Short-term Outcomes of Robotic Gastrectomy vs Laparoscopic Gastrectomy for Patients With Gastric Cancer: A Randomized Clinical Trial.

Importance: Robotic gastrectomy (RG) for gastric cancer may be associated with decreased incidence of intra-abdominal infectious complications, including pancreatic fistula, leakage, and abscess. Prospective randomized clinical trials comparing laparoscopic gastrectomy (LG) and RG are thus required. Objective: To compare the short-term surgical outcomes of RG with those of LG for patients with gastric cancer. Design, Setting, and Participants: In this phase 3, prospective superiority randomized clinical trial of RG vs LG regarding reduction of complications, 241 patients with resectable gastric cancer (clinical stages I-III) were enrolled between April 1, 2018, and October 31, 2020. Interventions: LG vs RG. Main Outcomes and Measures: The primary end point was the incidence of postoperative intra-abdominal infectious complications. Secondary end points were incidence of any complications, surgical results, postoperative courses, and oncologic outcomes. The modified intention-to-treat population excluded patients who had been randomized and met the postrandomization exclusion criteria. There was also a per-protocol population for analysis of postoperative complications. Results: This study enrolled 241 patients, with 236 patients in the modified intention-to-treat population (150 men [63.6%]; mean [SD] age, 70.8 [10.7] years). There was no significant difference in the incidence of intra-abdominal infectious complications (per-protocol population: 10 of 117 [8.5%] in the LG group vs 7 of 113 [6.2%] in the RG group). Of 241 patients, 122 were randomly assigned to the LG group, and 119 patients were randomly assigned to the RG group. Two of the 122 patients (1.6%) in the LG group converted from LG to open surgery, and 4 of 119 patients (3.4%) in the RG group converted from RG to open or laparoscopic surgery, with no significant difference. Finally, 117 patients in the LG group completed the procedure, and 113 in the RG group completed the procedure; these populations were defined as the per-protocol population. The overall incidence of postoperative complications of grade II or higher was significantly higher in the LG group (23 [19.7%]) than in the RG group (10 [8.8%]) (P = .02). Even in analysis limited to grade IIIa or higher, the complication rate was still significantly higher in the LG group (19 [16.2%]) than in the RG group (6 [5.3%]) (P = .01). Conclusions and Relevance: This study found no reduction of intra-abdominal infectious complications with RG compared with LG for gastric cancer. Trial Registration: umin.ac.jp/ctr Identifier: UMIN000031536.

Modified intramuscular adipose tissue content as a feasible surrogate marker for malnutrition in gastrointestinal cancer.

BACKGROUND & AIMS: Myosteatosis is gathering attention as a feasible indicator for sarcopenia and increased risk of morbidity. However, the prognostic value of intramuscular adipose tissue content (IMAC) as an assessment method for myosteatosis remains controversial. The objectives of this study are to compare the prognostic value of intramuscular adipose tissue content (IMAC) with our newly-developed modified IMAC (mIMAC), and to assess the clinical significance of mIMAC in colorectal cancer (CRC) and gastric cancer (GC). METHODS: We evaluated 892 patients with CRC or GC, and assessed preoperative IMAC and mIMAC to compare their prognostic and predictive values for postoperative infectious complications in both cohorts. RESULTS: Both preoperative IMAC and mIMAC were sex- and disease-dependent, and positively or negatively correlated with age in CRC and GC patients (IMAC: CRC: r = 0.33, P < 0.0001; GC: r = 0.304, P < 0.0001; mIMAC: CRC: r = -0.364, P < 0.0001; GC: r = -0.263, P < 0.0001). In contrast to IMAC, lower preoperative mIMAC was significantly associated with disease-development factors, and was an independent prognostic factor for both overall survival (OS) and disease-free survival (DFS) in both CRC (OS: hazard ratio (HR): 1.95, 95% confidence interval (CI): 1.25-3.03, p = 0.003; DFS: HR: 1.93, 95% CI: 1.22-3.04, p = 0.005) and GC patients (OS: HR: 2.11, 95% CI: 1.22-3.68, P = 0.008; DFS: HR: 2.03, 95% CI: 1.18-3.5, P = 0.011). Patients with postoperative remote infections had a poorer prognosis compared with those without in both cohorts (CRC: HR: 2.67, 95% CI: 1.46-4.89, P = 0.002; GC: HR: 3.01, 95% CI: 1.47-6.19, P = 0.003), and low mIMAC was an independent risk factor for postoperative remote infection in both cancers (CRC: odds ratio (OR): 2.56, 95% CI: 1.06-6.23, P = 0.038; GC: OR: 2.8, 95% CI: 1.03-7.58, P = 0.043). Finally, we assessed the correlation between IMAC or mIMAC and the representative frailty markers body mass index (BMI), serum albumin, and prognostic nutritional index (PNI). We found a positive correlation between preoperative mIMAC and all of these markers in both cohorts (CRC: BMI: r = 0.193, P < 0.0001; serum albumin: r = 0.42, P < 0.0001; PNI: r = 0.39, P < 0.0001; GC: BMI: r = 0.22, P < 0.0001; serum albumin: r = 0.212, P < 0.0001; PNI: r = 0.287, P < 0.0001). CONCLUSIONS: Preoperative mIMAC could be useful for perioperative and postoperative management in CRC and GC.

