Publications by authors named "Junji Okuda"

69 Publications

Clinical experience with near-infrared ray catheter, a fluorescent ureteral catheter, on laparoscopic surgery for colon diverticulitis: A case report.

Medicine (Baltimore) 2021 May;100(21):e26085

Department of General and Gastroenterological Surgery.

Rationale: As the world's population ages, the number of surgical cases of colovesical fistulas secondary to colon diverticulitis is also expected to increase. The key issue while performing laparoscopic surgery for these fistulas is the avoidance of iatrogenic ureteral injury. There are no reports of Near-infrared Ray Catheter being used in surgery for diverticulitis, which is one of the diseases with the highest risk of ureteral injury. We present a case of a male patient with colovesical fistulas secondary to sigmoid colon diverticulitis who underwent laparoscopic surgery with visualization of the ureter using a new surgical technique in laparoscopic surgery.

Patients Concern: An 82-year-old man presented to our urological department with general fatigue and air and fecal matter in the urine.

Diagnoses: Cystography showed delineation of the sigmoid colon. Abdominal computed tomography findings revealed multiple sigmoid colon diverticula with thickened walls as well as large stones and a small amount of air in the bladder. He was diagnosed with a urinary tract infection with colovesical fistulas and bladder stones due to sigmoid diverticulitis.

Interventions: After the creation of a transverse colostomy, we scheduled a laparoscopic anterior resection and cystolith removal.

Outcomes: Severe inflammatory adhesions around the sigmoid colon and a high risk of ureteral injury were expected preoperatively. After induction of anesthesia, we inserted a Near-infrared Ray Catheter, a fluorescent ureteral catheter, which allowed us to easily identify and visualize the ureter in real-time. This allowed bowel dissection without concerns of ureteral injury. The operative time for the gastrointestinal part of the procedure was 150 minutes, and the patient was in a good general condition after the operation and was discharged on postoperative day 7.

Lessons: The course of the ureter was easily and quickly identified by the green fluorescence from the ureteral catheter during laparoscopic surgery for fistulas associated with diverticulitis, where severe inflammation and dense fibrosis were present. Our technique is an easy and feasible approach that provides real-time urethral navigation during surgery for colovesical fistulas secondary to colon diverticulitis.
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http://dx.doi.org/10.1097/MD.0000000000026085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154449PMC
May 2021

Primary Tumor Resection Plus Chemotherapy Versus Chemotherapy Alone for Colorectal Cancer Patients With Asymptomatic, Synchronous Unresectable Metastases (JCOG1007; iPACS): A Randomized Clinical Trial.

J Clin Oncol 2021 04 9;39(10):1098-1107. Epub 2021 Feb 9.

National Cancer Center Hospital, Tokyo, Japan.

Purpose: It remains controversial whether primary tumor resection (PTR) before chemotherapy improves survival in patients with colorectal cancer (CRC) with asymptomatic primary tumor and synchronous unresectable metastases.

Patients And Methods: This randomized phase III study investigated the superiority of PTR followed by chemotherapy versus chemotherapy alone in relation to overall survival (OS) in patients with unresectable stage IV asymptomatic CRC and three or fewer unresectable metastatic diseases confined to the liver, lungs, distant lymph nodes, or peritoneum. Chemotherapy regimens of either mFOLFOX6 plus bevacizumab or CapeOX plus bevacizumab were decided before study entry. The primary end point was OS, which was analyzed by intention-to-treat.

Results: Between June 2012 and September 2019, a total of 165 patients were randomly assigned to either chemotherapy alone (84 patients) or PTR plus chemotherapy (81 patients). When the first interim analysis was performed in September 2019 with 50% (114/227) of the expected events observed among 160 patients at the data cutoff date of June 5, 2019, the Data and Safety Monitoring Committee recommended early termination of the trial because of futility. With a median follow-up of 22.0 months, median OS was 25.9 months (95% CI, 19.9 to 31.5) in the PTR plus chemotherapy arm and 26.7 (95% CI, 21.9 to 32.5) in the chemotherapy-alone arm (hazard ratio, 1.10; 95% CI, 0.76 to 1.59; one-sided = .69). Three postoperative deaths occurred in the PTR plus chemotherapy arm.

Conclusion: Given that PTR followed by chemotherapy showed no survival benefit over chemotherapy alone, PTR should no longer be considered a standard of care for patients with CRC with asymptomatic primary tumors and synchronous unresectable metastases.
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http://dx.doi.org/10.1200/JCO.20.02447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078424PMC
April 2021

Natural orifice specimen extraction in laparoscopic colorectal cancer surgery: A case series study.

Int J Surg Case Rep 2021 Jan 20;78:204-209. Epub 2020 Dec 20.

Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki 569-8686, Japan. Electronic address:

Introduction: In recent years, natural orifice specimen extraction (NOSE) has been attracting attention as a further minimally invasive operation for colorectal cancer, and not only improvement of appearance, but also reduction of pain and wound-related complications due to abdominal wall destruction has been reported. However, NOSE is technically complicated and difficult, and it has not yet been widely used. The aim of this study was to confirm the feasibility, safety, and short-term outcomes of total laparoscopic colon cancer surgery with NOSE.

Case Presentation: From May 2018 to October 2019, eight patients with stage 0 or I colon cancer underwent NOSE surgery in our hospital. Transanal specimen extraction was performed in six cases, and transvaginal specimen extraction was performed in two cases. All operations were successfully accomplished without conversion to open surgery. The anastomosis method was double stapling technique in three cases and overlap method in five cases. The median operative time was 224 min. The median blood loss was 10 mL. The median time to first flatus was 1 day, and the median time to first stool was 2 days. The median postoperative observation period was 18 months, but there was no recurrence. There were no postoperative complications in these cases.

Conclusion: Total laparoscopic colon cancer surgery with NOSE appears to be feasible, safe, and show promising efficacy for selected patients.
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http://dx.doi.org/10.1016/j.ijscr.2020.12.059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773675PMC
January 2021

Efficacy and safety of laparoscopic hepatectomy for hepatocellular carcinoma comorbid with cirrhosis.

