Exploratory analysis of serum HER2 extracellular domain for HER2 positive gastric cancer treated with SOX plus trastuzumab.

BACKGROUND: The aim of this study was to explore the clinical utility of serum HER2 extracellular domain (sHER2 ECD) using data from a clinical trial evaluating trastuzumab combined S-1 plus oxaliplatin (SOX) in HER2 positive gastric cancer. METHODS: sHER2 ECD were prospectively measured at baseline and subsequent treatment courses. Based on each quantile point of baseline sHER2 ECD levels and its early changes, patients were divided into two groups and compared clinical outcomes. RESULTS: 43 patients were enrolled, and 17 patients (39.5%) were positive for baseline sHER2 ECD. Higher baseline sHER2 ECD levels tended to have lower hazard ratios (HRs). When divided into two groups by baseline sHER2 ECD of 19.1 ng/ml, median progression-free survival (PFS) and overall survival (OS) was longer in the higher group (mPFS: 16.8 vs 8.7 months, p = 0.359. mOS: 35.5 vs 20.6 months, p = 0.270), respectively. After initiation of treatment, sHER2 ECD significantly decreased up until the third cycle. Higher reduction rates of sHER2 ECD within 3 cycles also tended to have lower HRs. When divided into two groups by reduction rate of 42.5%, mPFS and mOS was longer in the higher reduced group (mPFS: 17.2 vs 8.7 months, p = 0.095. mOS: 65.0 vs 17.8 months, p = 0.047), respectively. Furthermore, higher reduction rates could surrogate higher objective response rates (ORR) (ORR: 90% vs 63.2% for 29.5%, p = 0.065. 100% vs 70% for 42.5%, p = 0.085), respectively. CONCLUSIONS: Baseline sHER2 ECD levels and its early decline may be useful biomarkers for SOX plus trastuzumab efficacy in HER2 positive gastric cancer.

Risk factors for early recurrence after radical gastrectomy followed by adjuvant chemotherapy for stage II or III gastric cancer: a multicenter, retrospective study.

BACKGROUND: Radical gastrectomy followed by adjuvant chemotherapy is the standard treatment for stage II or III gastric cancer in Asian countries. Early recurrence during or after adjuvant chemotherapy is associated with poor prognosis; however, risk factors for early recurrence remain unclear. METHODS: In this multicenter, retrospective cohort study including six institutions, we evaluated the clinicopathological factors of 553 patients with gastric cancer undergoing gastrectomy followed by adjuvant chemotherapy between 2012 and 2016. Patients were divided into the following groups: early recurrence (recurrence during adjuvant chemotherapy or within 6 months after adjuvant chemotherapy completion) and non-early recurrence, which was further divided into late recurrence and no recurrence. Early-recurrence risk factors were investigated using multivariate Cox proportional hazard model. The chronological changes in the recurrence hazard were also examined for each factor. RESULTS: Early recurrence and late recurrence occurred in 83 (15.0%) and 73 (13.2%) patients, respectively. Based on the Cox proportional hazards model, a postoperative serum carcinoembryonic antigen level of ≥5 ng/mL (hazard ratio: 2.220, 95% confidence interval: 1.089-4.526) and a neutrophil-to-lymphocyte ratio of >1.8 (hazard ratio: 2.408, 95% confidence interval: 1.479-3.92) were identified as independent risk factors of early recurrence, but not late recurrence. The recurrence hazard ratios for neutrophil-to-lymphocyte ratio significantly decreased over time (P < 0.001) and carcinoembryonic antigen also had the same tendency (P = 0.08). CONCLUSIONS: A carcinoembryonic antigen level of ≥5 ng/mL and a neutrophil-to-lymphocyte ratio of >1.8 are predictors of early recurrence after radical gastrectomy and adjuvant chemotherapy for stage II or III gastric cancer.

Multicenter phase II study of capecitabine plus oxaliplatin in older patients with advanced gastric cancer: the Tokyo Cooperative Oncology Group (TCOG) GI-1601 study.

