Sphingosine-1-phosphate promotes tumor development and liver fibrosis in mouse model of congestive hepatopathy.

BACKGROUND AND AIMS: Chronic liver congestion reflecting right-sided heart failure (RHF), Budd-Chiari syndrome, or Fontan-associated liver disease (FALD) is involved in liver fibrosis and HCC. However, molecular mechanisms of fibrosis and HCC in chronic liver congestion remain poorly understood. APPROACH AND RESULTS: Here, we first demonstrated that chronic liver congestion promoted HCC and metastatic liver tumor growth using murine model of chronic liver congestion by partial inferior vena cava ligation (pIVCL). As the initial step triggering HCC promotion and fibrosis, gut-derived lipopolysaccharide (LPS) appeared to induce LSECs capillarization in mice and in vitro. LSEC capillarization was also confirmed in patients with FALD. Mitogenic factor, sphingosine-1-phosphate (S1P), was increased in congestive liver and expression of sphingosine kinase 1, a major synthetase of S1P, was increased in capillarized LSECs after pIVCL. Inhibition of S1P receptor (S1PR) 1 (Ex26) and S1PR2 (JTE013) mitigated HCC development and liver fibrosis, respectively. Antimicrobial treatment lowered portal blood LPS concentration, LSEC capillarization, and liver S1P concentration accompanied by reduction of HCC development and fibrosis in the congestive liver. CONCLUSIONS: In conclusion, chronic liver congestion promotes HCC development and liver fibrosis by S1P production from LPS-induced capillarized LSECs. Careful treatment of both RHF and liver cancer might be necessary for patients with RHF with primary or metastatic liver cancer.

Peripheral-dominant liver fibrosis and tumor distribution in a mouse model of congestive hepatopathy.

AIM: Congestive hepatopathy often leads to liver fibrosis and hepatocellular carcinoma. Imaging modalities provided clinical evidence that elevation of liver stiffness and tumor occurrence are mainly induced in the periphery of the liver in patients with congestive hepatopathy. However, clinical relevance of liver stiffness and liver fibrosis is unclear because liver congestion itself increases liver stiffness in congestive hepatopathy. It also unclear which factors configure such regional disparity of tumor development in patients with congestive hepatopathy. To answer these questions, we evaluated the macroscopic spatial distribution of liver fibrosis and tumors in the murine model of congestive hepatopathy. METHODS: Chronic liver congestion was induced by partial ligation of the suprahepatic inferior vena cava. Distribution of liver congestion, fibrosis, and tumors in partial ligation of the suprahepatic inferior vena cava mice were assessed by histological findings, laser microdissection (LMD)-based qPCR and enhanced computed tomography. LMD-based RNA-sequencing was performed to identify causal factors that promote tumor development in congestive hepatopathy. RESULTS: Liver fibrosis was mainly induced in the periphery of the liver and co-localized with distribution of liver congestion. Liver tumors were also induced in the periphery of the liver where liver congestion and fibrosis occurred. LMD-based RNA-sequencing revealed the upregulation of extracellular matrix/collagen fibril-, wound healing-, angiogenesis-, morphogenesis-, and cell motility-related signaling pathways in periphery of liver compared with liver center. CONCLUSIONS: Our findings showed the experimental relevance of liver congestion, fibrosis, and tumor development in congestive hepatopathy, and may provide important locational information. Macroscopic regional disparity observed in this murine model should be considered to manage patients with congestive hepatopathy.

Suppression of lysosomal acid alpha-glucosidase impacts the modulation of transcription factor EB translocation in pancreatic cancer.

Lysosomal degradation plays a crucial role in the metabolism of biological macromolecules supplied by autophagy. The regulation of the autophagy-lysosome system, which contributes to intracellular homeostasis, chemoresistance, and tumor progression, has recently been revealed as a promising therapeutic approach for pancreatic cancer (PC). However, the details of lysosomal catabolic function in PC cells have not been fully elucidated. In this study, we show evidence that suppression of acid alpha-glucosidase (GAA), one of the lysosomal enzymes, improves chemosensitivity and exerts apoptotic effects on PC cells through the disturbance of expression of the transcription factor EB. The levels of lysosomal enzyme were elevated by gemcitabine in PC cells. In particular, the levels of GAA were responsive to gemcitabine in a dose-dependent and time-dependent manner. Small interfering RNA against the GAA gene (siGAA) suppressed cell proliferation and promoted apoptosis in gemcitabine-treated PC cells. In untreated PC cells, we observed accumulation of depolarized mitochondria. Gene therapy using adenoviral vectors carrying shRNA against the GAA gene increased the number of apoptotic cells and decreased the tumor growth in xenograft model mice. These results indicate that GAA is one of the key targets to improve the efficacy of gemcitabine and develop novel therapies for PC.

