group. Therefore, avoiding EDR and early nutritional intervention after EDR may improve outcomes.

Squamous cell carcinoma of the anus successfully treated with multidisciplinary therapy for metachronous metastatic and local recurrences after DCF chemotherapy: a case report.

BACKGROUND: Docetaxel, cisplatin, and 5-fluorouracil (DCF) chemotherapy is reportedly an effective treatment strategy for squamous cell carcinoma of the anus (SCCA). However, studies regarding its use in Japanese patients remain scarce. CASE PRESENTATION: Here, we present the case of an 82-year-old woman with SCCA, cStage IIIB. Chemoradiotherapy was initiated after colostomy of the anorectal mass; however, para-aortic lymph node recurrence was observed 3 months after treatment completion. Five courses of DCF chemotherapy were subsequently administered, resulting in a complete response (CR). Two years and 1 month later, the aortic lymph node was enlarged again, and the patient achieved CR again after radiotherapy. Nine months later, local recurrence was detected in the anal canal, and laparoscopic perineal rectal amputation was performed. The patient remains progression-free 5 years and 10 months after the initial treatment and 1 year and 7 months after the final treatment. CONCLUSIONS: Our findings suggest that complementary treatment after DCF chemotherapy may be efficacious in Japanese patients with SCCA and help achieve CR. Despite occasional local recurrences, this approach may help achieve long-term progression-free survival.

Efficacy of thoracic endovascular aortic repair for aorto-esophageal fistula due to esophageal cancer: a systematic review and meta-analysis.

Aorto-esophageal fistula (AEF) due to esophageal cancer (EC) is a life-threatening condition characterized by sudden hemorrhage, which often causes sudden death. To evaluate the efficacy and safety of thoracic endovascular aortic repair (TEVAR) for AEF due to EC, we performed a systematic review and meta-analysis. We searched the MEDLINE (PubMed) databases, the Cochrane Library databases, Ichushi-Web (the databases of the Japan Medical Abstract Society), and CiNii (Academic information search service of the National Institute of Information from Japan) from January 2000 to November 2023 for articles about TEVAR for an emergent aortic hemorrhage (salvage TEVAR [S-TEVAR]), and the prophylactic procedure (P-TEVAR). Six studies (140 cases) were eligible for meta-analysis. The 90-day mortality of S-TEVAR and P-TEVAR was 40% (95% CI 23-60, I2 = 36%) and 8% (95% CI 3-17, I2 = 0%), respectively. Post-S-TEVAR hemorrhagic and infectious complications were 17% (95% CI 3-57, I2 = 71%) and 20% (95% CI 5-57, I2 = 66%), respectively. Post-P-TEVAR hemorrhagic and infectious complications were 2% (95% CI 0-10, I2 = 0%) and 3% (95% CI 1-12, I2 = 0%), respectively. TEVAR for AEF due to EC may be a useful therapeutic option to manage or prevent hemorrhagic oncological emergencies.

Prognostic value of a modified­immune scoring system in patients with pathological T4 colorectal cancer.

Tumor-infiltrating immune cells, such as lymphocytes and macrophages, have been associated with tumor aggressiveness, prognosis and treatment response in colorectal cancer (CRC). An immune scoring system, Immunoscore (IS), based on tumor-infiltrating T cells in stage I-III CRC, was used to predict prognosis. An alternative immune scoring signature of immune activation (SIA) reflects the balance between anti- and pro-tumoral immune components. The present study aimed to evaluate the prognostic value of modified IS (mIS) and modified SIA (mSIA) in locally advanced pathological T4 (pT4) CRC, including stage IV CRC. Immunohistochemical staining for immune cell markers, such as CD3 (pan-T cell marker), CD8 (anti-tumoral cytotoxic T cell marker) and CD163 (tumor-supportive macrophage marker), in specimens from patients with radically resected pT4 CRC at stages II-IV was performed. mIS levels in the T4 CRC cohort were not associated with prognosis. However, low mSIA levels were associated with low survival. Furthermore, low mSIA was an independent predictor of recurrence in patients with radically resected pT4 CRC. In patients with CRC who did not receive postoperative adjuvant chemotherapy, low mSIA was a major poor prognostic factor; however, this was not observed in patients receiving adjuvant chemotherapy. Evaluation of the tumor-infiltrating immune cell population could serve as a valuable marker of recurrence and poor prognosis in patients with locally advanced CRC. mSIA assessment after radical CRC resection may be promising for identifying high-risk patients with pT4 CRC who require aggressive adjuvant chemotherapy.

