Publications by authors named "Taku Aoki"

182 Publications

Volumetric assessment and clinical predictors of cirrhosis in patients undergoing hepatectomy for hepatocellular carcinoma with presumed normal liver function.

Hepatol Int 2021 Aug 23. Epub 2021 Aug 23.

Second Department of Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi, 321-0293, Japan.

Aim: Indocyanine green retention rate at 15 min (ICGR15) is a frequently used indicator of liver function. Herein, clinicopathological characteristics of cirrhotic patients with normal ICGR15 value (< 10%) were investigated, as these patients have risk of postoperative liver insufficiency when receiving a major hepatic resection.

Methods: Patients undergoing hepatectomy for hepatocellular carcinoma were divided into three groups: non-cirrhotic livers (Group A, n = 112): cirrhotic livers with ICGR15 < 10% (Group B, n = 71): and cirrhotic livers with ICGR15 > 10% (Group C, n = 296). Background characteristics and surgical outcomes were compared between groups. Functional liver volume (FLV) was computed using total liver volume and signal intensity ratio. Liver parenchymal cell volume ratio was measured in non-cancerous tissue obtained from resected specimens. Univariate and multivariate analyses were performed to detect clinical characteristics correlating with cirrhotic liver pathology with normal ICGR15.

Results: There was no significant difference between groups in TLV. FLV was gradually reduced from Group A toward Group C. Liver parenchymal cell volume ratio was also gradually reduced from Group A toward Group C. Multivariate analysis revealed that platelet count (< 12 × 10/mm) (p = 0.001) and prothrombin time (< 80%) (p = 0.025) were significantly associated with cirrhotic liver pathology among patients with normal ICGR15.

Conclusion: Our results suggested that cirrhotic liver pathology despite normal liver function was characterized by slightly decreasing liver parenchyma as well as slight degree of fibrosis. Platelet count and PT% are useful for predicting liver cirrhosis with normal ICGR15.
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http://dx.doi.org/10.1007/s12072-021-10246-yDOI Listing
August 2021

Postoperative Complications Associated With Intra- Versus Extracorporeal Anastomosis for Laparoscopic Right Colectomy.

Am Surg 2021 May 27:31348211023417. Epub 2021 May 27.

Department of Gastroenterological Surgery, 12756Dokkyo Medical University, Tochigi, Japan.

Objective: To compare the postoperative complications of intracorporeal anastomosis (ICA) and extracorporeal anastomosis (ECA) in patients undergoing laparoscopic right colectomy (LRC).

Background: Although several studies have compared postoperative complications of ICA and ECA after LRC, most were retrospective studies.

Methods: We performed a comprehensive electronic search of the literature to identify studies that compared postoperative complications between ICA and ECA in patients who underwent LRC. We performed meta-analysis using random-effects models to calculate the risk ratio (RR) and 95% confidence interval (CI) of experiencing complications, and we analyzed heterogeneity using statistics.

Results: Fifteen studies consist of randomized controlled trials, case-control studies, and propensity score matching studies involving a total of 3219 patients who underwent LRC were included. Among 1377 patients who received ICA, 255 (18.5%) had postoperative complications, whereas among 1652 patients who received ECA, 373 (22.6%) had such complications. The results of the meta-analysis revealed that ICA was associated with a significantly reduced risk of postoperative complications (RR, .73; 95% CI: .57-.95; = .02; = 57%) compared with ECA. Although there was no significant difference between the 2 groups in risk of anastomotic leakage (RR, .67; 95% CI: .39-1.17; = .16; = 8%), there was a significant difference between them in risk of surgical site infection (RR, .50; 95% CI: .34-.71; = .0002; = 0%).

Conclusions: Intracorporeal anastomosis is associated with a reduced risk of postoperative complications compared with ECA in patients undergoing LRC.
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http://dx.doi.org/10.1177/00031348211023417DOI Listing
May 2021

Predictors of Poor Pathological Response to Neoadjuvant Gemcitabine Plus S-1 Chemotherapy in Patients With Pancreatic Ductal Adenocarcinoma.

Pancreas 2021 May-Jun 01;50(5):744-750

From the Department of Gastroenterological Surgery, Dokkyo Medical University, Shimotsuga, Tochigi, Japan.

Objectives: Although neoadjuvant chemotherapy (NAC)-gemcitabine plus S-1 (GS) has been reported to have a survival benefit in patients with resectable pancreatic ductal adenocarcinoma (PDAC), optimal candidates for NAC-GS have not been clearly identified.

Methods: A total of 81 patients with PDAC who underwent pancreatectomy after NAC-GS between 2013 and 2019 were divided into 2 groups based on Evans classification: grade I (<10% tumor cell destruction, n = 19) and grades II and III (>10% tumor cell destruction, n = 62). Univariate and multivariate analyses using clinical characteristics available before initiation of NAC were performed to predict Evans classification grade I (Evans I).

Results: The overall survival in patients with Evans I was significantly lower than that in patients with Evans II and III (P < 0.001). Multivariate analysis revealed a carcinoembryonic antigen level of >3.6 ng/mL (P = 0.001) and C-reactive protein to albumin ratio of >0.062 (P = 0.017) as independent predictors for Evans I disease. Seven of 11 patients who met both criteria had Evans I disease.

Conclusions: Serum carcinoembryonic antigen and C-reactive protein to albumin ratio are associated with Evans I disease in patients with PDAC who receive NAC-GS. Patients who meet both predictors may not be optimal candidates for NAC-GS.
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http://dx.doi.org/10.1097/MPA.0000000000001826DOI Listing
May 2021

Omentectomy Does Not Affect the Postoperative Outcome of Patients With Locally Advanced Gastric Cancer: A Systematic Review and Meta-Analysis.

J Surg Res 2021 08 8;264:287-295. Epub 2021 Apr 8.

Department of Gastroenterological Surgery, Dokkyo Medical University, Tochigi, Japan.

Objective: To explore the influence of omentectomy on postoperative outcomes in patients with locally advanced gastric cancer (LAGC).