The Prognostic Significance of C-reactive Protein-To-Lymphocyte Ratio in Colorectal Liver Metastases.

BACKGROUND: The preoperative systemic inflammation has been reported to predict tumor recurrence and survival in various cancers, including colorectal liver metastases (CRLM). However, more sensitive biomarker is required to improve perioperative management of CRLM. Therefore, we developed a novel indicator; C-reactive protein-to-lymphocyte ratio (CLR). The aim of this study is to evaluate the prognostic significance of CLR in patients with CRLM after hepatic resection. MATERIALS AND METHODS: The study comprised 197 patients who had undergone hepatic resection for CRLM between January 2000 and December 2018. We retrospectively investigated the relation between CLR and disease-free survival and overall survival after hepatic resection and compared their prognostic significance with that of the C-reactive protein-to-albumin ratio and neutrophil-to-lymphocyte ratio. RESULTS: Optimal cutoff level of the CLR by receiver operating characteristics analysis was 62.8 × 10-6. By multivariate analysis, CLR was an independent predictor of disease-free survival [hazard ratio (HR): 1.463, 95% confidence interval (CI): 1.003-2.135, P = 0.048), whereas lymph node metastases>4 (HR: 1.804, 95% CI: 1.100-2.958, P = 0.019) and CLR (HR: 1.656, 95% CI: 1.007-2.724, P = 0.047) were independent predictors of overall survival, while the C-reactive protein-to-albumin ratio and neutrophil-to-lymphocyte ratio were not. CONCLUSIONS: CLR may be an independent and significant indicator of poor long-term outcomes in patients with CRLM after hepatic resection.

Association of autophagy status with amount of Fusobacterium nucleatum in colorectal cancer.

Fusobacterium nucleatum (F. nucleatum), which has been associated with colorectal carcinogenesis, can impair anti-tumour immunity, and actively invade colon epithelial cells. Considering the critical role of autophagy in host defence against microorganisms, we hypothesised that autophagic activity of tumour cells might influence the amount of F. nucleatum in colorectal cancer tissue. Using 724 rectal and colon cancer cases within the Nurses' Health Study and the Health Professionals Follow-up Study, we evaluated autophagic activity of tumour cells by immunohistochemical analyses of BECN1 (beclin 1), MAP1LC3 (LC3), and SQSTM1 (p62) expression. We measured the amount of F. nucleatum DNA in tumour tissue by quantitative polymerase chain reaction (PCR). We conducted multivariable ordinal logistic regression analyses to examine the association of tumour BECN1, MAP1LC3, and SQSTM1 expression with the amount of F. nucleatum, adjusting for potential confounders, including microsatellite instability status; CpG island methylator phenotype; long-interspersed nucleotide element-1 methylation; and KRAS, BRAF, and PIK3CA mutations. Compared with BECN1-low cases, BECN1-intermediate and BECN1-high cases were associated with lower amounts of F. nucleatum with odds ratios (for a unit increase in three ordinal categories of the amount of F. nucleatum) of 0.54 (95% confidence interval, 0.29-0.99) and 0.31 (95% confidence interval, 0.16-0.60), respectively (Ptrend < 0.001 across ordinal BECN1 categories). Tumour MAP1LC3 and SQSTM1 levels were not significantly associated with the amount of F. nucleatum (Ptrend > 0.06). Tumour BECN1, MAP1LC3, and SQSTM1 levels were not significantly associated with patient survival (Ptrend > 0.10). In conclusion, tumour BECN1 expression is inversely associated with the amount of F. nucleatum in colorectal cancer tissue, suggesting a possible role of autophagy in the elimination of invasive microorganisms. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Short- and long-term outcomes of laparoscopic versus open gastrectomy for locally advanced gastric cancer following neoadjuvant chemotherapy.

