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Abstract Background Lower gastrointestinal perforation (LGP) is an acute abdominal condition associated with a high mortality rate. Timely and accurate diagnosis is crucial. Nevertheless, a diagnostic delay has been estimated to occur in approximately one-third of the cases, and the factors contributing to this delay are yet to be clearly understood. This study aimed to evaluate the diagnostic process for appropriate clinical reasoning and availability of image interpretation in cases of delayed diagnosis of LGP. Methods A secondary data analysis of a large multicenter retrospective study was conducted. This descriptive study analyzed data from a multicenter, observational study conducted across nine hospitals in Japan from January 2015 to December 2019. Out of 439 LGP cases, we included 138 cases of delayed diagnosis, excluding patients with traumatic or iatrogenic perforations, or those secondary to mesenteric ischemia, appendicitis, or diverticulitis. Clinical history and computed tomography (CT) imaging information were collected for 138 cases. Additionally, information on the clinical course of 50 cases, which were incorrectly diagnosed as gastroenteritis, constipation, or small bowel obstruction, was also collected. Results In 42 (30.4%) cases of delayed diagnosis of LGP, CT imaging was performed before diagnosis, indicating a missed opportunity for timely diagnosis. Moreover, 33 of the 50 patients initially diagnosed with gastroenteritis, constipation, or small bowel obstruction at the time of initial examination had atypical findings that were not consistent with the initial diagnosis. Of the 138 cases with delayed diagnosis in our study, 67 cases (48.6%) showed problems with either the interpretation of CT scans or with the process of clinical reasoning. Conclusion Our retrospective study results indicate that approximately half of the cases with delayed diagnosis of LGP were due to problems in interpreting CT images or in clinical reasoning. This finding suggests that clinical reasoning and image interpretation by radiologists are important in improving the diagnostic process for LGP.

Abstract The AirSeal system (CONMED, NY, USA) can outstandingly keep pneumoperitoneum stable. However, water droplets form on the access port, impairing the performance of comfortable surgical procedures because of the resultant wet surgical field. This study was performed to clarify the mechanism of water droplet formation and to prevent it. Condensation was observed on the AirSeal system. A heater was wrapped around the tri-lumen tube, and the heating effect was assessed. The simulator experiments revealed that condensation formed in the tri-lumen tube and on the wall of the access port. The accumulated weight of the condensation on the wall of the access port was 41.6 g in the Heated group, 138.2 g in the Control group, and 479.4 g in the Cooled group. In the clinical assessment, the accumulated volume of the condensation attached to the inside wall was significantly smaller in the Heated group than in the Unheated group (111.7 g vs. 332.9 g, respectively). We clarified that the volume of condensation attached to the wall of the access port depended on the temperature of the tri-lumen tube. The clinical study revealed that the condensation on the access port was reduced by heating the tri-lumen tube. The development of a novel heating device for the insufflation tube would be effective and useful.

Abstract The patient was a 49‐year‐old female with a submucosal tumor (12×12 mm) located in the lesser curvature side of the stomach. The diagnosis by endoscopic ultrasound fine‐needle aspiration was of a gastrointestinal stromal tumor. Computed tomography and endoscopic ultrasound showed gastrointestinal stromal tumor with an intra‐luminal growth type. Endoscopic full‐thickness resection was then performed. To achieve good counter traction, enough safety margin, and minimal defect of muscle, full‐thickness resection via creating a submucosal tunnel was performed as a new technique. The final histological diagnosis was gastrointestinal stromal tumor with R0 resection.

Abstract Endoscopic therapy has recently undergone remarkable progress, including the use of suturing procedures within the gastrointestinal tract using flexible endoscopes. However, existing suturing techniques primarily involve closure using instruments or continuous sutures using an endoscopic needle holder, leaving a gap in nodal suturing methods with extracorporeal ligation. This paper introduces a novel approach, the endoscopic ligation technique, wherein a flexible endoscope is utilized for nodal suturing through extracorporeal ligation.