BACKGROUND: Capecitabine plus oxaliplatin (CapeOX) is a standard treatment option for advanced gastric cancer (AGC). We conducted a prospective multicenter phase II study to evaluate the efficacy and safety of CapeOX as a first-line therapy for AGC in older patients. METHODS: Chemotherapy-naive patients aged ≥ 70 years with AGC were eligible. Initial treatment comprised capecitabine (2000 mg/m2 on days 1-14) and oxaliplatin (130 mg/m2 on day 1) every 3 weeks. After the initial feasibility assessment, the dose was reduced considering toxicity (capecitabine, 1500 mg/m2 on days 1-14; and oxaliplatin, 100 mg/m2 on day 1 every 3 weeks). The primary endpoint was overall survival (OS). RESULTS: In total, 108 patients were enrolled, of whom 104 were evaluated. Thirty-nine patients received the original-dose treatment, whereas 65 received the reduced-dose treatment. The median OS, progression-free survival (PFS), and time to treatment failure (TTF) were 12.9 (95% CI 11.6-14.8), 5.7 (95% CI 5.0-7.0), and 4.3 (95% CI 3.9-5.7) months, respectively, for all patients; 13.4 (95% CI 9.5-16.0), 5.8 (95% CI 4.1-7.8), and 5.3 (95% CI 3.5-7.2) months in the original-dose group; and 12.8 (95% CI 11.3-15.3), 5.7 (95% CI 4.4-7.0), and 4.1 (95% CI 3.7-5.7) months in the reduced-dose group. The most common grade 3/4 toxicities were neutropenia (17.9%), anemia (12.8%), and thrombocytopenia (12.8%) in the original-dose group and neutropenia (13.8%) and anorexia (12.3%) in the reduced-dose group. CONCLUSIONS: These findings demonstrate CapeOX's efficacy and safety in older AGC patients.

A multi-institutional observational study evaluating the incidence and the clinicopathological characteristics of NeoRAS wild-type metastatic colorectal cancer.

PURPOSE: As circulating tumor DNA (ctDNA) measurement becomes more widespread, the "NeoRAS" phenomenon, where tissue rat sarcoma viral oncogene homolog (RAS) status converts from mutant (MT) to wild-type (WT) after treatment in metastatic colorectal cancer (mCRC), is gaining attention because ineffective epidermal growth factor receptor (EGFR) inhibitors may made effective. This study investigated its incidence and clinicopathological characteristics. PATIENTS AND METHODS: In total, 107 mCRC patients (refractory or intolerant to previous chemotherapies) with tissue RAS MT were enrolled in four institutions from June 2021 to August 2022. The RAS status in ctDNA was assessed using OncoBEAM™ RAS CRC assay. Clinicopathologic features were compared between patients according to their RAS status in ctDNA, whether WT conversion was noted or not. RESULTS: The incidence rate of NeoRAS WT mCRC was 21.5% (23/107). According to tissue RAS mutation sites, NeoRAS WT frequency in patients with KRAS mutation in exon 2 was significantly lower than those in exon 3 and 4 or NRAS (18.2% [18/99] vs 62.5% [5/8], P = 0.011). Regarding clinical background, there were significant differences in NeoRAS WT frequency between male vs female patients (30.6% [19/62] vs 8.9% [4/45], P = 0.008), and absence vs presence of liver metastasis (38.6% [17/44] vs 9.5% [6/63], P < 0.001). Comparing the two groups divided by the median value, NeoRAS WT was associated with smaller tumor diameter (>60.9 mm vs ≤, 3.8% [2/53] vs 38.9% [21/54], P < 0.001), lower carcinoembryonic antigen level (>38.2 ng/ml vs ≤, 11.3% [6/53] vs 31.5% [17/54], P = 0.018), and lower carbohydrate antigen 19-9 level (>158.0 U/ml vs ≤, 9.4% [5/53] vs 33.3% [18/54], P = 0.004). In the logistic regression multivariate analysis, liver metastasis absence (Odds ratio [OR], 4.62; P = 0.019), smaller tumor diameter (OR, 7.92; P = 0.012), and tissue RAS MT in other than KRAS exon 2 (OR, 9.04; P = 0.026) were significantly related to the conversion to NeoRAS WT in ctDNA. CONCLUSIONS: Original RAS variants in tissue, tumor diameter, and liver metastasis are related to conversion to NeoRAS WT mCRC in ctDNA.

Ultrasound evaluation of vagus nerve cross-sectional area in a community-dwelling elderly Japanese cohort.

