Visibility of esophageal squamous cell carcinoma under iodine staining on texture and color enhancement imaging.

Objective: Iodine staining on white light imaging (WLI) is the gold standard for detecting and demarcating esophageal squamous cell carcinoma (ESCC). We examined the effects of texture and color enhancement imaging (TXI) on improving the endoscopic visibility of ESCC under iodine staining. Methods: Twenty ESCC lesions that underwent endoscopic submucosal dissection were retrospectively included. The color difference between ESCC and the surrounding mucosa (ΔEe) on WLI, TXI, and narrow-band imaging was assessed, and ΔEe under 1% iodine staining on WLI and TXI. Furthermore, the visibility grade determined by endoscopists was evaluated on each imaging. Result: The median ΔEe was greater on TXI than on WLI (14.53 vs. 10.71, respectively; p < 0.005). Moreover, the median ΔEe on TXI under iodine staining was greater than the median ΔEe on TXI and narrow-band imaging (39.20 vs. 14.53 vs. 16.42, respectively; p < 0.005 for both). A positive correlation in ΔEe under iodine staining was found between TXI and WLI (correlation coefficient = 0.61, p < 0.01). Moreover, ΔEe under iodine staining on TXI in each lesion was greater than the corresponding ΔEe on WLI. The visibility grade assessed by endoscopists on TXI was also significantly greater than that on WLI under iodine staining (p < 0.01). Conclusions: The visibility of ESCC after iodine staining was greater on TXI than on WLI.

L-Menthol for Color Difference Change Between Early Gastric Cancer and Surrounding Mucosa: A Prospective Study.

BACKGROUND: L-Menthol sprayed on early gastric cancer (EGC) has been reported to improve the visibility of the lesion. However, its impact when used in combination with novel image-enhanced endoscopy has not been investigated. AIM: This study aimed to evaluate the visual effect of spraying L-menthol on EGC under linked color imaging (LCI). METHODS: This open-label, single-arm, prospective study investigated the color difference between EGC and the surrounding mucosa (ΔEG) before and after spraying L-menthol. The primary endpoint was the percentage of lesions with ΔEG ≥ 5 on LCI. The percentage of lesions with ΔEG ≥ 5 on white light imaging (WLI) and blue laser imaging (BLI), ΔEG before and after spraying L-menthol, and percentage of lesions with increased ΔEG after spraying L-menthol constituted the secondary endpoints. RESULTS: Sixty patients were included in the final analysis. 100% lesions had ΔEG ≥ 5, both before and after spraying L-menthol on LCI, with similar results observed in WLI as well as BLI. The median ΔEG on LCI, WLI, and BLI increased after spraying L-menthol (LCI: 16.9 vs. 21.5, p < 0.01; WLI: 10.4 vs. 13.4, p < 0.01; BLI; 12.1 vs. 15.7, before and after, respectively, p < 0.01); and LCI demonstrated the highest percentage of lesions with increased ΔEG (LCI, WLI, and BLI: 98.3%, 81.7%, and 76.7%, respectively, p < 0.01). CONCLUSION: Although spraying L-menthol did not improve the visibility of EGC under LCI observation, a significant increase in ΔEG was observed in LCI (jRCTs 021200027).

Factors Associated With Difficult Endoscopic Ultrasonography-guided Biliary Drainage.

BACKGROUND AND AIMS: When endoscopic retrograde cholangiopancreatography-guided biliary drainage is challenging, endoscopic ultrasound-guided biliary drainage (EUS-BD) can be used as an alternate treatment; however, this method requires operator expertise. Therefore, this study aimed to clarify the factors that are associated with a difficult EUS-BD. PATIENTS AND METHODS: Patients who successfully underwent EUS-BD were enrolled in this study. The patients were divided into the easy group and difficult group depending on whether the procedural time was more than 60 minutes, which was the cutoff value elicited from past reports. Patient characteristics and procedural factors were compared between the two groups. The factors associated with difficult procedures were also investigated. RESULTS: The patient characteristics were not significantly different between the easy group (n=22) and the difficult group (n=19). The diameter of the punctured bile duct was significantly different between the two groups. In the multivariate analysis, the diameter of the punctured bile duct was the only factor associated with a difficult EUS-BD (odds ratio 0.65, 95% confidence interval 0.46-0.91, P value=0.012). The cutoff value for the diameter of the punctured bile duct in predicting a difficult EUS-BD was 7.0 mm (area under the curve: 0.83, sensitivity 84.2%, specificity 86.4%). CONCLUSIONS: A nondilated bile duct might be a predictive factor for a difficult EUS-BD. For beginners of EUS-BD, the cutoff value for the punctured bile duct diameter found in this study, 7.0 mm, might become a barometer for puncture point selection.

