Publications by authors named "Suguru Hasegawa"

157 Publications

Standardized Methods Using EUS-guided Fine-needle Biopsy and a Minimal Medium Creates Three Pancreatic Cancer Organoids.

Anticancer Res 2022 Aug;42(8):4103-4109

Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.

Background/aim: Recently, endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has been conducted for diagnosing pancreatic ductal adenocarcinoma (PDAC), after which obtained samples were used in organoid cultures. However, no standardized method for PDAC organoid cultures exists. Therefore, to standardize or simplify sample collection and culture methods for PDAC organoids, we performed a floating culture using non-minced specimens obtained by EUS-FNB in a minimal medium, lacking growth factors or inhibitors for pancreatic organoids.

Patients And Methods: A total of 38 patients with clinically diagnosed PDAC were enrolled in the study. First, EUS-FNB was conducted using a 22- or 25-gauge biopsy needle. Then, a surplus of samples was collected for organoid formation after rapid on-site cytological evaluations of sample adequacy. Subsequently, the established organoids were compared with clinical data and pathological diagnosis, following periodic observations and evaluations for morphology.

Results: PDAC organoids were successfully created in 24 of the 38 cases (63.2%), including four cases with pathologically inconclusive EUS-FNB results. Afterward, PDAC organoid morphology was classified into ductal, dormant, and adhesive small cluster (ASC) types. Although the ductal and ASC types were seen separately, they were also seen together in other cases, which we named "mixed type".

Conclusion: We propose a feasible and straightforward method for establishing organoids, especially for diagnosing PDAC, particularly when the result of EUS-FNB is pathologically inconclusive. Furthermore, PDAC organoids are morphologically classified into three types reported for the first time.
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http://dx.doi.org/10.21873/anticanres.15908DOI Listing
August 2022

Comparison of oncological outcomes between low anterior resection and abdominoperineal resection for rectal cancer: A retrospective cohort study using a multicenter database in Japan.

Eur J Surg Oncol 2022 Jun 17. Epub 2022 Jun 17.

Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8510, Japan.

Background: It remains controversial whether the abdominoperineal resection (APR) procedure itself has a negative impact on prognosis compared with sphincter-saving surgery (SSS). The purpose of this study was to investigate whether the operation type affects the prognostic outcome in rectal cancer using a multicenter database in Japan.

Methods: The study involved 2533 patients who underwent APR or SSS and were registered in the Japanese Society for Cancer of the Colon and Rectum database, which includes data from 74 centers, between 2003 and 2007. The primary endpoints were overall survival (OS) and relapse-free survival (RFS). The secondary endpoints were local recurrence rate (LRR) and pathological radial margin (pRM) status.

Results: Multivariate analysis identified pathological tumor depth, lymph node status, and pRM status to be associated with oncological outcomes (OS, RFS, LRR). Although the oncological outcomes were worse after APR than after SSS in univariate analysis, there was no significant difference in OS (hazard ratio 1.08; 95% confidence interval [CI] 0.85-1.37) or RFS (hazard ratio 1.06; 95% CI 0.87-1.30) between APR and SSS. There was also no significant difference in LRR (odds ratio 1.11, 95% CI 0.70-1.77). Multivariate analysis showed that operation type was associated with positive pRM (odds ratio 3.13, 95% CI 0.18-0.56).

Conclusions: There was no significant difference in oncological outcomes between APR and SSS for rectal cancer. The risk of positive pRM was higher for APR and performing radial margin-negative surgery is an important factor in improving the oncological outcomes of APR.
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http://dx.doi.org/10.1016/j.ejso.2022.06.002DOI Listing
June 2022

Reconstruction with omental flap and negative pressure wound therapy after total pelvic exenteration of anal fistula cancer: a case report.

Surg Case Rep 2022 Jun 20;8(1):116. Epub 2022 Jun 20.

Department of Gastroenterological Surgery, Fukuoka University Hospital, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.

Introduction: Surgery for anal fistula cancer (AFC) associated with Crohn's disease usually entails extensive perineal wounds and dead space in the pelvis, which is often filled with a myocutaneous flap. However, use of a myocutaneous flap is invasive. We report a case of total pelvic exenteration (TPE) for AFC in which a myocutaneous flap was avoided by using an omental flap and negative pressure wound therapy (NPWT).

Case Presentation: The patient was a 47-year-old woman who had been treated for Crohn's disease involving the small and large intestine for 30 years and had repeatedly developed anal fistulas. She was referred with a diagnosis of AFC that had spread extensively in the pelvis. We performed laparoscopic TPE via a transperineal endoscopic approach. To prevent infection in the large skin defect and extensive pelvic dead space postoperatively, the perineal wound was reconstructed using an omental flap and NPWT. During 20 days of NPWT, the wound steadily decreased in size and closed on postoperative day (POD) 20. She was discharged without complications on POD 30.

Discussion: NPWT is useful for preventing perineal wound infection and promoting granulation tissue formation. However, direct contact with the intestine may lead to intestinal perforation. In this case, the combination of an omental flap with NPWT effectively prevented surgical site infection. The flap filled the large pelvic dead space and physically separated the intestine from the polyurethane foam used for NPWT.

Conclusion: NPWT and an omental flap may become an option when performing TPE.
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http://dx.doi.org/10.1186/s40792-022-01472-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9206969PMC
June 2022

Crucial Roles of the Assistant Surgeon During Laparoscopic Left Hemihepatectomy.

Cureus 2022 Apr 11;14(4):e24050. Epub 2022 Apr 11.

Department of Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, JPN.