OBJECTIVES: Although the vagus nerve (VN) is easily observed by ultrasonography, few studies have evaluated the cross-sectional area (CSA) of the VN in healthy older individuals from East Asia. In this study, we aimed to report reference values for the CSA of the VN in community-dwelling elderly Japanese individuals and to identify any associated medical history and/or lifestyle factors. METHODS: The present study included 336 participants aged ≥ 70 years from a prospective cohort study conducted in Yahaba, Japan from October 2021 to February 2022. The CSA of the VN was measured bilaterally at the level of the thyroid gland by ultrasonography. Simple linear regression analysis and generalized estimating equation were conducted to identify the associations between clinical and background factors and the CSA of the VN. RESULTS: In our cohort, the median CSA of the VN was 1.3 mm2 (interquartile range [IQR] 1.1-1.6) on the right side and 1.2 mm2 (IQR 1.0-1.4) on the left side. Generalized estimating equation showed that history of head injury (ß = 0.19, p < .01), current smoking habit (ß = -0.09, p = .03), and BMI (ß = 0.02, p < .01) were independently associated with the CSA of the VN. CONCLUSION: We have reported reference VN CSA values for community-dwelling elderly Japanese individuals. In addition, we showed that the CSA of the VN was positively associated with a history of head injury and BMI and inversely associated with current smoking habit.

Perioperative TAS-118 plus oxaliplatin in patients with locally advanced gastric cancer: APOLLO-11 study.

BACKGROUND: We investigated the feasibility of perioperative chemotherapy with S-1 and leucovorin (TAS-118) plus oxaliplatin in patients with locally advanced gastric cancer. METHODS: Patients with clinical T3-4N1-3M0 gastric cancer received four courses of TAS-118 (40-60 mg/body, orally, twice daily for seven days) plus oxaliplatin (85 mg/m2, intravenously, day one) every two weeks preoperatively followed by gastrectomy with D2 lymphadenectomy, followed by postoperative chemotherapy with either 12 courses of TAS-118 monotherapy (Step 1) or eight courses of TAS-118 plus oxaliplatin (Step 2). The primary endpoints were completion rates of preoperative chemotherapy with TAS-118 plus oxaliplatin and postoperative chemotherapy with TAS-118 monotherapy (Step 1) or TAS-118 plus oxaliplatin (Step 2). RESULTS: Among 45 patients enrolled, the preoperative chemotherapy completion rate was 88.9% (90% CI 78.0-95.5). Major grade ≥ 3 adverse events (AEs) were diarrhoea (17.8%) and neutropenia (8.9%). The R0 resection rate was 95.6% (90% CI 86.7-99.2). Complete pathological response was achieved in 6 patients (13.3%). Dose-limiting toxicity was not observed in 31 patients receiving postoperative chemotherapy (Step 1, n = 11; Step 2, n = 20), and completion rates were 90.9% (95% CI 63.6-99.5) for Step 1 and 80.0% (95% CI 59.9-92.9) for Step 2. No more than 10% of grade ≥ 3 AEs were observed in patients receiving Step 1. Hypokalaemia and neutropenia occurred in 3 and 2 patients, respectively, receiving Step 2. The 3-year recurrence-free and overall survival rates were 66.7% (95% CI 50.9-78.4) and 84.4% (95% CI 70.1-92.3), respectively. CONCLUSIONS: Perioperative chemotherapy with TAS-118 plus oxaliplatin with D2 gastrectomy is feasible.

Anatomical Position of the Pancreas as a Risk Factor for Pancreatic Fistula after Laparoscopic Gastrectomy for Gastric Cancer.

BACKGROUND: Laparoscopic gastrectomy is more frequently associated with postoperative pancreatic fistula than is open gastrectomy. We assumed that compression of the pancreas with various devices to obtain a proper operative view is associated with the higher incidence of PF in LG and that the extent of the compression differs depending on the anatomical position of the pancreas. The present study aimed to elucidate the correlation between the anatomical position of the pancreas and PF after LG for gastric cancer. METHODS: Patients who underwent LG for gastric cancer from 2005 to 2019 were retrospectively reviewed. Two anatomical parameters representing the height of the slope looking down the celiac artery from the top of the pancreas (P-A length) and the steepness of the slope (UP-CA angle) were measured in computed tomography sagittal projections. The correlation between PF and (1) P-A length, (2) UP-CA angle, and (3) other clinicopathological factors was analyzed using a logistic regression model. RESULTS: Among 3485 patients, grade ≥ II PF was observed in 140 (4.0%) patients. The UP-CA angle [odds ratio (OR), 2.472; 95% confidence interval (CI), 1.725-3.543; P < 0.001], a high BMI (OR 2.339; 95% CI 1.634-3.348; P < 0.001), and male sex (OR 2.602; 95% CI 1.590-4.257; P < 0.001) were independently correlated with grade ≥ II PF. CONCLUSIONS: The present study identified a significant correlation between anatomical position of the pancreas and PF after LG. High BMI and male sex were also significantly correlated with PF after LG.