High platelet × C-reactive protein level multiplier is a negative prognostic marker in rectal cancer treated by neoadjuvant chemoradiotherapy.

PURPOSE: The clinical significance of the platelet count × C-reactive protein level multiplier (P-CRP) in patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy followed by curative surgery has not been fully evaluated. METHODS: In this retrospective study, the correlation between the P-CRP and prognosis was evaluated in 135 patients with LARC. We also performed a subgroup analysis limited to patients with pathological TNM stage III [ypN(+)] LARC. RESULTS: The cut-off value of the P-CRP for prognosis was set at 4.11. The high and low P-CRP groups comprised 39 (28.89%) and 96 (71.11%) patients, respectively. Among the investigated clinicopathological factors, the serum carcinoembryonic antigen level and presence of recurrence were significantly associated with the P-CRP value. In the Kaplan-Meier analysis, both overall survival (OS) and disease-free survival (DFS) were shorter in the high P-CRP group (p < 0.0001 and p = 0.0002, respectively; log-rank test). Multivariate analysis using a Cox proportional hazards model showed that a high P-CRP was an independent prognostic factor for OS [hazard ratio (HR) 29.20; 95% confidence interval (CI), 3.42-294.44; p = 0.0024] and DFS (HR 5.89; 95%CI 1.31-22.69; p = 0.023) in patients with LARC. In addition, a high P-CRP predicted poor OS and DFS in patients with pathological TNM stage III [ypN(+)] LARC (p = 0.0001 and p = 0.0012, respectively; log-rank test). CONCLUSIONS: The P-CRP is a promising predictor of survival and recurrence in patients with LARC treated by neoadjuvant chemoradiotherapy followed by curative surgery.

Prognostic Potential of Lymphocyte-C-Reactive Protein Ratio in Patients with Rectal Cancer Receiving Preoperative Chemoradiotherapy.

PURPOSE: The systemic inflammatory response is attracting increasing attention as a predictive biomarker for oncological outcome in patients with colorectal cancer. This study is aimed at verifying if the lymphocyte-C-reactive protein (CRP) ratio (LCR) could be used as a predictor of oncological outcome in patients with rectal cancer (RC) receiving preoperative chemoradiotherapy (CRT). METHODS: We analyzed data for 86 patients with RC who received preoperative CRT followed by total mesorectal excision at our institution. A ratio of 6000 was used as the cut-off value for LCR for further analysis. RESULTS: The post-CRT LCR was significantly lower than the pre-CRT LCR in patients with RC. Although post-CRT LCR status was not significantly correlated with overall survival (OS), low pre-CRT LCR was significantly associated with shorter recurrence-free survival (RFS: p = 0.02) and OS (p = 0.017) in this population and was an independent prognostic factor for both RFS and OS (hazard ratio (HR) 3.19, 95% confidence interval (CI) 1.33-7.66, p = 0.009; HR 2.83, 95%CI 1.14-7.01, p = 0.025, respectively). Furthermore, low pre-CRT LCR was a stronger indicator of early recurrence (p = 0.001) and poor prognosis (p = 0.025) in RC patients without pathological lymph node metastasis compared with patients with pathological lymph node metastasis, and prognostic potential of pre-CRT LCR was clearly revealed especially RC patients receiving long-course CRT. CONCLUSIONS: Assessment of pretreatment LCR status might aid decision-making regarding postoperative treatment strategies in patients with RC receiving CRT followed by potentially curative resection.