Background Although left hemihepatectomy has been widely performed via the laparoscopic approach, the roles of the assistant surgeon have not been well-documented so far. We herein present our standardized procedures of laparoscopic left hemihepatectomy without Spiegel's lobe resection, focusing on the crucial roles of the assistant surgeon. Methods During laparoscopic left hemihepatectomy without Spiegel's lobe resection, countertraction by the assistant surgeon is quite important especially during isolating the left Glissonean pedicle and transecting liver parenchyma. When securing the left hepatic pedicle using the Glissonean approach, the assistant surgeon pushes Segment 4 of the liver cranially and pulls the tape encircling the hepatoduodenal ligament caudally in the opposite way, orthogonal to the direction of the laparoscopic forceps toward the left portal triad. During liver parenchymal transection, the assistant surgeon pulls the hanging tape across the left lobe of the liver in order to provide a wide and stable liver transection plane. With this standardized technique, nine cases of laparoscopic left hemihepatectomy were performed over the last two years in our department, and the perioperative data were retrospectively analyzed. Results The median age of the nine patients was 70 years (range: 58 - 84 years). Most of the patients were males (77.8%). Five of nine patients were diagnosed with colorectal liver metastasis, two with hepatocellular carcinoma (HCC), one with inflammatory pseudotumor, and the other one with hepaticolithiasis. There were no conversions to open surgery. The median operative time and estimated blood loss were 337 minutes (range: 219 - 478 minutes) and 100 ml (range: 41 - 375 ml), respectively. The median length of postoperative hospital stay was nine days (range: 7 - 16 days). Major complications (Clavien-Dindo classification grade III or more) were not encountered in our cohort postoperatively. Conclusion We presented here our standardized assistant roles during laparoscopic left hemihepatectomy without Spiegel's lobe resection, which was revealed to be safe and feasible in our cohort.
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http://dx.doi.org/10.7759/cureus.24050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9095429PMC
April 2022

Gallbladder Intramucosal Carcinoma Arising in a Cholesterol Polyp: A Case Report.

Cureus 2022 Mar 6;14(3):e22898. Epub 2022 Mar 6.

Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, JPN.

Cholesterol polyp is the most common benign disease of gallbladder polyps, and is considered not to be the origin of malignancy. Herein, we report a rare case of a well-differentiated adenocarcinoma arising in a gallbladder cholesterol polyp. A pedunculated mulberry-like gallbladder polyp diagnosed with a cholesterol polyp preoperatively consisted of two distinct components macroscopically: a yellow-whitish lobulated lesion and a brownish irregular lesion. Microscopically, the former revealed to be a cholesterol polyp, but the latter demonstrated a well-differentiated adenocarcinoma. Even if imaging findings suggest a gallbladder cholesterol polyp, it is important to keep in mind that carcinoma can coexist like our case.
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http://dx.doi.org/10.7759/cureus.22898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983120PMC
March 2022

Relationship between perioperative oncological evaluation and recurrence using circulating tumor DNA with KRAS mutation in patients with colorectal cancer.

Cancer Med 2022 Mar 21. Epub 2022 Mar 21.

Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan.

Background: The detection of circulating tumor DNA (ctDNA) in colorectal cancer (CRC) by liquid biopsy may have prognostic information. In this perioperative study, we evaluate if there is a relationship between mutant allele frequency (MAF) of Kirsten rat sarcoma viral oncogene homolog (KRAS) and tumor recurrence and how that could be useful in the early detection of recurrence.

Methods: Among 304 cases of colorectal cancer surgery, ctDNA was sampled from the perioperative blood of 84 patients with CRC with KRAS mutation (exon 4 p.A146T, exon 4 p.A146V, exon 2 p.G12A, exon 2 p.G12C, exon 2 p.G12D, exon 2 p.G12S, exon 2 p.G12V, exon 2 p.G13D, exon 3 p.Q61H) and analyzed using the digital polymerase chain reaction system. The median observation period was 26 months.

Results: Although the relationship between the perioperative MAF of KRAS and recurrence was not proved, tumor diameter, tumor depth, and stage were correlated with the preoperative MAF of KRAS (p = 0.034, p = 0.002, p = 0.008). However, tumor diameter, tumor depth, and stage did not correlate with MAF of KRAS at postoperative day 30.

Conclusions: In this study, pathological tumor size, tumor depth, and stage were correlated with preoperative MAF of KRAS, but it was unreliable to predict recurrence by detection of ctDNA with KRAS mutation in the perioperative period of colorectal surgery.
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http://dx.doi.org/10.1002/cam4.4677DOI Listing
March 2022

Endoscopic full-thickness resection of an esophageal leiomyoma located in close proximity to the azygos vein.

DEN open 2022 Apr 25;2(1):e30. Epub 2021 Aug 25.

Department of Gastroenterological Surgery Fukuoka University Faculty of Medicine Fukuoka Japan.

Third-space endoscopic techniques, such as peroral endoscopic tumor resection (POET) and submucosal tunneling endoscopic resection (STER), enable access to deep organs and tissues that have been previously inaccessible with an endoscope. We present a 29-year-old man with a submucosal tumor (40 × 25 mm) located at 5 o'clock in the upper thoracic esophagus. Histological diagnosis by endoscopic ultrasound-fine needle aspiration was leiomyoma. Computed tomography showed the azygos vein posterior to the tumor. However, because endoscopic ultrasound revealed space between them, POET was performed. Because the tumor originated from the deep layer of the muscularis propria, full-thickness resection was performed to achieve R0 resection. The azygos vein arch was seen through the mediastinal space after tumor enucleation. The final histopathological diagnosis was leiomyoma. POET is a potentially revolutionary endoscopic technique that enables full-thickness resection of nonepithelial lesions. Preoperative computed tomography or endoscopic ultrasound to determine peritumoral anatomy is important to ensure safety. During the procedure, it is important to operate under direct vision, accurately identify the tumor boundary, and dissect along the boundary to avoid damaging the tumor and surrounding structures.
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http://dx.doi.org/10.1002/deo2.30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8828190PMC
April 2022

Risk factors and long-term course of gastroesophageal reflux disease after peroral endoscopic myotomy: A large-scale multicenter cohort study in Japan.