Retrograde drainage for duodenal stump leakage using ileal decompression tube guided by double-balloon endoscopy: a novel case report.

BACKGROUND: Duodenal stump leakage is a serious post-gastrectomy complication, and there have been no reports on endoscopic drainage. CASE PRESENTATION: We report a case of duodenal stump leakage after laparoscopic gastrectomy with Roux-en-Y reconstruction in a 68-year-old man. First-line conservative management was ineffective. Reoperation was performed because of severe abdominal pain and increased ascites. After reoperation, duodenal stump leakage recurred with bleeding from the anterior superior pancreaticoduodenal artery. Coil embolization and pigtail catheter insertion were performed. Furthermore, we retrogradely inserted an ileal tube for tube decompression near the duodenal stump using double-balloon endoscopy for effective drainage. After tube insertion, duodenal stump leakage decreased; on the 47th primary postoperative day, the patient was discharged. The primary postoperative course was uneventful after 1 year and 9 months of follow-up. CONCLUSIONS: This is the first successful case of duodenal stump leakage treated with retrograde decompression tube insertion near the duodenal stump using double-balloon endoscopy.

Effectiveness of Combination Chemotherapy With Docetaxel, Nedaplatin, and 5-Fluorouracil for Advanced and Recurrent Esophageal Cancer.

BACKGROUND/AIM: Chemotherapy and immunotherapy have been recently developed as potentially useful first-line treatments for unresectable, advanced, or recurrent esophageal cancer. We performed a retrospective study of the therapeutic effectiveness of triplet chemotherapy with docetaxel, nedaplatin, and 5-fluorouracil therapy for advanced, recurrent, and unresectable advanced esophageal cancer at our hospital and compared the regimen's results with those of current and possible future treatment options. PATIENTS AND METHODS: The study cohort comprised 101 patients who received docetaxel, nedaplatin, and 5-fluorouracil for advanced or recurrent esophageal cancer at Gunma University from May 2008 to December 2017. We retrospectively evaluated the results of this combination chemotherapy and postulated future treatment strategies. RESULTS: The overall response and disease control rates, the latter including stable disease, for docetaxel, nedaplatin, and 5-fluorouracil were 33.6% and 61.4%, respectively. The median overall survival and progression-free survival were 12.26 months and 5.1 months, respectively. In patients with recurrence, the median overall and progression-free survivals were 14.97 months (449 days) and 5.1 months (152 days), respectively. No study patients developed acute kidney injury and there were no treatment-related deaths. However, leukopenia and neutropenia were frequent hematologic toxicities. CONCLUSION: Treatment with docetaxel, nedaplatin, and 5-fluorouracil for advanced or recurrent esophageal cancer is particularly useful for recurrent cases and has the advantage of not causing severe renal dysfunction.

Two-Team Transanal Total Mesorectal Excision and En Bloc Resection of the Lateral Pelvic Lymph Nodes, Main Iliac Vessels, and Pelvic Plexus for Locally Advanced Rectal Cancer With Lateral Lymph Node Metastasis.

BACKGROUND: Here, we describe the precise surgical technique for a novel procedure involving 2-team transanal total mesorectal excision with en bloc lateral pelvic lymph node (LPLN) dissection combined with resection of the involved main internal iliac vessels and pelvic plexus. METHODS: From September 2020 to May 2023, 4 patients underwent the procedure at our hospital. RESULTS: The operation time and blood loss were 272 to 412 minutes and 10 to 124 mL, respectively. No patients required conversion to open surgery or exhibited Clavien-Dindo grade III or worse postoperative complications, although 2 developed grade II urinary dysfunction. All surgical margins were negative. CONCLUSIONS: Our novel 2-team method can facilitate safe and satisfactory surgery, even for highly advanced rectal cancer. The transanal approach offers excellent visibility and operability, even during LPLN and adjacent structure dissection. Furthermore, initial dissection of the distal branches of the iliac vessels prevents excessive lymphatic tissue congestion, facilitating easier, and clearer dissection.

