Antineoplastic drugs play an important role in cancer therapy.  A growing number of patients and new fields of application have resulted in an increasing use of these agents.  Most antineoplastic drugs are classified as carcinogenic, mutagenic, or teratogenic for humans.  Antineoplastic drugs also cause adverse effects in health care workers who handle them.  In the late 1960s, acute symptoms by exposure to antineoplastic drugs were first reported.  In 1979, Falck reported a small increase in urine mutagenicity of nurse who handled antineoplastic drugs.  Thereafter several studies showed that association of occupational exposure to antineoplastic drugs with health effects such as DNA damage, chromosomal abnormalities, adverse reproductive outcomes, possibly leukemia and other cancers.  To prevent them, many guidelines for safe handling were published in various countries in 1980s, they are revised periodically afterward.  In 1990s, despite recommended safe handling procedures, environmental contamination with antineoplastic drugs was still observed in hospital and health care workers were still exposed.  In 2004, the National Institute for Occupational Safety and Health (NIOSH) published an Alert on hazardous drugs used in health care settings.  One recommendation was to consider the use of closed system drug transfer devices (CSTD) in addition to ventilated cabinets.  The effectiveness of CSTDs in reduction of environmental contamination and exposure of health care workers has been reported.  Here this report briefly reviews the history of the health effects of exposure to antineoplastic drugs and of safe handling.

Background/Aims: Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is the most common and serious complication of endoscopic retrograde cholangiopancreatography. To prevent this event, a unique precutting method, termed opening window fistulotomy, was performed in patients with a large infundibulum as the primary procedure for biliary cannulation, whereby a suprapapillary laid-down H-shaped incision was made without touching the orifice. This study aimed to assess the safety and feasibility of this novel technique. Methods: One hundred and ten patients were prospectively enrolled in this study. Patients with a papillary roof size ≥10 mm underwent opening window fistulotomy for primary biliary access. In addition, the incidence of complications and success rate of biliary cannulation were evaluated. Results: The median size of the papillary roof was 6 mm (range, 3–20 mm). Opening window fistulotomy was performed in 30 patients (27.3%), none of whom displayed PEP. Duodenal perforation was recorded in one patient (3.3%), which was resolved by conservative treatment. The cannulation rate was high (96.7%, 29/30 patients). The median duration of biliary access was 8 minutes (range, 3–15 minutes). Conclusions Opening window fistulotomy demonstrated its feasibility for primary biliary access by achieving great safety with no PEP complications and a high success rate for biliary cannulation.

Background/Aims: Hepatobiliary scintigraphy (HBS) is used to evaluate bile excretion. This study aimed to evaluate biliary excretion during endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) using HBS. Methods: We retrospectively evaluated 78 consecutive patients with malignant extrahepatic biliary obstruction, who underwent HBS after EUS-HGS between April 2015 and July 2022. The peak time and decay rate were scored with 0, 1, or 2 points based on thresholds of 20 and 35 minutes, and 10% and 50%, respectively. A total score of 4 or 3 was considered indicative of good bile excretion, whereas scores of 2, 1, or 0 indicated poor bile excretion. Results: The good and poor bile excretion groups included 40 and 38 cases, respectively. The group with good bile excretion had a significantly longer time to recurrent biliary obstruction compared to the poor bile excretion group (not reached vs. 124 days, p=0.026). Multivariate analysis identified the site of obstruction as a significant factor influencing good bile excretion (odds ratio, 3.39; 95% confidence interval, 1.01–11.4, p=0.049), with superior bile excretion observed in cases involving upper biliary obstruction compared to middle or lower biliary obstruction. Conclusions In patients with malignant biliary obstruction who underwent HGS, the site of obstruction is significantly associated with stent patency.