Prognostic Factors in Patients with Advanced HER2-Positive Gastric Cancer Treated with Trastuzumab-Based Chemotherapy: a Cohort Study.

PURPOSE: Prognostic factors for the survival of patients with advanced HER2-positive gastric cancer treated with trastuzumab-based chemotherapy remain controversial. The aim of this study was to identify the clinical factors that predict prognosis in patients with advanced HER2-positive gastric cancer. METHODS: We retrospectively reviewed the medical records of HER2-positive gastric cancer patients treated with trastuzumab-based chemotherapy at our institution. Clinical features and laboratory test results that considered prognostic factors were re-examined. Overall survival (OS) was estimated using the Kaplan-Meier method. Univariate analysis was performed with the log-rank test and multivariate analysis was performed using Cox's proportional hazard regression model. RESULTS: A total of 133 patients with advanced HER2-positive gastric cancer were enrolled. The median OS in this cohort was 18.7 months. Four prognostic factors: visceral metastasis (lung or liver), levels of hemoglobin (Hb) (< 11.6 g/dl), lactate dehydrogenase (LDH) (> 222 mg/dl), and C-reactive protein (CRP) (> 0.14 mg/dl), were identified as independent prognostic factors. The patients were placed into three groups according to their number of prognostic factors. These included low (0, 1), moderate (2, 3), and high (4) risk factors. The OS was separated into three categories with a median OS of 32.0, 18.7, and 10.1 months, respectively. Compared to the low-risk group, hazard ratios for the moderate- and high-risk groups were 1.75 and 3.49, respectively. CONCLUSION: Visceral metastasis and abnormal Hb, LDH, and CRP levels were associated with unfavorable OS. These findings may be beneficial for the management of advanced HER2-positive gastric cancer treated with trastuzumab-based chemotherapy.

Multicentre single-arm phase II trial evaluating the safety and effiCacy of Panitumumab and iRinOtecan in NeoRAS Wild-type mEtaStatic colorectal cancer patientS (C-PROWESS trial): study protocol.

INTRODUCTION: A new concept of 'NeoRAS wild-type (WT)', which means conversion of RAS status from RAS mutant to RAS WT after treatment, has been reported. Previous observational and proof-of-concept studies have demonstrated the efficacy of epidermal growth factor receptor inhibitors in patients with NeoRAS WT metastatic colorectal cancer (mCRC). Moreover, posthoc biomarker analyses of these studies have suggested that not only the RAS status in the circulating tumour DNA (ctDNA) but also other gene mutational status may be useful as biomarkers of epidermal growth factor receptor inhibitors for NeoRAS WT mCRC. METHODS AND ANALYSIS: This trial is a multicentre, single-arm, phase II trial to assess the efficacy and safety of panitumumab plus irinotecan therapy for patients with NeoRAS mCRC. The key eligibility criteria include RAS mutant mCRC initially proven in tumour tissue refractory or intolerant to fluoropyrimidine, oxaliplatin and irinotecan; RAS WT in ctDNA (defined as plasma mutant allele frequencies of all RAS ≤0.1%) within 28 days before enrolment and Eastern Cooperative Oncology Group performance status ≤2. The primary endpoint is the response rate. The target sample size is 30 patients. Biomarker analyses are planned to be performed using next-generation sequencing-based ctDNA analysis. ETHICS AND DISSEMINATION: This study was approved by the certified review board of National Cancer Center Hospital. The main results of the trial will be presented in international meetings and in medical journals. TRIAL REGISTRATION NUMBER: s031210565.

Initial Safety Analysis of CapeOx for Elderly Patients With Advanced Gastric Cancer Patients: A Phase II Trial.

BACKGROUND: Safety of combination chemotherapy using platinum and fluorouracil has not been evaluated adequately for advanced gastric cancer (AGC) in elderly patients. PATIENTS AND METHODS: We initiated a phase II study to evaluate the efficacy and safety of capecitabine plus oxaliplatin (CapeOX) as first-line therapy for patients with AGC aged ≥70 years. Planned assessment of toxicity was made upon recruitment of the first 20 patients. RESULTS: In five out of 20 patients, unacceptable toxicity was observed, including three patients who were unable to complete the initial two courses due to adverse events. Among the other 15 patients, dose reduction due to toxicity were needed in 10 and treatment delay for adverse events also occurred in 12 patients during the first two courses. CONCLUSION: Early analyses of safety suggest that the CapeOX regimen was not tolerated without dose reduction for elderly patients with AGC in this study.