Prz Gastroenterol 2020 19;15(3):225-233. Epub 2020 Sep 19.

Department of General and Gastroenterological Surgery, Osaka Medical College Hospital, Osaka, Japan.

Introduction: Laparoscopic hepatectomy (LH) is very difficult to perform in patients with cirrhosis because of the haemorrhagic and fibrotic nature of the liver, although there are various advantages to laparoscopic surgery.

Aim: To investigate the surgical outcomes, and efficacy and safety of LH versus open hepatectomy (OH) for hepatocellular carcinoma (HCC) resection.

Material And Methods: A total of 112 patients with cirrhosis, who underwent hepatectomy, were analysed retrospectively. We investigated the safety and efficacy of LH for HCC with cirrhosis. Student's and χ tests, Mann-Whitney's test, Wilcoxon's signed-rank test, and Fisher's exact test were used in the statistical analysis.

Results: Seventy-one patients underwent LH, and 41 underwent OH. The conversion rate from LH to OH was 12.7%. After propensity score matching, the estimated blood loss was significantly lower in the LH group than in the OH group (25 vs. 310 ml; < 0.001), and there was a significant difference between the groups in the operative time ( = 0.091). The LH group had complication rates of 3.6% and 0% for refractory ascites and pleural effusion, respectively, while those were 17.9% and 10.7%, respectively, in the OH group ( = 0.019 and = 0.005, respectively). The LH group had no mortality, whereas the OH group had a mortality rate of 10.7% ( = 0.038). The postoperative length of stay was significantly longer in the LH group than in the OH group (9 days vs. 14 days) ( = 0.002).

Conclusions: LH can be performed safely for HCC with cirrhosis. More favourable results are achieved with LH than with OH in terms of surgical outcomes.
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http://dx.doi.org/10.5114/pg.2020.99039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509897PMC
September 2020

γ-H2AX as a potential indicator of radiosensitivity in colorectal cancer cells.

Oncol Lett 2020 Sep 26;20(3):2331-2337. Epub 2020 Jun 26.

Department of General and Gastroenterological Surgery, Osaka Medical College, Osaka 569-8686, Japan.

Preoperative radiotherapy improves local disease control and disease-free survival in patients with advanced rectal cancer; however, a reliable predictive biomarker for the effectiveness of irradiation has yet to be elucidated. Phosphorylation of H2A histone family member X (H2AX) to γ-H2AX is induced by DNA double-strand breaks and is associated with the development of colorectal cancer (CRC). The current study aimed to clarify the relationship between γ-H2AX expression and CRC radiosensitivity and . H2AX levels were analyzed in datasets obtained from cohort studies and γ-H2AX expression was investigated by performing immunohistochemistry and western blotting using clinical CRC samples from patients without any preoperative therapy. In addition, the CRC cell lines WiDr and DLD-1 were subjected to irradiation and/or small interfering RNA-H2AX, after which the protein levels of γ-H2AX were examined in samples obtained from patients undergoing preoperative chemoradiotherapy. To quantify the observable effect of treatment on cancer cells, outcomes were graded as follows: 1, mild; 2, moderate; and 3, marked, with defined signatures of cellular response. Datasets obtained from cohort studies demonstrated that H2AX mRNA levels were significantly upregulated and associated with distal metastasis and microsatellite instability in CRC tissues, in contrast to that of normal tissues. In addition, γ-H2AX was overexpressed in clinical samples. , following irradiation, γ-H2AX expression levels increased and cell viability decreased in a time-dependent manner. Combined irradiation and γ-H2AX knockdown reduced the viability of each cell line when compared with irradiation or γ-H2AX knockdown alone. Furthermore, among clinical CRC samples from patients undergoing preoperative chemoradiotherapy, levels of γ-H2AX in the grade 1 group were significantly higher than those in grade 2 or grade 3. In conclusion, γ-H2AX may serve as a novel predictive marker and target for preoperative radiotherapy effectiveness in patients with CRC.
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http://dx.doi.org/10.3892/ol.2020.11788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400563PMC
September 2020

Closure of enterotomy after side-to-side ileocolic anastomosis with two barbed sutures in totally laparoscopic colectomy for right-sided colon cancer.

Surg Today 2021 Mar 11;51(3):457-461. Epub 2020 Aug 11.

Department of General and Gastroenterological Surgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, 569-8686, Japan.

Good short-term outcomes of intracorporeal ileocolic anastomosis (IIA) in totally laparoscopic colectomy for right-sided colon cancer (TLRC) have been shown in many reports, but no standardized technique for enterotomy closure after stapled side-to-side ileocolic anastomosis has so far been established. We retrospectively compared the short-term outcomes between 13 consecutive patients receiving either TLRC with IIA by conventional enterotomy closure (n = 6) or closure of the enterotomy using two barbed sutures (CEBAS) (n = 7) from July 2019 to April 2020. No anastomotic bleeding or leakage was observed in either group. Time to enterotomy closure was significantly shorter with the CEBAS method (16.5 ± 3.7 min) than with the conventional method (24.5 ± 4.7 min, p = 0.0059). The CEBAS method in TLRC with IIA was thus found to be technically feasible and it might reduce the stress associated with intracorporeal enterotomy closure.
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http://dx.doi.org/10.1007/s00595-020-02108-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892497PMC
March 2021

Preventing anastomotic leakage after laparoscopic intersphincteric resection without a diverting stoma: "pull-through/reborn".

Asian J Endosc Surg 2021 Apr 13;14(2):314-317. Epub 2020 Jul 13.

Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki, Osaka, Japan.

Introduction: Patients with very low rectal cancer who undergo intersphincteric resection (ISR) often experience anastomotic leakage (AL), even with a diverting stoma. The aim of this study was to introduce a technique for anastomosis after laparoscopic ISR to avoid AL.