Background: Although several meta-analyses have investigated the influence of bursectomy on postoperative outcomes in patients with LAGC, no meta-analyses have explored the influence of omentectomy on postoperative outcomes in such patients.

Methods: We performed a comprehensive electronic search of the literature up to December 2020 to identify studies that compared postoperative outcomes between patients with LAGC who did and did not undergo omentectomy. A meta-analysis was performed using random-effects models to calculate the risk ratio (RR) and 95% confidence interval (CI), and heterogeneity was analyzed using I statistics.

Results: Eight retrospective studies involving a total of 2658 patients with LAGC who underwent surgery were included in this meta-analysis. Among them, 3 propensity score matching (PSM) studies demonstrated that the 5-y recurrence-free survival (RFS) rate was 72.9% (314/431) in patients with LAGC who did not undergo omentectomy, whereas it was 70.3% (303/431) in those who did. The results revealed no significant difference in 5-y RFS between groups (RR, 0.91; 95% CI, 0.74-1.13; P = 0.41; I = 0%). Two PSM studies also revealed no significant difference in 5-y overall survival (OS) between groups (RR, 0.77; 95% CI, 0.52-1.13; P = 0.18; I = 47%).

Conclusions: The results of these meta-analyses show that omentectomy had no significant influence on 5-y OS, especially 5-y RFS, in patients with LAGC.
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http://dx.doi.org/10.1016/j.jss.2021.02.033DOI Listing
August 2021

Impact of adverse events of adjuvant and neoadjuvant chemotherapies on outcomes of patients with pancreatic ductal adenocarcinoma.

Cancer Chemother Pharmacol 2021 07 7;88(1):109-120. Epub 2021 Apr 7.

Department of Gastroenterological Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Shimotsuga, Tochigi, 321-0293, Japan.

Purpose: Recently, the number of patients with pancreatic ductal adenocarcinoma (PDAC) who have received both neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC) has been increasing. However, whether adverse events (AEs) during AC influence the prognosis of patients with resected PDAC who do or do not receive NAC remains uncertain.

Methods: Patients with PDAC who underwent a pancreatectomy between 2011 and 2019 were divided into two groups: an upfront surgery (UFS) group (n = 72), and an NAC group (n = 77). Patients who received AC were then divided into two groups: an AE grade 0/1/2 group (AE-G-0/1/2) and an AE grade 3/4 group (AE-G-3/4). The relationship between AEs and patient outcome and predictors of AE-G-3/4 were investigated.

Results: AC was used in 54 and 65 patients in the UFS and NAC groups, respectively. In the NAC group, the relative dose intensity (RDI) and AC completion rate as well as the overall survival rate of patients with AE-G-3/4 (n = 15) during AC were significantly worse than those of patients with AE-G-0/1/2 (n = 50). However, similar differences were not observed in the UFS group. A multivariate analysis revealed that AE-G-3/4 during NAC, AC agent (gemcitabine), an albumin level < 3.5 g/dL, and an estimated glomerular filtration rate < 90 mL/min/1.73 m before the initiation of AC were independent predictors of AE-G-3/4 during AC.

Conclusions: AE-G-3/4 during AC was associated with a lower RDI and AC completion rate and a worse outcome among patients with PDAC who had received NAC.
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http://dx.doi.org/10.1007/s00280-021-04267-5DOI Listing
July 2021

Survey of surgical resections for neuroendocrine liver metastases: A project study of the Japan Neuroendocrine Tumor Society (JNETS).

J Hepatobiliary Pancreat Sci 2021 Jun 20;28(6):489-497. Epub 2021 Apr 20.

Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan.

Background/purpose: Hepatic resection is considered the treatment of choice for neuroendocrine liver metastases (NELM). However, the safety and efficacy of resection have not been fully evaluated using a large cohort. The aim of the present study was to collect real-world data regarding hepatic resections for NELM.

Methods: A retrospective, multicenter survey was conducted. The background characteristics of patients undergoing an initial hepatic resection for NELM, the operative details, pathological findings, and patient outcomes were investigated.

Results: A total of 222 patients were enrolled from 30 institutions. The primary tumor site was the pancreas in 58.6%, and the presentation of NELM was synchronous in 63.1% of the cases. Concomitant resection of the primary tumor and liver metastases was performed for 66.4% of the synchronous metastases, and the 90-day morbidity and mortality rates were 12.6% and 0.9%, respectively. The operations resulted in R2 resections in 26.1% of the cases, and 83.4% of the patients experienced recurrence after R0/1 resections. However, the patients were treated using multiple modalities after R2 resection or recurrence, and the overall survival rate was relatively favorable, with 5-year and 10-year survival rates of 70.2%, and 43.4%, respectively. Univariable and multivariable analyses identified the tumor grading (G3) of the primary tumor as a significant prognostic factor for both the recurrence-free and overall survivals.

Conclusions: The present data confirmed the safety of the surgical resection of NELM. Although recurrences were frequent, the survival outcomes after resection were favorable when a multi-disciplinary treatment approach was used.
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http://dx.doi.org/10.1002/jhbp.956DOI Listing
June 2021

Efficacy of Adjuvant Chemotherapy According to the Pathological Response to Neoadjuvant Chemotherapy Among Patients With Pancreatic Ductal Adenocarcinoma.

Anticancer Res 2021 Mar;41(3):1629-1639

Department of Gastroenterological Surgery, Dokkyo Medical University, Tochigi, Japan.

Background/aim: An association between the pathological response to neoadjuvant chemotherapy (NAC) and the efficacy of adjuvant chemotherapy (AC) in patients with pancreatic ductal adenocarcinoma (PDAC) remains unknown.

Patients And Methods: A total of 121 patients with PDAC who underwent a pancreatectomy between January 2013 and March 2020 were divided into two groups: an upfront surgery (UFS) group (n=42), and an NAC (gemcitabine plus S-1) group (n=79). In the NAC group, the pathological response was evaluated using the Evans classification.

Results: The overall survival was significantly higher in patients with an AC relative dose intensity (RDI) ≥80% than in patients with an AC RDI <80% in the UFS, NAC-Evans IIa, and NAC-Evans IIb+III groups. However, this difference was not observed in the NAC-Evans I group.

