[Endoscopic closure of an esophago-pleural fistula resulting from a perforated esophageal ulcer due to systemic sclerosis:filling and shielding using polyglycolic acid sheets and fibrin glue].

A woman in her 70s with systemic sclerosis experienced dyspnea, and consequently, she was diagnosed with an esophago-pleural fistula, which was caused by a perforated esophageal ulcer. We administered conservative treatments including continuous pleural drainage and total parenteral nutrition. The fistula was closed but recurred, at which point we attempted to close the fistula by filling and shielding using polyglycolic acid (PGA) sheets and fibrin glue (FG). We were able to safely and smoothly fill and shield the fistula using the PGA sheets with a guidewire. We show that endoscopic closure of an esophago-pleural fistula using this technique is an effective, low-invasive treatment for gastrointestinal perforation and refractory fistulas.

[Subcapsular hepatic hematoma due to vessel injury from the rigid portion of a guidewire during endoscopic retrograde cholangiopancreatography].

A 58-year-old male receiving two types of antithrombotic medication developed acute obstructive suppressive cholangitis due to choledocholithiasis. During the first endoscopic retrograde cholangiopancreatography (ERCP) procedure, we performed biliary plastic stenting. Seven days after this procedure and with continued antithrombotic treatment, we performed ERCP with endoscopic sphincterotomy and stone extraction. Twelve hours after this procedure, the patient suffered transient unconsciousness and progression of anemia. Sixty hours after the procedure, he experienced right hypochondralgia and hiccups. Ultrasonography and computed tomography revealed a subcapsular hepatic hematoma. Bleeding was successfully arrested with selective arterial embolization. We suspected that the cause of these problems was vessel injury from the rigid portion of the guidewire during the ERCP procedure.

[Screening for colorectal cancer using immunological fecal occult blood test in inpatients].

We investigated the usefulness of screening for colorectal cancer (CRC) using immunological fecal occult blood test (FOBT) in 472 scheduled inpatients (median age, 68.6 years) who underwent screening for CRC via FOBT (single stool sample) at our hospital. The recall rate for further examination was 26.6% (126/472), and the rate of patients who underwent further examination was only 34.9% (44/126). The overall colorectal neoplasm detection rate, overall CRC detection rate, and positive predictive value for CRC in inpatients were 5.5% (26/472), 1.4% (7/472), and 5.5% (7/126), respectively, which were higher than those of population-based screening for CRC. Screening for CRC using FOBT in inpatients is a non-invasive and efficient method to detect latent CRC.

Filling of Polyglycolic Acid Sheets for Closure of Gastrointestinal Fistulas With an Easily Deliverable Technique Using a Guidewire.

BACKGROUND: This retrospective study aimed to investigate the suitable indications, methodology and long-term effect of the closure of gastrointestinal (GI) fistulas using polyglycolic acid (PGA) sheets and fibrin glue (FG) and to evaluate the usefulness of a delivery technique using a guidewire. METHODS: It involved 10 applications in six patients (median age 73 (range 53 - 78) years old, three men) with GI fistulas. A guidewire was introduced endoscopically or percutaneously into the fistula beyond the opposite orifice of the fistula with radiologic control. A tapered catheter was inserted over the guidewire, and the fistula was cleaned with an adequate quantity of saline. Subsequently, a small piece of PGA sheet was skewered onto the guidewire at the center and then pushed using the tapered catheter over the guidewire and delivered into the fistula. In cases of endoscopic procedure, the mucosa around the fistula was ablated, and the orifice of the fistula along with the surrounding mucosa was shielded with a piece of PGA sheet fixed with hemoclips and FG. RESULTS: Technical success of fistula closure was achieved in all applications, and no complications were observed after the procedure. The long-term occlusion of the fistula was ultimately achieved in four of six patients at 202 - 654 days (median duration, 244 days) after the last procedure with one or two applications. CONCLUSIONS: The closure of GI fistulas using PGA sheets and FG demonstrated long-term efficacy for upper GI fistula of a certain length, and the filling technique using a guidewire ensured a safe smooth procedure.

A box-shaped shielding device for reducing the risk of COVID-19 droplet infection during gastrointestinal endoscopic procedures.