Novel Photodynamic Therapy for Esophageal Squamous Cell Carcinoma following Radiotherapy.

Radiotherapy (RT) or chemoradiotherapy (CRT) are frequently selected as treatments for esophageal squamous cell carcinoma (ESCC). However, salvage treatment remains challenging when endoscopic resection is not indicated for residual or recurrent ESCC following RT or CRT. Recently, owing to the emergence of second-generation photodynamic therapy (PDT) using talaporfin sodium, PDT can be performed with less phototoxicity and therefore has regained popularity in the treatment of ESCC. In this study, the effectiveness and safety of second-generation PDT in patients with residual or recurrent ESCC following RT or CRT were examined. Local complete response (L-CR) rates, procedure-related adverse events, and prognosis were evaluated. In 12 patients with 20 ESCC lesions, the L-CR rates were 95.0%. Perforation, postoperative bleeding, and photosensitivity were not observed. Esophageal stricture following PDT developed in one patient, but this could be addressed using balloon dilation. During a median follow-up period of 12 (range, 3-42) months, the 3-year cause-specific survival rate was 85.7%. Even in patients with a Charlson comorbidity index score ≥ 3, the 2-year overall survival rates were 100%. In conclusion, PDT was an efficacious and a safe salvage treatment in patients with local residual or recurrent ESCC following RT or CRT.

Comparison of time to recurrent biliary obstruction between plastic stents and metallic stents for endoscopic ultrasound­guided biliary drainage.

Endoscopic ultrasound-guided biliary drainage (EUS-BD) may prevent stent placement at the bile duct stricture. Therefore, whether a plastic stent (PS) or metallic stent (MS) should be used for EUS-BD remains to be undetermined. The present study aimed to clarify whether a PS or MS was more efficient for EUS-BD. Patients with malignant biliary obstruction who were successfully treated with EUS-BD were enrolled in the present study. The clinical characteristics, procedural outcomes and time to recurrent biliary obstruction (TRBO) were compared between patients treated with a PS (PS group) and patients treated with an MS (MS group). Consequently, 28 patients underwent PS placement and 11 patients underwent MS placement. In the PS group, 12 patients also underwent EUS-antegrade stenting (AGS) using an MS. The TRBO was not significantly different between the two groups (P=0.25). When the patients with AGS were excluded, the TRBO was significantly longer in the MS group than in the PS group (P=0.036). However, the TRBO was not significantly different between the patients in the MS group and those in the PS group who underwent AGS (P=0.61). In EUS-BD, MS is expected to be associated with a longer TRBO than PS. However, combining EUS-BD with AGS may help overcome the shorter TRBO associated with the use of PS.

A follow-up questionnaire survey 2022 on radiation protection among 464 medical staff from 34 endoscopy-fluoroscopy departments in Japan.