Conclusion: AC is preferable for patients with NAC-Evans IIa or IIb+III, but more effective AC regimens may be needed for NAC-Evans I patients.
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http://dx.doi.org/10.21873/anticanres.14925DOI Listing
March 2021

Impact of anastomotic leakage on postoperative survival of patients with colorectal cancer: A meta-analysis using propensity score matching studies.

Surg Oncol 2021 Jun 6;37:101538. Epub 2021 Mar 6.

Department of Gastroenterological Surgery, Dokkyo Medical University, Tochigi, Japan.

Objective: To explore the influence of anastomotic leakage (AL) on postoperative survival in patients with colorectal cancer (CRC).

Background: Although several studies have compared the postoperative survival of patients with CRC with and without AL, the background characteristics of the two groups were not aligned in most studies.

Methods: We performed a comprehensive electronic search of the literature up to March 2020 to identify propensity score matching (PSM) studies that compared postoperative survival between CRC patients with and without AL. A meta-analysis was performed using random-effects models to calculate the risk ratio (RR) and 95% confidence interval (CI), and heterogeneity was analyzed using I (Akiyoshi et al., 2011) [2] statistics.

Results: Four PSM studies involving a total of 1676 patients with CRC undergoing surgery were included in this meta-analysis. Among 234 patients who had AL, 163 (69.7%) survived at 5 years after surgery, whereas among 1422 patients who did not have AL, 1156 (81.3%) survived at 5 years after surgery. Background characteristics of the two groups were adjusted with PSM in all 4 studies. The result of the meta-analysis revealed a significant difference between the two groups (RR, 1.63; 95% CI, 1.09-2.45; P = 0.02; I = 66%) in 5-year overall survival (OS).

Conclusions: The results of this meta-analysis demonstrate a significantly decreased 5-year OS in patients with CRC who had AL compared with patients with CRC who did not have AL.
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http://dx.doi.org/10.1016/j.suronc.2021.101538DOI Listing
June 2021

Safety assessment of laparoscopic liver resection: A project study of the Endoscopic Liver Surgery Study Group of Japan.

J Hepatobiliary Pancreat Sci 2021 Jun 12;28(6):470-478. Epub 2021 Mar 12.

Division of General and Gastroenterological Surgery, Department of Surgery, Toho University Faculty of Medicine, Tokyo, Japan.

Background/purpose: Laparoscopic liver resection (LLR) has been expanded rapidly and has been accepted worldwide; however, the safety assessment of LLR has not been fully conducted with a large-scale cohort. The aim of this study was to assess safety and identify clinical factors associated with postoperative major complications in LLR.

Methods: This project study retrospectively collected the data of LLRs performed before October 2015 in Japan. Patient characteristics, details of LLRs, and surgical outcomes were analyzed.

Results: A total of 4122 patients from 66 institutions were enrolled. The main indications were hepatocellular carcinoma (HCC) and colorectal liver metastases. The majority of the procedures were performed for solitary tumor-located liver segment 2, 3, 5, and 6 and the partial resection and left-lateral sectionectomy occupied 77.3%. The rate of conversion, accidental events were 7.1% and 2.1%, respectively. Postoperative major complication occurred in 205 cases (5.0%), and 14 in-hospital deaths were found among HCC patients with chronically diseased liver. Occurrence of postoperative major complication was associated with operation time (≥360 minutes), intraoperative blood loss (≥250 mL), red blood cell transfusion (yes), and the difficulty score (≥6). The 30- and 90-day mortality was 0.14% and 0.41%, respectively.

Conclusions: Laparoscopic liver resection was performed with an acceptable rate of conversion, accidental events, morbidity, and mortality. The indications for LLR should be cautiously judged considering tumor location, planned operative procedure, and liver function.
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http://dx.doi.org/10.1002/jhbp.917DOI Listing
June 2021

A Simple, Low-Cost Technique for Difficult-to-Close Laparoscopic Port Sites.

Am Surg 2021 Feb 10:3134821995080. Epub 2021 Feb 10.

Department of Gastroenterological Surgery, 12756Dokkyo Medical University, Tochigi, Japan.

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http://dx.doi.org/10.1177/0003134821995080DOI Listing
February 2021

Appendectomy Does Not Increase the Risk of Future Emergence of Parkinson's Disease: A Meta-analysis.

Am Surg 2021 Jan 30:3134821989034. Epub 2021 Jan 30.

Department of Gastroenterological Surgery, Dokkyo Medical University, Tochigi, Japan.

Objective: To explore the impact of appendectomy history on emergence of Parkinson's disease (PD).

Background: Although there are several studies to investigate the relationship between appendectomy history and emergence of PD, the results are still controversial.

Methods: We performed a comprehensive electronic search of the literature (the Cochrane Library, PubMed, and the Web of Science) up to April 2020 to identify studies that had employed databases allowing comparison of emergence of PD between patients with and those without appendectomy history. To integrate the impact of appendectomy history on emergence of PD, a meta-analysis was performed using random-effects models to calculate the risk ratio (RR) and 95% confidence interval (CI) for the selected studies, and heterogeneity was analyzed using statistics.

Results: Four studies involving a total of 6 080 710 patients were included in this meta-analysis. Among 1 470 613 patients with appendectomy history, 1845 (.13%) had emergences of PD during the observation period, whereas among 4 610 097 patients without appendectomy history, 6743 (.15%) had emergences of PD during the observation period. These results revealed that patients with appendectomy history and without appendectomy had almost the same emergence of PD (RR, 1.02; 95% CI, .87-1.20; = .83; = 87%).

Conclusion: This meta-analysis has demonstrated that there was no significant difference in emergence of PD between patients with and those without appendectomy history.
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http://dx.doi.org/10.1177/0003134821989034DOI Listing
January 2021

Is left-sided involvement of hepatocellular carcinoma an important preoperative predictive factor of poor outcome?

World J Surg Oncol 2020 Dec 3;18(1):317. Epub 2020 Dec 3.

Second Department of Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi, 321-0293, Japan.