BACKGROUND AND AIMS: Endoscopists and endoscopic assistants are easily exposed to germs, including COVID-19, during aerosol-generating procedures such as gastrointestinal endoscopy. This retrospective study investigated the utility of a box-shaped shielding device for reducing the risk of COVID-19 droplet infection during endoscopic procedures. METHODS: We created a cuboid box (500 × 650 × 450 mm) with four sides were covered with a transparent, vinyl-chloride sheet having two windows for endoscopic passage and assistance. The shielding box was then placed over a patient's head and shoulders and covered with another transparent vinyl sheet. We assessed its utility and safety using the medical data concerning the procedure time and vital signs and a questionnaire for the endoscopic staff and patients. RESULTS: We performed endoscopic retrograde cholangiopancreatography-related procedures using this device for two patients suspected of having COVID-19-associated pneumonia. Both patients were smoothly and successfully treated without any complications. No difficulties were noted with either endoscopic operation or in assisting the procedure, and the transparency was good enough to observe the patients' faces and movements. CONCLUSIONS: This box-shaped shielding device can be used to reduce the risk of COVID-19 droplet infection during endoscopic procedures in the clinical setting. RELEVANCE FOR PATIENTS: The COVID-19 outbreak has reminded healthcare personnel working in endoscopy units of the importance of infection prevention during endoscopy. The box-shaped shielding device can help endoscopic staff avoid hospital-setting COVID-19 infection.

IgG4-related Autoimmune Hepatitis with a Suspected Drug-induced Etiology.

A 69-year-old man was referred to our department with acute hepatitis. He had been newly treated with benidipine hydrochloride for two months. His blood test results were as follows: aspartate aminotransferase, 1,614 IU/L; alanine aminotransferase, 1,091 IU/L and anti-smooth muscle antibody, ×80. Needle liver biopsy specimen showed interface hepatitis with mainly lymphocytic infiltration and bridging fibrosis in the periportal area. Immunohistochemistry revealed lymphocytic infiltration positive for IgG4. We diagnosed him with IgG4-related AIH with an etiology that was suspected of being drug-induced. Oral prednisolone was started and then tapered after achieving biochemical remission. Hepatitis recurred after the cessation of steroids; however, remission was achieved with ursodeoxycholic acid.

A rare case of Goodpasture syndrome concomitant with bleeding jejunal Dieulafoy's lesion.

An 81-year-old man was diagnosed with Goodpasture syndrome (GS) because he met the criteria of positive anti-GBM antibodies, rapid progressive glomerulonephritis and pulmonary hemorrhage. After starting plasmapheresis and steroid pulse therapy, he experienced tarry stool and contrast-enhanced CT revealed an aneurysmal finding in the jejunum. Paroral enteroscopy showed a jejunal Dieulafoy's lesion (DL) with gush-out hemorrhage. Hemostasis was successfully achieved by hemoclipping, and he then experienced no re-bleeding events. GS can present as a jejunal DL, and contrast-enhanced CT is useful for investigating the etiology and site of small intestinal bleeding, which can lead to smooth, effective endoscopic hemostasis.

Management of Bleeding from Unresectable Gastric Cancer.

Bleeding from unresectable gastric cancer (URGC) is not a rare complication. Two major ways in which the management of this issue differs from the management of benign lesions are the high rate of rebleeding after successful hemostasis and that not only endoscopic therapy (ET) and transcatheter arterial embolization (TAE) but palliative radiotherapy (PRT) can be applied in the clinical setting. However, there are no specific guidelines concerning the management of URGC with bleeding. We herein discuss strategies for managing bleeding from URGC. A high rate of initial hemostasis for active bleeding is expected when using various ET modalities properly. If ET fails in patients with hemostatic instability, emergent TAE is considered in order to avoid a life-threating condition due to massive bleeding. Early PRT, especially, regimens with a high biologically effective dose (BED) of ≥39 Gy should be considered not only for patients with hemostatic failure but also for those with successful hemostasis and inactive hemorrhage, as longer duration of response with few complications can be expected. Further prospective, comparative studies considering not only the hemostatic efficacy of these modalities but the patients' quality of life are needed in order to establish treatment strategies for bleeding from URGC.

Endoscopic Gastrojejunostomy for Superior Mesenteric Artery Syndrome Using Magnetic Compression Anastomosis.