Objective:. To investigate the oncological outcomes after transanal total mesorectal excision (TaTME) for rectal cancer and risk factors for local recurrence (LR). Background:. A high LR rate with a multifocal pattern early after TaTME has been reported in Norway and the Netherlands, causing controversy over the oncological safety of this technique. Methods:. Twenty-six member institutions of the Japan Society of Laparoscopic Colorectal Surgery participated in this retrospective cohort study. A total of 706 patients with primary rectal cancer who underwent TaTME between January 2012 and December 2019 were included for analysis. The primary endpoint was the cumulative 3-year LR rate. Results:. A total of 253 patients had clinical stage III disease (35.8%) and 91 (12.9%) had stage IV. Intersphincteric resection was performed in 318 patients (45.0%) and abdominoperineal resection in 193 (27.3%). There was 1 urethral injury (0.1%). A positive resection margin (R1) was seen in 42 patients (5.9%). Median follow-up was 3.42 years, and the 2- and 3-year cumulative LR rates were 4.95% (95% confidence interval: 3.50–6.75) and 6.82% (95% confidence interval: 5.08–8.89), respectively. A multifocal pattern was observed in 14 (25%) of 56 patients with LR. Tumor height from the anal verge, pathological T4 disease, pathological stage III/IV, positive perineural invasion, and R1 resection were significant risk factors for LR in multivariable analysis. Conclusions:. In this selected cohort in which intersphincteric resection or abdominoperineal resection was performed in more than half of cases, oncological outcomes were acceptable during a median follow-up of more than 3 years.

Abstract Aim In Japan, we have not been able to validate the results of laparoscopic surgery for locally advanced rectal cancer using the universal index “circumferential resection margin (CRM).” Previously, we established a semi‐opened circular specimen processing method and validated its feasibility. In the PRODUCT trial, we aimed to assess CRM in patients with locally advanced rectal cancer who underwent laparoscopic rectal resection. Methods This was a multicenter, prospective, observational study. Eligible patients had histologically confirmed rectal adenocarcinoma located at or below 12 cm above the anal verge with clinical stage II or III and were scheduled for laparoscopic or robotic surgery. The primary endpoint was pathological CRM. CRM ≤1 mm was defined as positive. Results A total of 303 patients operated on between August 2018 and January 2020 were included in the primary analysis. The number of patients with clinical stage II and III was 139 and 164, respectively. Upfront surgery was performed for 213 patients and neoadjuvant therapy for 90 patients. The median CRM was 4.0 mm (IQR, 2.1‐8.0 mm), and CRM was positive in 26 cases (8.6%). Univariate and multivariate analyses demonstrated that a predicted CRM from the mesorectal fascia of ≤1 mm on MRI was the significant factor for positive CRM (P = .0012 and P = .0045, respectively). Conclusion This study showed the quality of laparoscopic rectal resection based on the CRM in Japan. Preoperative MRI is recommended for locally advanced rectal cancer to prevent CRM positivity.

Abstract The transanal/perineal (ta/tp) endoscopic approach has been widely used for anorectal surgery in recent years, but carbon dioxide embolism is a possible lethal complication. The frequency of this complication in this approach is not known. In this study, we investigated the frequency of intraoperative (including occult) carbon dioxide embolism using transesophageal echocardiography. Patients who underwent surgery via the ta/tp approach and consented to participate were included. Intraoperative transesophageal echocardiography was used to observe the right ventricular system in a four-chamber view. Changes in end-tidal carbon dioxide (EtCO2), oxygen saturation (SpO2), and blood pressure were taken from anesthesia records. Median maximum insufflation pressure during the ta/tp approach was 13.5 (12–18) mmHg. One patient (4.8%) was observed to have a bubble in the right atrium on intraoperative transesophageal echocardiography, with a decrease in EtCO2 from 39 to 35 mmHg but no obvious change in SpO2 or blood pressure. By lowering the insufflation pressure from 15 to 10 mmHg and controlling bleeding from the veins around the prostate, the gas rapidly disappeared and the operation could be continued. Among all patients, the range of variation in intraoperative EtCO2 was 5–22 mmHg, and an intraoperative decrease in EtCO2 of > 3 mmHg within 5 min was observed in 19 patients (median 5 mmHg in 1–10 times).Clinicians should be aware of carbon dioxide embolism as a rare but potentially lethal complication of anorectal surgery, especially when using the ta/tp approach.

Abstract 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.

Abstract 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.

Abstract 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.

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.

Abstract 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.

Abstract 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.

Acute appendicitis (AA) is one of the most common causes of acute abdominal pain, which can progress to perforation of the appendix and peritonitis. Recently, AA has been classified into uncomplicated (nonperforated, no phlegmon) or complicated (abscess, perforation, phlegmon) appendicitis, for an appropriate initial treatment. With respect to surgical treatment of AA, laparoscopic surgery has been widely accepted worldwide as a safe and feasible first-line treatment. Over the last decade, nonoperative treatment has been proposed as an alternative to surgery in uncomplicated AA, and has also played an important role in the management of complicated AA. AA is also the most common cause for abdominal surgery during pregnancy, though an accurate diagnosis of AA during pregnancy is challenging. In this review, the topics being discussed include: 1) Non-operative management for uncomplicated AA, 2) Management for AA in pregnancy, 3) Management for complicated appendicitis (especially immediate laparoscopic surgery for appendiceal abscess), 4) Appendiceal neoplasms related to complicated AA.