Endoscopy 2022 Feb 16. Epub 2022 Feb 16.

Digestive Diseases Center, Showa University Koto-Toyosu Hospital, Tokyo, Japan.

BACKGROUND : Gastroesophageal reflux disease (GERD) and reflux esophagitis remain problems after peroral endoscopic myotomy (POEM). This study aimed to elucidate the risk factors and long-term course of reflux esophagitis and symptomatic GERD after POEM. METHODS : This multicenter cohort study involved 14 high volume centers. Overall, 2905 patients with achalasia-related esophageal motility disorders treated with POEM were analyzed for reflux esophagitis, severe reflux esophagitis (Los Angeles classification C or D), and symptomatic GERD. RESULTS : Reflux esophagitis was diagnosed in 1886 patients (64.9 %). Age ≥ 65 years (risk ratio [RR] 0.85), male sex (RR 1.11), posterior myotomy (RR 1.12), esophageal myotomy > 10 cm (RR 1.12), and gastric myotomy > 2 cm (RR 1.17) were independently associated with reflux esophagitis. Severe reflux esophagitis was diagnosed in 219 patients (7.5 %). Age ≥ 65 years (RR 1.72), previous treatments (RR 2.21), Eckardt score ≥ 7 (RR 0.68), sigmoid-type achalasia (RR 1.40), and esophageal myotomy > 10 cm (RR 1.59) were factors associated with severe reflux esophagitis. Proton pump inhibitors (PPIs) were more effective for reflux esophagitis at 5-year follow-up ( = 0.03) than after 1 year ( = 0.08). Symptomatic GERD was present in 458 patients (15.9 %). Symptom duration ≥ 10 years (RR 1.28), achalasia diagnosis (RR 0.68), integrated relaxation pressure ≥ 26 (RR 0.60), and posterior myotomy (RR 0.80) were associated with symptomatic GERD. The incidence of symptomatic GERD was lower at 5-year follow-up compared with that after 1 year ( = 0.04), particularly in PPI users ( < 0.001). CONCLUSIONS : The incidence of severe reflux esophagitis was low after POEM, but excessive myotomy for older patients with previous treatments should be avoided. Early phase symptomatic GERD is non-acid reflux dependent and the natural course is favorable, basically supporting conservative treatment.
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http://dx.doi.org/10.1055/a-1753-9801DOI Listing
February 2022

Diagnostic error rates and associated factors for lower gastrointestinal perforation.

Sci Rep 2022 01 19;12(1):1028. Epub 2022 Jan 19.

Department of Diagnostic and Generalist Medicine, Dokkyo Medical University Hospital, Mibu, Tochigi, Japan.

Lower gastrointestinal perforation is rare and challenging to diagnose in patients presenting with an acute abdomen. However, no study has examined the frequency and associated factors of diagnostic errors related to lower gastrointestinal perforation. This large-scale multicenter retrospective study investigated the frequency of diagnostic errors and identified the associated factors. Factors at the level of the patient, symptoms, situation, and physician were included in the analysis. Data were collected from nine institutions, between January 1, 2015 and December 31, 2019. Timely diagnosis was defined as diagnosis at the first visit in computed tomography (CT)-capable facilities or referral to an appropriate medical institution immediately following the first visit to a non-CT-capable facility. Cases not meeting this definition were defined as diagnostic errors that resulted in delayed diagnosis. Of the 439 cases of lower gastrointestinal perforation identified, delayed diagnosis occurred in 138 cases (31.4%). Multivariate logistic regression analysis revealed a significant association between examination by a non-generalist and delayed diagnosis. Other factors showing a tendency with delayed diagnosis included presence of fever, absence of abdominal tenderness, and unavailability of urgent radiology reports. Initial misdiagnoses were mainly gastroenteritis, constipation, and small bowel obstruction. In conclusion, diagnostic errors occurred in about one-third of patients with a lower gastrointestinal perforation.
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http://dx.doi.org/10.1038/s41598-021-04762-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8770624PMC
January 2022

Combined laparoscopic and transperineal endoscopic total pelvic exenteration for the vaginal stump recurrence of cervical cancer.

J Gynecol Oncol 2022 01 30;33(1):e16. Epub 2021 Nov 30.

Department of Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.

Total pelvic exenteration (TPE) is sometimes required for radical treatment of locally advanced or recurrent gynecologic cancer [1]. However, TPE with a transabdominal approach requires highly advanced techniques in the case of repeated surgery due to the effects of primary surgery and/or chemoradiotherapy, especially when a transabdominal approach is used. Recent technical advances in transanal/transperineal endoscopic surgery have proved beneficial for complicated surgery in the deep pelvis [2]. Here we introduce our surgical procedure for combined laparoscopic and transperineal endoscopic TPE (TpTPE) for pelvic recurrence of cervical cancer. A 42-year-old woman was diagnosed with vaginal stump recurrence of cervical cancer involving the rectum, bladder, and ureters following hysterectomy and pelvic lymph node dissection as primary surgery and chemotherapy/chemoradiotherapy for previous recurrences. We decided to perform TpTPE with a combined laparoscopic approach. The GelPOINT advanced access platform was fixed through a perineal skin incision around the tightly closed anus, external urethral orifice, and vagina. With sufficient pneumopelvic pressure (12 mmHg), TpTPE was performed under a good surgical view without any effect of the primary surgery. A ureterostomy and sigmoid colostomy were created and a right gracilis muscle flap was used to reconstruct the pelvic defect. The total operative time and estimated blood loss were 887 minutes and 497 mL, respectively. Histopathological examination revealed recurrent cervical cancer invading the rectum, bladder, and bilateral ureters with negative surgical margins. The postoperative course was uneventful except for paralytic ileus. The patient was discharged on postoperative day 18. TpTPE is a technically feasible and effective approach for locally advanced pelvic tumors.
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http://dx.doi.org/10.3802/jgo.2022.33.e16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728673PMC
January 2022

Intraoperative pressure monitoring of the lower leg for preventing compression-related complications associated with the lithotomy position.

