Two onset types of achalasia and the long-term course to diagnosis.

BACKGROUND: Recently, the incidence of achalasia has been increasing, but its cause remains unknown. This study aimed to examine the initial symptoms and the course of symptoms and to find new insights into the cause and course of the disease. METHODS: Altogether, 136 patients diagnosed with achalasia by high-resolution manometry (HRM) were enrolled. Questionnaires and chart reviews were conducted to investigate the initial symptoms, time from onset to diagnosis, and comorbidities, as well as the relationship between HRM results, time to diagnosis, and symptom severity. RESULTS: In total, 67 of 136 patients responded to the questionnaire. The median ages of onset and diagnosis were 42 and 58 years, respectively. The median time from onset to diagnosis was 78.6 months, with 25 cases (37.3%) taking > 10 years to be diagnosed. The symptom onset was gradual and sudden in 52 (77.6%) and 11 (16.4%) patients, respectively. Of the 11 patients with acute onset, three (27.3%) developed anhidrosis at the same time. There was no correlation between the time from onset to diagnosis and esophageal dilatation, resting LES pressure, or mean integrated relaxation pressure (IRP). No correlation was also found between the degree of symptoms and resting LES pressure or IRP. CONCLUSION: Esophageal achalasia can have acute or insidious onsets. This finding may help to elucidate the cause of achalasia.

CT-derived skeletal muscle change before immunotherapy predicts survival of advanced gastric cancer: associations with inflammatory markers and liver lipid metabolism.

BACKGROUND: Skeletal muscle (SM) is a key factor in cancer treatment. However, it is unclear whether pretreatment SM change affects the outcome of immune checkpoint inhibitors (ICIs) therapy in gastric cancer (GC). METHODS: Advanced GCs treated with ICIs were retrospectively investigated. SM evaluated by psoas muscle area at the third lumbar vertebra was measured on CT acquired within 1 month from the start of ICIs therapy (CT-1), and on CT acquired 2.8 ± 0.84 months before CT-1. Monthly change rate of SM (MCR-SM) was defined as the change rate of SMs between those two CTs divided by the period between those CTs (month). Monthly change rate of body weight (MCR-BW) during the same period was also calculated. They were compared with disease-specific survival (DSS) and progression-free survival (PFS). MCR-SM was compared with pretreatment markers including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), C-reactive protein (CRP), and liver-to-spleen CT attenuation ratio (LSR) as a marker of liver lipid metabolism. RESULTS: This study enrolled eighty-three GC patients. MCR-SM significantly correlated with DSS and PFS (P < 0.0001, 0.001, respectively), whereas MCR-BW did not. Kaplan-Meier analyses demonstrated that higher MCR-SM (MCR-SM ≥ -0.7185%) significantly associated with better DSS and PFS (P = 0.0002, 0.03, respectively). Patients with positive MCR-SM showed significantly lower NLR, MLR, and CRP than those with negative (P = 0.01, 0.006, 0.003, respectively). MCR-SM showed a significant positive correlation with LSR (P = 0.007, R = 0.30). CONCLUSIONS: Pretreatment SM loss, associated with high systemic inflammation and hepatic fat accumulation, related to poor outcome of ICIs therapy in GC.

Remarkable response as a new indicator for endoscopic evaluation of local efficacy of non-surgical treatments for esophageal cancer.

In Japan, standard of care of the patients with resectable esophageal cancer is neoadjuvant chemotherapy (NAC) followed by esophagectomy. Patients unfitted for surgery or with unresectable locally advanced esophageal cancer are generally indicated with definitive chemoradiotherapy (CRT). Local disease control is undoubtful important for the management of patients with esophageal cancer, therefore endoscopic evaluation of local efficacy after non-surgical treatments must be essential. The significant shrink of primary site after NAC has been reported as a good indicator of pathological good response as well as favorable survival outcome after esophagectomy. And patients who could achieve remarkable shrink to T1 level after CRT had favorable outcomes with salvage surgery and could be good candidates for salvage endoscopic treatments. Based on these data, "Japanese Classification of Esophageal Cancer, 12th edition" defined the new endoscopic criteria "remarkable response (RR)", that means significant volume reduction after treatment, with the subjective endoscopic evaluation are proposed. In addition, the finding of local recurrence (LR) at primary site after achieving a CR was also proposed in the latest edition of Japanese Classification of Esophageal Cancer. The findings of LR are also important for detecting candidates for salvage endoscopic treatments at an early timing during surveillance after CRT. The endoscopic evaluation would encourage us to make concrete decisions for further treatment indications, therefore physicians treating patients with esophageal cancer should be well-acquainted with each finding.