Background: Treatment with TAS-102 has significantly improved the progression-free survival (PFS) and overall survival (OS) of patients with metastatic colorectal cancer (mCRC). Reportedly, the combination of TAS-102 plus bevacizumab extends the median PFS. The present study aimed to confirm the efficacy and safety of TAS-102 plus bevacizumab (biweekly administration) as third-line chemotherapy for patients with mCRC. Methods/Design: This is a single-arm, open-label, prospective, nonrandomized, multicenter phase II trial conducted in Japan. With a threshold and expected PFS of 2.1 and 3.5 months, respectively, the simulation results showed a sample size of 42 with α = 0.05 (both sides) for 90% power, based on the One-Arm Binomial test using the SWOG statistical tool. If the estimated dropout is 7%-8%, the target sample size is estimated to be 45. The TAS-CC4 study regimen comprised 28-day cycles with biweekly oral administration of TAS-102 (35 mg/m2 twice daily on days 1-5 and 15-19 of every 28-day cycle) and bevacizumab (5.0 mg/kg on days 1 and 15). The primary end point is the PFS; secondary end points include response rate (RR), OS, grade 3 neutropenia, and genetic alterations (KRAS/BRAF mutations) in the circulating cell-free DNA. Discussion: The present study can contribute to the determination of the effective dosing interval of TAS-102 and bevacizumab in patients with mCRC and is thought to lead to prophylaxis of neutropenia and prolongation of the treatment period.

Transanal total mesorectal excision (taTME) has been developed to overcome the difficulty of laparoscopic dissection and transection in the deep pelvis. TaTME has several clinical benefits over laparoscopic surgery, such as better exposure of the distal rectum and direct determination of distal resection margin. Although evidence demonstrating the true benefits of taTME over laparoscopic TME (LapTME) is still insufficient, accumulating data have revealed that, as compared with LapTME, taTME is associated with shorter operative time and a lower conversion rate without jeopardizing other short-term outcomes. However, taTME is a technically demanding procedure with specific complications such as urethral injury, and so sufficient experience of LapTME and step-by-step acquisition of the skills needed for this procedure are requisite. The role of transanal endoscopic surgery is expected to change, along with the recent progress in the treatment of rectal cancer, such as robotic surgery and the watch-and-wait strategy. Optimization of treatment will be needed in the future in terms not only of oncological but also of functional outcomes.

Objective: This retrospective multicenter study compared short- and long-term results between Japanese patients with asymptomatic stage IV colorectal cancer who underwent palliative laparoscopic surgery (LS) versus those who underwent conventional open surgery (OS). Methods: Among 968 patients treated for stage IV colorectal cancer from January 2006 to December 2007 in 41 surgical units that were participating in the Japan Society of Laparoscopic Colorectal Surgery group, we studied 398 patients who received palliative resection of their asymptomatic primary colorectal tumor. Results: We analyzed data from patients undergoing LS (LS group, n=106) and OS (OS group, n=292). Fourteen (13.2%) LS group patients were converted to OS. Although the differences between groups for postoperative complications were not significant, the mean time to solid food intake and postoperative length of hospital stay for the LS group were significantly shorter than those for the OS group (2 vs. 3 days, p

Abstract Background Anastomotic leakage (AL) is one of the most dreadful postoperative complications because it can result in increased morbidity and mortality as well as poorer long-term prognosis. Although most studies of AL limited their investigation time to a period of 30 days postoperatively, only a few studies have shown that AL can occur after that period. Here, we report four patients of rectal cancer with delayed AL following laparoscopic intersphincteric resection (ISR) and conduct a literature review on delayed AL. Case presentation Case 1 was a 67-year-old male who underwent laparoscopic partial ISR in July 2009. Although the patient was asymptomatic, an anastomotic-urethral fistula was observed 57 months after ISR. Case 2 was a 44-year-old female who underwent laparoscopic partial ISR in July 2008. She presented with discharge of gas and feces from her vagina, and an anastomotic-vaginal fistula was observed 14 months after ISR. Case 3 was a 74-year-old man who underwent laparoscopic partial ISR in August 2007. He presented with pneumaturia and fecaluria, and an anastomotic-urethral fistula was observed 4 months after ISR. Case 4 was a 68-year-old woman who underwent laparoscopic subtotal ISR for rectal cancer in February 2013 and partial hepatic resection for liver metastases in March 2013. She presented with anal pain and purulent perineal discharge, and an anastomotic-perineal fistula was observed 9 months after ISR. All four cases presented with fistula formation and required reoperation (establishment of a diverting ileostomy). Conclusions Since delayed AL is not a rare postoperative complication, surgeons need to provide long-term follow-up and remain alert to the possible development of delayed AL.