BACKGROUND: This study aimed to investigate the short- and long-term outcomes of laparoscopic gastrectomy (LG) in patients with advanced gastric cancer following neoadjuvant chemotherapy (NAC) to determine its safety and feasibility. METHODS: We retrospectively investigated 51 patients who underwent gastrectomy for locally advanced gastric cancer [cT3-4/N1-3 or macroscopic type 3 (> 80 mm) or type 4] following NAC between November 2009 and January 2018. After excluding two patients who underwent palliative surgery due to peritoneal dissemination, 49 patients were ultimately selected for this cohort study. The patients were then divided into the LG group and open gastrectomy (OG) group, after which the clinicopathological characteristics as well as short- and long-term outcomes were examined. RESULTS: Compared with the OG group, the LG group demonstrated a significantly lower amount of intraoperative blood loss and a shorter hospital stay. The overall complication rates were 10% (2 of 20 patients) and 24% (7 of 29 patients) in the LG and OG groups (P = 0.277), respectively. No significant differences in 5-year disease-free (LG 44.4% vs. OG 53.3%; P = 0.382) or overall survival rates (LG 46.9% vs. OG 54.0%; P = 0.422) were observed between the groups. Multivariate analysis revealed that the surgical procedure (LG vs. OG) was not an independent risk factor for disease-free (P = 0.645) or overall survival (P = 0.489). CONCLUSIONS: LG may be a potential therapeutic option for patients with gastric cancer following NAC considering its high success rates and acceptable short- and long-term outcomes.

Preoperative controlling nutritional status (CONUT) score predicts long-term outcomes in patients with non-B non-C hepatocellular carcinoma after curative hepatic resection.

PURPOSE: The controlling nutritional status (CONUT) score has been reported to predict outcomes in patients with hepatocellular carcinoma (HCC). However, the prognostic significance of the CONUT score in patients with non-B non-C (NBNC) HCC remains to be established. METHODS: The study comprised 246 patients who had undergone elective hepatic resection for HCC between April 2003 and October 2017. We retrospectively investigated the relation between preoperative CONUT score as well as clinicopathological characteristics and disease-free survival (DFS) as well as overall survival (OS). RESULTS: In univariate analyses, CONUT score was associated with DFS and OS in patients with NBNC-HCC (p ≤ 0.01), while there was no significant association of CONUT score with DFS and OS in patients with HBV- and HCV-related HCC (p ≥ 0.1). Of the 111 patients with NBNC-HCC, 97 (87.4%) had CONUT score ≤ 3 (low CONUT score) and the other 14 (12.6%) had CONUT score ≥ 4 (high CONUT score). In the patients with NBNC-HCC, multivariate analysis identified age ≥ 65 years (p = 0.03), multiple tumors (p < 0.01), and high CONUT score (p = 0.03) as the independent and significant predictors of DFS, while multiple tumors (p = 0.01), microvascular invasion (p < 0.01), and high CONUT score (p = 0.01) were the independent and significant predictors of OS. CONCLUSIONS: The CONUT score seems to be a reliable and independent predictor of both DFS and OS after hepatic resection for NBNC-HCC.

Six autoantibodies as potential serum biomarkers of hepatocellular carcinoma: A prospective multicenter study.

Serum autoantibodies have been reported to react with tumor-associated antigen (TAA) in various cancers. This multicenter study evaluated the diagnostic and prognostic value of six autoantibodies against a panel of six hepatocellular carcinoma (HCC)-associated antigens, including Sui1, p62, RalA, p53, NY-ESO-1 and c-myc. A total of 160 patients with HCC and 74 healthy controls were prospectively enrolled from six institutions. Serum antibody titers were determined by enzyme-linked immunosorbent assays. The sensitivities were 19% for Sui1, 18% for p62, 17% for RalA, 11% for p53, 10% for NY-ESO-1 and 9% for c-myc. Overall sensitivity of the TAA panel (56%) was higher than that of α-fetoprotein (41%, P < .05). The combined sensitivity of the TAA panel and α-fetoprotein was significantly higher than that of α-fetoprotein alone (P < .001). The difference in overall survival of TAA panel-positive and panel-negative patients was significant when the Stage I/II patients were combined (P = .023). Overall survival was worse in NY-ESO-1 antibody-positive than in NY-ESO-1 antibody-negative patients (P = .002). Multivariate analysis found that positivity for the TAA panel was independently associated with poor prognosis (P = .030). This TAA panel may have diagnostic and prognostic value in the patients with HCC.

Quantitative Assessment of Blood Flow in the Gastric Conduit With Thermal Imaging for Esophageal Reconstruction.