Rare presentation of tuberculous hypertrophic pachymeningitis diagnosed by a biopsy of abdominal lymphadenopathy.

A 59-year-old man with medical history of diabetes mellitus and hypertension presented with a persistent fever of unknown origin and developed a headache. Laboratory tests, including polymerase chain reaction assays for Mycobacterium tuberculosis, showed no specific abnormal findings in blood or cerebrospinal fluid. Contrast-enhanced computed tomography revealed abdominal paraaortic lymphadenopathy. Abdominal lymph node biopsy showed caseous necrosis and suggested tuberculous lymphadenopathy. Intensive examinations revealed positive T-SPOT.TB test and multiple dural nodular hypertrophic lesions in brain magnetic resonance imaging. After antitubercular treatment, all clinical manifestations and dural nodular lesions improved. Finally, we diagnosed the patient with tuberculous hypertrophic pachymeningitis. To our knowledge, this is the first report of tuberculous hypertrophic pachymeningitis concomitant with abdominal tuberculous lymphadenopathy and no other dissemination. Systematic investigation of tuberculosis is important for pachymeningitis.

Additive effect of evaluating microsurface and microvascular patterns using magnifying endoscopy with narrow-band imaging in gastric cancer: a post-hoc analysis of a single-center observational study.

BACKGROUND: No studies have compared the performance of microvascular and microsurface patterns alone with their combination in patients undergoing magnifying endoscopy with narrow-band imaging for diagnosing gastric cancer. This study aimed to clarify the differences in diagnostic performance among these methods. METHODS: Thirty-three participating endoscopists who had received specialized training in magnifying endoscopy evaluated the microvascular and microsurface patterns of images of 106 cancerous and 106 non-cancerous lesions. If classified as "irregular," the lesion was diagnosed as gastric cancer. To evaluate diagnostic performance, we compared the diagnostic accuracy, sensitivity, and specificity of these methods. RESULTS: Performance-related items did not differ significantly between microvascular and microsurface patterns. However, the diagnostic accuracy and sensitivity were significantly higher when using a combination of these methods than when using microvascular (82.1% [76.4-86.7] vs. 76.4% [70.3-81.6] and 69.8% [60.5-77.8] vs. 63.2% [53.7-71.8]; P < 0.001 and P = 0.008, respectively) or microsurface (82.1% [76.4-86.7] vs. 73.6% [67.3-79.1] and 69.8% [60.5-77.8] vs. 52.8% [43.4‒62.1]; both, P < 0.001) patterns alone. The additive effect on diagnostic accuracy and sensitivity was 5.7‒8.6% and 6.6‒17.0%, respectively. CONCLUSIONS: We demonstrate the superiority of the combination of microvascular and microsurface patterns over microvascular or microsurface patterns alone for diagnosing gastric cancer. Our data support the use of the former method in clinical practice. Although a major limitation of this study was its retrospective, single-center design, our findings may help to improve the diagnosis of gastric cancer.

Non-operative management after chemoradiotherapy plus consolidation or sandwich (induction with bevacizumab and consolidation) chemotherapy in patients with locally advanced rectal cancer: a multicentre, randomised phase II trial (NOMINATE trial).

INTRODUCTION: Total mesorectal excision (TME) and postoperative adjuvant chemotherapy following neoadjuvant chemoradiotherapy (CRT) is the standard treatment for locally advanced rectal cancer (LARC). However, neoadjuvant CRT has no recognised impact on reducing distant recurrence, and patients suffer from a long-lasting impairment in quality of life (QOL) associated with TME. Total neoadjuvant therapy (TNT) is an alternative approach that could reduce distant metastases and increase the proportion of patients who could safely undergo non-operative management (NOM). This study is designed to compare two TNT regimens in the context of NOM for selecting a more optimal regimen for patients with LARC. METHODS AND ANALYSIS: NOMINATE trial is a prospective, multicentre, randomised phase II selection design study. Patients must have clinical stage II or III (T3-T4Nany) LARC with distal location (≤5 cm from the anal verge or for those who are candidates for abdominoperineal resection or intersphincteric resection). Patients will be randomised to either arm A consisting of CRT (50.4 Gy with capecitabine) followed by consolidation chemotherapy (six cycles of CapeOx), or arm B consisting of induction chemotherapy (three cycles of CapeOx plus bevacizumab) followed by CRT and consolidation chemotherapy (three cycles of CapeOx). In the case of clinical complete response (cCR) or near cCR, patients will progress to NOM. Response assessment involves a combination of digital rectal examination, endoscopy and MRI. The primary endpoint is the proportion of patients achieving pathological CR or cCR≥2 years, defined as the absence of local regrowth within 2 years after the start of NOM among eligible patients. Secondary endpoints include the cCR rate, near cCR rate, rate of NOM, overall survival, distant metastasis-free survival, locoregional failure-free survival, time to disease-related treatment failure, TME-free survival, permanent stoma-free survival, safety of the treatment, completion rate of the treatment and QOL. Allowing for a drop-out rate of 10%, 66 patients (33 per arm) from five institutions will be accrued. ETHICS AND DISSEMINATION: The study protocol was approved by Wakayama Medical University Certified Review Board in December 2020. Trial results will be published in peer-reviewed international journals and on the jRCT website. TRIAL REGISTRATION NUMBER: jRCTs051200121.