Impact of Perioperative Immunonutrition on Postoperative Outcomes for Patients Undergoing Head and Neck or Gastrointestinal Cancer Surgeries: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To clarify whether perioperative immunonutrition is effective in adult patients with or without malnutrition undergoing elective surgery for head and neck (HAN) or gastrointestinal (GI) cancers. BACKGROUND: It is important to avoid postoperative complications in patients with cancer as they can compromise clinical outcomes. There is no consensus on the efficacy of perioperative immunonutrition in patients with or without malnutrition undergoing HAN or GI cancer surgery. MATERIALS AND METHODS: We searched MEDLINE (PubMed), MEDLINE (OVID), EMBASE, Cochrane Central Register of Controlled Trials, Web of Science Core Selection, and Emcare from 1981 to 2022 using search terms related to immunonutrition and HAN or GI cancer. We included randomized controlled trials. Intervention was defined as immunonutritional therapy including arginine, n-3 omega fatty acids, or glutamine during the perioperative period. The control was defined as standard nutritional therapy. The primary outcomes were total postoperative and infectious complications, defined as events with a Clavien-Dindo classification grade ≥ II that occurred within 30 days after surgery. RESULTS: Of the 4825 patients from 48 included studies, 19 had upper GI cancer, 9 had lower, and 8 had mixed cancer, whereas 12 had HAN cancers. Immunonutrition reduced the total postoperative complications (relative risk ratio: 0.78; 95% CI, 0.66-0.93; certainty of evidence: high) and infectious complications (relative risk ratio: 0.71; 95% CI, 0.61-0.82; certainty of evidence: high) compared with standard nutritional therapy. CONCLUSIONS: Nutritional intervention with perioperative immunonutrition in patients with HAN and GI cancers significantly reduced total postoperative complications and infectious complications.

A Novel Method for Thoracoscopic Overlap Esophagogastric Reconstruction With Pleural Closure following Minimally Invasive Ivor-Lewis Esophagectomy for Esophagogastric Junction Cancer.

BACKGROUND: Intrathoracic esophagogastric anastomosis following minimally invasive Ivor-Lewis esophagectomy is a technically demanding surgical technique that can result in serious intrathoracic infections when anastomotic leakage occurs. Herein, we report a novel side-overlap esophagogastric anastomosis with pleural closure for esophagogastric junction cancer. METHODS: The 3 key points of our novel technique were the following: (1) overlap esophagogastric anastomosis and closure of the entry hole were all performed using a linear stapler; (2) the pleura was closed to separate the anastomotic site from the thoracic cavity; and (3) the mediastinal drain was inserted transhiatally from the abdominal cavity. RESULTS: This modified anastomosis procedure was performed on 8 consecutive patients at our institution. The median overall/thoracoscopic operating time and estimated blood loss were 652.5/241.5 min and 89 mL, respectively. No mortality or serious postoperative complications occurred, and the median postoperative hospital stay was 22 days (range, 17 to 37 d). CONCLUSION: This novel thoracoscopic overlap esophagogastric reconstruction procedure with pleural closure is safe and feasible.

Usefulness of the preoperative inflammation-based prognostic score and the ratio of visceral fat area to psoas muscle area on predicting survival for surgically resected adenocarcinoma of the esophagogastric junction.