An 89-year-old woman who was bedridden suffered repeated vomiting due to superior mesenteric artery syndrome (SMAS). We performed gastrojejunostomy via the magnetic compression anastomosis (MCA) technique because her situation was not improved by conservative therapy and because the operative risk was high. We prepared two neodymium magnets: a flat plate-shaped magnet (15 × 3 mm) and a ring-shaped magnet of the same size. The ring-shaped magnet which passed through a guidewire was pushed to the duodenum by an endoscope over the guidewire. The duodenal stricture was balloon-dilated in front of the magnet, and the magnet was pushed all together beyond the stricture and placed at the duodenojejunal junction. Subsequently, the flat plate-shaped magnet was delivered endoscopically to the stomach using a biopsy forceps. The magnets were attracted towards each other transmurally after one more flat plate-shaped magnet was added to the gastric-side magnet. Completion of gastrojejunostomy was confirmed while retrieving the magnets 10 days after starting compression. She has been asymptomatic for 1 month since anastomosis. Endoscopic gastrojejunostomy using MCA was an effective, low-invasive treatment for SMAS.

A Rare Case of Local Recurrence Following Curative Endoscopic Submucosal Dissection of Intramucosal Differentiated-Type Gastric Cancer.

A 78-year-old man underwent endoscopic submucosal dissection (ESD) of early gastric cancer (EGC) (type 0-IIa) in the anterior wall of the antrum. En bloc resection was achieved. The histopathological examination revealed very well-differentiated tubular adenocarcinoma (tub1) of 30 × 22 mm in size, confined to the mucosa. No lymphovascular invasion or ulceration was observed, and there was no undifferentiated-type component and the margins were tumor-free. Therefore, this lesion fulfilled the eCuraA criteria. Two years after ESD, esophagogastroduodenoscopy revealed an irregular, slightly-depressed lesion within the post-ESD scar. Tubular adenocarcinoma was suspected based on histopathological examination of a biopsy specimen. The tumor was resected by ESD. A histopathological examination revealed well-differentiated tubular adenocarcinoma (tub1) of 6 × 4 mm in size, confined to the mucosa. No lymphovascular invasion was detected and the margins were tumor-free. These findings indicated a curative resection. Recurrence following a curative ESD of an intramucosal differentiated-type EGC which fulfilled the eCuraA criteria is rare. Careful endoscopic observation using magnifying narrow band imaging (NBI) is needed after ESD, even when curative resection is achieved.

Experience of Manual Compression Hemostasis Under Endoscopic Observation for Acute Hemorrhagic Rectal Ulcer.

We experienced two cases in which manual compression hemostasis under endoscopic observation was used in patients with acute hemorrhagic rectal ulcer (AHRU). The patients experienced an episode of massive fresh hematochezia, requiring the blood transfusion. Emergent sigmoidoscopy revealed multiple ulcers with a large protuberant visible vessel or with gush-out hemorrhage on the lower rectum. Endoscopic hemostasis by hemoclips and hypertonic saline-epinephrine injection was attempted; however, mechanical mucosal injury induced by hemoclips and needles caused another gush-out hemorrhage. Thus, the site of bleeding was manually compressed by a forefinger under endoscopic observation. After 5 min, compression hemostasis was achieved, and the postoperative course was uneventful. Manual compression hemostasis under endoscopic observation is useful and worth attempting for AHRU.

Experience of Endoscopic Jejunojejunostomy for Anastomotic Obstruction After Subtotal Gastrectomy Using Magnetic Compression Anastomosis.

Magnetic compression anastomosis (MCA) was developed as a low-invasive treatment for gastro-enteric or entero-enteric obstruction. A 72-year-old man underwent subtotal gastrectomy with Billroth II reconstruction for early gastric cancer. After the operation, he suffered from repeated aspiration pneumonia due to anastomotic obstruction caused by jejunal kinking at the efferent loop of anastomosis. We therefore performed jejunojejunostomy via the MCA technique, as his situation was not improved despite conservative therapy and he had a high reoperative risk. We prepared two flat plate-shaped neodymium magnets (15 × 3 mm) each with a small hole, and a nylon thread was passed through each hole. Each magnet was then delivered endoscopically to the anal side of the jejunal kinking, subsequently to the anastomosis, using biopsy forceps. The two magnets immediately became attracted towards each other transmurally. Oozing hemorrhage with clot at the mated magnets was observed 10 days after starting the compression. After retrieving the magnets, we confirmed the completion of jejunojejunostomy and then successfully achieved hemostasis of the anastomotic hemorrhage using argon plasma coagulation. The widely patent anastomosis was confirmed endoscopically 1 month after canalization; and he has been asymptomatic and able to eat a normal diet ever since. Endoscopic MCA is an effective, low-invasive treatment for anastomotic obstruction after subtotal gastrectomy. A standardized, safer procedure should be established for general use in the clinical setting.