Materials And Surgical Technique: In the first ISR procedure, the rectum was mobilized, the mesorectum was excised, and total, subtotal, or partial internal sphincter incision was performed transanally. In the second surgery, the adhesions between the prolapsed colon and the anal canal were bluntly dissected only as needed for suturing. After sufficient blood flow was confirmed using indocyanine green fluorescence imaging, coloanal transanal anastomosis was performed without a diverting stoma. We call this method "pull-through/reborn".

Discussion: "Pull-through/reborn" method can prevent AL after laparoscopic ISR. However, more cases and more experience are necessary to analyze anal functions after this method is applied.
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http://dx.doi.org/10.1111/ases.12841DOI Listing
April 2021

Ultimate Stomaless Technique of Two-Stage Operation for Lower Rectal Cancer Performed on a Patient with a High Body Mass Index: The Reborn Operation (Novel Pull-Through Method).

Case Rep Gastroenterol 2020 Jan-Apr;14(1):248-254. Epub 2020 Apr 29.

Division of Surgery, Gastroenterological Center, Medico Shunju Shiroyama Hospital, Osaka, Japan.

A 58-year-old Japanese man, with a body mass index of 41.7 kg/m2 (height: 179.8 cm; weight: 133.8 kg), underwent a laparoscopic pull-through procedure with delayed coloanal anastomosis performed in two surgical stages for lower rectal cancer. This method was selected because the volume of the abdominal wall was fairly thick and it would have been impossible to perform diverting ileostomy and colostomy, which are routinely conducted. First, a colonic pull-through segment of about 10 cm was left outside the anal canal without any tension and was fixed by sutures under indocyanine green fluorescence imaging (ICG FI). The second surgical stage was performed 10 days after the first operation under general anesthesia. Final coloanal anastomosis was performed with near-infrared light without diverting the stoma under ICG FI. The patient demonstrated a good postoperative course and was discharged from our hospital in remission 15 days after the latest operation. We could inspect the coloanal flow of the anastomosis under ICG FI before the reconstruction. This procedure was considered to be a standard method, but it was overtaken by new technology, ICG FI. This procedure is an ultimate stomaless surgery for ultralow rectal cancer that can be performed in selected cases, such as in patients with a high body mass index and with hope for stomaless operation.
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http://dx.doi.org/10.1159/000507076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252201PMC
April 2020

Long-term survival outcomes following laparoscopic surgery for clinical stage 0/I rectal carcinoma.

Ann Gastroenterol Surg 2020 May 20;4(3):294-300. Epub 2020 May 20.

Department of Surgery Kitasato Institute Hospital Kitasato University Tokyo Japan.

Aim: To clarify and evaluate the long-term outcomes of laparoscopic surgery for clinical stage 0/I rectal carcinoma patients.

Methods: This single-arm phase II trial involved accredited surgeons from 43 Japanese institutions. Patients were registered preoperatively. The planned sample size was 490. The primary endpoint was overall survival, and long-term outcomes were evaluated.

Results: A total of 495 patients were registered between February 2008 and August 2010. Eight patients (1.6%) required conversion to open surgery. Sphincter-preserving procedures were performed in 477 (97%) patients. Positive radial resection margin was found in two (0.4%) patients. Of 490 patients, 22, 314, 38, 115, and one patient had final pathological stages (p-stage) 0, I, II, III, and IV, respectively. Pathologically, 31.4% (154/490) of the patients did not have p-stage 0/I. The 5-year overall survival (OS) rates in p-stages 0, I, II, and III were 100%, 98%, 97%, and 94%, respectively. The 5-year OS of all patients at 96.6% (95% CI 94.6-97.9) was significantly better than the expected 5-year OS of 81.1% (< .0001). The 5-year relapse-free survival in p-stages 0, I, II, and III were 100%, 93%, 81%, and 79%, respectively. The 5-year relapse-free survival of all patients was 90.1%. Fifty patients (10.2%) had recurrence; lung recurrence was found in 22 patients, local recurrence in 14, liver in seven, distant lymph node in nine, and bone in three.

Conclusions: Laparoscopic surgery for clinical stage 0/I rectal carcinoma has feasible long-term outcomes. (ClinicalTrials.gov No.NCT00635466.).
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http://dx.doi.org/10.1002/ags3.12333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240150PMC
May 2020

The Relationship Between the Number of Ports and Surgical Outcomes in Laparoscopic Hepatectomy.

Surg Laparosc Endosc Percutan Tech 2020 Feb;30(1):85-90

Department of General and Gastroenterological Surgery.

Introduction: Reduced port surgery (RPS) has been garnering interest as a novel minimally invasive surgery lately.

Aim: The authors examined the relationship between the number of ports and surgical outcomes after laparoscopic hepatectomy (LH).

Materials And Methods: Between January 2012 and April 2019, 209 patients who underwent laparoscopic partial resection and lateral sectionectomy were retrospectively analyzed with respect to operative variables and surgical outcomes. Patients were divided into 5 groups by the number of ports used. Student's t test, the χ test, the likelihood-ratio test, Fisher exact test, or Mann-Whitney U test were used to analyze the data.

Results: Operative duration was significantly longer in patients with a larger number of ports than in those with a smaller number of ports. Chronological pain scores according to the visual analog scale (VAS) on postoperative days 1, 2, 4, and 7 were not associated with the number of ports and wound length in the umbilical region. The frequency of using additional analgesic agents was not significantly different between the groups. VAS scores and the number of additional analgesic agents used were smaller in patients in whom non-steroidal anti-inflammatory drugs were regularly administered postoperatively than in those in whom the drug was not regularly administered postoperatively. LH had a 3.4% complication rate (Clavien-Dindo classification >IIIA); however, this was not significantly different between the groups.

Conclusions: No significant difference in postoperative pain was observed between RPS and conventional methods, although operative durations were shorter with RPS. However, RPS for LH may be associated with excellent cosmetic results compared with conventional methods.
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http://dx.doi.org/10.1097/SLE.0000000000000750DOI Listing
February 2020

An In Vivo Mouse Model of Pelvic Recurrence of Human Colorectal Cancer.

Sci Rep 2019 12 23;9(1):19630. Epub 2019 Dec 23.