Background: The tumor location is the most simple clinical factor and important in liver surgery to make surgical procedure. However, no previous study has investigated the prognostic differences and clinical features of hepatocellular carcinoma showing specific laterality. This study is the first report to focus on the laterality and aimed to lead to more simple and useful predictive factor rather than recent complicated predictive models.

Methods: Patients who underwent liver resection for the first time for single tumors located within each lobe between 2000 and 2018 were enrolled. We divided them into two groups based on tumor location: a right-sided group and a left-sided group. Univariable and multivariable analyses were performed to assess survival differences in relation to several other factors.

Results: There were 595 eligible patients; the 5-year survival rates and disease-free survival rates were 49.5% and 19.1% in the left-sided group and 55.6% and 24.5% in the right-sided group, respectively (p = 0.026). Statistical analyses revealed that the following preoperative prognostic factors were independently significant (p < 0.05) in the left-sided group: indocyanine green retention rate at 15 min, alpha fetoprotein, protein induced by vitamin K absence or antagonists-II level, and larger tumor size.

Conclusion: The left-sided group had a poorer prognosis than the right-sided group. A left-sided tumor location is a significant preoperative factor predictive of poor outcome in patients with hepatocellular carcinoma.
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http://dx.doi.org/10.1186/s12957-020-02100-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716469PMC
December 2020

Clinical practice guidelines for the management of biliary tract cancers 2019: The 3rd English edition.

J Hepatobiliary Pancreat Sci 2021 Jan 23;28(1):26-54. Epub 2020 Dec 23.

Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.

Background: The Japanese Society of Hepato-Biliary-Pancreatic Surgery launched the clinical practice guidelines for the management of biliary tract cancers (cholangiocarcinoma, gallbladder cancer, and ampullary cancer) in 2007, then published the 2nd version in 2014.

Methods: In this 3rd version, clinical questions (CQs) were proposed on six topics. The recommendation, grade for recommendation, and statement for each CQ were discussed and finalized by an evidence-based approach. Recommendations were graded as Grade 1 (strong) or Grade 2 (weak) according to the concepts of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.

Results: The 31 CQs covered the six topics: (a) prophylactic treatment, (b) diagnosis, (c) biliary drainage, (d) surgical treatment, (e) chemotherapy, and (f) radiation therapy. In the 31 CQs, 14 recommendations were rated strong and 14 recommendations weak. The remaining three CQs had no recommendation. Each CQ includes a statement of how the recommendations were graded.

Conclusions: This latest guideline provides recommendations for important clinical aspects based on evidence. Future collaboration with the cancer registry will be key for assessing the guidelines and establishing new evidence.
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http://dx.doi.org/10.1002/jhbp.870DOI Listing
January 2021

Pancreatic Head Adenocarcinoma Complicated by Portal Venous Aneurysm.

J Gastrointest Surg 2021 06 9;25(6):1628-1630. Epub 2020 Nov 9.

Department of Gastroenterological Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi, 321-0293, Japan.

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http://dx.doi.org/10.1007/s11605-020-04865-3DOI Listing
June 2021

Analysis of Patient Outcome after Non-curative Resection for Hepatocellular Carcinoma Using Nationwide Survey Data in Japan.

World J Surg 2021 Feb 26;45(2):607-614. Epub 2020 Oct 26.

Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka, Japan.

Background: Non-curative (debulking) hepatic resection for hepatocellular carcinoma (HCC) is occasionally applied for selected cases with bulky tumors or for oncologic emergency cases; however, the clinical usefulness of this procedure has not yet been fully evaluated. The aim of the present study was to evaluate the patient outcomes of non-curative hepatic resections for HCC using data from bi-annual nationwide surveys conducted in Japan.

Method: Data of 1084 non-curative hepatic resections for HCC were collected. The patient outcomes were compared with those of curative resections, transcatheter arterial chemoembolization (TACE), and hepatic arterial infusion chemotherapy (HAIC).

Results: Patient survival after the non-curative resection was poorer than that after curative resection (P < 0.001) and was especially dismal in cases with extrahepatic tumor spread (lymph node metastasis, peritoneal seeding, or distant metastasis). As compared to cases receiving TACE without surgery, non-curative resections for multiple intrahepatic tumors were applied to cases with advanced tumors with good liver functional reserve. The survival outcomes were significantly more favorable in the TACE group, but the results became similar after propensity score matching of the patients. The survival outcome of patients receiving non-curative resections was better than that of cases treated by HAIC, with median survival times of 26.0 months and 10.0 months, respectively.

Conclusion: The indications for non-curative hepatic resection in patients with HCC should be judged cautiously, especially in patients with extrahepatic tumor spread. This treatment approach may be beneficial for selected patients with intermediate- or advanced-stage HCC limited in liver and with good liver functional reserve.
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http://dx.doi.org/10.1007/s00268-020-05830-6DOI Listing
February 2021

Impact of Primary Tumor Location on Survival After Curative Resection in Patients with Colon Cancer: A Meta-Analysis of Propensity Score-Matching Studies.

Oncologist 2021 03 21;26(3):196-207. Epub 2020 Oct 21.

Department of Gastroenterological Surgery, Dokkyo Medical University, Tochigi, Japan.

Background: Recent retrospective subgroup analyses of patients with unresectable colon cancer (CC) receiving systemic chemotherapy have demonstrated that there is a significant difference in treatment outcome between patients with right-sided CC (RSCC) and those with left-sided CC (LSCC). However, it is impossible to divide patients with CC randomly into RSCC and LSCC groups before surgery. Therefore, the aim of this study is to explore the impact of primary tumor location (PTL) on survival after curative surgery for patients with CC using propensity score-matching (PSM) studies instead of randomization.

Materials And Methods: We performed a comprehensive electronic search of the literature up to January 2019 to identify studies that had used databases allowing comparison of postoperative survival between patients with RSCC and those with LSCC. To integrate the impact of PTL on 5-year overall survival (OS) after curative surgery, a meta-analysis was performed using random-effects models to calculate the risk ratio (RR) and 95% confidence interval (CI) for the selected PSM studies.