Intestinal Perforation Caused by Lumboperitoneal Shunt Insertion Repaired with an Over-the-Scope Clip.

Lumboperitoneal or ventriculoperitoneal shunt insertion is a standard therapy for hydrocephalus that diverts cerebrospinal fluid from the subarachnoid space into the peritoneal cavity. Gastrointestinal perforations due to this procedure occur rarely; however, accepted treatment strategies have not yet been established. Hence, the most common treatment approaches are open surgery or spontaneous closure without endoscopy. We report the case of a small intestinal perforation in a 73-year-old-woman that occurred after the insertion of a lumboperitoneal shunt. A positive cerebrospinal fluid culture and high cerebrospinal fluid white blood cell count indicated a retrograde bacterial infection, and computed tomography revealed that the peritoneal tip of the shunt catheter was located in the lumen of the gastrointestinal tract. We repaired the perforation endoscopically using an over-the-scope clip, and the patient's recovery was uneventful. Use of an over-the-scope clip could be an effective and minimally invasive treatment for intestinal perforations caused by lumboperitoneal or ventriculoperitoneal shunt insertion.

Risk factors and oncological impact of positive resection margins in gastrectomy for cancer: are they salvaged by an additional resection?

BACKGROUND: The situation of positive resection margins (PRMs) varies notably between Western and Asian countries. In the West, PRMs are associated with advanced disease and R1, whereas in Asia, PRMs are also considered in early disease because stomach preservation was recently prioritized. Furthermore, PRMs are usually resected to obtain R0. However, the oncological impact of PRMs and additional resection remains unclear. The aim of this study is to evaluate the oncological impact of PRMs in laparoscopic gastrectomy (LG) for clinical stage (cStage) I gastric cancer. METHODS: A total of 2121 patients who underwent LG for cStage I gastric cancer between 2007 and 2015 were enrolled. Survival outcomes were compared between patients with PRMs (group P) and those without (group N). Furthermore, prognostic factors were analyzed using multivariate analysis. RESULTS: Twenty-seven patients (1.3%) had PRMs. Patients in group P had upper and more advanced disease, and the 5-year relapse-free survival (RFS) rate was worse in group P compared with group N (76.3% vs. 95.1%, P = 0.003). The 5-year RFS of patients with pT2 or deeper (pT2-4) disease in group P was significantly worse than that of patients in group N (66.7% vs. 89.5%, P = 0.030) although that of patients with pT1 was not. Likelihood ratio tests showed that there was a significant interaction between pT status and PRM (P = 0.005). CONCLUSION: PRM in cStage I gastric cancer is associated with advanced upper disease. It remains an independent prognostic factor in pT2-4 disease even after an additional resection to obtain R0.

Evaluation of Microvascular Patterns Alone Using Endocytoscopy with Narrow-Band Imaging for Diagnosing Gastric Cancer.

INTRODUCTION: Although endocytoscopy (EC) with narrow-band imaging (NBI) is effective in diagnosing gastric cancer, no diagnostic system has been validated. We explored a specific diagnostic system for gastric cancer using EC with NBI. METHODS: Equal numbers of images from cancerous and noncancerous areas (114 images each) were assessed by endoscopists with (development group: 33) and without (validation group: 28) specific training in magnifying endoscopy with NBI. Microvascular and microsurface patterns (MS) in each image were evaluated. Lesions were diagnosed as cancerous when patterns were deemed "irregular." The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of a diagnosis according to patterns on EC with NBI (microvascular pattern [MV] alone, MS alone, and both) were evaluated and compared between groups to determine the diagnostic performance. RESULTS: In the development and validation groups, diagnoses based on the MV alone had significantly higher accuracy (91.7% vs. 76.3%, p < 0.0001 and 92.5% vs. 67.5%, p < 0.0001, respectively) and sensitivity (88.6% vs. 68.3%, p < 0.0001 and 89.5% vs. 38.6%, p < 0.0001, respectively) than those based on the MS alone. In both groups, there were no significant differences in diagnostic accuracy between using the MV alone and both patterns. DISCUSSION/CONCLUSION: Evaluation of the MV alone is a simple and accurate diagnostic method for gastric cancer. This system could find widespread applications in clinical practice.