Surg Endosc 2022 Aug 1;36(8):5873-5881. Epub 2021 Dec 1.

Department of Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jounan-ku, Fukuoka, 814-0180, Japan.

Background: Several serious complications are associated with the lithotomy position, including well-leg compartment syndrome and peroneal nerve paralysis. The aims of this study were to identify risk factors for the intraoperative elevation of lower leg pressure and to evaluate the effectiveness of monitoring external pressure during surgery for preventing these complications.

Methods: The study included 106 patients with a diagnosis of sigmoid colon or rectal cancer who underwent elective laparoscopic surgery between June 2019 and December 2020. We divided the posterior side of the lower leg into four parts (upper outside, upper inside, lower outside, lower inside) and recorded the peak pressure applied to each area at hourly intervals during surgery (called "regular points") and when the operating position was changed (e.g., by head-tilt or leg elevation; called "points after change in position"). When the pressure was observed to be higher than 50 mmHg, we adjusted the position of the leg and re-recorded the data. Data on postoperative leg-associated complications were also collected.

Results: The pressure was measured at a total of 1125 points (regular, n = 620; after change of position, n = 505). The external pressure on the upper outer side of the right leg (median, 36 mmHg) was higher than that on any other area of the lower leg. The pressure increase to more than 50 mmHg was observed not only during the change of position (27.5%) but also during regular points (22.4%). Bodyweight, strong leg elevation, and low head position were identified as factors associated with increased external pressure. There have been no compression-related complications in 534 cases at our institution since the introduction of intraoperative pressure monitoring.

Conclusions: Several risk factors associated with increased external pressure on the lower leg were identified. Intraoperative pressure monitoring might help reduction of pressure-related complications, needing further and larger prospective data collections.
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http://dx.doi.org/10.1007/s00464-021-08921-0DOI Listing
August 2022

[Management of advanced and recurrent colorectal cancer].

Nihon Shokakibyo Gakkai Zasshi 2021 ;118(11):999-1003

Department of Gastroenterological Surgery, Fukuoka University, Faculty of Medicine.

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http://dx.doi.org/10.11405/nisshoshi.118.999DOI Listing
November 2021

A Trial Protocol to Investigate the Incidence of Postoperative Bowel Obstruction after Laparoscopic Colorectal Cancer Surgery Using an Absorbable Adhesion Barrier Material (INTERCEED) (Balsam CEED Study): A Prospective, Multicenter, Observational Study.

J Anus Rectum Colon 2021 28;5(4):414-418. Epub 2021 Oct 28.

Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background: Some studies have reported that adhesion prevention barriers (APBs) reduce adhesion after abdominal surgery; however, evidence showing that APBs reduce the incidence of postoperative small bowel obstruction (SBO), one of the most serious complications after abdominal surgery, is little. One concern is that APBs are usually applied only under the midline incision, although adhesion can occur at any place in the peritoneum where an incision is made during surgery. INTERCEED is an APB that reportedly prevents postoperative SBO after surgery. This study aims to assess the clinical utility of INTERCEED for the prevention of SBO after laparoscopic colorectal cancer surgery and determine whether the application site of INTERCEED affects the incidence of SBO.

Methods/design: This study is a prospective, multicenter, observational study conducted in Japan. The primary end point is the incidence of postoperative SBO 2 years after laparoscopic colorectal cancer surgery. The secondary end points include whether the site of the application of INTERCEED affects the incidence of SBO. Each surgeon selects one of the following three procedures: 1) INTERCEED is placed only under the midline incision; 2) INTERCEED is placed at the site of bowel mobilization and/or lymph node dissection, but not under the midline incision; and 3) INTERCEED is placed at both sites.

Discussion: This is the first study to assess whether the placement of APBs affects the incidence of SBO. The study results may lead to a subsequent randomized study.
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http://dx.doi.org/10.23922/jarc.2021-030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553355PMC
October 2021

Papillary hyperplasia of the gallbladder diagnosed as gallbladder cancer before surgery: A case report.

Int J Surg Case Rep 2021 Nov 3;88:106542. Epub 2021 Nov 3.

Department of Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.

Introduction And Importance: Gallbladder cancer has a poor prognosis. Therefore, an accurate diagnosis is required, for which various tests are performed. However, in some cases, it is difficult to distinguish between benign and malignant diseases before surgery. Papillary hyperplasia of the gallbladder is known for its secondary changes. Papillary hyperplasia of the gallbladder, which is known for its secondary changes, is a benign disease. We encountered papillary hyperplasia of the gallbladder with morphological changes over the course of 1 year. In addition, the tumor was suggested to be malignant during various examinations. We present a case of papillary hyperplasia of the gallbladder showing an increasing tendency and findings indicative of malignancy on imaging.

Presentation Of Case: A 70-year-old man underwent routine abdominal ultrasonography every year. We observed that the gallbladder wall was thickened. The tumor size was 24 mm. FDG-PET and other examinations indicated malignancy requiring surgery.

Clinical Discussion: Accurate diagnosis of gallbladder tumor is difficult only by diagnostic imaging. There are problems with preoperative cytology and histology. FS can be an important test to avoid extended surgery.

Conclusion: We report a rare case of papillary hyperplasia of the gallbladder, which was difficult to diagnose. Even when morphological changes and imaging findings suggest malignancy, similar findings could appear in papillary hyperplasia of the gallbladder owing to chronic inflammation.
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http://dx.doi.org/10.1016/j.ijscr.2021.106542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581500PMC
November 2021

Safety and effectiveness of sling fiber preservation POEM to reduce severe post-procedural erosive esophagitis.

Surg Endosc 2022 06 29;36(6):4255-4264. Epub 2021 Oct 29.