Results: Five studies involving a total of 398,687 patients with CC were included in this meta-analysis. Among 205,641 patients with RSCC, 69,091 (33.6%) died during the observation period, whereas among 193,046 patients with LSCC, 63,380 (32.8%) died during the same period. These results revealed that patients with RSCC and those with LSCC had almost the same 5-year OS (RR, 0.98; 95% CI, 0.89-1.07; p = .64; I = 97%).

Conclusion: This meta-analysis has demonstrated that there was no significant difference in 5-year OS between patients with RSCC and those with LSCC after curative resection.

Implications For Practice: To integrate the impact of primary tumor location (PTL) on 5-year overall survival (OS) after curative surgery, five propensity score-matching (PSM) studies involving a total of 398,687 patients with colon cancer (CC) were included in this meta-analysis. Among 205,641 patients with right-sided CC (RSCC), 69,091 (33.6%) died during the observation period, whereas among 193,046 patients with left-sided CC (LSCC), 63,380 (32.8%) died during the same period. These results revealed that patients with RSCC and those with LSCC had almost the same 5-year OS (risk ratio, 0.98; 95% confidence interval, 0.89-1.07; p = .64; I = 97%).
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http://dx.doi.org/10.1002/onco.13555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930413PMC
March 2021

The clinical influence of the preoperative lymphocyte-to-monocyte ratio on the postoperative outcome of patients with early-stage gastrointestinal cancer.

Ann Gastroenterol Surg 2020 Sep 8;4(5):580-590. Epub 2020 Jul 8.

Second Department of Surgery Dokkyo Medical University Tochigi Japan.

Aim: The lymphocyte-to-monocyte ratio (LMR) is useful for predicting the prognosis of patients with gastric cancer (GC) and those with colorectal cancer (CRC) undergoing surgery. The relationship between the LMR and postoperative outcome of patients with early-stage gastrointestinal cancers such as stage I GC and CRC remains unclear.

Methods: We retrospectively evaluated 323 stage I GC and 152 stage I CRC patients undergoing surgery. Univariate and multivariate analyses using the Cox proportional hazards model were performed to identify the clinical characteristics associated with overall survival (OS), and the cut-off values of these variables were determined by receiver operating characteristic analysis. The Kaplan-Meier method and log-rank test were used for postoperative survival comparisons according to the LMR (GC: LMR < 4.2 vs ≥4.2; CRC: LMR < 3.0 vs ≥3.0).

Results: Univariate and multivariate analyses revealed that OS was significantly associated with the LMR (<4.2/≥4.2) (HR, 2.489; 95% CI, 1.317-4.702;  = 0.005), as well as age (>75/≤75 years) (HR, 3.511; 95% CI, 1.881-6.551;  < 0.001) and albumin level (≤3.5/>3.5 g/dL) (HR, 3.040; 95% CI, 1.575-5.869;  = 0.001), in stage I GC patients. Survival analysis demonstrated a significantly poorer OS in stage I GC patients with a LMR < 4.2 compared with ≥4.2 ( < 0.001). In stage I CRC patients, despite a significant difference in OS according to the LMR (<3.0 vs ≥3.0) ( = 0.040), univariate analysis revealed no significant association between the LMR and OS.

Conclusion: LMR is a useful predictor of the postoperative outcome of stage I GC patients treated surgically.
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http://dx.doi.org/10.1002/ags3.12369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511555PMC
September 2020

Effects of branched-chain amino acids on postoperative tumor recurrence in patients undergoing curative resection for hepatocellular carcinoma: A randomized clinical trial.

J Hepatobiliary Pancreat Sci 2020 Nov 8;27(11):819-829. Epub 2020 Oct 8.

Second Department of Surgery, Dokkyo Medical University, Tochigi, Japan.

Background/purpose: No effective postoperative adjuvant therapies have been established for patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate the effect of oral administration of branched-chain amino acids (BCAA) on the recurrence-free survival (RFS) after hepatic resection in HCC patients.

Methods: In this randomized clinical trial, HCC patients undergoing curative resections were randomly assigned in a 1:1 ratio to the BCAA group or surgery-alone group. The BCAA group received BCAA (Livact ) for up to 4 years. The primary endpoint was RFS. The secondary endpoint was overall survival (OS). Multivariate analysis was performed to detect the clinical characteristics significantly associated with RFS.

Results: Between January 2010 and October 2014, 156 patients (75 in BCAA group and 81 in surgery-alone group) were enrolled in the study. Of these, two patients were excluded from the efficacy analysis. Comparison of the survival curves by the log rank test demonstrated no significant difference in the RFS (P = .579) or OS (P = .268) between the BCAA and the control group. Multivariate analysis revealed that the RFS was significantly associated with age and number of tumors. A beneficial effect of BCAA on the RFS was found in patients younger than 72 years old with a HbA1c level of < 6.4%.

Conclusions: Oral BCAA supplementation could not reduce the risk of recurrence after hepatic resection in HCC patients; however, the results suggested that BCAA supplementation may be beneficial for selected patients who were younger and had mildly impaired glucose tolerance.
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http://dx.doi.org/10.1002/jhbp.830DOI Listing
November 2020

Features of Hepatocellular Carcinoma With Micro Hepatic Vein Invasion and their Correlation With Hepatitis B and C Virus.

Anticancer Res 2020 Jul;40(7):3983-3990

Second Department of Surgery, Dokkyo Medical University, Tochigi, Japan.

Background/aim: Few studies have studied micro hepatic vein invasion in hepatocellular carcinoma (HCC). We explored the correlation between hepatic vein invasion and hepatitis B/C virus infection.

Patients And Methods: Between April 2000 and February 2018, 869 patients underwent liver resection for HCC at a single center. The patients were divided into two groups: those with micro hepatic vein invasion (VV+) and those without (VV-). The clinical data, overall survival (OS) and correlations with the presence of hepatitis B and C viruses were investigated.

Results: There were 817 VV- patients and 43 VV+ patients. OS was 66.2 months for VV- patients and 9.9 months for VV+ patients (p=0.0010). VV+ patients had significantly higher levels of serum HBV DNA (p=0.016).