Departments of General and Gastroenterological Surgery, Osaka Medical College, Osaka, Japan.

Pelvic recurrence of colorectal cancer is a crucial problem because radical surgery can lead to excessive invasion. Novel therapeutic strategies are required instead of surgery. However, there are few suitable models because of the difficulty in transplanting and observing tumors in the pelvis. We have established an appropriate injection site suitable for the establishment of colorectal cancer pelvic recurrence that allows for the observation of tumor growth. DLD-1 cells stably expressing luciferase (DLD-1 clone#1-Luc) were inoculated into various points of female BALB/c nude mice and the engrafted cells were analyzed with an imaging system employing bioluminescent signals and computed tomography. Weekly analysis with the imaging system showed that a triangular area defined by the vagina, the anus, and the ischial spine was suitable for the engraftment of pelvic tumors. The imaging system was able to detect the engrafted tumor 7 days after the inoculation of cells. Weight loss was observed in our model, and overall survival was 21-42 days. Tumor involvement of adjacent organs was detected histopathologically, as is the case in the clinical situation. These findings suggest that this model is valid for evaluations of the therapeutic effects of novel treatments under development. It is hoped that this model will be used in preclinical research.
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http://dx.doi.org/10.1038/s41598-019-56152-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928073PMC
December 2019

Male sex and anterior wall tumor location as risk factors for urinary dysfunction after laparoscopic rectal surgery.

Surg Endosc 2020 08 11;34(8):3567-3573. Epub 2019 Oct 11.

Department of General and Gastroenterological Surgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, 569-8686, Japan.

Background: Total mesorectal excision (TME) has decreased the local recurrence rate and improved the overall survival of rectal cancer patients. However, urinary dysfunction remains a clinical problem after rectal cancer surgery. The aim was to assess the risk factors for postoperative urinary dysfunction.

Methods: This study was a single-center, retrospective analysis of 104 patients who underwent laparoscopic rectal surgery between November 2016 and October 2017. Postoperative urinary dysfunction was defined as the need for urinary catheter re-insertion or the presence of residual urine (≥ 150 mL) postoperatively.

Results: Postoperative urinary dysfunction was seen in 18 patients (17%). Multivariate analysis showed that male sex (odds ratio 3.89, p = 0.034) and anterior wall tumor location (odds ratio = 4.07, p = 0.037) were the predictors of postoperative urinary dysfunction. Compared with patients without risk factors, those with the two risk factors needed longer hospital stays (16 days vs. 30 days, p = 0.0022).

Conclusion: Male sex and anterior wall tumor location were the risk factors for urinary dysfunction after laparoscopic rectal surgery.
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http://dx.doi.org/10.1007/s00464-019-07186-yDOI Listing
August 2020

The Management of Recurrence within Six Months after Hepatic Resection for Colorectal Liver Metastasis.

Dig Surg 2020 9;37(4):282-291. Epub 2019 Oct 9.

Department of General and Gastroenterological Surgery, Osaka Medical College Hospital, Takatsuki, Osaka, Japan.

Background: Hepatectomy is currently recommended as the most reliable treatment for colorectal liver metastases. However, the association between the choice of treatment for recurrence and the timing of recurrence remains controversial.

Methods: Two-hundred ninety-five patients who underwent hepatectomy were retrospectively analyzed for the risk factors and the outcomes for early recurrence within 6 months. The remnant liver volumes (RLVs) and laboratory data were measured postoperatively using multidetector computed tomography on days 7 and months 1, 2, and 5 after the operation.

Results: Early recurrence developed in 88/295 patients (29.8%). Colorectal cancer lymph node metastasis, synchronous liver metastasis, and multiple liver metastases were independent risk factors for the occurrence of early recurrence (p < 0.001, 0.032, and 0.019, respectively). Patients with early recurrence had a poorer prognosis than did patients who developed later recurrence (p < 0.001). Patients who underwent surgery or other local treatment had better outcomes. The changes in RLV and laboratory data after postoperative month 2 were not significantly different between the 2 groups.

Conclusion: Patients with early recurrence within 6 months had a poorer prognosis than did patients who developed later recurrence. However, patients who underwent repeat hepatectomy for recurrence had a better prognosis than did those who underwent other treatments, with good prospects for long-term survival.
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http://dx.doi.org/10.1159/000503420DOI Listing
April 2021

Novel technique with the IRIS U kit to prevent urethral injury in patients undergoing transanal total mesorectal excision.

Ann Med Surg (Lond) 2019 Oct 13;46:1-3. Epub 2019 Aug 13.

Department of Colorectal Surgery Osaka Medical College, Osaka, Japan.

Background: Low anterior resection of the rectum with total mesorectal excision (TME) has been the gold standard for the surgical treatment of rectal cancer as it has the lowest recurrence rates. The key issue while performing transanal TME (TaTME) is avoiding iatrogenic urethral injury. We introduce our surgical technique for TaTME.

Surgical Technique: Intraurethral indocyanine green injection using the IRIS U kit with subsequent visualization under NIR was safely utilized during the TaTME. We were able to easily detect and visualize the IRIS urethral kit. The prostatic segment of the urethra can be identified in real-time using the infrared illumination system urethral kit (IRIS U kit).

Benefits: The prostatic segment of the urethra was easily and quickly identified by the green fluorescence during TaTME.

Conclusion: Our TaTME technique is an easy and feasible approach that provides real-time urethral images.
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http://dx.doi.org/10.1016/j.amsu.2019.08.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706455PMC
October 2019

Delta-like 3 localizes to neuroendocrine cells and plays a pivotal role in gastrointestinal neuroendocrine malignancy.

Cancer Sci 2019 Oct 14;110(10):3122-3131. Epub 2019 Aug 14.

Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki, Japan.