Background/Aims: Hepatobiliary scintigraphy (HBS) is used to evaluate bile excretion. This study aimed to evaluate biliary excretion during endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) using HBS. Methods: We retrospectively evaluated 78 consecutive patients with malignant extrahepatic biliary obstruction, who underwent HBS after EUS-HGS between April 2015 and July 2022. The peak time and decay rate were scored with 0, 1, or 2 points based on thresholds of 20 and 35 minutes, and 10% and 50%, respectively. A total score of 4 or 3 was considered indicative of good bile excretion, whereas scores of 2, 1, or 0 indicated poor bile excretion. Results: The good and poor bile excretion groups included 40 and 38 cases, respectively. The group with good bile excretion had a significantly longer time to recurrent biliary obstruction compared to the poor bile excretion group (not reached vs. 124 days, p=0.026). Multivariate analysis identified the site of obstruction as a significant factor influencing good bile excretion (odds ratio, 3.39; 95% confidence interval, 1.01–11.4, p=0.049), with superior bile excretion observed in cases involving upper biliary obstruction compared to middle or lower biliary obstruction. Conclusions In patients with malignant biliary obstruction who underwent HGS, the site of obstruction is significantly associated with stent patency.

Background/Aims: Hepatobiliary scintigraphy (HBS) is used to evaluate bile excretion. This study aimed to evaluate biliary excretion during endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) using HBS. Methods: We retrospectively evaluated 78 consecutive patients with malignant extrahepatic biliary obstruction, who underwent HBS after EUS-HGS between April 2015 and July 2022. The peak time and decay rate were scored with 0, 1, or 2 points based on thresholds of 20 and 35 minutes, and 10% and 50%, respectively. A total score of 4 or 3 was considered indicative of good bile excretion, whereas scores of 2, 1, or 0 indicated poor bile excretion. Results: The good and poor bile excretion groups included 40 and 38 cases, respectively. The group with good bile excretion had a significantly longer time to recurrent biliary obstruction compared to the poor bile excretion group (not reached vs. 124 days, p=0.026). Multivariate analysis identified the site of obstruction as a significant factor influencing good bile excretion (odds ratio, 3.39; 95% confidence interval, 1.01–11.4, p=0.049), with superior bile excretion observed in cases involving upper biliary obstruction compared to middle or lower biliary obstruction. Conclusions In patients with malignant biliary obstruction who underwent HGS, the site of obstruction is significantly associated with stent patency.

Benign biliary stricture (BBS) is a complication of chronic pancreatitis (CP). Despite endoscopic biliary stenting, some patients do not respond to treatment, and they experience recurrent cholangitis. We report two cases of CP with refractory BBS treated using endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) fistula creation. A 50-year-old woman and a 60-year-old man both presented with obstructive jaundice secondary to BBS due to alcoholic CP. They underwent repeated placement of a fully covered self-expandable metal stent for biliary strictures. However, the strictures persisted, causing repeated episodes of cholangitis. Therefore, an EUS-CDS was performed. The stents were eventually removed and the patients became stent-free. These fistulas have remained patent without cholangitis for more than 2.5 years. Fistula creation using EUS-CDS is an effective treatment option for BBS.

Background/Aims: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is a standard diagnostic method for biliary tract cancer (BTC), and samples obtained in this manner may be used for comprehensive genomic profiling (CGP). This study evaluated the utility of EUS-TA for CGP in a clinical setting and determined the factors associated with the adequacy of CGP in patients with BTC. Methods: CGP was attempted for 105 samples from 94 patients with BTC at the Aichi Cancer Center, Japan, from October 2019 to April 2022. Results: Overall, 77.1% (81/105) of the samples were adequate for CGP. For 22-G or 19-G fine-needle biopsy (FNB), the sample adequacy was 85.7% (36/42), which was similar to that of surgical specimens (94%, p=0.45). Univariate analysis revealed that 22-G or larger FNB needle usage (86%, p=0.003), the target primary lesions (88%, p=0.015), a target size ≥30 mm (100%, p=0.0013), and number of punctures (90%, p=0.016) were significantly positively associated with CGP sample adequacy. Conclusions EUS-TA is useful for CGP tissue sampling in patients with BTC. In particular, the use of 22-G or larger FNB needles may allow for specimen adequacy comparable to that of surgical specimens.