Intraoperative assessment of blood flow using transabdominal ultrasound during laparoscopic surgery of celiac artery compression syndrome.

Surgical treatment of celiac artery (CA) compression syndrome (CACS) is to release the median arcuate ligament (MAL) by removing the abdominal nerve plexus surrounding CA. In laparoscopic surgery of CACS, objective intraoperative assessment of blood flow in CA is highly desirable. We herein demonstrate a case of laparoscopic surgery of CACS with use of intraoperative transabdominal ultrasound. A 52-year-old woman was presented with epigastric pain and vomiting after eating. Contrast-enhanced computed tomography demonstrated significant stenosis at the origin of CA. Doppler study of CA was also performed, and she was diagnosed as CACS. Laparoscopic surgery was performed, and the MAL was divided. And then, Doppler study using intraoperative transabdominal ultrasound confirmed the successful decompression of CA. This patient was discharged on postoperative day 11, and her symptoms was improved. Intraoperative assessment of blood flow in CA using transabdominal ultrasound was a simple and useful method for laparoscopic surgery of CACS.

Use of inducible and limiting fluorescence in laparoscopic endoscopic cooperative surgery.

Video 1Demonstration of the special use of the near-infrared fluorescent clip in laparoscopic endoscopic cooperative surgery.

Peripherally inserted central catheter securement with cyanoacrylate glue and bloodstream infection: A retrospective cohort study.

BACKGROUND: Treatment via a peripherally inserted central venous catheter is important for anticancer treatment, perioperative management, and nutrition management. In this study, we aimed to investigate the usefulness of cyanoacrylate glue (CG) in managing peripherally inserted central venous catheters in adults. METHODS: This retrospective cohort study enrolled 411 adults requiring a central venous catheter for treatment in the Chiba University Esophageal-Gastro-Intestinal Surgery department between January 2021 and October 2022. The preventive effect of CG in reducing adverse events, including infection, tip migration, and thrombus formation, was evaluated by reviewing electronic medical records, chest radiographs, and contrast-enhanced computed tomography scans. RESULTS: CG and other dressings were used in 158 (CG group) and 253 (control group) patients, respectively. The incidence of catheter infection based on the clinical course was lower in the CG group (3.2%) than in the control group (9.1%; P = 0.03). However, cases of infection confirmed by blood or catheter cultures did not differ between the CG (1.3%) and control (1.9%) groups (P = 1.0). Chest radiographs revealed that catheter tip migration (mean ± SD) was lesser in the CG group (8.2 ± 6.7 mm) than in the control group (15.0 ± 15.8 mm; P < 0.01). There were two cases of venous thrombus formation in the control group. CONCLUSION: In a population dominated by esophago-gastroenterological malignancy, peripherally inserted central catheter securement via CG was associated with decreased catheter removal because of suspected catheter infection. Further research on larger cohorts is needed to determine if other adverse events decrease following peripherally inserted central catheter securement via CG.

Inflammatory and Nutritional Indices as Prognostic Markers in Elderly Patients With Gastric Cancer.