Conclusion: HCC patients with micro hepatic vein invasion showed significantly shorter OS. A higher level of HBV DNA appears to be a risk factor for micro hepatic vein invasion.
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http://dx.doi.org/10.21873/anticanres.14391DOI Listing
July 2020

The ABO Blood Group Impacts the Survival of Patients Undergoing Pancreatoduodenectomy for Biliary Tract Cancer.

In Vivo 2020 Jul-Aug;34(4):1893-1900

Department of Gastroenterological Surgery, Dokkyo Medical University, Tochigi, Japan.

Background/aim: Although ABO blood group has been reported to be associated with the outcome of patients with pancreatic cancer, little is known about its impact on patients with biliary tract cancer (BTC). We evaluated the prognostic relevance of ABO blood group in patients who had undergone resection of BTC.

Patients And Methods: A total of 154 patients with BTC undergoing pancreatoduodenectomy were retrospectively reviewed. Associations between ABO blood group and patient survival were evaluated by univariate and multivariate analysis.

Results: The 5-year overall survival rate was higher in group O patients (n=46) than in other blood group patients (n=108) (65.8% vs. 47%, p=0.005). Multivariate analysis revealed that a non-O blood group was an independent risk factor for poor survival (p=0.021).

Conclusion: ABO blood group is associated with the prognosis of patients with resected BTC; group O patients have a better outcome.
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http://dx.doi.org/10.21873/invivo.11985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439892PMC
June 2021

Optimal strategy of systemic treatment for unresectable pancreatic neuroendocrine tumors based upon opinion of Japanese experts.

Pancreatology 2020 Jul 9;20(5):944-950. Epub 2020 Jun 9.

Department of Surgery, Otsu Red Cross Hospital, Otsu, Japan.

Background/objectives: A number of therapeutic agents have been reported to be clinically useful for the management of the patients with unresectable pancreatic neuroendocrine tumors (PanNETs) including somatostatin analogues, molecular-targeted agents and cytotoxic agents. However, the optimal strategy for selection among those treatment modalities above in these patients has remained unexplored.

Methods: Japanese experts for PanNET discussed and determined the optimal treatment strategies according to the results of previously reported studies.

Results: The tumor volume of liver metastases and the Ki-67 labeling index were unanimously accepted as indicators of the tumor burden and tumor aggressiveness, respectively, which are two most clinically pivotal factors for determining the strategy of systemic treatment for unresectable PanNETs. In addition, for those with a relatively small tumor burden and slow disease progression, somatostatin analogues were selected as the first-line treatment agents. For those with a relatively large tumor burden and rapid tumor progression, cytotoxic agents were selected, possibly aiming at tumor shrinkage. For those of intermediate tumor volume and/or growth rate, molecular-targeted agents were selected as the first choice. Based on this strategy discussed among the experts, we tentatively prepared a MAP for proposing optimal treatment strategy and examined its validity in some patients with unresectable PanNETs. Results validated the usefulness of this MAP proposed for patients harbouring unresectable PanNETs.

Conclusion: We herein propose a tentative MAP for optimal treatment selection for the patients harbouring unresectable PanNETs. Further large scale studies are, however, warranted to validate the usefulness of this MAP proposed in this study.
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http://dx.doi.org/10.1016/j.pan.2020.06.002DOI Listing
July 2020

PD-L1 is induced on the hepatocyte surface via CKLF-like MARVEL transmembrane domain-containing protein 6 up-regulation by the anti-HBV drug Entecavir.

Int Immunol 2020 07;32(8):519-531

Division of Hematological Malignancy, Institute of Medical Sciences, Tokai University, Isehara, Japan.

Chronic hepatitis B is now controllable when treated with nucleoside reverse transcriptase inhibitors (NRTIs), which inhibit hepatitis B virus (HBV) replication. However, once the NRTIs are discontinued, most patients relapse, necessitating lifelong NRTIs treatment. HBV infection relapse is assumed to be caused by the persistent existence of covalently closed circular DNA (cccDNA) in the nuclei of infected hepatocytes. The mechanism by which cccDNA-positive hepatocytes escape immune surveillance during NRTIs treatment remains elusive. Entecavir (ETV), a commonly used NRTI, post-transcriptionally up-regulates programmed cell death-ligand 1 (PD-L1), an immune checkpoint molecule, on the cell surface of hepatocytes regardless of HBV infection. Up-regulation by ETV depends on up-regulation of CKLF-like MARVEL transmembrane domain-containing 6, a newly identified potent regulator of PD-L1 expression on the cell surface. ETV-treated hepatic cells suppressed the activity of primary CD3 T cells and programmed cell death protein-1 (PD-1)-over-expressed Jurkat cells. Finally, ETV induces PD-L1 in primary hepatocytes infected by HBV. These results provide evidence that ETV considerably up-regulates PD-L1 on the cell surface of infected hepatocytes, which may be one of the mechanisms by which infected hepatocytes subvert immune surveillance.
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http://dx.doi.org/10.1093/intimm/dxaa018DOI Listing
July 2020

[Preoperative C-reactive protein predicts recurrence after curative resection in advanced gastric cancer patients receiving postoperative adjuvant chemotherapy using S-1].

Nihon Shokakibyo Gakkai Zasshi 2020 ;117(2):150-156

Second Department of Surgery, Dokkyo Medical University.