Department of Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jyounan-ku, Fukuoka, 814-0180, Japan.

Background: Peroral endoscopic myotomy (POEM) is standard treatment for achalasia. Gastroesophageal reflux disease (GERD) after POEM has been an important challenge since the early days of POEM implementation. The esophagogastric junction anti-reflux barrier consists of internal lower esophageal sphincter (LES) (i.e., intrinsic muscles of distal esophagus with sling fibers) and external LES (crural diaphragm and phrenoesophageal ligament anchors the distal esophagus to the crural diaphragm). During conventional POEM, the entire internal LES is unintentionally dissected. Preservation of the sling fiber may reduce post-POEM GERD, but its safety and effectiveness have been unclear. In this study, we investigated the safety and effectiveness of sling fiber preservation POEM (SP-POEM) for reducing severe post-procedural erosive esophagitis.

Methods: We analyzed data of 236 patients who underwent POEM; of these, 203 patients underwent posterior myotomy without (Group 1) or with attempted (Group 2) sling fiber preservation. Group 1 (N = 79; sling fiber excision, N = 68) and Group 2 (N = 90; sling fiber preservation, N = 81) were compared. Post-procedural erosive esophagitis (Los Angeles classification) were assessed and the area (direction and length) of mucosal break was also investigated. The gastroesophageal flap valve was evaluated by Hill's classification.

Results: Severe erosive esophagitis exceeding grade C (Los Angeles classification) occurred in 44.1% of patients (30/68) in Group 1 and in 18.5% of patients (15/81) in Group 2. In mapping of erosive esophagitis, mucosal breaks appeared widely in all directions in Group 1; they tended to be limited in Group 2 (especially in the 2 o'clock direction). Assessment using the Hill's classification showed that the gastroesophageal flap valve was preserved after SP-POEM.

Conclusion: SP-POEM is safe and effective, with a success rate of 90%. The rate of severe erosive esophagitis can be decreased by preserving sling fibers.
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http://dx.doi.org/10.1007/s00464-021-08763-wDOI Listing
June 2022

Efficacy and safety of peroral endoscopic myotomy in 100 older patients.

Esophagus 2022 04 9;19(2):324-331. Epub 2021 Oct 9.

Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, 7-45-1 Nanakuma, Jyounan-ku, Fukuoka, 814-0180, Japan.

Background: Peroral endoscopic myotomy (POEM) is a standard treatment for achalasia. Several reports have described the efficacy and safety of POEM for elderly patients, but none has reported the efficacy and safety of POEM in a large number of elderly patients for > 3 years postoperatively. In this study, we examined the safety and outcome of POEM for 3 years postoperatively in 100 elderly patients.

Methods: One hundred consecutive patients aged > 65 years who underwent POEM from September 2011 to March 2020 were included in this study. In analysis 1, we retrospectively investigated the safety and efficacy of POEM in all patients. In analysis 2, the efficacy and safety of POEM were statistically compared between two groups: the early elderly (65-74 years of age, 55 patients) and late elderly (≥ 75 years of age, 45 patients).

Results: The technical success rate of POEM was 100%. In analysis 1, the 3-month, 1-year, 2-year, and 3-year efficacies of POEM (Eckardt score of ≤ 3) were 100% (92/92 cases), 100% (91/91 cases), 97.8% (88/90 cases), and 100% (92/92 cases), respectively. Procedure-related adverse events occurred in 11% of patients, but none was fatal. Two late elderly patients developed aspiration pneumonia due to delirium and underwent long-term hospitalization. In analysis 2, there were no significant differences in the efficacy and safety of POEM between the two age groups.

Conclusions: POEM is effective and safe for elderly patients. However, precautions are needed regarding the risk of adverse events associated with delirium when POEM is performed in elderly patients.
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http://dx.doi.org/10.1007/s10388-021-00881-7DOI Listing
April 2022

Is laparoscopic liver resection safe for super-elderly patients (aged ≥80)? A propensity score-matched analysis.

Asian J Endosc Surg 2022 Apr 5;15(2):279-289. Epub 2021 Oct 5.

Department of Gastroenterological Surgery, Fukuoka University, Fukuoka, Japan.

Background/purpose: The safety of laparoscopic liver resection in super-elderly patients with comorbidities is unknown. We used propensity score matching to evaluate the utility and safety of laparoscopic liver resection in super-elderly patients.

Methods: Two-hundred and five patients who underwent laparoscopic liver resection were retrospectively reviewed. They were classified into two groups based on age: ≥80 years (elderly group, n = 49) and <80 years (control group, n = 156). Propensity score matching (PSM) was performed based on preoperative clinical parameters. The intraoperative and postoperative outcomes were compared.

Results: After matching, 45 patients were included in each group. The intraoperative blood loss was identical between the control and elderly groups (60 vs 60 mL, respectively, P = .588); the frequency of serious postoperative complications (Clavien-Dindo class ≥3, 1/45 vs 1/45, P = 1.00) was also similar. There was no significant difference in terms of the exacerbation of malignancy (22.2% vs 11.1%, P = .258) or other diseases (8.9% vs 22.2%, P = .144). There was no difference in overall survival before and after PSM. However, 5-year overall survival excluding primary cancer-related death showed a difference after PSM (90.7% vs 70.4%; P = .048).

Conclusions: Laparoscopic liver resection is feasible and safe in super-elderly patients. The long-term prognosis was poor in patients affected by other illnesses compared to the younger population with similar risk profiles, but there was no difference in overall survival.
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http://dx.doi.org/10.1111/ases.12994DOI Listing
April 2022

Oncological evaluation in the perioperative period using cfDNA with BRAF V600E mutation in patients with colorectal cancer.

Sci Rep 2021 06 24;11(1):13263. Epub 2021 Jun 24.

Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.