BACKGROUND/AIM: Peripheral blood inflammatory and nutritional indices are independent prognostic factors for various cancers. However, as society's longevity and the demand for surgery in the elderly increase, it remains unclear whether these indices are valuable for patients aged ≥80 years. This study aimed to assess the utility of peripheral blood indices as prognostic markers in elderly patients with gastric cancer (GC). PATIENTS AND METHODS: This study included 103 elderly patients (aged ≥80 years) who underwent radical gastrectomy at our hospital between 2008 and 2020. Preoperative systemic inflammatory and nutritional indices, including the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and prognostic and nutritional index (PNI), were evaluated. Prognostic evaluation was performed using Kaplan-Meier analysis and Cox regression. RESULTS: There were no statistically significant differences in NLR, PLR, and LMR regarding overall survival (OS) and relapse-free survival (RFS). However, patients with low PNI had a markedly worse prognosis (3-year OS: 63.9% vs. 81.2%, p=0.002; 3-year RFS: 55.3% vs. 77.6%, p=0.002). Multivariate analysis revealed that male sex and low PNI were independent predictors of OS (p=0.007p=0.003, respectively) and RFS, with only PNI showing significance (p=0.023). CONCLUSION: Preoperative PNI is an independent prognostic factor for survival in elderly patients with GC who undergo radical gastrectomy.

Gut microbiome can predict chemoradiotherapy efficacy in patients with esophageal squamous cell carcinoma.

PURPOSE: The gut microbiome plays an important role in cancer pathogenesis and therapy. Some studies have reported that specific bacteria in tumor tissues may contribute to the prognosis and treatment of esophageal squamous cell carcinoma (ESCC). However, there is limited evidence that the gut microbiome is associated with ESCC. This study assessed the utility of the gut microbiome as a predictive marker of the therapeutic effect in patients with ESCC undergoing chemo-radiotherapy (CRT). PATIENTS AND METHODS: Fecal samples were collected from 51 patients with ESCC who had never undergone treatment between April 2021 and May 2022 in the Department of Frontier Surgery, Chiba University. The gut microbiome was analyzed using 16S metagenomics sequencing. The association between the gut microbiome composition and stage according to the TNM classification (American Joint Committee on Cancer 7.0) and CRT response according to the RECIST criteria was evaluated. RESULTS: The relative abundance of Fusobacteriaceae was enriched in cStage III-IVb group. Among the 27 patients who received CRT, the relative abundance of Lactobacillaceae was enriched in those with a partial and complete response. Lactobacillaceae also did not correlate with any clinical data, but the high Lactobacillales group had a higher LMR (P = 0.032) and lower PLR (P = 0.045) than in the low Lactobacillales group. CONCLUSIONS: In conclusion, we found that the relative abundance of Lactobacillaceae was enriched in patients with a partial or complete response among CRT those with ESCC, thus suggesting that the relative abundance of Lactobacillaceae can predict the effect of CRT.

Analysis of patients with colorectal cancer shows a specific increase in serum anti-ING1 autoantibody levels.

Colorectal cancer (CRC) is the third most prevalent cancer in the world, yet the sensitivity and specificity of biomarkers for CRC diagnosis are insufficient. In the present study, we performed a protein microarray screening method to identify antibody markers for CRC. Inhibitor of growth family 1 (ING1) was identified as a candidate tumor antigen for CRC using protein microarrays (ProtoArray). Subsequent amplified luminescence proximity homogeneous assay-linked immunosorbent assay using recombinant ING1 protein showed that the serum levels of anti-ING1 antibodies were increased not only in patients with CRC but also in those with esophageal cancer (EC), gastric cancer (GC), breast cancer (BrC), and pancreatic cancer (PC) compared with those of healthy donors (HDs). Antibodies against the ING1 amino acids between 239 and 253 were present at significantly higher levels in patients with CRC than in those with EC, GC, BrC, or PC. Anti-ING1 antibody levels were significantly higher in the patients with CRC at any stages than in the HDs. Immunohistochemical staining revealed higher expression of ING1 protein in CRC cells than in the adjacent normal tissues. In luciferase reporter assays using a CRC cell line, ING1 augmented p53-mediated NOXA promoter activity but attenuated p53-stimulated Bax, p21, and PUMA promoter activities. Consequently, serum anti-ING1 antibodies can be used for sensitive and specific diagnoses of CRC.

ypTNM staging is a potentially useful prognostic stratification tool in patients with advanced gastric cancer after preoperative chemotherapy.