Genomewide Expression Profiling Identifies a Novel miRNA-based Signature for the Detection of Peritoneal Metastasis in Patients With Gastric Cancer.

OBJECTIVE: This study aimed to conduct a genomewide transcriptomic profiling to develop a microRNA (miRNA)-based signature for the identification of peritoneal metastasis (PM) in patients with gastric cancer (GC). SUMMARY BACKGROUND DATA: Even though PM in patients with GC has long been recognized to associate with poor prognosis, currently there is lack of availability of molecular biomarkers for its robust diagnosis. METHODS: We performed a systematic biomarker discovery by analyzing miRNA expression profiles in primary tumors from GC patients with and without PM, and subsequently validated the expression of candidate miRNA biomarkers in 3 independent clinical cohorts of 354 patients with advanced GC. RESULTS: Five miRNAs (miR-30a-5p, -134-5p, -337-3p, -659-3p, and -3917) were identified during the initial discovery phase; three of which (miR-30a-5p, -659-3p, and -3917) were significantly overexpressed in the primary tumors from PM-positive patients in the testing cohort (P = 0.002, 0.04, and 0.007, respectively), and distinguished patients with versus without peritoneal metastasis with the value of area under the curve (AUC) of 0.82. Furthermore, high expression of these miRNAs also associated with poor prognosis (hazard ratio = 2.18, P = 0.04). The efficacy of the combination miRNA signature was subsequently validated in an independent validation cohort (AUC = 0.74). Finally, our miRNA signature when combined together with the macroscopic Borrmann's type score offered a much superior diagnostic in all 3 cohorts (AUC = 0.87, 0.76, and 0.79, respectively). CONCLUSIONS: We have established an miRNA-based signature that have a potential to identify peritoneal metastasis in GC patients.

Clinical significance of advanced lung cancer inflammation index, a nutritional and inflammation index, in gastric cancer patients after surgical resection: A propensity score matching analysis.

BACKGROUND: The advanced lung cancer inflammation index (ALI) has recently been shown as a prognostic marker for several cancers. However, its predictive value for surgical and oncological outcomes in gastric cancer (GC) remains unclear. METHODS: We retrospectively reviewed the preoperative ALI in 620 GC patients receiving gastrectomy to elucidate the prognostic value for overall survival (OS) and disease-free survival (DFS) and to clarify its predictive value for perioperative risk of surgical site infection (SSI) in GC patients. Propensity score matching (PSM) analysis was also conducted to certify these potentials of preoperative ALI. RESULTS: Preoperative low ALI was significantly correlated with advanced tumor-node-metastasis stage classification. Patients with low ALI showed poorer OS (p < 0.0001) and DFS (p < 0.0001) compared to those with high ALI, and multivariate analysis showed that decreased ALI was an independent prognostic factor for OS [hazard ratios of 1.59; 95% confidence interval (CI) of 1.15-2.19, p = 0.006]. Meanwhile, preoperative low ALI was also an independent risk factor for overall SSI [odds ratio (OR) of 2.04, 95% CI of 1.24-3.35, p = 0.005] or organ-space SSI (OR of 2.69, 95% CI of 1.40-5.23, p = 0.003). We further conducted PSM analysis and verified all of these findings in the PSM cohort. CONCLUSION: Quantification of preoperative ALI can identify patients with high risk of adverse perioperative and oncological outcomes in GC patients.

Preoperative computed tomography predicts the risk of recurrent laryngeal nerve paralysis in patients with esophageal cancer undergoing thoracoscopic esophagectomy in the prone position.