Prophylactic Biliary Stenting Before Cholecystectomy in Patients With Gallstones and Common Bile Duct Stones.

BACKGROUND: The usefulness of prophylactic biliary stenting for patients with common bile duct stones (CBDS) and gallstones (GS) to prevent recurrent biliary events after endoscopic sphincterotomy (EST) and CBDS extraction before elective cholecystectomy remains controversial. The aim of this study was to evaluate the risk of recurrent CBDS around the perioperative period and clarify its risk factors. METHODS: The clinical data of all patients who received prophylactic biliary stenting after EST for CBDS and later underwent cholecystectomy for GS followed by stent extraction in our institution were retrospectively reviewed. The numbers of residual CBDS at the end first and second endoscopic retrograde cholangiography (ERC) studies were compared. Univariate and multivariate analyses were performed using a logistic regression model to determine risk factors for recurrent CBDS in the perioperative period. RESULTS: Forty-two consecutive patients received prophylactic biliary stenting and subsequent cholecystectomy for GS. Three of these patients were excluded from this study because the number of residual stones was not confirmed. The median maximum CBDS diameter at second ERC was 0 mm (range, 0 - 10 mm); six patients had multiple CBDS (≥ 5). The number of CBDS at second ERC was increased in comparison to that at the first ERC in 15 patients (38.4%), and was unchanged or decreased in 24 patients. The median minimum cystic duct diameter was 4 mm (range, 1 - 8 mm). The median interval between first ERC and operation was 26 days (range, 2 - 131 days). The median interval between operation and second ERC was 41 days (range, 26 - 96 days). Laparoscopic cholecystectomy (LC) was performed in 38 patients, one of whom was converted from LC to open cholecystectomy. Postoperative complications (transient bacteremia) occurred in one patient. The cystic duct diameter was an independent risk factor for an increased number of CBDS at second ERC in the multivariate analysis (odds ratio 0.611 (95% confidence interval (0.398 - 0.939)), P = 0.03). CONCLUSION: Recurrent CBDS around the perioperative period of cholecystectomy is not a rare complication after EST and the removal of CBDS with concomitant GS. Prophylactic biliary stenting is considered useful for preventing CBDS-associated complications, especially for patients in whom the cystic duct diameter is larger (≥ 5 mm).

Endoscopic closure of an anastomo-cutaneous fistula: Filling and shielding using polyglycolic acid sheets and fibrin glue with easily deliverable technique.

Background and study aims Recently, endoscopic closure of gastrointestinal fistulas using polyglycolic acid (PGA) sheets with fibrin glue (FG) has been attempted. A 70-year-old woman who had undergone pancreaticoduodenectomy for pancreatic cancer suffered from a refractory anastomo-cutaneous fistula at the site of gastro-jejunostomy. We attempted endoscopic closure with filling and shielding using PGA sheets and FG. After introducing a guidewire into the fistula, a small piece of PGA sheet was skewered onto the guidewire and then pushed using a tapered catheter over the guidewire and delivered into the fistula. A total of 10 sheets were delivered via the same procedure. Next, the mucosa around the fistula was ablated, and the orifice of the fistula along with the surrounding mucosa was shielded with a piece of PGA sheet fixed with hemoclips and FG. After this procedure, the leakage disappeared and the fistula was undetectable on contrast radiograms. Endoscopic closure of anastomo-cutaneous fistula with filling and shielding using PGA sheets and FG is an effective, safe, low-invasive treatment, and the filling technique using a guidewire ensures a safe, smooth procedure.

Intraductal Ultrasonography as a Local Assessment Before Magnetic Compression Anastomosis for Obstructed Choledochojejunostomy.