Objectives: We surveyed and reported low protective equipment usage and insufficient knowledge among endoscopy-fluoroscopy departments in Japan in 2020. Two years later, we conducted a follow-up survey of doctors, nurses, and technologists in Japan. Methods: We conducted a questionnaire survey on radiation protection from May to June 2022. The participants were medical staff, including doctors, nurses, and radiological and endoscopy technicians in endoscopy-fluoroscopy departments. The questionnaire included 17 multiple-choice questions divided into three parts: background, equipment, and knowledge. Results: We surveyed 464 subjects from 34 institutions. There were 267 doctors (58%), 153 nurses (33%), and 44 technologists (9%). The rate of wearing a lead apron was 98% in this study. The rates of wearing a thyroid collar, lead glasses, and radiation dosimeter were 27%, 35%, and 74%, respectively. The trend of the protective equipment rate was similar to that of our previous study; however, radiation dosimetry among doctors was still low at 58%. The percentage of subjects who knew the radiation exposure (REX) dose of each procedure was low at 18%. Seventy-six percent of the subjects attended lectures on radiation protection, and 73% knew about the three principles of radiation protection; however, the concept of diagnostic reference levels was not well known (18%). Approximately 60% of the subjects knew about the exposure dose increasing cancer mortality (63%) and the 5-year lens REX limit (56%). Conclusions: There was some improvement in radiation protection equipment or education, but relatively little compared to the 2020 survey of endoscopy departments.

Clinical benefit of subsequent chemotherapy after drug-induced interstitial lung disease in pancreatic cancer patients: a multicenter retrospective study from Japan.

PURPOSE: Drug-induced interstitial lung disease (ILD) is not a rare adverse event in the current chemotherapy strategy for pancreatic ductal adenocarcinoma (PDAC). Thus, we aimed to find the optimal management for PDAC patients with a history of ILD induced by a gemcitabine-based regimen. METHODS: We conducted a multicenter retrospective study. The primary endpoint was the overall survival (OS) of patients who underwent either S-1 monotherapy or FOLFOX after the onset of ILD. Toxicity data was also analyzed in the 2 groups. RESULTS: Twenty-four patients were diagnosed with ILD and 17 patients who received subsequent chemotherapy were enrolled in the study. Among 17 patients who were managed with subsequent chemotherapy after recovering from ILD, we did not observe significant difference in OS between S-1 and FOLFOX (290.0 days vs. undefined, p = 0.39). Relapse of drug-induced ILD was not observed in all cases during the course. Overall, severe adverse events (CTCAE Grade 3 or 4) were observed in 3 patients (23.1%) in S-1 treatment group and 1 patient (25.0%) in FOLFOX treatment group (p = 0.93). CONCLUSIONS: S-1 monotherapy and FOLFOX are comparable as the subsequent chemotherapy after gemcitabine-based chemotherapy-induced ILD in unresectable PDAC.

Radiation dose and factors related to exceeding the diagnostic reference level in 496 transnasal ileus tube placement procedures from the REX-GI study.

OBJECTIVE: We aimed to examine the factors contributing to radiation exposure exceeding the DRL of the transnasal ileus tube placement in this post hoc analysis from the cohort of the REX-GI study. METHODS: Patients with transnasal ileus tubes were enrolled in the rex-gi study from may 2019 to december 2020. We investigated the endoscope insertion time (min), procedure time (min), tube insertion length (cm), fluoroscopy time (FT: min), air kerma at the patient entrance reference point (Ka.r: mGy), and air kerma-area product (PKA: Gycm2). The third quartile value of the PKA value was calculated as the diagnostic reference level (DRL) value. We explored the factors associated with radiation exposure exceeding the DRL. RESULTS: In the REX-GI study, 496 patients who underwent transnasal ileus tube placement were enrolled. The median age of the patients was 71 years. The median endoscopy insertion time, procedure time, and tube insertion length were 6 min, 20 min, and 170 cm, respectively. The third quartile/median FT, Ka.r, and PKA were 18/11.9 min, 99.2/54.4 mGy, and 46.9/28 Gycm2, respectively. The third quartile value of PKA (47 Gycm2) was set as the DRL value. There were differences in distribution by the hospital. Compared with procedures under the DRL, the FT (19 vs 10 min), procedure time (25 vs 18 min), and tube insertion length (185 vs 165 cm) were significantly longer for procedures above the DRL. CONCLUSION: We report the DRL for transnasal ileus tube placement in Japan. A longer procedure time and tube insertion length may be associated with DRL exceedance. ADVANCES IN KNOWLEDGE: Transnasal ileus tube placement under fluoroscopy guidance is a standard clinical procedure for bowel obstruction. However, the appropriate radiation dose level has not yet been established.We report the (DRL) for transnasal ileus tube placement in Japan. A longer procedure time and tube insertion length may be associated with DRL exceedance.