The detection of circulating cell-free DNA (cfDNA) by liquid biopsy is reported to provide prognostic information in colorectal cancer (CRC). Although the frequency of BRAF V600E mutation in CRC is less than 10%, it is associated with poor responses to conventional chemotherapy. We conducted a prospective study to investigate the relationship between the perioperative mutant allele frequency (MAF) of BRAF V600E and tumor recurrence, and to evaluate the possibility of early detection of recurrence. Among 362 patients who underwent radical resection, cfDNA was extracted from the perioperative blood of 11 CRC patients with BRAF V600E mutation and analyzed using the digital polymerase chain reaction (dPCR) system. The median follow-up time was 22 months, and there were four cases of recurrence. Although there was no correlation between recurrence and the perioperative MAF of BRAF V600E, tumor diameter was correlated with the MAF (p = 0.024), and the MAF increased with time in two patients from whom additional samples were obtained prior to recurrence. In this study, we identified a correlation between the pathological tumor diameter and the MAF, but it was difficult to predict recurrence by measuring cfDNA with BRAF V600E mutation in the perioperative period of radical resection of CRC.
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http://dx.doi.org/10.1038/s41598-021-92795-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225636PMC
June 2021

Preoperative T staging of advanced colorectal cancer by computed tomography colonography.

Int J Colorectal Dis 2021 Nov 18;36(11):2489-2496. Epub 2021 Jun 18.

Department of Gastroenterological Surgery, Fukuoka University Hospital, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.

Purpose: Accurate preoperative T staging is important when determining the treatment strategy for advanced colorectal cancer. We have previously reported the usefulness of preoperative T staging based on the spatial relationship of tumors and "bordering vessels" by computed tomography colonography (CTC) with multiplanar reconstruction (MPR). The aims of this study were to evaluate the external validity of this method and to determine whether there is a difference in the accuracy of T staging between the mesenteric and antimesenteric sides.

Methods: The study subjects were 110 patients with colorectal cancer who underwent preoperative CTC and surgical resection from June 2016 to March 2018. Preoperative T stage was determined by CTC based on the relationship between the tumor and the bordering vessels and compared with the pathological T stage. The influence of tumor location, namely, whether the tumor was on the antimesenteric or mesenteric side, on preoperative T staging was assessed in 78 patients with colorectal cancer.

Results: Sensitivity, specificity, accuracy, positive, and negative predictive values were respectively, 65%, 91%, 83%, 76%, and 85% for T2 (n = 34); 76%, 82%, 81%, 50%, and 94% for T3 (n = 23); and 77%, 93%, 87%, 86%, and 88% for T4a disease (n = 39). Overall right answer rate was 83.3% (15/18) for the mesenteric side and 65% (39/60) for the antimesenteric side (n = 0.14).

Conclusion: Diagnostic criteria based on the bordering vessels seen on CTC images with MPR are useful for T staging of colorectal cancer. However, the accuracy differs between the antimesenteric and mesenteric sides.
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http://dx.doi.org/10.1007/s00384-021-03971-1DOI Listing
November 2021

The Pre-treatment Lymphocyte-to-Monocyte Ratio Predicts Efficacy in Metastatic Colorectal Cancer Treated With TAS-102 and Bevacizumab.

Anticancer Res 2021 Jun;41(6):3131-3137

Department of Surgery, Teikyo University Chiba Medical Center, Ichihara, Japan.

Background/aim: Our multicenter phase II TAS-CC3 study demonstrated favorable median progression-free survival (PFS) and overall survival (OS) of 32 metastatic colorectal cancer (mCRC) patients treated with TAS-102 + bevacizumab as 3-line treatment.

Patients And Methods: We investigated the predictive and prognostic values of pre-treatment blood inflammation-based scores, including the neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR) and lymphocyte-to-monocyte ratio (LMR) on disease-control (DC), PFS and OS by a post-hoc analysis.

Results: Receiver operating characteristic curve analyses of the 3 inflammation-based scores versus DC showed the best predictive performance for LMR, followed by NLR and PLR. The high-LMR group had a significantly higher DC rate than the low group (87.5 vs. 43.8%). The high-LMR group showed significantly longer survival than the low group (4.9 vs. 2.3 m for median PFS) (21.0 vs. 6.1 m for median OS).

Conclusion: The pre-treatment LMR is a valid predictive and prognostic biomarker for mCRC patients undergoing TAS-102 and bevacizumab treatment.
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http://dx.doi.org/10.21873/anticanres.15098DOI Listing
June 2021

Two case of bilateral approach in laparoscopic pancreas-sparing distal duodenectomy for duodenal neoplasms arising from the distal duodenum.

Int J Surg Case Rep 2021 Mar 16;80:105642. Epub 2021 Feb 16.

Department of Gastroenterological Surgery, Fukuoka University School of Medicine, 7-45-1 Nanakuma Jonanku, Fukuoka, 8140180, Japan.

Introduction: Laparoscopic pancreas-sparing distal duodenectomy is a less invasive surgical therapy; however, the anatomical complexity of the duodenum increases the difficulty of laparoscopic procedures. We introduce our technique for laparoscopic pancreas-sparing distal duodenectomy for distal duodenal tumors.

Presentation Of Cases: A first patient was 47-year-old woman who had 30 mm of duodenal tumor which located in third portion of duodenum. A second patient was 66-year-old man who had 35 mm of submucosal tumor which located in the third portion of duodenum. Laparoscopic pancreas-sparing duodenectomy was performed using bilateral approach for both cases. We began by dissecting an avascular area on the right side of the transverse mesocolon to mobilize the second and third portions of the duodenum with the uncinate process of the pancreas. Next, from the left side, the jejunum and the fourth portion of the duodenum were fully mobilized orally from the surrounding tissue, connecting the dissection plane with the right-side area. The jejunum and duodenum were cut with a linear stapler. Intracorporeal reconstruction was performed in an overlapped manner. We performed this procedure in two patients. Operative time was 326 and 370 min, respectively. Patients were discharged on postoperative days 9-12 without postoperative complications.