PURPOSE: Although the usefulness of the ypStage in neoadjuvant chemotherapy for advanced gastric cancer (GC) has been reported, whether or not the ypStage is applicable to all GC patients who receive preoperative chemotherapy, including conversion surgery cases, is unclear. Therefore, this retrospective study evaluated the value of the ypTNM staging system in all advanced GC patients who received chemotherapy prior to gastrectomy. METHODS: A total of 66 patients who underwent chemotherapy prior to gastrectomy for advanced GC at Chiba University Hospital from January 2008 to December 2020 were enrolled in the current study. The prognostic impact of the ypStage on the overall survival (OS) and relapse-free survival (RFS) were examined via univariate and multivariate analyses. RESULTS: The 5-year OS rates for ypStage I, II, III, and IV were 87.5%, 64.7%, 52.9%, and 28.6%, respectively, while the 5-year RFS rates were 81.3%, 57.4%, 44.4%, and 28.6%, respectively. The univariate analysis revealed that the ypStage was significantly correlated with the OS (p = 0.037) and the ypT status and ypStage showed a significant correlation with the RFS (p = 0.043 and p = 0.021, respectively). The multivariate analysis demonstrated that only the ypStage was an independent prognostic factor for the OS and RFS (p = 0.024 and p = 0.018, respectively). CONCLUSION: The ypTNM stage may be a useful tool for the risk stratification of all advanced GC patients treated with chemotherapy followed by gastrectomy, including not only neoadjuvant but also conversion surgery cases.

Prognostic Impact of Hepatic Steatosis Evaluated by CT on Immunotherapy for Gastric Cancer: Associations with Sarcopenia, Systemic Inflammation, and Hormones.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) are expected to improve the prognosis of gastric cancer (GC). Also, hepatic steatosis has been reported to be associated with cancer cachexia and is expected to be a cancer biomarker. The purpose of this study was to evaluate prognostic impact of hepatic steatosis in ICI therapy for GC. METHODS: Unresectable or recurrent GC treated with ICIs was investigated. Using unenhanced CT, the liver-to-spleen CT attenuation ratio (LSR) was calculated as a parameter of hepatic steatosis. LSR was compared with the presence of sarcopenia and inflammatory markers including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR). These parameters were also compared with disease-specific survival (DSS) and progression-free survival (PFS). Associations of LSR with insulin-like growth factor 1 (IGF-1) and growth hormone were also evaluated. RESULTS: A total of 70 patients were investigated. LSR of sarcopenia patients was significantly lower than that of non-sarcopenic ones (p = 0.02). LSR showed significant negative correlations with NLR, PLR, and MLR (p = 0.003, 0.03, 0.01, respectively). Lower LSR was significantly associated with a higher level of serum IGF-1 (p = 0.03). In univariate analysis, LSR was significantly correlated with DSS and PFS (both p < 0.0001), and multivariate analysis demonstrated that LSR was the independent prognostic factor for both DSS and PFS (both p = 0.01). ROC analysis demonstrated that LSR >1.263 was a good predictive marker for favorable DSS (>5.3 months) with an AUC of 0.80. CONCLUSION: Hepatic steatosis can be a promising prognostic biomarker for ICI therapy of GC, associated with sarcopenia and the elevation of inflammatory markers. Our data suggested that GC with steatohepatitis might be less responsive to ICI therapy.

Why is endosonography insufficient for residual diagnosis after neoadjuvant therapy for esophageal cancer? Solutions using muscle layer evaluation.