OBJECTIVE: The study's primary aim was to evaluate the effectiveness of thermal imaging (TI) and its secondary aim was to compare TI and indocyanine green (ICG) fluorescence angiography, with respect to the evaluation of the viability of the gastric conduit. SUMMARY BACKGROUND DATA: The optimal method for evaluating perfusion in the gastric conduit for esophageal reconstruction has not been established. METHODS: We reviewed the prospectively collected data of 263 patients who had undergone esophagectomy with gastric conduit reconstruction. TI was used in all patients. ICG fluorescence was concomitantly used in 24 patients to aid comparison with TI. A cut-off value of the anastomotic viability index (AVI) was calculated using the receiver operating characteristic curve in TI. RESULTS: Anastomotic leak was significantly less common in patients with AVI > 0.61 compared with those with AVI ≤ 0.61 (2% vs 28%, P< 0.001). Microvascular augmentation was performed in 20 patients with a low AVI score and/or preoperative chemoradiotherapy. Overall ability was comparable between TI and ICG fluorescence regarding the qualitative evaluation of the gastric conduit. However, TI was superior in the quantitative assessment of viability. CONCLUSIONS: TI could delineate the area of good perfusion in the gastric conduit for esophageal reconstruction, which can help identify patients at high risk of anastomotic leak.

Correction to: Signification of Systemic Immune-Inflammation Index for prediction of prognosis after resecting in patients with colorectal cancer.

The authors regrets that there is a typo error on Tables 1, 2 and 3 of their published paper.

Signification of Systemic Immune-Inflammation Index for prediction of prognosis after resecting in patients with colorectal cancer.

PURPOSE: Systemic inflammatory response has been reported to be associated with prognosis in cancer patients. The aim of this study is to investigate the association between Systemic Immune-Inflammation Index (SII), a novel inflammation-based prognostic score and long-term outcomes among patients with colorectal cancer (CRC) after resection. METHODS: We retrospectively investigated 733 patients who underwent resection for CRC between January 2010 and December 2014 at the Jikei University Hospital and explored the relationship between SII, calculated by multiplying the peripheral platelet count by neutrophil count and divided by lymphocyte count, and overall survival. In survival analyses, we conducted Cox proportional hazards models, adjusting potential confounders including TNM stage, serum CEA, serum CA 19-9, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and platelet count. RESULTS: In multivariate analysis, age ≥ 65 years (p = 0.003), tumor location (p = 0.043), advanced TNM stage (p < 0.001), serum CA 19-9 > 37 mU/ml (p < 0.001), and SII (P for trend = 0.017) were independent and significant predictors of poor patient survival. Compared to patients with low SII, those with high and intermediate SII patients had poorer survival (Hazard ratio 2.48; 95% CI 1.31-4.69, Hazard ratio 1.65; 95% CI 0.83-3.27, respectively). CONCLUSION: The Systemic Immune-Inflammation Index might be an independent and significant indicator of poor long-term outcomes in patients with CRC after resection.

De novo hepatocellular carcinoma in living donor liver grafts: A Japanese multicenter experience.

AIM: Direct-acting antivirals for hepatitis C virus have reduced the decompensation risk. Immunosuppressants for transplantation raise the risk of occurrence of de novo malignancies. We assessed the probabilities of and risk factors for de novo hepatocellular carcinoma (HCC) development post-living donor liver transplantation (LDLT). METHODS: We retrospectively evaluated the data of developed HCC in a graft including metastatic HCC post-LDLT from 2779 adult cases collected from nine major liver transplantation centers in Japan. RESULTS: Of 2779 LDLT adult recipients, 34 (1.2%) developed HCCs in their grafts. Of 34, five HCCs appeared to be de novo because of a longer period to tumor detection (9.7 [6.4-15.4] years) and no HCC within the native liver of the two recipients. The donor origin of three of five de novo HCCs was confirmed using microsatellite analysis in resected tissue. Primary disease of all five was hepatitis C virus-related cirrhosis, of which two were treated with direct-acting antivirals. Four of five developed HCC de novo in the hepatitis B core antibody-positive grafts. De novo HCCs had favorable prognosis; four of five were cured with complete remission. However, recurrent HCC (n = 29) in the graft had a poorer outcome, especially in patients with neutrophil to lymphocyte ratio scores above 4 (median survival time, 262 [19-463] days). CONCLUSION: Analysis of the database from major liver transplantation institutes in Japan revealed that de novo HCCs determined by microsatellite analysis were rarely detected, but the majority were successfully treated. LDLT recipients with higher risks of de novo HCC, including those with hepatitis B core antibody-positive grafts, should be carefully followed by surveillance of the liver graft.