New chemotherapeutic regimens such as S-1 plus docetaxel, S-1 plus oxaliplatin and capecitabine plus oxaliplatin are reported to be effective and safe as postoperative adjuvant chemotherapy (PAC) for advanced gastric cancer (GC) patients. Although the use of these PACs is increasing, it is still unclear how to choose the best regimen for advanced GC patients. Therefore, we aimed to investigate which clinical characteristics are associated with recurrence after curative surgery in patients receiving S-1 as PAC. Thirty-nine patients who received a PAC regimen with S-1 for more than 1 year after curative surgery for advanced GC were enrolled. Univariate and multivariate analyses using the Cox proportional hazard model were performed to detect clinical characteristics that correlated with recurrence. Patients were divided into two groups, recurrence, and non-recurrence, and receiver operating characteristic (ROC) curve analysis was used to identify the cut-off values. Kaplan-Meier analysis and the log-rank test were used for comparison of relapse-free survival (RFS). Fifteen patients had a recurrence after surgery (38.5%, 15/39). Multivariate analysis using clinical characteristics revealed that preoperative C-reactive protein (CRP) (>0.3/≤0.3, mg/dL) (HR 10.73;95% C.I., 1.824-63.14;P=0.009) was significantly associated with recurrence. Kaplan-Meier analysis and the log-rank test demonstrated that preoperative CRP (>0.3/≤0.3, mg/dL) was also significantly associated with RFS (P<0.001). Therefore, preoperative CRP is significantly associated with recurrence and RFS after curative surgery in advanced GC patients receiving S-1 as PAC.
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http://dx.doi.org/10.11405/nisshoshi.117.150DOI Listing
February 2020

Clinical Significance of Neoadjuvant Chemotherapy With Gemcitabine Plus S-1 for Resectable Pancreatic Ductal Adenocarcinoma.

In Vivo 2019 Nov-Dec;33(6):2027-2035

Department of Gastroenterological Surgery, Dokkyo Medical University, Tochigi, Japan

Background/aim: Little is known about the efficacy of neoadjuvant chemotherapy (NAC) with gemcitabine plus S-1 (GS) for patients with resectable pancreatic ductal adenocarcinoma (R-PDAC). The aim of this study was to investigate differences in the long-term outcome of patients with R-PDAC undergoing pancreatectomy with and without NAC-GS to clarify the clinical significance of NAC-GS.

Patients And Methods: A total of 77 patients with R-PDAC who were scheduled for pancreatectomy between January 2012 and December 2017 were enrolled. Of these patients, 39 received NAC-GS (GS group) and 38 had upfront surgery (UFS group).

Results: Among the 77 patients, one patient in each group did not undergo pancreatectomy due to intraoperative non-curative factors. Median tumor size and the number of lymph nodes with metastasis were significantly lower in the GS group than in the UFS group (p=0.002 and p=0.017). However, the 5-year overall survival rate was similar in the two groups (26.1% versus 21.5%, p=0.930).

Conclusion: NAC-GS may not be recommended for patients with R-PDAC since it does not seem to offer any survival benefits.
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http://dx.doi.org/10.21873/invivo.11700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899096PMC
March 2020

Microsatellite Analysis of Recurrent Lesions Confirms Merit of Anatomical Liver Resection for Hepatocellular Carcinoma.

Anticancer Res 2019 Aug;39(8):4315-4324

Second Department of Surgery, Dokkyo Medical University, Tochigi, Japan.

Background/aim: This study aimed to obtain accurate differential diagnosis (DDx) of multicentric carcinogenesis (MC) and intrahepatic metastasis (IM) in recurrent lesions of hepatocellular carcinoma.

Materials And Methods: A total of 79 patients who underwent re-hepatectomy (2000-2013) were examined. PCR was used to analyze 13 chromosomal microsatellite loci by PCR. On the basis of this genetic analysis, the recurrent lesions were diagnosed as IM, MC or not determined (ND). Subsequently, DDx was compared with types of resection and outcome.

Results: The recurrent lesions were diagnosed as IM in 33 patients, MC in 44, and ND in 2. The anatomical resection group included 14 IM lesions (28%) and 36 MC lesions (72%), while the non-anatomical resection group included 19 IM lesions (70%) and 8 MC lesions (30%) (p<0.001).

Conclusion: Anatomical resection at initial hepatectomy may reduce the likelihood of IM recurrence, leading to a better outcome for patients with HCC.
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http://dx.doi.org/10.21873/anticanres.13597DOI Listing
August 2019

Impact of preoperative percutaneous transhepatic biliary drainage on post-operative survival in patients with distal cholangiocarcinoma.

ANZ J Surg 2019 09 7;89(9):E363-E367. Epub 2019 Jul 7.

Department of Gastroenterological Surgery, Dokkyo Medical University, Mibu, Tochigi, Japan.

Background: The aim of this study was to investigate the long-term impact of the type of preoperative biliary drainage used for patients undergoing pancreatoduodenectomy for distal cholangiocarcinoma (DCC).

Methods: A total of 84 patients with DCC who underwent preoperative biliary drainage between June 2000 and December 2016 were divided into groups for whom percutaneous transhepatic biliary drainage (PTBD) (n = 24) or endoscopic biliary drainage (EBD) (n = 60) was used.

Results: The 5-year overall survival in the PTBD group was significantly worse than that in the EBD group (16.7% versus 52.3%, P = 0.007). After propensity score matching (22 patients in each group), the 5-year overall survival in the PTBD group was still worse than that in the EBD group (13.6% versus 61.2%, P = 0.003). Multivariate analysis revealed that PTBD was independent risk factor for both poor survival (P = 0.028) and peritoneal recurrence (P = 0.018). The incidence of multiple sites at initial recurrence tended to be higher in the PTBD group than in the EBD group (P = 0.080).

Conclusions: PTBD should not be performed for patients undergoing pancreatoduodenectomy for DCC, except when EBD is contraindicated, as PTBD is significantly associated with shorter survival and peritoneal recurrence.
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http://dx.doi.org/10.1111/ans.15329DOI Listing
September 2019

Use of the National Clinical Database to evaluate the association between preoperative liver function and postoperative complications among patients undergoing hepatectomy.

J Hepatobiliary Pancreat Sci 2019 Aug 15;26(8):331-340. Epub 2019 Jul 15.

The Japanese Society of Hepato-Biliary-Pancreatic Surgery, Tokyo, Japan.

Background: The aim of the present study was to clarify the association between preoperative liver function and complications after hepatectomy.