Oncologic Outcomes of Laparoscopic Radical Hysterectomy Using the No-Look No-Touch Technique for Early Stage Cervical Cancer: A Propensity Score-Adjusted Analysis.

We evaluated oncologic outcomes of laparoscopic radical hysterectomy using the no-look no-touch technique (NLNT). We analyzed patients with early stage (IA2, IB1, and IIA1, FIGO2008) cervical cancer treated between December 2014 and December 2019. The primary endpoint was disease-free survival (DFS). We compared the outcomes of the abdominal radical hysterectomy (ARH) and NLNT groups using a Cox model with inverse probability of treatment weighting (IPTW), according to propensity scores. We also evaluated NLNT's non-inferiority to ARH using an evaluation of heterogeneity between the results of the Laparoscopic Approach to Cervical Cancer (LACC) trial and our study. ARH and NLNT were performed in 118 and 113 patients, respectively. The median follow-up duration was 3.2 years. After IPTW adjustment, the 3-year DFS rates (NLNT 92.4%; ARH 94.0%) and overall survival rates did not differ significantly between the groups. Furthermore, the 3-year DFS rates for patients with tumor sizes ≥ 2 cm in the NLNT (85.0%) and ARH (90.3%) groups did not differ significantly. No significant heterogeneity was observed between the LACC trial and our study (I2 = 60.5%, p = 0.111), although there was a trend toward a lower hazard ratio in our study. Laparoscopic radical hysterectomy using NLNT provides a favorable prognosis for early stage cervical cancer.

Preliminary prospective study of real-time post-gastrectomy glycemic fluctuations during dumping symptoms using continuous glucose monitoring.

BACKGROUND: Although dumping symptoms constitute the most common post-gastrectomy syndromes impairing patient quality of life, the causes, including blood sugar fluctuations, are difficult to elucidate due to limitations in examining dumping symptoms as they occur. AIM: To investigate relationships between glucose fluctuations and the occurrence of dumping symptoms in patients undergoing gastrectomy for gastric cancer. METHODS: Patients receiving distal gastrectomy with Billroth-I (DG-BI) or Roux-en-Y reconstruction (DG-RY) and total gastrectomy with RY (TG-RY) for gastric cancer (March 2018-January 2020) were prospectively enrolled. Interstitial tissue glycemic profiles were measured every 15 min, up to 14 d, by continuous glucose monitoring. Dumping episodes were recorded on 5 patient-selected days by diary. Within 3 h postprandially, dumping-associated glycemic changes were defined as a dumping profile, those without symptoms as a control profile. These profiles were compared. RESULTS: Thirty patients were enrolled (10 DG-BI, 10 DG-RY, 10 TG-RY). The 47 early dumping profiles of DG-BI showed immediately sharp rises after a meal, which 47 control profiles did not (P < 0.05). Curves of the 15 late dumping profiles of DG-BI were similar to those of early dumping profiles, with lower glycemic levels. DG-RY and TG-RY late dumping profiles (7 and 13, respectively) showed rapid glycemic decreases from a high glycemic state postprandially to hypoglycemia, with a steeper drop in TG-RY than in DG-RY. CONCLUSION: Postprandial glycemic changes suggest dumping symptoms after standard gastrectomy for gastric cancer. Furthermore, glycemic profiles during dumping may differ depending on reconstruction methods after gastrectomy.

Safety of Small Circular Staplers in Double Stapling Technique Anastomosis for Sigmoid Colon and Rectal Cancer.