Early prediction of complex benign anastomotic stricture after esophagectomy using early postoperative endoscopic findings.

BACKGROUND: Benign anastomotic stricture after esophagectomy and reconstruction adversely affects oral intake and can increase the risk of aspiration pneumonia. Some patients experience relapse that requires frequent endoscopic dilatations. This study aimed to investigate whether the endoscopic appearance of anastomosis during the early postoperative period is associated with the complexity of subsequent anastomotic strictures. METHODS: Data of 213 patients who underwent esophagectomy with gastric tube reconstruction and early postoperative endoscopy between July 2008 and September 2018 were prospectively collected. Relationships among various risk factors, including the severity of mucosal degeneration of the anastomosis and complexity of anastomotic stricture, were studied using multivariate logistic regression analysis. RESULTS: Fifty-three patients (25%) developed anastomotic strictures at a median of 55 days after surgery, requiring a median of 5 endoscopic dilations. In multivariate analysis, severe mucosal degeneration was the only significant risk factor for any type of anastomotic stricture (P < 0.001). Twenty-seven patients (51%) developed refractory anastomotic strictures. In multivariate analysis, younger age (< 65 years) (P = 0.01), lack of neoadjuvant therapy (P = 0.02), severe mucosal degeneration (P = 0.03), and stricture development within 55 days (P = 0.01) were the risk factors for refractory stricture. The analysis of the risk factors for severe mucosal degeneration revealed that comorbidities and anastomotic techniques were independently correlated (P < 0.01). CONCLUSIONS: Early postoperative severe mucosal degeneration of esophagogastrostomy was the only predictor of strictures, regardless of their type. Mucosal degeneration, early postoperative stricture, younger age, and front surgery were associated with refractory anastomotic strictures.

A Preoperative Scoring System to Predict Carcinoma in Patients with Gallbladder Polyps.

INTRODUCTION: A preoperative scoring system to predict carcinoma in patients with gallbladder polyps (GBPs). METHODS: Preoperative parameters of patients with GBPs who underwent cholecystectomies were used to construct a scoring system to ascertain the risk of malignancy (reference group). The scoring system developed from this approach was applied to the validation group. RESULTS: In the reference group, 11.5% of patients had carcinomas, in whom the median age was 68 years and the polyp size was 16.9 mm. According to the univariate analysis, the significant factors for carcinoma were age ≥65 years, the presence of gallstones, polyp size ≥13 mm, solitary polyp, and sessile polyp. Age ≥65 years and polyp size ≥13 mm were significant factors according to the multivariate analysis. From these results, we developed a preoperative scoring system to predict carcinoma. The patients were divided into 1 of 2 groups: low-risk and high-risk and their malignancy rates were 4.1 and 61.1% respectively (p < 0.001). In the validation group, the malignancy rate was higher for those in the high-risk group (p = 0.016). CONCLUSIONS: The proposed preoperative scoring system based on simple clinical variables appears to be useful for predicting malignancy in patients with GBPs.

Multidisciplinary treatment for colorectal liver metastases in elderly patients.

BACKGROUND: Limited data describe the therapeutic practice and outcomes of colorectal liver metastases (CRLMs) in elderly patients. We aimed to evaluate the impact of age on multidisciplinary treatment for CRLMs. METHODS: We reviewed treatment and outcomes for patients in different age groups who underwent initial hepatectomy for CRLMs from 2004 through 2012. RESULTS: We studied 462 patients who were divided into three groups by age: ≤ 64 years (n = 265), 65-74 years (n = 151), and ≥ 75 years (n = 46). The rate of major hepatectomy and incidence of postoperative complications did not differ between groups. Adjuvant chemotherapy was used less in the ≥ 75-year group (19.6%) than that in the ≤ 64 (54.3%) or 65-74 age group (43.5%). Repeat hepatectomy for liver recurrence was performed less in the ≥ 75-year group (35%) than in the ≤ 64 (57%) or 65-74 (66%) age group. The 5-year disease-specific survival (DSS) rate of 44.2% in the ≥ 75-year group was lower than in the ≤ 64 (59.0%) or 65-74 (64.7%) age group. Multivariate analysis revealed age ≥ 75 years was an independent predictor of poor DSS. CONCLUSIONS: Liver resection for CRLMs can be performed safely in elderly patients. However, repeat resection for recurrence are performed less frequently in the elderly, which may lead to the poorer disease-specific prognosis.