A multicenter comparative study of endoscopic ultrasound-guided fine-needle biopsy using a Franseen needle versus conventional endoscopic ultrasound-guided fine-needle aspiration to evaluate microsatellite instability in patients with unresectable pancreatic cancer.

BACKGROUND/AIMS: Immune checkpoint blockade has recently been reported to be effective in treating microsatellite instability (MSI)-high tumors. Therefore, sufficient sampling of histological specimens is necessary in cases of unresectable pancreatic cancer (UR-PC). This multicenter study investigated the efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen needle for MSI evaluation in patients with UR-PC. METHODS: A total of 89 patients with UR-PC who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or EUS-FNB using 22-G needles at three hospitals in Japan (2018-2021) were enrolled. Fifty-six of these patients (FNB 23 and FNA 33) were followed up or evaluated for MSI. Patient characteristics, UR-PC data, and procedural outcomes were compared between patients who underwent EUS-FNB and those who underwent EUS-FNA. RESULTS: No significant difference in terms of sufficient tissue acquisition for histology was observed between patients who underwent EUS-FNB and those who underwent EUS-FNA. MSI evaluation was possible significantly more with tissue samples obtained using EUS-FNB than with tissue samples obtained using EUS-FNA (82.6% [19/23] vs. 45.5% [15/33], respectively; p<0.01). In the multivariate analysis, EUS-FNB was the only significant factor influencing the possibility of MSI evaluation. CONCLUSION: EUS-FNB using a Franseen needle is desirable for ensuring sufficient tissue acquisition for MSI evaluation.

Endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma in patients with cirrhosis and esophageal varices.

Endoscopic submucosal dissection (ESD) has become the standard treatment for superficial esophageal squamous cell carcinoma (SESCC). However, the treatment strategy for SESCC complicated by esophageal varices (EVs) has not been established. We report two cases of SESCC in patients with alcoholic cirrhosis complicated by EVs who underwent ESD. Case 1 presented with EVs on the anal side of the SESCC, and endoscopic variceal ligation (EVL) was performed before ESD. After EVL, the SESCC was successfully treated by ESD without any adverse events. Case 2 presented EVs from the anal side of the SESCC to the submucosa just below the SESCC. Then, EVL and endoscopic injection sclerotherapy with polidocanol were performed before ESD. However, ESD was not completed because of severe bleeding by uncontrolled blood flow below and around the SESCC. Bleeding during ESD was controlled in case 1, but not in case 2.

Medical radiation exposure during gastrointestinal enteral metallic stent placement: Post hoc analysis of the REX-GI study.

Background and Aim: Recently, the use of various endoscopic procedures performed under X-ray fluoroscopy guidance has increased. With the popularization of such procedures, diagnostic reference levels (DRLs) have been widely accepted as the global standard for various procedures with ionizing radiation. The Radiation Exposure from Gastrointestinal Fluoroscopic Procedures (REX-GI) study aimed to prospectively collect actual radiation exposure (RE) data and establish DRLs in gastrointestinal endoscopy units. In this post hoc analysis of the REX-GI study, we established DRLs for each disease site by analyzing cases of gastrointestinal enteral metallic stent placement. Methods: The REX-GI study was a multicenter, prospective observational study conducted to collect actual RE data during gastrointestinal enteral metallic stent placement. To establish DRL values for three disease sites, namely the esophagus, gastroduodenum, and colon, we examined fluoroscopy time (FT; min), number of X-ray images, air kerma at the patient entrance reference point (K a,r; mGy), and the air kerma-area product (P KA; Gy cm2) during enteral metallic stent placement. Results: Five-hundred and twenty-three stenting procedures were performed. The DRL values of FT (min) and the number of X-ray images for the esophagus/gastroduodenum/colon were 9/16/18 min and 9/15/11 min, respectively. Furthermore, the DRL values of K a,r and P KA for each disease site were 43.3/120/124 mGy and 10.3/36.6/48.4 Gy cm2, respectively. Among the procedures, esophageal stents were significantly associated with the lowest values (P < 0.001). Conclusion: The characteristics of RE vary according to disease site among gastrointestinal enteral metallic stent placements. Thus, it is desirable to set DRL values based on the disease site.