Delta-like 3 (DLL3) is a member of the Delta/Serrate/Lag2 (DSL) group of Notch receptor ligands. Five DSL ligands are known in mammals, among which DLL3 has a unique structure. In the last few years, DLL3 has attracted attention as a novel molecular targeting gene in neuroendocrine carcinoma of the lung due to its high expression. However, the expression pattern and functions of DLL3 in the gastrointestinal tract and gastrointestinal neuroendocrine carcinoma remain unclear. In this study, we examined the expression and role of DLL3 in the gastrointestinal tract, as well as in gastrointestinal neuroendocrine carcinoma. Immunohistochemical staining of the human normal gastrointestinal tract revealed that DLL3 localized in neuroendocrine cells. DLL3 showed intense staining in chromogranin A-positive gastric cancer specimens. Real-time quantitative RT-PCR and western blotting analyses showed considerable upregulation of DLL3 in gastrointestinal neuroendocrine carcinoma cell lines. Immuno-electron microscopy demonstrated abundant expression of DLL3 in neurosecretory granules in these cells. Furthermore, gene silencing of DLL3 caused significant growth inhibition through the induction of intrinsic apoptosis. Our findings suggest that DLL3 is expressed in neuroendocrine cells of the gastrointestinal tract and that it has a pivotal role in gastrointestinal neuroendocrine carcinoma cells. Based on these findings, further investigations are required to achieve a breakthrough in developing therapeutic strategies for gastrointestinal neuroendocrine carcinoma.
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http://dx.doi.org/10.1111/cas.14157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778628PMC
October 2019

Laparoscopic Repeat Hepatic Resection for the Management of Liver Tumors.

J Gastrointest Surg 2019 11 16;23(11):2314-2321. Epub 2019 Jul 16.

Department of General and Gastroenterological Surgery, Osaka Medical College Hospital, 2-7 Daigaku-machi, Takatsuki City, Osaka, 569-8686, Japan.

Background: Laparoscopic hepatic resection has been developed as a minimally invasive surgery; however, laparoscopic repeat minor hepatic resection (LRH) carries a higher risk of damage to other organs because of postoperative changes to and losses of anatomical landmarks. The current standard approach at many facilities has been to perform open repeat minor hepatic resection (ORH). This paper describes the surgical outcomes, procedure safety, and utility of ORH versus LRH, as well as the laparoscopic techniques used in LRH.

Methods: Between February 2010 and May 2018, the data of 142 patients who underwent LRH or ORH at a single institution were retrospectively reviewed. Surgical outcomes, procedure safety, and procedure utility data were analyzed.

Results: Forty-five patients underwent LHR and 97 patients underwent ORH. The conversion rate from LHR to OHR was 13.3%. After propensity score matching (PSM), the estimated blood loss was significantly lower in the LRH group than in the ORH group (50 mL vs. 350 mL; P < 0.001). The LRH group had an 8.1% complication rate, while the ORH group had a complication rate of 24.3% (P = 0.044). The postoperative length of stay was significantly shorter in the LHR group than in the OHR group (9 days vs. 11 days) (P = 0.024).

Conclusion: LRH can be performed safely using various surgical devices. More favorable results are achieved with LRH than with ORH in terms of surgical outcomes including intraoperative bleeding, postoperative complications, and postoperative lengths of stay.
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http://dx.doi.org/10.1007/s11605-019-04276-zDOI Listing
November 2019

Long-term results of a multicenter phase II study of preoperative chemoradiotherapy with S-1 plus oxaliplatin for locally advanced rectal cancer (JACCRO CC-04: SHOGUN Trial).

Radiother Oncol 2019 05 26;134:199-203. Epub 2019 Feb 26.

Japan Clinical Cancer Research Organization, Tokyo, Japan.

Purpose: The study was designed to evaluate the safety and efficacy of adding oxaliplatin to py (CRT) with S-1 in patients with locally advanced rectal carcinoma (LARC). We report here the final results of the study.

Patients And Methods: Patients with histopathologically confirmed LARC (cT3-T4, any N) were eligible. They received oral S-1 (80 mg/m/day on days 1-5, 8-12, 22-26, and 29-33) and infusional oxaliplatin (60 mg/m/day on days 1, 8, 22, 29) plus radiotherapy (1.8 Gy/day, total dose of 50.4 Gy in 28 fractions), with a chemotherapy gap in the third week of radiotherapy. Primary endpoint of the study was pathological complete response (pCR) rate. Secondary endpoints were rates of R0 resection, down-staging, cumulative 3-year local recurrence, 3-year disease-free survival (DFS), and toxicity.

Results: Forty-five patients were enrolled at six centers in Japan. All patients received CRT, and 44 underwent operation. The pCR rate was 27.3% (12/44). The R0 resection rate was 95.5% (42/44). T-down-staging rate was 59.1% (26/44), and N-down staging rate was 65.9% (29/44); the combined pathological down-staging rate was 79.5% (35/44). There were no grade 4 adverse events, but 11.1% of the patients had grade 3 adverse events. Cumulative 3-year local recurrence rate was 0%. However, 13 (30.0%) patients suffered from distant metastasis, and one patient suffered from secondary esophageal cancer that was unrelated to rectal cancer. Eight patients had lung metastasis, 4 had liver metastasis, and 3 patients died of the metastatic disease. The 3-year DFS rate of the 44 patients was 67.5% (median follow-up 36.3 months), and the 3-year overall survival (OS) rate was 93.0% (median follow-up 39.6 months). The patients were then divided into the pCR (12 patients) group and non pCR (32 patients) group. The 3-year rate of DFS for each group was 91.7% and 58.1% and that of OS was 100% and 90.3%, respectively.

Conclusions: The study showed a high pCR rate with no severe toxicity, good follow-up results, and good loco-regional control. Therefore, addition of oxaliplatin to preoperative CRT with S-1 in patients with LARC might be feasible and lead to better local control than standard treatment.
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http://dx.doi.org/10.1016/j.radonc.2019.02.006DOI Listing
May 2019

Totally extraperitoneal approach to laparoscopic lateral lymph node dissection for patients with recurrent lateral pelvic lymph nodes after rectal cancer surgery: a novel technique-M TEP LLND.

Surg Today 2019 Nov 10;49(11):981-984. Epub 2019 Apr 10.