BACKGROUND: Sarcopenic obesity is associated with gastrointestinal cancer prognosis through systemic inflammation. However, in patients with adenocarcinoma of the esophagogastric junction (AEG), the relationship between the inflammation-based prognostic score (IBPS), muscle loss, visceral fat mass, and prognosis has not been sufficiently evaluated. We investigated the prognostic value of the preoperative IBPS and the visceral fat area ratio to the psoas muscle area (V/P ratio) in patients with AEG undergoing surgery. METHODS: We retrospectively analyzed 92 patients with AEG who underwent surgery. The prognostic value of the preoperative neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio, systemic inflammation response index, C-reactive protein-to-albumin ratio, prognostic nutritional index, modified Glasgow Prognostic Score, and V/P ratio at the third lumbar vertebra was investigated using univariate and multivariate survival analyses. RESULTS: Multivariate analysis revealed that a high pathological stage (p = 0.0065), high PLR (p = 0.0421), and low V/P ratio (p = 0.0053) were independent prognostic factors for poor overall survival (OS). When restricted to patients with body mass index (BMI) ≥ 25 kg/m2, a high V/P ratio was a poor prognostic factor (p = 0.0463) for OS. Conversely, when restricted to patients with BMI < 25 kg/m2, a low V/P ratio was a poor prognostic factor (p = 0.0021) for OS. CONCLUSIONS: Both PLR and V/P ratios may be useful prognostic biomarkers in surgical cases of AEG. V/P ratio and BMI may provide an accurate understanding of the muscle and fat mass's precise nature and may help predict AEG prognosis.

Importance of Progression-free Survival in Second-line Chemotherapy in Patients With Advanced or Recurrent Gastric Cancer.

BACKGROUND/AIM: Impact of second-line chemotherapy in unresectable advanced/recurrent gastric/esophagogastric junction cancer (AGC) remains unclear. This retrospective analysis aimed to identify factors affecting prognosis in chemotherapy for patients with AGC, including the importance of progression-free survival in second-line chemotherapy (PFS-2). PATIENTS AND METHODS: Data from a total of 109 patients with AGC that received second-line treatment were analyzed with the aim of clarifying prognostic factors. Furthermore, the correlation between PFS-2 and clinical characteristics and the association between PFS-2 and inflammation-based and/or nutritional markers were investigated. RESULTS: Multivariate analysis identified the following prognostic factors: ECOG PS ≥1, presence of peritoneal dissemination, metastasis in two or more organs, and taxane use on second-line chemotherapy. Short PFS-2 was strongly associated with prognosis in the univariate analysis [hazard ratio (HR)=3.107, 95% confidence interval (CI)=1.969-4.904, p<0.001]. The duration of PFS-2 was significantly correlated with ECOG PS (p=0.019), liver metastasis rates (p=0.035) and taxane use on second-line chemotherapy (p=0.001). In addition, weight loss rate during first-line treatment (p=0.042), white blood cell count (p=0.008), C-reactive protein (p=0.032), c-reactive protein to albumin ratio (p=0.039), prognostic index (p=0.028), and modified Glasgow prognostic score (p=0.027) were significantly associated with the duration of PFS-2. CONCLUSION: The duration of PFS-2 significantly correlated with ECOG PS, liver metastasis, and taxane use on second-line treatment, and strongly affected OS. It was suggested that the presence of malnutrition and inflammation at the start of second-line therapy had a negative impact on PFS-2 and OS.

HLA Class I Expression Is Associated with DNA Damage and Immune Cell Infiltration into Dysplastic and Neoplastic Lesions in Ulcerative Colitis.

Human leukocyte antigen class I (HLA-I) is considered a genetic pathogen for ulcerative colitis (UC). This study aimed to investigate the significance of DNA damage and HLA-I expression in infiltrating immune cells and immune checkpoint protein PD-L1 expression in dysplasia/colitic cancer (CC) and sporadic colorectal cancer (SCRC). We performed immunohistochemical staining for HLA-I, PD-L1, γH2AX (DNA damage marker), and immune cell markers such as CD8, FOXP3, CD68, and CD163 (in surgically resected specimens from 17 SCRC patients with 12 adjacent normal mucosa (NM) and 9 UC patients with 18 dysplasia/CC tumors. The ratio of membrane HLA-I-positive epithelial cells in UC and dysplasia/CC tissues was significantly higher than that in NM and SCRC. High HLA-I expression in dysplasia/CC was associated with high positivity of γH2AX and PD-L1 expression compared to SCRC. The infiltration of CD8-positive T cells and CD68-positive macrophages in HLA-I-high dysplasia/CC was significantly higher than in UC and SCRC. Dysplasia/CC specimens with DNA damage exhibited high levels of HLA-I-positive epithelial cells with high CD8- and CD68-positive immune cell infiltration compared to UC and SCRC specimens. Targeting DNA damage in UC may regulate immune cell infiltration, immune checkpoint proteins, and carcinogenesis by modulating DNA damage-induced HLA-I antigen presentation.