Background/Aims: Nutritional factors associated with gastric cancer (GC) are not completely understood. We aimed to determine the effect of nutrient intake on the incidence of GC. Methods: This was a post hoc analysis of a prospective trial that evaluated modalities for GC screening in participants aged 30 to 74 years living in high-risk areas for GC in Japan between June 2011 and March 2013. The patients were followed up for GC incidence for 6 years. All participants completed a self-administered food frequency questionnaire (FFQ) upon enrollment before GC screening. Daily nutrient intake was calculated from the FFQ and dichotomized at each cutoff value using receiver operating characteristic analysis. Risk factors associated with GC incidence were investigated in terms of nutrient intake and participant characteristics using Cox proportional hazards regression analysis. Results: Overall, 1,147 participants were included in this analysis. The median age was 62 years, and 50.7% of the participants were men. The median follow-up period was 2,184 days.GC was detected in 25 participants during the follow-up. Multivariate Cox proportional hazards regression analysis revealed that the intake of sodium (adjusted hazards ratio [aHR], 3.905; 95% confidence interval [CI], 1.520 to 10.035; p=0.005) and vitamin D (aHR, 2.747; 95% CI, 1.111 to 6.788, p=0.029) were positively associated with GC incidence, whereas the intake of soluble dietary fiber (aHR, 0.104; 95% CI, 0.012 to 0.905; p=0.040) was inversely associated with GC incidence. Conclusions Daily high intake of sodium and vitamin D and low soluble dietary fiber intake are associated with GC incidence.

OBJECTIVESMucosal immunity plays a pivotal role for body defense against infection and allergy. The aim of this study was to clarify the effects of 2,3,7,8-tetraclorodibenzo-p-dioxin (TCDD) on mucosal immunity in the gut.

METHODSFecal IgA level and oral tolerance induction were examined in TCDD-treated mice. Flow cytometric and histological analyses were also performed.

RESULTSSingle oral administration of low dose 2,3,7,8-TCDD resulted in a marked decrease in IgA secretion in the gut without any effects on the cellular components of gut-associated lymphoid tissues (GALT) including Peyer's patches (PPs) and mesenteric lymph nodes (LNs). Decressed IgA secretion by TCDD was not observed in aryl hydrocarbon receptor (AhR)-deficient mice. Flow cytometric analysis revealed that IgA B cells in PPs and the mesenteric LNs remained unchanged in the TCDD-treated mice. An immunofluorescence study also demonstrated that a significant number of cytoplasmic IgA cells were present in the lamina propria of the gut in the TCDD-treated mice. Furthermore, oral tolerance induction by ovalbumin (OVA) was impaired in the TCDD-treated mice and OVA-specific T cell proliferation occurred in the peripheral lymphoid tissues including the spleen and LNs.

CONCLUSIONSThese results suggest that a relatively low dose of TCDD impairs mucosal immunity in the gut and induces systemic sensitization by oral antigens.

Background/Aims: Endoscopic ultrasound (EUS)-guided hepaticogastrostomy (EUS-HGS) performed at the intrahepatic bile duct segment 3 (B3) is widely used for biliary drainage. Although performing post-puncture procedures is easier in the intrahepatic bile duct segment 2 (B2) when using a conventional oblique-viewing (OV) EUS scope, this method may cause transesophageal puncture and severe adverse events. We evaluated the safety and efficacy of B2 puncture using a novel OV-EUS scope. Methods: In this single-center retrospective study, we prospectively enrolled and collected data from 45 patients who consecutively underwent EUS-HGS procedures with a novel OV-EUS scope between September 2021 and December 2022 at our cancer center. Results: The technical success rates of B2-EUS-HGS and EUS-HGS were 93.3% (42/45) and 97.8% (44/45), respectively. The early adverse event rate was 8.9% (4/45) with no cases of scope changes or transesophageal punctures. The median procedure time was 13 minutes (range, 5–30). Conclusions B2-EUS-HGS can be performed safely with the novel EG-740UT (Fujifilm) OV-scope without transesophageal puncture and with a high success rate. B2-EUS-HGS using this novel OV scope may be the preferred strategy for EUS-HGS.