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.

Esophageal squamous cell carcinoma complicated with varices successfully treated by endoscopic injection sclerotherapy and argon plasma coagulation: A case report.

Treatment guidelines for esophageal squamous cell carcinoma (ESCC) with concomitant esophageal varices (EVs), which increase the risk of bleeding, are unavailable. A 66-year-old man with a history of total gastrectomy was admitted to the hospital owing to hematemesis. Emergency upper gastrointestinal endoscopy revealed variceal bleeding near the anastomosis between the esophagus and jejunum, and endoscopic clipping stopped the bleeding. Upper gastrointestinal endoscopy following hemostasis revealed four EVs and a two-thirds ESCC circumference. The ESCC depth was suspected to be up to the mucosa. The patient underwent intravariceal endoscopic injection sclerotherapy (EIS) for EVs, followed by paravariceal EIS. However, after these treatments, blood flow in the EVs just below the ESCC remained, and endoscopic resection of the ESCC was judged to be difficult to perform. Therefore, we prioritized EV treatment and performed a second EIS on the ESCC, followed by argon plasma coagulation (APC). APC was expected to not only solidify the EVs but also eliminate the ESCC existing in the mucosa. Finally, EVs and ESCC were treated by EIS and APC. EIS followed by APC may be useful for treating concurrent EVs and intramucosal ESCC in patients with liver cirrhosis when embolization of the EVs is ineffective.

Surveillance esophagogastroduodenoscopy using linked color imaging and narrow-band imaging: A multicenter randomized controlled trial.

BACKGROUND AND AIM: There has been no report on a direct comparison between linked color imaging (LCI) and second-generation narrow-band imaging (2G-NBI) for surveillance of epithelial neoplasms in the upper gastrointestinal tract (UGIT). The aim of this study was to verify the superiority of LCI to 2G-NBI for surveillance esophagogastroduodenoscopy and to clarify how each endoscopic system should be used. METHODS: This study was conducted as an open-label, two-arm-parallel (1:1), multicenter, randomized controlled trial at six institutions. Patients aged 20-85 years with a treatment history of epithelial neoplasms in the UGIT were recruited. Patients were assigned to a 2G-NBI group and an LCI group, and esophagogastroduodenoscopy was performed with primary image-enhanced endoscopy followed by white light imaging (WLI). The primary endpoint was the detection rate of one or more epithelial neoplasms in the primary image-enhanced endoscopy. A WLI-detected epithelial neoplasm was defined as a lesion that was detected in only WLI. RESULTS: A total of 372 patients in the 2G-NBI group and 378 patients in the LCI group were analyzed. Epithelial neoplasms in the UGIT were detected by 2G-NBI in 18 patients (4.6%) and were detected by LCI in 20 patients (5.3%) (P = 0.87). WLI-detected epithelial neoplasms were in 11 patients in the 2G-NBI group (3.0%) and in 1 patient in the LCI group (0.27%) (P = 0.003). CONCLUSIONS: Linked color imaging did not show superiority to 2G-NBI for the detection of epithelial neoplasms. Also, the percentage of WLI-detected epithelial neoplasms in primary NBI was significantly higher than that in primary LCI.

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.

Endoscopic ultrasound-guided fine-needle aspiration for gastrointestinal subepithelial lesions.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the first-choice procedure for obtaining pathological tissue samples from gastrointestinal (GI) subepithelial lesions (SELs). However, its diagnostic accuracy is lower than that for pancreatic masses owing to puncture difficulty and the need for immunostaining for definitive diagnosis. The advent of fine-needle biopsy needles, which have become well known in recent years, improves the diagnostic accuracy of EUS-FNA for GI SELs. The forward-viewing echoendoscope and rapid on-site evaluation (ROSE) have also helped to improve diagnostic accuracy. Furthermore, in facilities where ROSE is not available, endosonographers perform a macroscopic on-site evaluation. With these procedural innovations, EUS-FNA is now performed aggressively even for SELs smaller than 20 mm. The incidence of procedure-related adverse events such as bleeding and infection is low, and thus, EUS-FNA can be safely performed to diagnose SELs.

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.

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.

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.

Clinical outcomes of laparoscopic and endoscopic cooperative surgery for gastric gastrointestinal stromal tumor.

BACKGROUND: Laparoscopic and endoscopic cooperative surgery (LECS) is a well-recognized surgical procedure for gastric gastrointestinal stromal tumor (GIST). In this report, we describe the clinical outcomes of LECS procedures for gastric GIST in our institution. METHODS: We performed LECS procedures, including classical LECS, inverted LECS, closed LECS, and combination of laparoscopic and endoscopic approaches to neoplasia with non-exposure technique (CLEAN-NET), in 40 gastric intraluminal and intramural type GIST patients, whose tumors were ≤ 50 mm in diameter, between September 2012 and December 2020. The patient background, surgical outcomes, postoperative morbidity and mortality, as well as the tumors' clinicopathological characteristics were analyzed retrospectively. RESULTS: Pathological findings showed that most patients had a low or very low risk of tumor recurrence, while one patient had a high risk according to the modified-Fletcher's classification. The median length of postoperative hospital stay was 7 days. Only one patient had severe postoperative grade III complications according to the Clavien-Dindo (C-D) classification, after closed LECS, but was treated successfully with endoscopic hemostasis for postoperative hemorrhage. The remaining patients treated with LECS did not have severe complications. During the follow-up period (median, 31 months), all patients were disease-free, with no tumor recurrence or metastases. CONCLUSION: LECS is a safe surgical procedure for gastric intraluminal and intramural type GIST ≤ 50 mm in diameter, with good clinical outcomes.

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.

Combination of photodynamic therapy and endoscopic mucosal resection for recurrent esophageal squamous cell carcinoma after chemoradiotherapy.

Photodynamic therapy (PDT) was developed for residual or recurrent esophageal cancer after radiotherapy. Here, we report a case of successful treatment of highly elevated esophageal squamous cell carcinoma (ESCC) that recurred after definitive chemoradiotherapy (dCRT) using PDT combined with endoscopic resection (ER). An 86-year-old man was found to have an ESCC in the mid-thoracic esophagus. One year and two months after dCRT, a local recurrence was seen. The recurrent ESCC had a highly elevated component. The ESCC was estimated to have invaded the deep submucosa at the highly elevated component. PDT was selected as a treatment option since no lymph node or distant metastases were found. However, there was concern that the laser would not be able to penetrate deep into the ESCC due to its high elevated component. Therefore, ER was performed to remove the highly elevated component, and PDT was performed later. However, after the ER, the circumference of the recurrent ESCC was found to be approximately half the circumference, and post-PDT stenosis was also a concern due to the wide circumference of the ESCC. Therefore, we limited the area of laser irradiation in one session of PDT. Four sessions of PDT were needed over 13 months, but a local complete response was achieved without adverse events.

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.