Clinical factors affecting the distal margin in rectal cancer surgery.

PURPOSE: In rectal cancer surgery, an insufficient distal margin (DM) is associated with a high risk of local recurrence, whereas an excessive DM will cause low anterior resection syndrome, impairing quality of life. This study aimed to identify the factors that affect the distance between the colorectal resection site and the tumor to optimize achieving the correct DM. METHODS: The subjects of this study were 219 patients who underwent resection for primary rectal cancer in our department between January 2006 and July 2014. According to Japanese guidelines, DM (rDM) was based on the tumor location, but the pathological DM (pDM) was measured from surgical specimens. The patients were divided into two groups: the pDM-less-than-rDM group (pDM < rDM) and the pDM-greater-or-equal-to-rDM group (pDM ≥ DM). The factors associated with the DM in the two groups were compared. RESULTS: In the pDM < rDM group, the tumor distance from the anal verge was shorter (p = 0.001) and significantly more patients underwent laparotomy (p = 0.047). CONCLUSION: The DM tended to be shorter than that planned by the surgeon in patients with lower rectal cancers and those treated by laparotomy,; therefore, when performing rectal resection, care must be taken to ensure that the pDM is not shorter than the rDM.

Needlescopic versus conventional laparoscopic Heller-Dor procedure for achalasia: a propensity score-matched analysis.

PURPOSE: To compare the treatment results of needlescopic surgery with those of the conventional method for achalasia, using propensity score-matching. METHODS: Propensity score-matching was performed based on five factors: age, gender, body mass index, extended form, and maximum expansion diameter, to extract 28 cases each for a needlescopic group and a conventional group. RESULTS: There were no significant differences between the needlescopic group and the conventional group, in operative time (165 min vs. 170 min, p = 0.682), estimated blood loss (both ≒ 0 ml, p = 0.426), or post-operative hospital stay (4 vs. 4 days, p = 0.248). Although the follow-up period was significantly longer in the conventional group (6 vs. 105 months, respectively; p < 0.001), there was no difference in the post-operative symptom scores for difficulty in swallowing and chest pain or the degree of satisfaction (p = 0.563, p = 0.142, p = 0.342, respectively). Furthermore, there was no difference in the post-operative clearance rate, with both groups found to be favorable (p = 0.758, p = 0.790, p = 1.000, p = 1.000, respectively). CONCLUSIONS: The short-term results of needlescopic surgery for achalasia were good and equivalent to those of the conventional method.

The segment IV approach: a useful method for achieving the critical view of safety during laparoscopic cholecystectomy in patients with anomalous bile duct.

BACKGROUND: The critical view of safety (CVS) method can be achieved by avoiding vasculo-biliary injury resulting from misidentification during laparoscopic cholecystectomy (LC). Although achieving the CVS has become popular worldwide, there is no established standardized technique to achieve the CVS in patients with an anomalous bile duct (ABD). We recently reported our original approach for securing the CVS using a new landmark, the diagonal line of the segment IV of the liver (D-line). The D-line is an imaginary line that lies on the right border of the hilar plate. The cystic structure can be securely isolated along the D-line without any misidentification, regardless of the existence of an ABD. We named this approach the segment IV approach in LC. METHODS: In this study, we adopted the segment IV approach in patients with an ABD. RESULTS: From October 2015 to June 2020, 209 patients underwent LC using the segment IV approach. Among them, three (1.4%) were preoperatively diagnosed with an ABD. The branching point of the cystic duct was the posterior sectional duct, anterior sectional duct, or left hepatic duct in each patient. The CVS was achieved in all cases without any complications. CONCLUSION: It is a promising technique, especially even for patients with an ABD during LC.

Circumferential Heller myotomy can relieve chest pain in patients with achalasia: a prospective clinical trial.