Department of General and Gastroenterological Surgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, 569-8686, Japan.

Lateral lymph node dissection (LLND) for recurrence of lateral pelvic lymph node metastasis after rectal cancer surgery is technically demanding because of the need for re-do surgery. We herein report a novel technique of laparoscopic LLND via a totally extraperitoneal (TEP) approach. Since October 2018, we have performed LLND based on a TEP approach, called "M TEP LLND", with two cases treated. By peeling in the caudal direction in the dorsal layer of the rectus abdominis muscle, a working space is created once the extraperitoneal space is reached, and LLND is performed. All lateral pelvic lymph node dissection procedures have been successfully completed, and there have been no intraoperative or postoperative complications. This procedure allows TEP-experienced colorectal surgeons to perform safe and complete LLND without any influence of intraperitoneal adhesion or intestinal obstruction. M TEP LLND is less invasive than the conventional intraperitoneal approach and appears to be useful, particularly for recurrence of lateral pelvic lymph node metastasis.
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http://dx.doi.org/10.1007/s00595-019-01808-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6800883PMC
November 2019

International consensus on natural orifice specimen extraction surgery (NOSES) for colorectal cancer.

Gastroenterol Rep (Oxf) 2019 Feb 23;7(1):24-31. Epub 2019 Jan 23.

Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.

In recent years, natural orifice specimen extraction surgery (NOSES) in the treatment of colorectal cancer has attracted widespread attention. The potential benefits of NOSES including reduction in postoperative pain and wound complications, less use of postoperative analgesic, faster recovery of bowel function, shorter length of hospital stay, better cosmetic and psychological effect have been described in colorectal surgery. Despite significant decrease in surgical trauma of NOSES have been observed, the potential pitfalls of this technique have been demonstrated. Particularly, several issues including bacteriological concerns, oncological outcomes and patient selection are raised with this new technique. Therefore, it is urgent and necessary to reach a consensus as an industry guideline to standardize the implementation of NOSES in colorectal surgery. After three rounds of discussion by all members of the International Alliance of NOSES, the consensus is finally completed, which is also of great significance to the long-term progress of NOSES worldwide.
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http://dx.doi.org/10.1093/gastro/goy055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375350PMC
February 2019

Clinical impact of single-incision laparoscopic right hemicolectomy with intracorporeal resection for advanced colon cancer: propensity score matching analysis.

Surg Endosc 2019 11 14;33(11):3616-3622. Epub 2019 Jan 14.

Departments of General and Gastroenterological Surgery, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka, 569-8686, Japan.

Background: Laparoscopic right hemicolectomy has become an acceptable treatment for right-sided colon cancer. Most centers use multiport laparoscopic right hemicolectomy extracorporeally (MRHE), whereas single-incision laparoscopic right hemicolectomy intracorporeally (SRHI) remains controversial. The aim of this study was to compare these two techniques using propensity score matching analysis.

Methods: We analyzed the data from 111 patients who underwent laparoscopic right hemicolectomy between December 2015 and December 2016. The propensity score was calculated according to age, gender, body mass index, the American Society of Anesthesiologists score, previous abdominal surgery, and D3 lymph node dissection. Postoperative pain was evaluated using a visual analogue scale (VAS) and postoperative analgesic use was an outcome measure.

Results: The length of skin incision in SRHI was significantly shorter than in MRHE [3 (3.5-6) versus 4 (3-6) cm, respectively; P = 0.007]. The VAS score on day 1 and day 2 after surgery was significantly less in SRHI than in MRHE [30 (10-50) versus 50 (20-69) on day 1, P = 0.037; 10 (0-50) versus 30 (0-70) on day 2, P = 0.029]. Significantly fewer patients required analgesia after SRHI on day 1 and day 2 after surgery [1 (0-3) versus 2 (0-4) on day 1, P = 0.024; 1 (0-2) versus 1 (0-4) on day 2, P = 0.035]. There were no significant differences in operative time, intraoperative blood loss, number of lymph nodes removed, and postoperative course between groups.

Conclusions: SRHI appears to be safe and technically feasible. Moreover, SRHI reduces the length of the skin incision and postoperative pain compared with MRHE.
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http://dx.doi.org/10.1007/s00464-018-06647-0DOI Listing
November 2019

A Concealed "Natural Orifice": Umbilicus Anatomy for Minimally Invasive Surgery.

Surg Innov 2019 Feb 7;26(1):46-49. Epub 2018 Sep 7.

1 Osaka Medical College, Osaka, Japan.

Introduction: A recent development in minimally invasive surgery (MIS) is single-port surgery, where a single large multiport trocar is placed in the umbilicus. All medical schools require that students complete an anatomy course as part of the medical curriculum. However, there is limited instruction regarding the detailed parts of the "umbilicus." In several famous anatomy atlases, the umbilicus is not dissected at all and is merely represented as a button. Until now, the true nature of the umbilicus has not been anatomically demonstrated.

Methods: Five cadavers were obtained from the Osaka Medical College medical student anatomy class. The umbilicus was dissected in the anatomy laboratory, to demonstrate all the layers. A detailed dissection was performed, focusing on the exact center of the umbilicus, in order to ascertain whether there exists a "natural orifice" or a fascial defect.

Results: In all cadavers, a small defect of fascia was identified just below the center of the umbilicus. Yellow fatty tissue was present just below the skin in the exact center of the umbilicus. A probe placed exactly in the middle of this defect passes easily through into the abdominal cavity.

Conclusions: With the widespread use of MIS, umbilical incision is commonly used to reduce pain and improve cosmetic results. This study consistently revealed a natural defect of fascia in the center of the umbilicus. Therefore, the umbilicus can be called a concealed "natural orifice." It is important to recognize and utilize this defect effectively to minimize unnecessary tissue trauma during MIS.
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http://dx.doi.org/10.1177/1553350618797619DOI Listing
February 2019

The impact of preoperative carbohydrate loading on intraoperative body temperature: a randomized controlled clinical trial.