BACKGROUND: The diagnosis of residual tumors using endoscopic ultrasound (EUS) after neoadjuvant therapy for esophageal cancer is considered challenging. However, the reasons for this difficulty are not well understood. AIM: To investigate the ultrasound imaging features of residual tumors and identify the limitations and potential of EUS. METHODS: This exploratory prospective observational study enrolled 23 esophageal squamous cell carcinoma patients receiving esophagectomy after neoadjuvant therapy [15 patients after neoadjuvant chemotherapy (NAC) and 8 patients after chemoradiotherapy (CRT)] at the Department of Surgery, Chiba University Hospital, between May 2020 and October 2021. We diagnosed the T stage for specimens using ultrasound just after surgery and compared ultrasound images with the cut surface of the fixed specimens of the same level of residual tumor. The ratio of esophageal muscle layer defect measured by ultrasound was compared with clinicopathological factors. Furthermore, the rate of reduction for the muscle layer defect was evaluated using EUS images obtained before and after neoadjuvant therapy. RESULTS: The accuracy of T stage rate was 61% (n = 14/23), which worsened after CRT (38%, n = 3/8) than after NAC (73%, n = 11/15) because of overstaging. Moreover, pT0 could not be diagnosed in all cases. The detection rate of residual tumor for specimens using ultrasound retrospectively was 75% (n = 15/20). There was no correlation between after-NAC (79%, n = 11/14) and after-CRT (67%, n = 4/6) detection rate. The detection of superficial and submucosal types was poor. The pathologic tumor size and pathological response were correlated. Tumor borders were irregular and echogenicity was mixed type after CRT. There was a correlation between the pT stage (pT0/1 vs pT2/3) and the length of muscle layer circumference (P = 0.025), the length of muscle layer defect (P < 0.001), and the ratio of muscle layer defect (P < 0.001). There was also a correlation between the pT stage and the rate of muscle layer defect reduction measured by EUS (P = 0.001). CONCLUSION: Compared to pathological images, some tumors are undetectable by ultrasound. Focusing on the esophageal muscle layer might help diagnose the depth of the residual tumor.

HIF-1α stimulates the progression of oesophageal squamous cell carcinoma by activating the Wnt/ß-catenin signalling pathway.

BACKGROUND: This study aimed to clarify the significance of the crosstalk between hypoxia-inducible factor-1α (HIF-1α) and the Wnt/ß-catenin pathway in oesophageal squamous cell carcinoma (ESCC). METHODS: The oncogenic role of HIF-1α in ESCC was investigated using in vitro and in vivo assays. The clinicopathological significance of HIF-1α, ß-catenin and TCF4/TCF7L2 in ESCC were evaluated using quantitative real-time PCR and immunohistochemistry. RESULTS: The expression level of HIF-1α, ß-catenin, and TCF4/TCF7L2 in T.Tn and TE1 cell lines were elevated under hypoxia in vitro. HIF-1α knockdown suppressed proliferation, migration/invasion and epithelial-mesenchymal transition (EMT) progression, induced G0/G1 cell cycle arrest, promoted apoptosis and inhibited 5-fluorouracil chemoresistance in vitro. In vivo assays showed that HIF-1α is essential in maintaining tumour growth, angiogenesis, and 5-fluorouracil chemoresistance. Mechanically, we identified the complex between HIF-1α and ß-catenin, HIF-1α can directly bind to the promoter region of TCF4/TCF7L2. The mRNA level of HIF-1α, ß-catenin and TCF4/TCF7L2 were increased in ESCC tumour tissues compared to the corresponding non-tumour tissues. High levels of HIF-1α and TCF4/TCF7L2 expression were correlated with aggressive phenotypes and poor prognosis in ESCC patients. CONCLUSIONS: HIF-1α serves as an oncogenic transcriptional factor in ESCC, probably by directly targeting TCF4/TCF7L2 and activating the Wnt/ß-catenin pathway.

Comparison of estimated treatment effects between randomized controlled trials, case-matched, and cohort studies on laparoscopic versus open distal gastrectomy for advanced gastric cancer: a systematic review and meta-analysis.