BACKGROUND: Recurrent laryngeal nerve paralysis (RLNP) after thoracoscopic esophagectomy for esophageal cancer (EC) is known to be a major complication leading to poor quality of life. RLNP is mainly associated with surgical procedures performed near the RLN. Therefore, with focus on the region of the RLN, we used preoperative computed tomography to investigate the risk factors of RLNP in patients with EC undergoing thoracoscopic esophagectomy. METHODS: We retrospectively examined 77 EC patients who underwent thoracoscopic esophagectomy in the prone position at our department between January 2010 and December 2018. Bilateral cross-sectional areas (mm2) of the fatty tissue around the RLN at the level of the lower pole of the thyroid gland were measured on preoperative axial computed tomography (CT) images. Univariate and multivariate logistic regression analysis was used to evaluate the association between the incidence of RLNP and patient clinical factors, including the cross-sectional areas. RESULTS: RLNP occurred in 24 of 77 patients (31.2%). The incidence of RLNP was significantly more frequent on the left side than on the right. (26% vs. 5.2%, respectively). Univariate analysis identified the following left RLNP risk factors: intrathoracic operative time (> 235 min), and area around the RLN (> 174.3 mm2). Multivariate analysis found that the area around the RLN was an independent risk factor of left RLNP. CONCLUSION: An increased area around the RLN measured on an axial CT view at the level of the lower pole of the thyroid gland was a risk factor of RLNP in EC patients undergoing thoracoscopic esophagectomy in the prone position.

Risk factors for arthropathy in patients with ulcerative colitis after total colectomy.

OBJECTIVE: Patients with ulcerative colitis (UC) often develop arthropathy. The purpose of this study was to determine the frequency of and risk factors for arthropathy in patients with UC who underwent total colectomy which is the final radical treatment lead to remission. METHODS: Patients who underwent total colectomy from January 2007 to April 2016 were analyzed for the development of arthropathy. The type of arthropathy and risk factors for developing arthropathy were analyzed by clinical and endoscopic severity classification, extraintestinal manifestations (EIMs) and medical treatment. RESULTS: Total of 219 patients who underwent total colectomy with sufficient medical records were analyzed. Forty-eight cases (21.9%) had EIMs, and 40 cases (18.2%) developed arthropathy (57.0% polyarthropathy; 42.5% peripheral arthropathy). Multivariate analysis showed that severity of Matts classification grade 3 or 4 versus grade 1 or 2 (hazard ratio [HR] 2.31, 95% confidence interval [CI] 1.22-4.36, p < .05) and EIMs other than arthropathy (HR 3.29, 95% CI 1.43-7.58, p < .05) were risk factors for the development of arthropathy. CONCLUSION: This study showed that approximately one fifth of patients with UC who underwent total colectomy developed arthropathy. The risk factors for the development of arthropathy were preoperative endoscopic disease activity and EIMs.

Advanced Lung Cancer Inflammation Index Predicts Outcomes of Patients With Colorectal Cancer After Surgical Resection.