TAS-102 significantly improves overall survival in patients with metastatic colorectal cancer. The most common adverse event of TAS-102 is bone marrow suppression, which leads to neutropenia. The incidence of neutropenia is high, and there is no known effective prevention method. Furthermore, the administration method of TAS-102 is complicated. We reported that neutropenia could be avoided by changing to a simple administration method of TAS-102.

A number of clinical trials have shown that KRAS mutations of colorectal cancer (CRC) can predict a lack of responses to anti-epidermal growth factor receptor–based therapy. Recently, there have been several studies to elucidate metabolism reprogramming in cancer. However, it remains to be investigated how mutated KRAS can coordinate the metabolic shift to sustain CRC tumor growth. In this study, we found that KRAS mutation in CRC caused alteration in amino acid metabolism. KRAS mutation causes a marked decrease in aspartate level and an increase in asparagine level in CRC. Using several human CRC cell lines and clinical specimens of primary CRC, we demonstrated that the expression of asparagine synthetase (ASNS), an enzyme that synthesizes asparagine from aspartate, was upregulated by mutated KRAS and that ASNS expression was induced by KRAS-activated signaling pathway, in particular PI3K-AKT-mTOR pathway. Importantly, we demonstrated that KRAS-mutant CRC cells could become adaptive to glutamine depletion through asparagine biosynthesis by ASNS and that asparagine addition could rescue the inhibited growth and viability of cells grown under the glutamine-free condition in vitro. Notably, a pronounced growth suppression of KRAS-mutant CRC was observed upon ASNS knockdown in vivo. Furthermore, combination of L-asparaginase plus rapamycin markedly suppressed the growth of KRAS-mutant CRC xenografts in vivo, whereas either L-asparaginase or rapamycin alone was not effective. These results indicate ASNS might be a novel therapeutic target against CRCs with mutated KRAS.

BACKGROUND AND STUDY AIMS:Detecting esophageal achalasia remains a challenge. We describe the diagnostic utility of corona appearance, a novel endoscopic finding specific to esophageal achalasia. PATIENTS AND METHODS:Corona appearance and seven conventional endoscopic findings were compared for sensitivity and consistency (κ-value) among 53 untreated esophageal achalasia patients who underwent endoscopy at our hospital. The following criteria had to be met during lower esophageal sphincter examination using the attached ST Hood short-type for positive corona appearance: A) congestion inside the hood, B) ischemic change around the hood, and C) palisade vessels outside the hood. RESULTS:Corona appearance had the highest sensitivity (91%; κ-value, 0.71). Other findings in descending order of sensitivity included 1) functional stenosis of the esophagogastric junction (EGJ; 86%; κ-value, 0.58), 2) mucosal thickening and whitish change (71%; κ-value, 0.27), 3) abnormal contraction of the esophageal body (59%; κ-value, 0.32), 4) dilation of the esophageal lumen (58%; κ-value, 0.53), 5) liquid remnant (57%; κ-value, 0.51), 6) Wrapping around EGJ (49%; κ-value, 0.14), and 7) food remnant (30%; κ-value, 0.88). Even in 22 patients with poor (grade 1) intraluminal expansion, corona appearance had highest sensitivity (88%) compared to other endoscopic findings (κ-value, 0.63). CONCLUSIONS:Among endoscopic findings using a ST Hood short-type to diagnose esophageal achalasia, corona appearance had the highest sensitivity and its consistency (κ-value) among endoscopists was substantial compared to other endoscopic findings. Similar results were obtained for esophageal achalasia cases with poor expansion. Endoscopic diagnosis of esophageal achalasia with hood attached is useful.