Magnetic compression anastomosis (MCA) has been developed as a non-surgical alternative treatment for biliary obstruction without serious complications. A 70-year-old woman who had undergone pancreaticoduodenectomy with modified Child reconstruction for pancreatic head cancer suffered from obstructed choledochojejunostomy with no recurrent findings 4 months after the operation. Cholangiography using the percutaneous transhepatic cholangiographic drainage (PTCD) and fluoroscopy revealed complete obstruction of the upper common bile duct, and the length of the obstruction was 7 mm. Intraductal ultrasonography (IDUS) showed fibrous heterogenous hyperechoic appearance without fluid collection, vessels or foreign bodies at the site of the obstruction. We performed choledochojejunostomy using the MCA technique. One magnet was inserted into the obstruction of the hepatic side through the PTCD fistula. Another was delivered endoscopically to the obstruction of the jejunal side. The two magnets were immediately attracted towards each other transmurally, and reanastomosis was confirmed 7 days after starting the compression. The magnets were easily retrieved endoscopically. A 16-Fr indwelling drainage tube was placed in the jejunum through the PTCD. The internal tube is still in place 6 months after reanastomosis, and no MCA-related complications have been observed. In conclusion, MCA is a safe, effective, low-invasive treatment for biliary obstruction, and IDUS is useful for the pretreatment assessment of feasibility and safety.

Antitumor effects of vitamins K1, K2 and K3 on hepatocellular carcinoma in vitro and in vivo.

A number of studies have shown that various K vitamins, specifically vitamins K2 and K3, possess antitumor activity on various types of rodent- and human-derived neoplastic cell lines. In the present study, we examined the antitumor effects of vitamins K1, K2 and K3 on PLC/PRF/5 human hepatocellular carcinoma (HCC) cells in vitro and in vivo. Furthermore, we examined the mechanisms of antitumor actions of these vitamins in vitro and in vivo. Although vitamin K1 did not inhibit proliferation of PLC/PRF/5 cells at a 90-microM concentration (the highest tested), vitamins K2 and K3 suppressed proliferation of the cells at concentrations of 90 and 9 microM, respectively. By flow cytometric analysis, it was shown that not only vitamin K1, but also vitamin K2 did not induce apoptosis or cell cycle arrest on PLC/PRF/5 cells. In contrast, vitamin K3 induced G1 arrest, but not apoptosis on PLC/PRF/5 cells. Subsequent in vivo study using subcutaneous HCC-bearing athymic nude mice demonstrated that both vitamins K2 and K3 markedly suppressed the growth of HCC tumors to similar extent. Protein expression of cyclin D1 and cyclin-dependent kinase 4 (Cdk4), but not p16INK4a Cdk inhibitor in the tumor was significantly reduced by vitamin K2 or K3 treatment, indicating that vitamins K2 and K3 may induce G1 arrest of cell cycle on PLC/PRF/5 cells in vivo. Taken collectively, vitamins K2 and K3 were able to induce potent antitumor effects on HCC in vitro and in vivo, at least in part, by inducing G1 arrest of the cell cycle. The results indicate that vitamins K2 and K3 may be useful agents for the treatment of patients with HCC.

In vitro and in vivo antitumor effects of vitamin K5 on hepatocellular carcinoma.

Although a number of studies have shown that vitamins K1, K2 and K3 exerted antitumor effects on various types of rodent- and human-derived neoplastic cell lines, it has not been examined whether or not vitamin K5 also possesses antitumor activity. In the present study, we examined the antitumor effects of vitamin K5 on PLC/PRF/5 human hepatocellular carcinoma (HCC) cells in vitro and in vivo. Furthermore, we examined the mechanisms of antitumor actions of vitamin K5 not only in vitro but also in vivo. Vitamin K5 was shown to suppress the proliferation of PLC/PRF/5 cells at a concentration of 30 microM. By a flow cytometric analysis, it was shown that although vitamin K5 did not induce apoptosis on PLC/PRF/5 cells, it did induce G1 arrest on PLC/PRF/5 cells. Subsequent in vivo study using subcutaneous HCC-bearing athymic nude mice demonstrated that vitamin K5 markedly suppressed the growth of HCC tumors. Although protein expression levels of cyclin D1 and p16INK4a cyclin-dependent kinase (Cdk) inhibitor in HCC tumors were not decreased by vitamin K5 treatment, those of Cdk4 were reduced significantly by the treatment. Taken collectively, vitamin K5 could induce potent antitumor effects on HCC not only in vitro but also in vivo, at least in part by inducing G1 arrest of cell cycle through downregulation of Cdk4 expression. The results demonstrated here indicate that vitamin K5 may be a useful agent for the treatment of patients with HCC.