BACKGROUND: The advanced lung cancer inflammation index is considered a useful prognostic biomarker of clinical outcomes in patients with malignancies. However, the prognostic value of the advanced lung cancer index in patients with colorectal cancer who underwent surgical resection remains unclear. OBJECTIVE: In this study, we evaluated the prognostic value of the advanced lung cancer index in patients with colorectal cancer. DESIGN: Prospectively obtained data of patients with colorectal cancer were retrospectively evaluated to clarify the clinical relevance of the advanced lung cancer index. SETTINGS: We conducted this study at a single expert center. PATIENTS: We enrolled 298 patients with colorectal cancer who underwent surgical resection in this retrospective study. MAIN OUTCOME MEASURES: The primary outcome was the clinical relevance of the advanced lung cancer index in patients with rectal cancer. RESULTS: Low status of advanced lung cancer index was significantly correlated with undifferentiated histology (p = 0.004), T stage progression (p < 0.001), R1/R2 resection for primary surgery (p = 0.004), and distant metastasis (p < 0.001). Multivariate analysis showed that low advanced lung cancer index status was an independent prognostic factor for both overall survival (HR = 3.21 (95% CI, 1.97-5.19); p < 0.001) and disease-free survival (HR = 2.13 (95% CI, 1.23-3.63); p = 0.008) in patients with colorectal cancer. Furthermore, the clinical burden of the advanced lung cancer index was consistent between sexes, and its prognostic value was verified in patients with clinically relevant stage III colorectal cancer. LIMITATIONS: The present study had several limitations, including retrospective observation and a small sample size of Japanese patients from a single institution. CONCLUSIONS: The advanced lung cancer index could be a useful prognostic indicator of clinical outcomes in patients who underwent surgical resection for colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B267. EL ÍNDICE AVANZADO DE INFLAMACIÓN DEL CÁNCER DE PULMÓN, PREDICE LOS RESULTADOS DE LOS PACIENTES CON CÁNCER COLORRECTAL DESPUÉS DE LA RESECCIÓN QUIRÚRGICA: El índice avanzado de inflamación del cáncer de pulmón, es considerado como un útil biomarcador pronóstico, en los resultados clínicos de pacientes con neoplasias malignas. Sin embargo, aún no está claro el valor pronóstico del índice avanzado de cáncer de pulmón, en pacientes con cáncer colorrectal sometidos a resección quirúrgica.Evaluar el valor pronóstico del índice avanzado del cáncer de pulmón, en pacientes con cáncer colorrectal.Los datos obtenidos prospectivamente de pacientes con cáncer colorrectal, fueron evaluados retrospectivamente, para aclarar la relevancia clínica del índice avanzado del cáncer de pulmónEstudio realizado en un solo centro experto.Estudio retrospectivo, incluyendo 298 pacientes con cáncer colorrectal, sometidos a resección quirúrgica.El resultado primario fue la relevancia clínica del índice avanzado de cáncer de pulmón, en pacientes con cáncer rectal.Un índice avanzado de cáncer de pulmón bajo, se correlacionó significativamente con la histología indiferenciada (p = 0.004), la progresión de la etapa T (p <0.001), la resección R1 / R2 para cirugía primaria (p = 0.004) y la metástasis a distancia (p <0.001). El análisis multivariante mostró que el índice avanzado de cáncer de pulmón bajo, era un factor pronóstico independiente, tanto para la supervivencia general (HR = 3.21 IC 95% 1.97-5.19 p <0.001) como para la supervivencia libre de enfermedad (HR = 2.13, IC 95% 1.23-3.63, p = 0,008), en pacientes con cáncer colorrectal. Además, la carga clínica del índice avanzado de cáncer de pulmón, fue consistente entre los sexos y su valor pronóstico se verificó clínicamente relevante, en pacientes con cáncer colorrectal en estadio III.El presente estudio tuvo varias limitaciones, incluyendo la observación retrospectiva y la pequeña muestra de pacientes japoneses, en una sola institución.El índice avanzado de cáncer de pulmón, podría ser un indicador pronóstico útil, en los resultados clínicos de pacientes sometidos a resección quirúrgica por cáncer colorrectal. Consulte Video Resumen http://links.lww.com/DCR/B267.

Remote ischemic conditioning counteracts the intestinal damage of necrotizing enterocolitis by improving intestinal microcirculation.

Necrotizing enterocolitis (NEC) is a devastating disease of premature infants with high mortality rate, indicating the need for precision treatment. NEC is characterized by intestinal inflammation and ischemia, as well derangements in intestinal microcirculation. Remote ischemic conditioning (RIC) has emerged as a promising tool in protecting distant organs against ischemia-induced damage. However, the effectiveness of RIC against NEC is unknown. To address this gap, we aimed to determine the efficacy and mechanism of action of RIC in experimental NEC. NEC was induced in mouse pups between postnatal day (P) 5 and 9. RIC was applied through intermittent occlusion of hind limb blood flow. RIC, when administered in the early stages of disease progression, decreases intestinal injury and prolongs survival. The mechanism of action of RIC involves increasing intestinal perfusion through vasodilation mediated by nitric oxide and hydrogen sulfide. RIC is a viable and non-invasive treatment strategy for NEC.