Surg Endosc 2018 11 18;32(11):4393-4401. Epub 2018 Jun 18.

Department of General and Gastroenterological Surgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, 569-8686, Japan.

Background: Preoperative carbohydrate loading (CHO) is one element of the enhanced recovery after surgery protocol. No clinical trial has investigated the impact of preoperative CHO on intraoperative body temperature.

Methods: This study was a single-center, prospective, randomized controlled clinical trial involving patients undergoing laparoscopic colon cancer surgery. The primary end point was the intraoperative core temperature during surgery, which was measured at 30-min intervals for 150 min after starting surgery. The secondary end points were short-term outcomes and body composition changes.

Results: From July 2013 to May 2014, we randomized 70 patients into the control group (n = 33) or CHO group (n = 31); six patients were excluded. The core temperature of the CHO group 90, 120, and 150 min after starting surgery was significantly lower than that of the control group (control vs. CHO, respectively: 90 min; 36.26 ± 0.41 vs. 36.05 ± 0.43 °C, p = 0.0233, 120 min; 36.30 ± 0.44 vs. 36.06 ± 0.50 °C, p = 0.0283, 150 min; 36.33 ± 0.50 vs. 36.01 ± 0.56 °C, p = 0.0186). We also found a significant difference in body weight loss (control vs. CHO, respectively: - 1.6 ± 0.8 vs. - 0.9 ± 1.4 kg, p = 0.0304) and loss of lower limb muscle mass (- 0.7 ± 0.7 vs. - 0.3 ± 0.6 kg, p = 0.0110) between the control and CHO groups, respectively.

Conclusion: CHO had no effect on raising the intraoperative core temperature, and no negative impact on the perioperative outcome. CHO prevented the loss of lower limb muscle mass, which may lead to better postoperative recovery.
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http://dx.doi.org/10.1007/s00464-018-6273-2DOI Listing
November 2018

Peranal endoscopic myectomy (PAEM) for rectal lesions with severe fibrosis and exhibiting the muscle-retracting sign.

Endoscopy 2018 08 8;50(8):813-817. Epub 2018 Jun 8.

Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki, Japan.

Background: Although endoscopic submucosal dissection has enabled complete tumor resection and accurate pathological assessment in a manner that is less invasive than surgery, the complete resection of lesions with severe fibrosis in the submucosal layer and exhibiting the muscle-retracting sign is often difficult. We have devised a new method, peranal endoscopic myectomy (PAEM), for rectal lesions with severe fibrosis, in which dissection is performed between the inner circular and outer longitudinal muscles, and have examined the usefulness and safety of this new technique.

Methods: All of the patients who underwent PAEM in our hospital and affiliated hospitals between July 2015 and June 2017 were retrospectively reviewed.

Results: 10 rectal lesions were treated with PAEM. En bloc resection with a negative vertical margin was achieved in eight patients (80 %), whose lesions were mucosal (n = 2), shallow submucosal (n = 1), deep submucosal (n = 4), and muscle invasive (n = 1). The clinical course of all patients after PAEM was favorable. In patients who underwent additional surgery, anus preservation was achieved on the basis of the pathological results from PAEM.

Conclusions: PAEM for lesions with severe fibrosis exhibiting the muscle-retracting sign appears to be both safe and useful.
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http://dx.doi.org/10.1055/a-0602-3905DOI Listing
August 2018

Nogo-B (Reticulon-4B) functions as a negative regulator of the apoptotic pathway through the interaction with c-FLIP in colorectal cancer cells.

Biochim Biophys Acta Mol Basis Dis 2018 Aug 21;1864(8):2600-2609. Epub 2018 Apr 21.

Department of General and Gastroenterological Surgery, Osaka Medical College, Osaka, Japan.

Nogo-B is a member of the Nogo/Reticulon-4 family and has been reported to be an inducer of apoptosis in certain types of cancer cells. However, the role of Nogo-B in human cancer remains less understood. Here, we demonstrated the functions of Nogo-B in colorectal cancer cells. In clinical colorectal cancer specimens, Nogo-B was obviously overexpressed, as determined by immunohistochemistry; and Western blot analysis showed its expression level to be significantly up-regulated. Furthermore, knockdown of Nogo-B in two colorectal cancer cell lines, SW480 and DLD-1, by transfection with si-RNA (siR) resulted in significantly reduced cell viability and a dramatic increase in apoptosis with insistent overexpression of cleaved caspase-8 and cleaved PARP. The transfection with Nogo-B plasmid cancelled that apoptosis induced by siRNogoB in SW480 cells. Besides, combinatory treatment with siR-Nogo-B/staurosporine (STS) or siR-Nogo-B/Fas ligand (FasL) synergistically reduced cell viability and increased the expression of apoptotic signaling proteins in colorectal cancer cells. These results strongly support our contention that Nogo-B most likely played an oncogenic role in colorectal cancer cells, mainly by negatively regulating the extrinsic apoptotic pathway in them. Finally, we revealed that suppression of Nogo-B caused down-regulation of c-FLIP, known as a major anti-apoptotic protein, and activation of caspase-8 in the death receptor pathway. Interaction between Nogo-B and c-FLIP was shown by immunoprecipitation and immunofluorescence studies. In conclusion, Nogo-B was shown to play an important negative role in apoptotic signaling through its interaction with c-FLIP in colorectal cancer cells, and may thus become a novel therapeutic target for colorectal cancer.
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http://dx.doi.org/10.1016/j.bbadis.2018.04.018DOI Listing
August 2018

Intestinal endometriosis combined with colorectal cancer: a case series.

J Med Case Rep 2018 Jan 30;12(1):21. Epub 2018 Jan 30.

Departments of General and Gastroenterological Surgery, Osaka Medical College, Osaka, Japan.

Background: Intestinal endometriosis is a common benign disease among menstruating women that affects the intestinal tract.

Case Presentation: This case report presents seven Japanese cases of intestinal endometriosis with colorectal cancer treated by laparoscopic surgery. Five of the seven cases reported here are women presenting with bowel obstruction due to colorectal endometriosis with colorectal cancer. It can be confused with serious lesions such as advanced colorectal cancer with peritoneal involvement or invasion of adjacent organs (T4).