Cancer stem cells (CSCs) are considered to be responsible for the dismal prognosis of cancer patients. However, little is known about the molecular mechanisms underlying the acquisition and maintenance of CSC properties in cancer cells because of their rarity in clinical samples. We herein induced CSC properties in cancer cells using defined factors. We retrovirally introduced a set of defined factors (OCT3/4, SOX2 and KLF4) into human colon cancer cells, followed by culture with conventional serum-containing medium, not human embryonic stem cell medium. We then evaluated the CSC properties in the cells. The colon cancer cells transduced with the three factors showed significantly enhanced CSC properties in terms of the marker gene expression, sphere formation, chemoresistance and tumorigenicity. We designated the cells with CSC properties induced by the factors, a subset of the transduced cells, as induced CSCs (iCSCs). Moreover, we established a novel technology to isolate and collect the iCSCs based on the differences in the degree of the dye-effluxing activity enhancement. The xenografts derived from our iCSCs were not teratomas. Notably, in contrast to the tumors from the parental cancer cells, the iCSC-based tumors mimicked actual human colon cancer tissues in terms of their immunohistological findings, which showed colonic lineage differentiation. In addition, we confirmed that the phenotypes of our iCSCs were reproducible in serial transplantation experiments. By introducing defined factors, we generated iCSCs with lineage specificity directly from cancer cells, not via an induced pluripotent stem cell state. The novel method enables us to obtain abundant materials of CSCs that not only have enhanced tumorigenicity, but also the ability to differentiate to recapitulate a specific type of cancer tissues. Our method can be of great value to fully understand CSCs and develop new therapies targeting CSCs.

Background/Aim: Although the frequency of small bowel obstructions after liver surgery is generally considered low, previous studies have followed-up patients for less than a year, thus the incidence of small bowel obstructions several years after surgery is unknown. Furthermore, the rise in laparoscopic surgeries and the use of adhesion prevention materials may influence the occurrence of small bowel obstructions. This study aimed to assess the incidence of small bowel obstructions within a five-year period following liver surgery and identify the associated risk factors. Patients and Methods: This case series analysis analyzed patients who underwent liver surgery between April 2012 and March 2014 from 32 participating hospitals. Multivariate analysis was conducted to examine risk factors for small bowel obstructions. Results: A total of 953 patients were included in the analysis, and the incidence of small bowel obstructions was 1.6%. The incidence was significantly higher at 3.4% for surgeries related to metastatic liver cancer compared to other types of surgeries. Laparoscopic surgery had no significant effect on the incidence of SBO (p=0.72). There was no significant difference in the incidence of small bowel obstructions between surgeries that employed adhesion prevention materials and those that did not. Multivariable analysis revealed that longer surgical time and re-operation were independent risk factors for small bowel obstructions. Conclusion: The incidence of small bowel obstructions following surgery for metastatic liver cancer is significantly higher compared to other liver surgeries. Neither laparoscopic surgery nor adhesion prevention materials reduce its occurrence. Longer surgical time and re-operation are independent risk factors for small bowel obstructions. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the effect of continuing preoperative aspirin monotherapy on surgical outcomes in patients receiving antiplatelet therapy (APT). Background: The effectiveness of continuing preoperative aspirin monotherapy in patients undergoing APT in preventing thromboembolic consequences is mostly unknown. Methods: This prospective multicenter cohort study on the Safety and Feasibility of Gastroenterological Surgery in Patients Undergoing Antithrombotic Therapy (GSATT study) conducted at 14 clinical centers enrolled and screened patients between October 2019 and December 2021. The participants (n= 1170) were assigned to the continued-APT group, discontinued-APT group, or non-APT group, and the surgical outcomes of each group were compared. Propensity score matching performed between the continued and discontinued-APT groups to investigate the effect of continuing preoperative aspirin therapy on thromboembolic complications. Results: The rate of thromboembolic complications in the continued- APT group was substantially lower than that in the non-APT or discontinued- APT groups (0.5% vs 2.6% vs. 2.9%; P=0.027). Multivariate investigation of the entire cohort revealed that discontinuation of APT (P< 0.001) and chronic anticoagulant use (P<0.001) were independent risk factors for postoperative thromboembolism. The post-matching evaluation demonstrated that the rates of thromboembolic complications were significantly different between the continued and discontinued-APT groups (0.6% vs 3.3%; P=0.012). Conclusions: APT discontinuation after elective gastroenterological surgery increases the risk of thromboembolic consequences, whereas continuing preoperative aspirin greatly reduces this risk. The continuation of preoperative aspirin therapy in APT-received patients is considered one of the best alternatives for preventing thromboembolism during elective gastroenterological surgery. [ABSTRACT FROM AUTHOR]