Preoperative heat shock protein 47 levels identify colorectal cancer patients with lymph node metastasis and poor prognosis.

Accumulating evidence suggests that overexpression of heat shock protein 47 (HSP47) increases cancer progression, and that HSP47 level in the tumor-associated stroma may serve as a diagnostic marker in various cancers. The present study aimed to evaluate whether HSP47 gene expression in colorectal cancer (CRC) tissues could be used to identify lymph node (LN) metastasis status preoperatively in patients with CRC. To do so, HSP47 gene expression was determined and its association with the clinicopathological characteristics of patients with CRC was analyzed. A total of 139 surgical specimens from patients with CRC and 36 patients with benign colonic disease undergoing surgery at Mie University Hospital were analyzed. HSP47 gene expression was determined by reverse transcription quantitative PCR using Power SYBR Green PCR methods. Expression level of HSP47 was significantly higher in CRC tissues compared with normal tissue from patients with benign colonic disease. Furthermore, high HSP47 expression was significantly associated with tumor progression, including high T stage, lymph node metastasis and venous invasion, and high TNM stage. High HSP47 expression may therefore serve as a novel predictive biomarker for determining patients with CRC and LN metastasis. According to Kaplan-Meier analysis, patients with high HSP47 expression level had significantly poorer overall survival than those with low HSP47 expression level. Furthermore, multivariate analyses identified HSP47 expression as an independent predictive marker for LN metastasis and poor overall survival in patients with CRC. In summary, the present study demonstrated that HSP47 expression may be considered as a novel biomarker for predicting LN metastasis status and prognosis in patients with CRC.

The relationship between preoperative T helper cytokines in the ileal mucosa and the pathogenesis of pouchitis.

BACKGROUND: Although the etiology of pouchitis remains unknown, inflammatory cytokines are significantly associated with the pathogenesis of pouchitis. The cytokine responses that characterize inflammatory bowel diseases (IBD) are key pathogenic components of the disease. Although cytokine profiles in the colonic mucosa have been investigated in experimental colitis models or IBD patients, cytokine profiles in the ileal mucosa at colectomy have been rarely assessed. AIM: To assess the relationship between pouchitis and T helper (Th) cytokines in the ileal mucosa collected at the time of colectomy and pouch construction. METHODS: This retrospective study involved 68 consecutive patients from January 2004 to May 2011 who underwent ileal pouch-anal anastomosis for ulcerative colitis. Samples were obtained from the terminal ileum of resected specimens at time of total colectomy or subtotal colectomy. mRNA expression levels of Th cytokines (IFN-γ, IL-23A, IL-5, IL-13 and IL-17A) were determined. RESULTS: Forty of 68 patients (58.8%) developed pouchitis. There was no association between IL-23A expression levels and incidence of pouchitis (p = 0.301). Patients with elevated IFN-γ had a significantly higher incidence of pouchitis compared with low IFN-γ patients (p = 0.043). Univariate analysis demonstrated a total dose of prednisolone > 7000 mg administered before colectomy (p = 0.04) and high IFN-γ expression (p = 0.02) were significant risk factors for pouchitis onset. In multivariate analysis, elevated IFN-γ messenger(m)RNA levels were significantly associated with pouchitis onset (p = 0.03). CONCLUSION: IFN-γ expression in the normal ileal mucosa at the time of colectomy may be an important factor in the pathophysiology of pouchitis.

Lymphocyte-C-reactive Protein Ratio as Promising New Marker for Predicting Surgical and Oncological Outcomes in Colorectal Cancer.