Methods: The study included 11,686 patients registered in the National Clinical Database for 2015 for whom data on indocyanine green at 15 min (ICG15) and hepatectomy were available. The patients were divided into four groups: group A (ICG15 <10%; n = 5,661), group B (ICG15 10% to <20%; n = 4,381), group C (ICG15 20% to <30%; n = 1,173) and group D (ICG15 >30%; n = 463). Hepatectomy procedures were classified as partial resection (n = 3,934), systematic subsegmentectomy (n = 2,055), monosectionectomy (n = 2,043), bisectionectomy (n = 2,993) and trisectionectomy (n = 208). Complications were classified using the Clavien-Dindo classification (CD) and evaluated by ICG15 category and procedure type.

Results: Complications more severe than CD III increased significantly as the operation time lengthened and the intraoperative bleeding volume increased (P < 0.001). ICG15 category was positively associated with operative death, >CD III complications, surgical site infection (SSI), liver failure, and intractable ascites for many of the major hepatectomy procedures, but not with bile leakage. More complications were observed in patients outside the Makuuchi criteria than in those within the criteria.

Conclusions: Operation time and intraoperative bleeding volume are significantly associated with severe postoperative complications in patients undergoing hepatectomy. ICG15 is a good indicator predictive of operative death, >CD III complications, SSI, liver failure and intractable ascites.
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http://dx.doi.org/10.1002/jhbp.644DOI Listing
August 2019

Preoperative lymphocyte-to-monocyte ratio is useful for stratifying the prognosis of hepatocellular carcinoma patients with a low Cancer of the Liver Italian Program score undergoing curative resection.

Ann Gastroenterol Surg 2019 May 23;3(3):325-335. Epub 2019 Apr 23.

Second Department of Surgery Dokkyo Medical University Tochigi Japan.

Background And Aim: Although the Cancer of the Liver Italian Program (CLIP) score is useful for prognostication of patients with hepatocellular carcinoma (HCC), a previous study has reported that the CLIP score was unable to stratify the postoperative outcomes of HCC patients in whom the score was low (0-1). Recent studies have reported that the preoperative lymphocyte-to-monocyte ratio (LMR) is useful for prognostication of patients with various cancer.

Methods: We reviewed 329 HCC patients with a low CLIP score (0-1) undergoing curative resection. This study had the approval of the Institutional Review Board (28068). Multivariate analyses were carried out to detect clinical factors correlating with overall survival (OS). Kaplan-Meier analysis and the log-rank test were used for comparison of OS.

Results: Multivariate analysis showed that LMR (<4.35/≥4.35) was significantly associated with OS (hazard ratio [HR], 2.022; 95% CI, 1.141-3.583; =0.016) as well as portal vein invasion (HR, 2.410; 95%CI, 1.258-4.618; =0.008). Kaplan-Meier analysis and the log-rank test showed a significant difference in OS and relapse-free survival between patients with high LMR and those with low LMR.

Conclusion: Preoperative LMR is useful for stratifying the prognosis of HCC patients with a low CLIP score (0-1) undergoing curative resection.
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http://dx.doi.org/10.1002/ags3.12251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524078PMC
May 2019

A technique for taping inferior vena cava caudal to the duodenum: duodenal penetration by IVC filter strut after retroperitoneal lymph node dissection-usefulness of the mesenteric approach.

Surg Case Rep 2019 Apr 24;5(1):69. Epub 2019 Apr 24.

Second Department of Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi, 321-0293, Japan.

Background: Although an inferior vena cava (IVC) filter is used for preventing pulmonary thromboembolism (PTE) in patients with deep vein thrombosis, IVC filter penetration in the duodenum is a rare complication.

Case Presentation: A 35-year-old man had previously undergone retroperitoneal lymph node dissection (RPLND) for testicular cancer and IVC filter placement for prevention of PTE. Esophagogastroduodenoscopy (EGD) for his epigastric pain revealed penetration of the IVC filter in the duodenum. The IVC filter was retrieved through cavotomy, and the duodenal penetration was repaired using EGD clipping. Although it was difficult to mobilize the duodenum due to adhesion resulting from RPLND, the use of a mesenteric approach enabled encircling of the IVC caudal to the duodenum. The mesenteric approach is useful and safe for taping the IVC caudal to the duodenum in cases where it is difficult to mobilize the duodenum.

Conclusion: IVC taping using the mesenteric approach allowed safe retrieval of the IVC filter after RPLND without postoperative complications.
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http://dx.doi.org/10.1186/s40792-019-0626-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482199PMC
April 2019

Gastrografin reduces the need for additional surgery in postoperative small bowel obstruction patients without long tube insertion: A meta-analysis.

Ann Gastroenterol Surg 2019 Mar 17;3(2):187-194. Epub 2018 Dec 17.

Department of Gastroenterological Surgery Dokkyo Medical University Tochigi Japan.

Background: Small bowel obstruction (SBO) is a well-known major postoperative complication requiring immediate diagnosis and treatment to avoid additional invasive surgical procedures. Water-soluble contrast medium is often given not only for diagnosis but also for treatment. Although numerous studies have investigated the significance of this treatment, no consensus has yet been established regarding its indications and efficacy.

Objective: To explore whether Gastrografin can reduce the need for additional surgery in patients with postoperative SBO (PSBO).

Methods: We carried out a comprehensive electronic search of the literature (Cochrane Library, MEDLINE, PubMed and the Web of Science) up to February 2017 to identify studies that had shown efficacy of Gastrografin in reducing the need for surgery in patients with PSBO. To integrate the individual effects of Gastrografin, a meta-analysis was done using random-effects models to calculate the risk ratio (RR) and 95% confidence interval (CI), and heterogeneity was analyzed using statistics.

Results: Twelve studies involving a total of 1153 patients diagnosed as having PSBO were included in this meta-analysis. Not all patients received long-tube insertion. Among 580 patients who received Gastrografin, 100 (17.2%) underwent surgery, whereas among 573 patients who did not receive Gastrografin, 143 (25.0%) underwent surgery. Giving Gastrografin significantly reduced the need for surgery (RR, 0.66; 95% CI, 0.46-0.95;  = 0.02;  = 52%) in comparison with patients who did not receive Gastrografin.

Conclusion: Results of this meta-analysis show that giving Gastrografin reduces the need for surgery in PSBO patients without long-tube insertion.
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http://dx.doi.org/10.1002/ags3.12223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422814PMC
March 2019
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