Conclusions: Therefore, we should consider the probability that the cause of bowel obstruction is not T4 but intestinal endometriosis. For surgical treatment, we recommend laparoscopic surgery for colorectal resection because of its benefits of differential diagnosis of T4, preserving fertility, and preventing excessive surgical stress. We performed laparoscopic resection in seven patients with intestinal endometriosis and colorectal cancer. These cases demonstrate the difficulty of establishing a differential diagnosis of intestinal endometriosis with colorectal cancer from T4.
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http://dx.doi.org/10.1186/s13256-017-1537-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789683PMC
January 2018

Risk factors for surgical site infection after stoma closure comparison between pursestring wound closure and conventional linear wound closure: Propensity score matching analysis.

Am J Surg 2018 Jan 6;215(1):58-61. Epub 2017 Oct 6.

Departments of General and Gastroenterological Surgery, Osaka Medical College Hospital, Takatsuki, Osaka, Japan.

Purpose: Stoma closure has been associated with a high rate of surgical site infection (SSI) and the optimal skin closure method is still controversial. The aim of this study was to compare the short-term and long-term outcomes between the conventional linear closure (CC) and the persestring closure (PC) using propensity score matching analysis.

Methods: We analysed the data of 360 patients who underwent stoma closure with CC or PC between January 2000 and December 2014. The propensity score was calculated from age, gender, body mass index, primary disease, type of stoma, diabetes mellitus, history of smoking, steroid use, the American Society of Anesthesiologists score, Prognostic Nutritional Index and modified Glasgow Prognostic Score.

Results: There was no difference in operative variables between the two groups. The CC group and the PC group were comparable with regards to overall SSI (25.0 vs. 7.8%; P = 0.007), superficial SSI (21.9 vs. 4.7%; P = 0.003). Significant risk factor for SSI was conventional linear closure (OR, 4.14; 95% CI, 1.448-13.91).

Conclusion: Our study suggests that a pursestring stoma closure leads to less SSI.
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http://dx.doi.org/10.1016/j.amjsurg.2017.09.031DOI Listing
January 2018

The metabolic profile of a rat model of chronic kidney disease.

PeerJ 2017 23;5:e3352. Epub 2017 May 23.

Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Background: The kidney is always subjected to high metabolic demand. The aim of this study was to characterize metabolic profiles of a rat model of chronic kidney disease (CKD) with cardiorenal syndrome (CRS) induced by prolonged hypertension.

Methods: We used inbred male Dahl salt-sensitive (DS) rats fed an 8% NaCl diet from six weeks of age (high-salt; HS group) or a 0.3% NaCl diet as controls (low-salt; LS group). We analyzed function, pathology, metabolome, and the gene expression related to energy metabolism of the kidney.

Results: DS rats with a high-salt diet showed hypertension at 11 weeks of age and elevated serum levels of creatinine and blood urea nitrogen with heart failure at 21 weeks of age. The fibrotic area in the kidneys increased at 21 weeks of age. In addition, gene expression related to mitochondrial function was largely decreased. The levels of citrate and isocitrate increased and the gene expression of alpha-ketoglutaratedehydrogenase and succinyl-CoA synthetase decreased; these are enzymes that metabolize citrate and isocitrate, respectively. In addition, the levels of succinate and acetyl Co-A, both of which are metabolites of the tricarboxylic acid (TCA) cycle, decreased.

Conclusions: DS rats fed a high-salt diet were deemed a suitable model of CKD with CRS. Gene expression and metabolites related to energy metabolism and mitochondria in the kidney significantly changed in DS rats with hypertension in accordance with the progression of renal injury.
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http://dx.doi.org/10.7717/peerj.3352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5444364PMC
May 2017

Laparoscopic versus open resection for transverse and descending colon cancer: Short-term and long-term outcomes of a multicenter retrospective study of 1830 patients.

Asian J Endosc Surg 2017 Aug 7;10(3):268-275. Epub 2017 Apr 7.

Department of Surgery, Tokyo Medical and Dental University Hospital, Tokyo, Japan.

Introduction: Previous randomized controlled trials demonstrated similar oncological outcomes between laparoscopic and open colectomies, except for cases involving transverse colon and splenic flexure colon cancer. The objective of this study was to confirm the oncological safety and advantages of the short-term results of laparoscopic surgery for transverse and descending colon cancer in comparison with open surgery.

Methods: The study data were retrospectively collected from the databases of 45 hospitals. Patients with transverse or descending colon cancer who underwent laparoscopic or open R0 resection were registered. The primary end-points were the 3-year overall survival and relapse-free survival rates according to pathological stage. The secondary end-points were the short-term results, including blood loss, operative time, diet intake, hospital stay, and postoperative complications.

Results: Of the 1830 eligible patients, 872 underwent open colectomy and 958 underwent laparoscopic colectomy. The median follow-up period was 38.4 months. The conversion rate to open resection was 4.5%. The 3-year overall survival rate of the laparoscopic group was significantly higher than that of the open group for stage I patients (96.2% vs 99.2%; P = 0.04); it was also higher for stage II (94.0% vs 95.5%) and stage III (87.4% vs 90.2%) patients, but there were no significant differences. The 3-year relapse-free survival rate of the laparoscopic group was significantly higher than that of the open group for stage I patients; there were no differences between the open and laparoscopic groups among the stage II and III patients. In the multivariate analyses, laparoscopic resection was a significant factor in relapse-free survival. Laparoscopic patients had significantly lower blood loss and a significantly longer operative time than the open groups. Also, postoperative hospital stay was significantly shorter and postoperative morbidity was significantly lower in the laparoscopic group.

Conclusion: Although this retrospective study has limitations, we can conclude that laparoscopic surgery for transverse and descending colon cancer is oncologically safe and yields better short-term results than open surgery.
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http://dx.doi.org/10.1111/ases.12373DOI Listing
August 2017
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