BACKGROUND: Systemic inflammation via host-tumor interactions is currently recognized as a hallmark of cancer. The aim of this study was to evaluate the prognostic value of various combinations of inflammatory factors using preoperative blood, and to assess the clinical significance of our newly developed inflammatory score in colorectal cancer (CRC) patients. METHOD: In total 477 CRC patients from the discovery and validation cohorts were enrolled in this study. We assessed the predictive impact for recurrence using a combination of nine inflammatory markers in the discovery set, and focused on lymphocyte-C-reactive protein ratio (LCR) to elucidate its prognostic and predictive value for peri-operative risk in both cohorts. RESULTS: A combination of lymphocytic count along with C-reactive protein levels demonstrated the highest correlation with recurrence compared with other parameters in CRC patients. Lower levels of preoperative LCR significantly correlated with undifferentiated histology, advanced T stage, presence of lymph node metastasis, distant metastasis, and advanced stage classification. Decreased preoperative LCR (using an optimal cut-off threshold of 6000) was an independent prognostic factor for both disease-free survival and overall survival, and emerged as an independent risk factor for postoperative complications and surgical-site infections in CRC patients. Finally, we assessed the clinical feasibility of LCR in an independent validation cohort, and confirmed that decreased preoperative LCR was an independent prognostic factor for both disease-free survival and overall survival, and was an independent predictor for postoperative complications and surgical-site infections in CRC patients. CONCLUSION: Preoperative LCR is a useful marker for perioperative and postoperative management of CRC patients.

Changes in surgical therapies for rectal cancer over the past 100 years: A review.

Advances in surgical and adjuvant therapies have resulted in a dramatic improvement in outcomes of rectal cancer in terms of both oncology and functional preservation. Surgery plays a central role in therapy as it is the only means of achieving a complete cure. These surgical advancements result from extensive pioneering research in the fields of anatomy and physiology. Much history lies behind the recent surgical breakthroughs of total mesorectal excision (TME) and intersphincteric resection (ISR). This article outlines the changes that have taken place in surgical therapies for rectal cancer over more than a century based on clinical trials performed to provide scientific evidence for these therapies.

Prognostic impacts of tumoral expression and serum levels of PD-L1 and CTLA-4 in colorectal cancer patients.

BACKGROUND: Programmed cell death ligand-1 (PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) play a pivotal role in cancer immunotherapy. Each of these molecules has a membrane-bound receptor form (mPD-L1/mCTLA-4) and a soluble form (sPD-L1/sCTLA-4). However, these prognostic impacts in colorectal cancer (CRC) remain unclear. METHODS: We immunohistochemically scored tumoral mPD-L1/mCTLA-4 expression and quantified preoperative circulating sPD-L1/sCTLA-4 levels using matched serum specimens from 131 patients with pStage I-III CRC. We also examined the association between these statuses and tumor infiltrating lymphocytes (TILs) in these patients. RESULTS: Elevated levels of mPD-L1, mCTLA-4, sPD-L1 and sCTLA-4 were significantly correlated with poor overall survival (OS) and disease-free survival (DFS). Co-high expression of tumoral mPD-L1 and mCTLA-4 or co-elevated levels of serum sPD-L1 and sCTLA-4 were strongly correlated with poor OS and DFS. Multivariate analysis revealed that both statuses were negative independent prognostic factors for OS [hazard ratio (HR) 3.86, 95% confidence interval (95% CI) 1.71-8.51, p = 0.001; HR 5.72, 95% CI 1.87-14.54, p = 0.004, respectively] and DFS (HR 2.53, 95% CI 1.23-4.95, p = 0.01; HR 6.88, 95% CI 2.42-17.13, p = 0.0008, respectively). Although low expression of tumoral mCTLA-4 was significantly correlated with increased CD8(+) TILs, there was no correlation in any other combination. CONCLUSIONS: We verified the prognostic impacts of mPD-L1, mCTLA-4, sPD-L1 and sCTLA-4 in pStage I-III CRC patients. Dual evaluation of immune checkpoint molecules in primary tissues or preoperative serum could identify a patient population with poor prognosis in these patients.

Billroth-I Reconstruction with Overlap Anastomosis Using an EndoWrist Linear Stapler After Robotic Distal Gastrectomy.