Discussion: Duodenal tumors are found increasingly often because of developments in endoscopic technology and techniques; therefore, establishing safe surgical procedures for duodenal tumor excision is imperative. Our surgical approach was simple and safe procedure.

Conclusion: Laparoscopic pancreas-sparing distal duodenectomy with a bilateral approach is a useful approach without wide mobilization of duodenum.
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http://dx.doi.org/10.1016/j.ijscr.2021.02.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933491PMC
March 2021

[A Case of Internal Jugular Vein Thrombosis Caused by Gravity-Induced Catheter Excursion following Subcutaneous Implantable Central Venous Port Insertion for Colorectal Cancer Treatment].

Gan To Kagaku Ryoho 2021 Feb;48(2):227-229

Dept. of Gastroenterological Surgery, Fukuoka University Faculty of Medicine.

The patient was a 66-year-old woman. She underwent central venous port insertion as part of postoperative adjuvant chemotherapy for sigmoid colon cancer. At the beginning of the 2 cycle, she experienced discomfort in the neck, and computed tomography was performed. As a result, catheter deviation and a thrombus in the internal jugular vein were observed. It was considered that breast displacement due to gravity caused the catheter deviation and that the position of the tip of the catheter deviating to immediately above the venous valve caused thrombus formation. We examined the factors that may cause catheter deviation.
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February 2021

Onset of Arterial and Venous Thrombosis and Safety of Antithrombic Therapy in Patients with Gastrointestinal Cancer.

Gulf J Oncolog 2020 Sep;1(34):13-18

Department of Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, Fukuoka/Japan.

Background: The objective of this study was to clarify the onset of arterial and venous thrombosis and the safety of antithrombic therapy in patients with gastrointestinal cancer.

Patients And Methods: In a retrospective cohort study of adults aged ≥ 18 years, 1187 patients with gastrointestinal cancer were admitted to our hospital between January 1, 2015 and December 31, 2017. We investigated the incidence of arterial thromboembolism (ATE) and venous thromboembolism (VTE) and serious bleeding following antithrombotic therapy.

Results: In the 1187 patients diagnosed with gastrointestinal cancer, VTE occurred in 4.5% of cases and ATE in 2.8% of cases, and in 7.2% of cases overall. Among 239 patients who received antithrombotic therapy, the combination antithrombotic therapy group (n = 43), such as dual antiplatelet therapy, had more major bleeding events than the monotherapy group (n = 196; 49% vs. 17%, p < 0.01).

Discussion: In our gastroesophageal cancer patients, arterial thrombosis occurred more frequently than venous thrombosis (17/393, 4.3% vs. 9/393, 2.3%, respectively). This result may be affected by chemotherapy or radiation therapy and needs further analysis.

Conclusion: The risk of ATE also needs to be considered in gastrointestinal cancer patients. Combination therapy with antithrombotics increases bleeding events, so it is necessary to determine the risk of thrombosis as well as bleeding.
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September 2020

Reduced port laparoscopic surgery using umbilical zigzag incision for Meckel's diverticulitis.

Int J Surg Case Rep 2021 Feb 24;79:24-27. Epub 2020 Dec 24.

Department of Gastroenterological Surgery, Fukuoka University School of Medicine, 7-45-1, Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.

Introduction: Reduced port laparoscopic surgery using an umbilical zigzag incision is comparable to conventional multiport laparoscopic surgery. This method is associated with improved cosmesis and decreased wound pain.

Presentation Of Case: A 67-year-old man visited our hospital. He presented emergency room with a chief complaint of right lower abdominal pain by walking. The patient was diagnosed Meckel's diverticulitis by computed tomography (CT). At first, antibiotics therapy and fasting were performed. Three months later, the patient underwent resection of Meckel' diverticulum with zigzag transumbilical laparoscopic surgery. The patient's postoperative course was good, and he rarely felt wound pain. The patient started oral intake three days after surgery, and was discharged 10 days after surgery.

Discussion: Zigzag transumbilical laparoscopic surgery is very useful for resection of the small intestine. This method is associated with improved cosmesis and decreased wound pain. In the case of Meckel's diverticulitis, we suggest that interval resection of Meckel's diverticulum was very useful as it was an operation that could be performed easily.

Conclusion: Reduced port laparoscopic surgery using an umbilical zigzag incision is considered to be an excellent technique in terms of operability and aesthetic outcomes.
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http://dx.doi.org/10.1016/j.ijscr.2020.12.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808904PMC
February 2021

Inhibition of NLRP3 inflammasome by MCC950 improves the metabolic outcome of islet transplantation by suppressing IL-1β and islet cellular death.

Sci Rep 2020 10 21;10(1):17920. Epub 2020 Oct 21.

Department of Regenerative Medicine and Transplantation, Fukuoka University, 7-45-1 Nanakuma Jonan-ku, Fukuoka, 814-0180, Japan.

Early rejection is a critical issue to be overcome to achieve successful islet transplantation. NLRP3 inflammasome is a protein complex that mediates the maturation of pro-interleukin (IL)-1β and pro-IL-18 to IL-1β and IL-18, respectively, which induce cellular death. Here, we investigated the impact of NLRP3 inflammasome and the effect of its inhibition by MCC950 in a rodent model of islet transplantation. We assessed the therapeutic effects of MCC950, a specific inhibitor of NLRP3 inflammasome, on gene expression, islet survival ratio and viability, and islet transplantation in mice. NLRP3 inflammasome-related gene (Nlrp3 and Il1b) expression was upregulated in islets stimulated with proinflammatory cytokines and suppressed when incubated with MCC950. Survival ratio and viability of incubated islets were reduced by cytokine stimulation and improved by MCC950. Regarding islet transplantation, the number of apoptotic cells in transplanted islets was reduced by MCC950. Furthermore, the expression of IL-1β in transplanted islets, migration of macrophages around islets, and fluctuation of blood glucose levels were suppressed by MCC950. Our study revealed that NLRP3 inflammasome worsened the therapeutic outcomes of islet transplantation and that MCC950 administration improved glycaemic control in syngeneic mice that underwent islet transplantation by inhibiting inflammation, which suppressed islet death.
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http://dx.doi.org/10.1038/s41598-020-74786-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578017PMC
October 2020

Combination of TAS-102 and bevacizumab as third-line treatment for metastatic colorectal cancer: TAS-CC3 study.