Intracellular C3 Modulates EMT via the Akt/Smad Pathway in Pancreatic Cancer Cells.

BACKGROUND/AIM: We aimed to explore the role of intracellular C3 in pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: We evaluated C3 expression in PDAC using a gene expression database and tissue microarray. To clarify the role of C3 expression in PDAC, we conducted knockdown experiments using C3 short hairpin RNA (shRNA) in BxPC-3 cells. Differences in protein expression and cell behaviours were analysed. RESULTS: C3 was highly expressed in PDAC and correlated with cancer metastasis. In vitro experiments using BxPX-3 cells showed that C3 and its active form, C3a, were expressed in tumour cells. C3 knockdown reduced cell migration and invasion by inhibiting Akt/Smad pathway activation. TNF-α, not IL-6, enhanced C3 expression in this PDAC cell line. CONCLUSION: Intracellular C3 may regulate epithelial-mesenchymal transition in pancreatic cancer.

Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer in the Remnant Stomach.

Endoscopic submucosal dissection (ESD) in patients with early gastric cancers (EGCs) in the remnant stomach is technically difficult, owing to the limited space and fibrosis under the suture lines and anastomoses. Conversely, ESD for patients with EGCs in the remnant stomach is less invasive and provides better quality of life than completion total gastrectomy. To clarify the effectiveness and safety of ESD, we reviewed the medical records of patients with EGCs in the remnant stomach who underwent ESD between July 2006 and October 2020 at our institution. All identified patients were included in the analysis. Of 25 patients with 27 lesions, the en bloc and R0 resection rates were 88.9% and 85.2%, respectively. Neither perforation nor postoperative bleeding was observed. During a median follow-up period of 48 (range, 5-162) months, the 5-year overall survival rate was 71.0%, whereas the 5-year cause-specific survival rate was 100%. No obvious differences in the outcomes of procedures with suture line involvement and without suture line or anastomosis involvement were noted. In conclusion, ESD was effective and safe in patients with EGCs in the remnant stomach despite the suture line involvement.

Association between Submucosal Fibrosis and Endoscopic Submucosal Dissection of Recurrent Esophageal Squamous Cell Cancers after Chemoradiotherapy.

Endoscopic resection is a treatment of choice for a metachronous early-stage esophageal squamous cell carcinoma (ESCC) appearing after a radical cure of esophageal cancer by chemoradiotherapy (CRT). However, non-curative resection, and procedural complications including perforation due to radiation-induced submucosal fibrosis, are a concern. This study aimed to evaluate the association between submucosal fibrosis and the usefulness and safety of endoscopic submucosal dissection (ESD) in ESCC after CRT. This study retrospectively analyzed 13 lesions in 11 patients in our institute. Submucosal fibrosis under the lesion (F score) was classified into three levels (F0: none or mild, F1: moderate, and F2: severe) based on endoscopic and histopathologic findings. All lesions were F1 or greater (F1: 8 lesions and F2: 5 lesions). En bloc and R0 resection rates were both 100%. The procedural speed was slower in F2 than in F1 (F1 vs. F2; 15.1 mm2/min vs. 7.1 mm2/min, p = 0.019), without procedure-related adverse events. At a median follow-up of 42 months (range: 14-117 months) after ESD, 7 of 11 (63.6%) patients were alive without recurrence, and without ESCC-related death. ESCC after CRT reliably and safely resected en bloc by ESD but was more difficult in lesions with strong submucosal fibrosis.

Screening for hilar biliary invasion in ampullary cancer patients.