Vitamins K2, K3 and K5 exert in vivo antitumor effects on hepatocellular carcinoma by regulating the expression of G1 phase-related cell cycle molecules.

A number of studies have shown that various vitamins K, specifically vitamin K2, possessed antitumor activity on various types of rodent- and human-derived neoplastic cell lines. However, there are only a small number of reports demonstrating in vivo antitumor effects of vitamins K. Furthermore, the mechanism of antitumor effects of vitamins K still remains to be examined. In the present study, we examined the antitumor effects of vitamins K2, K3 and K5 on PLC/PRF/5 human hepatocellular carcinoma (HCC) cells in vivo. Furthermore, to examine the mechanism of antitumor actions of these vitamins K, mRNA expression levels of various G1 phase-related cell cycle molecules were evaluated by using a real-time reverse transcription-polymerase chain reaction (RT-PCR) method. HCC-bearing animals were produced by implanting PLC/PRF/5 cells subcutaneously into athymic nude mice, and drinking water containing vitamin K2, K3 or K5 was given to the animals. Treatments with vitamins K2, K3 and K5 were shown to markedly inhibit the growth of HCC tumors. To examine the mechanism of in vivo antitumor effects of vitamins K, total RNA was extracted from HCC tumors, and the expression of G1 phase-related cell cycle molecules was quantitatively examined. Real-time RT-PCR demonstrated that the expression of the cell cycle-driving molecule, cyclin-dependent kinase 4 (Cdk4), in HCC was significantly reduced by the treatments with vitamin K2, K3 and K5. Conversely, the expression of the cell cycle-suppressing molecules, Cdk inhibitor p16INK4a and retinoblastoma, in HCC was significantly enhanced by the treatments with vitamins K2, K3 and K5. These results indicate that vitamins K2, K3 and K5 exert antitumor effects on HCC by regulating the expression of G1 phase-related cell cycle molecules. These results also indicate that vitamins K2, K3 and K5 may be useful agents for the treatment of patients with HCC.

Proliferative capability of hepatocytes and expression of G1-related cell cycle molecules in the development of liver cirrhosis in rats.

Liver cirrhosis is the end stage of various chronic liver diseases and its prognosis is very poor. One of the most important causes of liver cirrhosis appears to be impaired proliferative capability of hepatocytes caused by continuous hepatic damage. Cell cycle-related molecules have been shown to play essential roles in cell proliferation. Specifically, G1-related cell cycle molecules are important, because they are requisite for the entry into the cell cycle from the quiescent state. However, the role of these cell cycle molecules during the development of liver cirrhosis remains to be examined. In the present study, liver cirrhosis was produced in rats by intraperitoneally administering dimethylnitrosamine (DMN). Proliferative capability of hepatocytes estimated immunohistochemically by proliferating cell nuclear antigen staining was markedly increased at an early stage of cirrhosis development. However, it was gradually decreased thereafter and suppressed substantially at the time of cirrhosis manifestation. Cyclin D1 expression estimated by a real-time reverse transcription-polymerase chain reaction (RT-PCR) method was also increased markedly at an early stage of cirrhosis development but decreased substantially thereafter. mRNA levels of catalytic subunits of cyclin D1, cyclin-dependent kinase 4 (Cdk4) and Cdk6, did not show significant changes during the development of liver cirrhosis. Among G1-specific Cdk inhibitors, expression of p15INK4b and p16INK4a estimated by an RT-PCR method was increased according to the progression of cirrhosis and reached a peak at the time of cirrhosis manifestation. Conversely, p18INK4c expression did not change significantly during the development of liver cirrhosis. These results suggest that cyclin D1 plays an essential role in hepatocyte proliferation in response to hepatic damage. However, with the decrease of cyclin D1 expression and increase of p15INK4b and p16INK4a expression, proliferative capability of hepatocytes is severely impaired and extracellular matrix components are deposited to retrieve space lost by the destruction of hepatic parenchyma, resulting in establishment of liver cirrhosis.