PURPOSE: In actual surgical research, case-matched studies are frequently conducted as an alternative to randomized controlled trials (RCTs). However, it is still unclear what differences there are between RCTs and case-matched studies in upper gastrointestinal surgery, and clarifying them is a very important clinical issue. Thus, the purpose of this study was to investigate estimated treatment effects between RCTs, case-matched studies, and cohort studies regarding laparoscopic distal gastrectomy (LDG) for advanced gastric cancer (AGC). METHODS: We searched the PubMed, Cochrane Central Register of Controlled Trials, and Web of Science databases for studies that compared LDG versus open distal gastrectomy for AGC published from the inception of the databases until July 2021. A meta-analysis was performed using the Review Manager version 5.3 software program from the Cochrane Collaboration, and six short-term outcomes and three long-term outcomes were assessed. RESULTS: Twenty-three studies with 13698 patients were included. There was no difference in estimated treatment effects between RCTs and case-matched studies for all outcomes except for the number of retrieved lymph nodes and postoperative complications. In terms of intraoperative blood loss, postoperative hospital stay, number of retrieved lymph nodes, and recurrence, observational studies tended to overestimate the treatment effects. CONCLUSION: The estimated treatment effects of LDG for AGC in the case-matched study were almost the same as in the RCTs. However, to assess the true magnitude of the treatment effect, the design and actual implementation of the analysis must be critically evaluated.

Lowering the setting value of the esophageal endoscopic submucosal dissection device enabled tissue damage control in vitro porcine model.

One of the complications of esophageal endoscopic submucosal dissection (ESD) is postoperative stricture formation. Stenosis formation is associated with inflammation and fibrosis in the healing process. We hypothesized that the degree of thermal damage caused by the device is related to stricture formation. We aimed to reveal the relationship between thermal damage and setting value of the device. We energized a resected porcine esophagus using the ESD device (Flush Knife 1.5). We performed 10 energization points for 1 s, 3 s, and 5 s at four setting values of the device. We measured the amount of current flowing to the conducted points and the temperature and evaluated the effects of thermal damage pathologically. As results, the mean highest temperatures for 1 s were I (SWIFT Effect3 Wat20): 61.19 °C, II (SWIFT Effect3 Wat30): 77.28 °C, III (SWIFT Effect4 Wat20): 94.50 °C, and IV (SWIFT Effect4 Wat30): 94.29 °C. The mean heat denaturation areas were I: 0.84 mm2, II: 1.00 mm2, III: 1.91 mm2, and IV: 1.54 mm2. The mean highest temperature and mean heat denaturation area were significantly correlated (P < 0.001). In conclusion, Low-current ESD can suppress the actual temperature and thermal damage in the ESD wound.

A case report of duodenal arteriovenous malformation: usefulness of intraoperative indocyanine green angiography for precise identification of the lesion.

BACKGROUND: Arteriovenous malformation (AVM) of the gastrointestinal (GI) tract can cause bleeding. The treatment choice for GI tract AVM is surgical resection of the involved bowel segment with complete resection of the nidus. The AVM formed in the duodenum or pancreatic head could also cause gastrointestinal bleeding, and there are several reports of pancreaticoduodenectomy as its treatment. However, if the area of AVM can be accurately identified during surgery, it may be possible to completely resect the AVM while preserving the organ. We report a case of duodenal AVM in a patient successfully treated with a subtotal stomach-preserving duodenal bulb resection using intraoperative indocyanine green (ICG) angiography technique. CASE PRESENTATION: An 18-year-old man was diagnosed with duodenal AVM after several examinations for anemia and was referred to our hospital for further treatment. Preoperative imaging studies showed that the inflow vessels of this duodenal AVM were the inferior pyloric artery and the superior duodenal artery, and the AVM was localized to the duodenal bulb. Thereafter, stomach-preserving duodenal bulb resection preceded by ligation of the inflow vessels was performed. During the surgery, ICG angiography clearly demonstrated the area, where the nidus was distributed, and a duodenal bulb resection with complete resection of the AVM was successfully performed. There was no recurrence at the 6-month follow-up. CONCLUSIONS: Intraoperative ICG angiography was a useful procedure for precise identification of the AVM of the GI tract.