Introduction: Robotic distal gastrectomy (RDG) is now thought to be less invasive than conventional laparoscopic distal gastrectomy (LDG) for gastric cancer. Although the delta-shaped anastomosis is an established, widely performed procedure for intracorporeal Billroth-I (B-I) gastroduodenostomy after LDG, it has some difficulties and is performed in the ischemic region of the duodenum. We therefore developed a novel overlap B-I gastroduodenostomy after RDG. Materials and Methods: We started using the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, CA) for RDG in May 2017. The robotic overlap B-I reconstruction was performed via side-to-side anastomosis, as follows: Two small incisions were made, one on the greater curvature of the remnant stomach, 5 cm from the edge of the remnant gastric stump, and one on the superior edge of the anterior wall of the duodenal stump. A 45-mm EndoWrist linear stapler device (EWLS) loaded with a blue cartridge was inserted through the incision. After the remnant stomach and duodenum were attached to the V-shaped form by the EWLS, the incisions were closed by the EWLS. Results: Seven patients underwent RDG followed by a robotic overlap B-I procedure up to March 2019. Short-term outcomes were determined from medical records and operative videos. No intraoperative complications or conversions to open or conventional laparoscopic surgery occurred. The mean time for the anastomosis was 37 (range 29-45 minutes) minutes. No postoperative complications occurred following the robotic overlap B-I procedure. Discussion: RDG followed by an overlap B-I gastroduodenostomy might be feasible and safe. However, long-term follow-up is required to identify additional benefits.

Safety of double-balloon enteroscopy in postoperative pediatric patients.

BACKGROUND: The aim of the present study was to investigate the efficacy and safety of double-balloon enteroscopy (DBE) in postoperative pediatric patients. METHODS: This was a retrospective analysis of pediatric patients 18 years and younger referred to Mie University Hospital. Twenty procedures in 11 children occurred postoperatively; 29 children (42 procedures) had not undergone surgery. RESULTS: Among postoperative patients, five DBE procedures were performed via the oral route, 12 via the anal route, and three via a stomal route. Among nonoperative patients, 14 DBE procedures were performed via the oral route and 28 via the anal route. Four postoperative patients and two nonoperative patients had difficult pleating via the transanal route because of adhesions or thickening of the intestinal wall resulting from inflammation (P = 0.02). Excluding patients with stenosis, the mean length of endoscopic insertion for transanal procedures was significantly shorter among postoperative patients than among nonoperative patients (73.6 cm vs 160.5 cm, P < 0.01). There were no major complications in either group. CONCLUSIONS: Insertion difficulty was encountered in postoperative pediatric patients. However, our findings indicate that DBE is a safe procedure in postoperative pediatric patients.

Risk factors and intraoral breast milk application for methicillin-resistant Staphylococcus aureus colonization in surgical neonates.

BACKGROUND: Our previous study identified methicillin-resistant Staphylococcus aureus (MRSA) colonization as an independent risk factor for neonatal surgical site infection. Here we introduce intraoral breast milk application (IBMA) during a fasting state to prevent MRSA colonization. We aimed to evaluate both the risk factors for MRSA colonization and the efficacy of IBMA in neonatal surgical patients. METHODS: A retrospective review was performed using admission data from 2007 to 2016. Neonatal patients who underwent surgery and were tested periodically for MRSA colonization were evaluated for an association between MRSA colonization and perinatal or perioperative factors. RESULTS: The overall incidence of MRSA colonization for the 159 patients enrolled in this study was 16.4%. Univariate analysis showed that MRSA colonization was significantly more frequent in the following patients: those with Down syndrome, those admitted on their day of birth, those in need of fasting immediately after birth, and those not receiving IBMA. Multivariate analysis showed that comorbid Down syndrome was an independent risk factor (hazard ratio: 4.6; 95% confidence interval: 1.2-19.5, P = 0.03) and implementation of IBMA was an independent preventive factor for MRSA colonization (hazard ratio: 0.4; 95% confidence interval: 0.1-0.9, P = 0.04). MRSA-positive patients admitted significantly earlier and stayed longer preoperatively than MRSA-negative patients. CONCLUSIONS: In neonates undergoing surgery, and patients with Down syndrome, early diagnosis after birth and a long waiting period before operation may be associated with MRSA colonization. Intraoral breast milk application may be beneficial for preventing MRSA colonization.