BACKGROUND: The treatment for ampullary cancer is pancreatoduodenectomy or local ampullectomy. However, effective methods for the preoperative investigation of hilar biliary invasion in ampullary cancer patients have not yet been identified. AIM: To determine the necessity of and an appropriate method for investigating hilar biliary invasion of ampullary cancer. METHODS: Among 43 ampullary cancer patients, 34 underwent endoscopic treatment (n = 9) or surgery (n = 25). The use of imaging findings (thickening and enhancement of the bile duct wall on contrast-enhanced computed tomography, irregularity on endoscopic retrograde cholangiography, thickening of the entire bile duct wall on intraductal ultrasonography (IDUS), and partial thickening of the bile duct wall on IDUS) and biliary biopsy results for diagnosing hilar biliary invasion of ampullary cancer was compared. RESULTS: Hilar invasion was not observed in every patient. Among the patients who did not undergo biliary stent insertion, the combination of partial thickening of the bile duct wall on IDUS and biliary biopsy results showed the highest accuracy (100%) for diagnosing hilar biliary invasion. However, each imaging method and biliary biopsy yielded some false-positive results. CONCLUSION: Although some false-positive results were obtained with each method, the combination of partial thickening of the bile duct wall on IDUS and biliary biopsy results was useful for diagnosing hilar biliary invasion of ampullary cancer. However, hilar invasion of ampullary cancer is rare; therefore, the investigation of hilar biliary invasion of ampullary cancer might be unnecessary.

Clinical usefulness and acceleratory effect of macrophage inhibitory cytokine-1 on biliary tract cancer: an experimental biomarker analysis.

BACKGROUND: Biliary tract cancer (BTC) has a poor prognosis; therefore, useful biomarkers and treatments are needed. Serum levels of macrophage inhibitory cytokine-1 (MIC-1), a member of the TGF-ß superfamily, are elevated in patients with pancreaticobiliary cancers. However, the effect of MIC-1 on BTC is unknown. Therefore, we investigated the effect of MIC-1 on BTC and assessed whether MIC-1 is a biomarker of or therapeutic target for BTC. METHODS: MIC-1 expression in BTC cells was determined by performing histological immunostaining, tissue microarray (TMA), western blotting, and reverse transcription PCR (RT-PCR). Cell culture experiments were performed to investigate the effect of MIC-1 on BTC cell lines (HuCCT-1 and TFK-1). The relationships between serum MIC-1 levels and either the disease state or the serum level of the apoptosis marker M30 were retrospectively verified in 118 patients with pancreaticobiliary disease (individuals with benign disease served as a control group, n = 62; BTC, n = 56). The most efficient diagnostic marker for BTC was also investigated. RESULTS: MIC-1 expression was confirmed in BTC tissue specimens and was higher in BTC cells than in normal bile duct epithelial cells, as determined using TMA, western blotting and RT-PCR. In cell culture experiments, MIC-1 increased BTC cell proliferation and invasion by preventing apoptosis and inhibited the effect of gemcitabine. In serum analyses, serum MIC-1 levels showed a positive correlation with BTC progression and serum M30 levels. The ability to diagnose BTC at an early stage or at all stages was improved using the combination of MIC-1 and M30. The overall survival was significantly longer in BTC patients with serum MIC-1 < the median than in BTC patients with serum MIC-1 ≥ the median. CONCLUSIONS: MIC-1 is a useful diagnostic and prognostic biomarker and might be a potential therapeutic target for BTC.

Transjejunal endoscopic ultrasound-guided pancreatic drainage for pancreatic jejunostomy stricture using a forward-viewing echoendoscope in a patient with altered anatomy.

Pancreatic jejunostomy stricture (PJS) is one of the major late complications after pancreaticoduodenectomy. Endoscopic ultrasound-guided pancreatic drainage (EUS-PD) is considered a salvage treatment for symptomatic PJS after endoscopic retrograde pancreatography failure; however, the technical success rate of the endoscopic treatment of PJS remains unsatisfactory, mainly due to surgically altered anatomy. Herein, we describe a case of PJS successfully treated with transjejunal EUS-PD using a forward-viewing echoendoscope. A 62-year-old man who suffered from repetitive severe back pain due to PJS was referred to our hospital. Since transgastric EUS-PD was difficult, we attempted transjejunal EUS-PD using a forward-viewing echoendoscope. To facilitate scope insertion, we first straightened the afferent jejunal loop and placed a stiff guidewire. With this scheme, we successfully performed transjejunal EUS-PD and placed a 5-Fr plastic stent. In conclusion, this technique is useful for treating patients with PJS when transgastric EUS-PD is difficult.