BACKGROUND: Although smaller circular staplers are easier to insert and less likely to involve the vagina and levator ani muscles when performing double stapling technique anastomosis, surgeons often consider that larger circular staplers would be safer in reducing the risk of postoperative anastomotic strictures. OBJECTIVE: This study aimed to investigate the safety of using 25-mm circular staplers compared with 28/29-mm staplers in the double stapling technique anastomosis regarding the development of anastomotic strictures and other complications. DESIGN: This is a retrospective observational study. SETTING: This study was conducted at a single comprehensive cancer center. PATIENTS: Consecutive patients undergoing curative colorectal resection with double stapling technique anastomosis for stage I to III sigmoid colon and rectal cancer between 2013 and 2016 were included. MAIN OUTCOME MEASURES: The incidence of anastomotic complications (strictures, leakage, and bleeding) was compared between the 25- and 28/29-mm circular staplers. Predictors for anastomotic strictures were investigated with multivariable logistic regression. RESULTS: Small (25-mm) staplers were used in 186 (22.8%) of 815 eligible patients. The 25-mm staplers were associated with use in female patients, splenic flexure take down, high tie of the inferior mesenteric artery, and low anastomosis. Overall anastomotic complications (11.8% vs 13.7%, p = 0.51), strictures (5.9% vs 3.3%, p = 0.11), leakage (2.7% vs 3.8%, p = 0.47), and bleeding (4.8% vs 7.6%, p = 0.19) were not different between the 25- and 28/29-mm staplers. From multivariable logistic regression, independent predictors of anastomotic strictures included diverting ostomy and anastomotic leakage, but not small circular stapler use. Most of the 32 anastomotic strictures were successfully treated without surgical intervention (finger dilation, n = 25; endoscopic intervention, n = 5). LIMITATIONS: This was a single-center retrospective study. CONCLUSIONS: Use of 25-mm circular staplers for double stapling technique anastomosis is safe and does not increase the risk of anastomotic strictures and other anastomotic complications in comparison with larger staplers. See Video Abstract at http://links.lww.com/DCR/B576. SEGURIDAD DE ENGRAPADORAS CIRCULARES PEQUEAS EN ANASTOMOSIS, CON TCNICA DE DOBLE ENGRAPADO PARA CNCER DE RECTO Y COLON SIGMOIDE: ANTECEDENTES:Aunque las engrapadoras circulares más pequeñas son más fáciles de insertar y menos probable que involucren a la vagina y los músculos elevadores del ano, cuando se realiza una anastomosis con técnica de doble engrapado, frecuentemente los cirujanos consideran que las engrapadoras circulares más grandes, serían más seguras para disminuir los riesgos de estenosis anastomóticas postoperatorias.OBJETIVO:El estudio se dirigió para investigar la seguridad en el uso de engrapadoras circulares de 25 mm, en comparación con engrapadoras de 28/29 mm, en anastomosis con técnica de doble engrapado, en relación al desarrollo de estenosis anastomóticas y otras complicaciones.DISEÑO:Estudio observacional retrospectivo.AJUSTE:Centro oncológico integral único.PACIENTES:Se incluyeron pacientes consecutivos sometidos a resección colorrectal curativa, con anastomosis y técnica de doble engrapado, para cáncer de recto y colon sigmoide en estadios I-III entre 2013 y 2016.PRINCIPALES MEDIDAS DE RESULTADO:Se compararon las incidencias de complicaciones anastomóticas (estenosis, fugas y sangrados) entre las engrapadoras circulares de 25 y 28/29 mm. Los predictores para estenosis anastomóticas se investigaron con regresión logística multivariable.RESULTADOS:Entre un total de 815 pacientes elegibles, se utilizaron engrapadoras de 25 mm en 186 (22,8%). Las engrapadoras de 25 mm se asociaron con el uso en pacientes femeninas, descenso del ángulo esplénico, ligadura alta de arteria mesentérica inferior y anastomosis baja. Complicaciones anastomóticas generales (11,8% vs. 13,7%, p = 0,51), estenosis (5,9% vs. 3,3%, p = 0,11), fugas (2,7% vs. 3,8%, p = 0,47) y sangrado (4,8% vs. 7,6%, p = 0,19). No hubo diferencia entre las engrapadoras de 25 y 28/29 mm. En la regresión logística multivariable, predictores independientes de estenosis anastomóticas incluyeron ostomía derivativa y fuga anastomótica, pero no incluyeron el uso de engrapadoras circulares pequeñas. La mayoría de las 32 estenosis anastomóticas se trataron con éxito sin intervención quirúrgica (dilatación del dedo, n = 25; intervención endoscópica, n = 5).LIMITACIONES:Fue un estudio retrospectivo de un solo centro.CONCLUSIONES:El uso de engrapadoras circulares de 25 mm para la anastomosis con técnica de doble engrapado, es seguro y no aumenta el riesgo de estenosis anastomóticas y de otras complicaciones anastomóticas, cuando son comparadas con engrapadoras más grandes. Consulte Video Resumen en http://links.lww.com/DCR/B576. (Traducción-Dr. Fidel Ruiz-Healy).