Int J Clin Oncol 2021 Jan 21;26(1):111-117. Epub 2020 Oct 21.

Department of Surgery, Teikyo University Chiba Medical Center, Chiba, Japan.

Background: TAS-102 improved the overall survival of metastatic colorectal cancer (CRC) patients with a median progression-free survival (PFS) in the RECOURSE trial. Subsequently, the combination of TAS-102 and bevacizumab was shown to extend the median PFS (C-TASK FORCE study). However, the study included patients who received second- and third-line treatment. Our study exclusively examined patients receiving this combination as a third-line treatment to investigate the clinical impact beyond cytotoxic doublets.

Methods: This investigator-initiated, open-label, single-arm, multi-centered phase II study was conducted in Japan. Eligible CRC patients were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin in first- and second-line therapy. TAS-102 (35 mg/m) was given orally twice daily on days 1-5 and 8-12 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion every 2 weeks. The primary endpoint was PFS and the secondary endpoints were time-to-treatment failure, response rate, overall survival (OS), and safety.

Results: Between June 2016 and August 2017, 32 patients were enrolled. All patients previously received bevacizumab. The median PFS was 4.5 months; the median overall survival was 9.3 months. Partial response was observed in two patients. The most common adverse events above grade 3 were neutropenia followed by thrombocytopenia. There were no non-hematological adverse events above grade 3 and no treatment-related deaths occurred.

Conclusions: This study met its primary endpoint of PFS, which is comparable to the results of the C-TASK FORCE study. The TAS-102 and bevacizumab combination has the potential to be a therapeutic option for third-line treatment of metastatic CRC.
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http://dx.doi.org/10.1007/s10147-020-01794-8DOI Listing
January 2021

A case of carbon dioxide embolism during the transperineal approach in total pelvic exenteration for advanced anorectal cancer.

Asian J Endosc Surg 2021 Jan 12;14(1):97-101. Epub 2020 Aug 12.

Department of Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.

The transanal and transperineal endoscopic approaches are useful advanced surgical options for removing rectal and anorectal cancers. Intraoperative carbon dioxide (CO ) embolisms, however, have been increasingly reported as potentially fatal complications associated with surgery employing these approaches. We report our experience with a CO embolism that was detected because of a sudden drop in end-tidal CO with decreasing saturation of percutaneous arterial oxygen during total pelvic exenteration using the transperineal endoscopic approach under pneumopelvis/pneumoperitoneum. Transesophageal echocardiography confirmed that it was a CO embolus. We reversed the pneumopelvis and pneumoperitoneum, which alleviated the cardiopulmonary problems, and the surgery then proceeded to achieve R0 resection. The patient was discharged without severe complications other than the CO embolism.
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http://dx.doi.org/10.1111/ases.12832DOI Listing
January 2021

Changes in Immunological Status in Patients With Metastatic Colorectal Cancer Treated With First-line Chemoimmunotherapy.

Anticancer Res 2020 Aug;40(8):4763-4771

Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan.

Background/aim: Chemoimmunotherapy is a promising treatment for various malignant diseases. In this study, we examined whether first-line chemoimmunotherapy using adoptive immune-cell therapy was effective for metastatic colorectal cancer (mCRC).

Patients And Methods: The therapeutic efficacy and safety of the standard first-line chemoimmunotherapy with adoptive αβ T cell therapy and bevacizumab were assessed using thirty-two patients with mCRC in our hospital. Immunological status after this chemoimmunotherapy was also evaluated.

Results: The response and disease control rates were 68.8% and 87.5%, respectively. Further, median progression-free and overall survival were 14.2 and 35.3 months. Immunotherapy-associated toxicity was minimal. Significant decrease in the change of monocyte number (p=0.006) and increase in the change of rate of lymphocyte-to-monocyte ratio (p=0.039) were seen in the complete response group.

Conclusion: First-line chemoimmunotherapy with adoptive αβ T cell therapy may be useful for mCRC.
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http://dx.doi.org/10.21873/anticanres.14478DOI Listing
August 2020

Mutant Promotes NKG2D T Cell Infiltration and CD155 Dependent Immune Evasion.

Anticancer Res 2020 Aug;40(8):4663-4674

Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan

Background/aim: Roles for mutant (mt) KRAS in the innate immune microenvironment in colorectal cancer (CRC) were explored.

Materials And Methods: Human CRC HCT116-derived, mtKRAS-disrupted (HKe3) cells that express exogenous mtKRAS and allogenic cytokine-activated killer (CAK) cells were co-cultured in 3D floating (3DF) culture. The anti-CD155 antibody was used for function blocking and immuno histochemistry.

Results: Infiltration of CAK cells, including NKG2D T cells, into the deep layer of HKe3-mtKRAS spheroids, was observed. Surface expression of CD155 was found to be up-regulated by mtKRAS in 3DF culture and CRC tissues. Further, the number of CD3 tumor-infiltrating cells in the invasion front that show substantial CD155 expression was significantly larger than the number showing weak expression in CRC tissues with mtKRAS. CD155 blockade decreased the growth of spheroids directly and indirectly through the release of CAK cells.

Conclusion: CD155 blockade may be useful for therapies targeting tumors containing mtKRAS.
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http://dx.doi.org/10.21873/anticanres.14465DOI Listing
August 2020
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