A double-scope technique enabled a patient with an esophageal plastic fork foreign body to avoid surgery: a case report and review of the literature.

Foreign body ingestion is a common problem, and endoscopic removal is often performed with ancillary equipment. However, long, sharp foreign bodies are much more difficult to remove endoscopically than other objects and require emergent surgery. A 68-year-old man with a history of distal gastrectomy accidentally swallowed a plastic fork. He complained of chest pain at the visit. The plastic fork was located between the thoracic esophagus and remnant stomach. Endoscopic removal of the plastic fork was considered difficult, and surgery was deemed necessary. However, we were able to avoid surgery to remove the object using two endoscopes with hoods and a polypectomy snare. The first endoscope covered the sharp edge with a hood, and the snare grasped the neck of the plastic fork. The second endoscope covered the remaining sharp tip. A single operator held the two endoscopes and the snare and pulled them out together. This new double-scope technique is simple and useful for removing long, sharp foreign bodies, such as forks, from the esophagus.

Does thoracoscopic esophagectomy really reduce post-operative pneumonia in all cases?

It has been said that "thoracoscopy suppresses the occurrence of pneumonia in comparison to thoracotomy", but does it reflect real clinical practice? To resolve this clinical question, we compared the results of randomized controlled trials (RCTs) and retrospective cohort studies from limited institutes (CLIs) in which a large number of high-volume centers were the main participants to those of retrospective cohort studies based on nationwide databases (CNDs) in which both high-volume centers and low-volume hospitals participated. A systematic review and meta-analysis were conducted to compare the short-term outcomes of thoracoscopic to open esophagectomy for esophageal cancer in the three above-mentioned research formats. In total, 43 studies with 21,057 patients, which included 1 RCT with 115 patients, 38 CLIs with 6,126 patients and 4 CNDs with 14,816 patients, were selected. Pneumonia was one of the most important complications. Although significant superiority in thoracoscopic esophagectomy was observed in RCTs (p = 0.005) and CLIs (p = 0.003), no such difference was seen in findings using nationwide databases (p = 0.69). In conclusion, unlike RCTs and CLIs, CNDs did not show the superiority of thoracoscopic surgery in terms of post-operative pneumonia. RCTs and CLIs were predominantly performed by high-volume hospitals, while CNDs were often performed by low-volume hospitals. In actual clinical practice including various types of hospitals, the superiority of thoracoscopic over open esophagectomy regarding the incidence of pneumonia may, therefore, decrease.

Development of imaging biomarker for esophageal cancer using intravoxel incoherent motion MRI.

BACKGROUND: Intravoxel incoherent motion MRI (IVIM-MRI) can quantify micro-perfusion at the capillary level in the tissue. The purpose of this study is to measure tumor perfusion using IVIM-MRI, and evaluate its value as a biomarker to predict prognosis in esophageal squamous cell carcinoma (ESCC) patients. METHODS: 109 ESCC patients (93 men and 16 women; median age: 72) who underwent IVIM-MRI prior to treatment between February 2018 and August 2020 were retrospectively investigated. Both mean apparent diffusion coefficient (ADC) value and mean perfusion-related parameter (PP) value of the primary tumor were measured using three b values of 0, 400, and 1000 s/mm2 based on the IVIM model. We analyzed associations of these parameters with clinical stage and disease-specific survival (DSS). RESULTS: Lower ADC and PP values of the tumor were significantly associated with the higher clinical T stage (p < 0.0001, p < 0.0001, respectively). In Kaplan-Meier analyses, patients with lower PP value tumors (< 18.94, median) had significantly worse DSS (p < 0.0001), while tumor ADC value did not show a significant correlation with DSS. In a multivariate analysis, PP value of the tumor was an independent prognostic factor for DSS (p = 0.0027). CONCLUSIONS: Quantification of tumor perfusion using IVIM-MRI can be a non-invasive prognostic biomarker of ESCC, reflecting clinical stage and survival.