Surgical Techniques and Stoma-related Complications Associated With Emergency Stoma Creation.

BACKGROUND/AIM: Determination of risk factors for stoma-related complications associated with emergency stoma creation may impact on reducing complications and improving the quality of life of ostomy patients; however, there are only few reports on stoma-related complications associated with emergency stoma creation. Our study aimed to identify risk factors associated with stoma-related complications after emergency surgery, and evaluate surgical techniques for good stoma creation in the emergency setting. PATIENTS AND METHODS: A retrospective analysis of patient and surgical characteristics was performed in 104 consecutive patients who underwent ileostomy or colostomy as emergency surgery between January 2020 and December 2022 at the Gunma University Hospital. RESULTS: Preoperative stoma site marking was performed in 70 (67.3%) patients. Colostomies and ileostomies were performed in 78 (75.0%) and 26 (25.0%) patients, respectively. The skin bridge technique was used in 13 (12.5%) patients. Stoma-related complications were diagnosed in 62 (59.6 %) patients, with peristomal skin disorders (47.1%) as the most common complication, followed by mucocutaneous separation (31.7%), and stoma retraction (19.2%). In the multivariate analysis, body mass index (BMI) [odds ratio (OR)=5.570, 95% confidence interval (CI)=1.233-25.167, p=0.026], skin bridge technique (OR=0.144, 95% CI=0.031-0.670, p=0.014), and stoma height (OR=0.134, 95% CI=0.038-0.469, p=0.002) were independent risk factors for stoma-related complications after emergency stoma creation. CONCLUSION: In emergency stoma creation, higher BMI and lower stoma height are associated with stoma-related complications. Using the skin bridge technique could reduce the risk of stoma-related complications after emergency stoma creation.

Significance of Lipopolysaccharides in Gastric Cancer and Their Potential as a Biomarker for Nivolumab Sensitivity.

Lipopolysaccharides are a type of polysaccharide mainly present in the bacterial outer membrane of Gram-negative bacteria. Recent studies have revealed that lipopolysaccharides contribute to the immune response of the host by functioning as a cancer antigen. We retrospectively recruited 198 patients with gastric cancer who underwent surgery. The presence of lipopolysaccharides was determined using immunohistochemical staining, with the intensity score indicating positivity. The relationship between lipopolysaccharides and CD8, PD-L1, TGFBI (a representative downstream gene of TGF-ß signaling), wnt3a, and E-cadherin (epithelial-mesenchymal transition marker) was also investigated. Thereafter, we identified 20 patients with advanced gastric cancer receiving nivolumab and investigated the relationship between lipopolysaccharides and nivolumab sensitivity. After staining for lipopolysaccharides in the nucleus of cancer cells, 150 negative (75.8%) and 48 positive cases (24.2%) were found. The lipopolysaccharide-positive group showed increased cancer stromal TGFBI expression (p < 0.0001) and PD-L1 expression in cancer cells (p = 0.0029). Lipopolysaccharide positivity was significantly correlated with increased wnt3a signaling (p = 0.0028) and decreased E-cadherin expression (p = 0.0055); however, no significant correlation was found between lipopolysaccharide expression and overall survival rate (p = 0.71). In contrast, high TGFBI expression in the presence of LPS was associated with a worse prognosis than that in the absence of LPS (p = 0.049). Among cases receiving nivolumab, the lipopolysaccharide-negative and -positive groups had disease control rates of 66.7% and 11.8%, respectively (p = 0.088). Lipopolysaccharide positivity was associated with wnt3a, TGF-ß signaling, and epithelial-mesenchymal transition and was considered to tend to promote therapeutic resistance to nivolumab.