BACKGROUND: Noncardiac chest pain often coexists with dysphagia in patients diagnosed with achalasia. The current standard treatment for achalasia, laparoscopic Heller myotomy with Dor fundoplication, has an insufficient effect on noncardiac chest pain. The aim of this study is to investigate the efficacy of circumferential Heller myotomy on esophageal chest pain in patients with achalasia. METHODS: Twenty patients diagnosed with achalasia who complained of noncardiac chest pain were recruited and underwent circumferential Heller myotomy. Using an institutional achalasia database, we randomly selected 60 patients who underwent standard laparoscopic Heller myotomy with Dor fundoplication, based on a 3-to-1 propensity score-matching analysis. We compared surgical outcomes between the circumferential Heller myotomy and the laparoscopic Heller myotomy with Dor fundoplication groups. RESULTS: Patients undergoing circumferential Heller myotomy had a higher rate of postoperative noncardiac chest pain relief than the laparoscopic Heller myotomy with Dor fundoplication group [95% (19/20) vs. 75% (45/60), p = 0.045]. No differences in dysphagia and vomiting were found between groups (p = 0.783 and p = 0.645, respectively). Patients in the circumferential Heller myotomy group had significantly better esophageal clearance. The prevalence of reflux endoscopic esophagitis was higher in the circumferential Heller myotomy group than in the control group [35.0% (7/20) vs. 10.0% (6/60), p = 0.015]. CONCLUSIONS: There is promising early evidence that circumferential Heller myotomy may be effective in the treatment of achalasia-related chest pain. Further research, including larger randomized studies with long-term follow-up, is warranted.

The evaluation of recumbent reflux by multichannel intraluminal impedance pH testing for patients with gastroesophageal reflux disease and sleep disturbance.

BACKGROUND AND AIM: The relationship between gastroesophageal reflux disease (GERD) and sleep disturbance has recently been pointed out and is garnering substantial attention. Although there are reports that point out the effectiveness of medical treatment for sleep disturbance associated with GERD, examinations of the pathological condition, including reflux during sleep, are inadequate. In the present study, we evaluated the recumbent reflux in patients with GERD and sleep disturbance using multichannel intraluminal impedance pH (MII-pH), and attempted to suppress recumbent reflux by surgical treatment to examine the pathophysiology of patients with GERD and sleep disturbance. MATERIALS AND METHODS: Of the 47 patients with GERD-related diseases in whom laparoscopic fundoplication was performed at The Jikei University Hospital from January 2016 to June 2017, 31 patients (average age: 55.9 ± 13.8 years, male in 25), excluding 9 with surgical indications only for esophageal hiatal hernia and 7 without postoperative evaluation, were the subjects of this study. All surgical procedures were performed by the Toupet method. We used the Pittsburgh Sleep Quality Index (PSQI) to evaluate sleep disturbance, setting 5.5 as the cut-off value, based on the report by Doi et al., with any conditions beyond this value deemed sleep disturbance. The evaluation of gastroesophageal reflux was carried based on the MII-pH using the Sleuth, manufactured by Sandhill Corporation, with an automatic analysis carried out by computer. Furthermore, recumbent abnormal reflux was defined as recumbent all reflux (times) > 7. All evaluations were performed preoperatively and at 3 months after the operation. The data were expressed in medians and interquartile ranges, with p < 0.05 defined as statistically significant by the Mann-Whitney, Wilcoxon, or Chi-squared test. RESULTS: Although sleep disturbance was found in 19 cases (61%), 8 (42%) of which were actually confirmed as nighttime abnormal reflux, of whom 5 cases (63%) showed significant improvement in their sleep disturbance following the operation, with a PSQI score of lower than 5.5. Among these 5 cases, postoperative recumbent abnormal reflux was also significantly reduced as compared with the preoperative condition (17 vs. 2 times/day, p = 0.042). Furthermore, sleep disturbance improved and recumbent abnormal reflux also decreased in two cases, with sleep disturbance improved by controlling the nighttime reflux via surgery in a total of 7 cases (87.5%). Although the PSQI score was as high as 14 points before and after the operation in one case, the rate of recumbent abnormal reflux was remarkably reduced, with sleep disturbance and recumbent reflux considered irrelevant. Furthermore, regarding the frequency of recumbent acid/non-acid reflux, while non-acid reflux was significantly more frequent in the patients with recumbent reflux complications (9 vs. 1 time/day, p < 0.001), there was no marked difference in the frequency of acid reflux. CONCLUSIONS: Among cases with GERD and sleep disturbance, approximately one-third of them showed findings suggestive of the involvement of recumbent reflux in sleep disturbance, with reflux characterized by non-acid reflux.