Methods and timing of biliary drainage for acute cholangitis: Tokyo Guidelines

Biliary drainage is a radical method to relieve cholestasis, a cause of acute cholangitis, and takes a central part in the treatment of acute cholangitis. Emergent drainage is essential for severe cases, whereas patients with moderate and mild disease should also receive drainage as soon as possible if they do not respond to conservative treatment, and their condition has not improved. Biliary drainage can be achieved via three different routes/procedures: endoscopic, percutaneous transhepatic, and open methods. The clinical value of both endoscopic and percutaneous transhepatic drainage is well known. Endoscopic drainage is associated with a low morbidity rate and shorter duration of hospitalization; therefore, this approach is advocated whenever it is applicable. In endoscopic drainage, either endoscopic nasobiliary drainage (ENBD) or tube stent placement can be used. There is no significant difference in the success rate, effectiveness, and morbidity between the two procedures. The decision to perform endoscopic sphincterotomy (EST) is made based on the patient's condition and the number and diameter of common bile duct stones. Open drainage, on the other hand, should be applied only in patients for whom endoscopic or percutaneous transhepatic drainage is contraindicated or has not been successfully performed. Cholecystectomy is recommended in patients with gallbladder stones, following the resolution of acute cholangitis with medical treatment, unless the patient has poor operative risk factors or declines surgery.     

Preoperative biliary drainage for biliary tract and ampullary carcinomas

We posed six clinical questions (CQ) on preoperative biliary drainage and organized all pertinent evidence regarding these questions. CQ 1. Is preoperative biliary drainage necessary for patients with jaundice? The indications for preoperative drainage for jaundiced patients are changing greatly. Many reports state that, excluding conditions such as cholangitis and liver dysfunction, biliary drainage is not necessary before pancreatoduodenectomy or less invasive surgery. However, the morbidity and mortality of extended hepatectomy for biliary cancer is still high, and the most common cause of death is hepatic failure; therefore, preoperative biliary drainage is desirable in patients who are to undergo extended hepatectomy. CQ 2. What procedures are appropriate for preoperative biliary drainage? There are three methods of biliary drainage: percutaneous transhepatic biliary drainage (PTBD), endoscopic nasobiliary drainage (ENBD) or endoscopic retrograde biliary drainage (ERBD), and surgical drainage. ERBD is an internal drainage method, and PTBD and ENBD are external methods. However, there are no reports of comparisons of preoperative biliary drainage methods using randomized controlled trials (RCTs). Thus, at this point, a method should be used that can be safely performed with the equipment and techniques available at each facility. CQ 3. Which is better, unilateral or bilateral biliary drainage, in malignant hilar obstruction? Unilateral biliary drainage of the future remnant hepatic lobe is usually enough even when intrahepatic bile ducts are separated into multiple units due to hilar malignancy. Bilateral biliary drainage should be considered in the following cases: those in which the operative procedure is difficult to determine before biliary drainage; those in which cholangitis has developed after unilateral drainage; and those in which the decrease in serum bilirubin after unilateral drainage is very slow. CQ 4. What is the best treatment for post-drainage fever? The most likely cause of high fever in patients with biliary drainage is cholangitis due to problems with the existing drainage catheter or segmental cholangitis if an undrained segment is left. In the latter case, urgent drainage is required. CQ 5. Is bile culture necessary in patients with biliary drainage who are to undergo surgery? Monitoring of bile cultures is necessary for patients with biliary drainage to determine the appropriate use of antibiotics during the perioperative period. CQ 6. Is bile replacement useful for patients with external biliary drainage? Maintenance of the enterohepatic bile circulation is vitally important. Thus, preoperative bile replacement in patients with external biliary drainage is very likely to be effective when highly invasive surgery (e.g., extended hepatectomy for hilar cholangiocarcinoma) is planned.     

Trisomy 8-positive Polycythemia Vera Complicated with Intestinal Behçet's-like Disease: A New Perspective for a Clinical Approach

Behçet''s disease (BD) is a multisystem inflammatory disease of unknown origin. It rarely but occasionally occurs together with myelodysplastic syndrome and primary myelofibrosis. Trisomy 8 is one of the most common cytogenetic abnormalities in myeloid neoplasms; however, the association of BD with polycythemia vera (PV) and trisomy 8 has not been reported. A 70-year-old woman, diagnosed with PV and treated with hydroxyurea, had bloody stool due to multiple ulcers in the ileocecal region. Considering the lack of a response to treatment and other features, we suspected complication with intestinal Behçet''s-like disease. Our case suggests relationships among BD, trisomy 8, and PV.     

Epidemiology and Genetic Analysis of SARS-CoV-2 in Myanmar during the Community Outbreaks in 2020

We aimed to analyze the situation of the first two epidemic waves in Myanmar using the publicly available daily situation of COVID-19 and whole-genome sequencing data of SARS-CoV-2. From March 23 to December 31, 2020, there were 33,917 confirmed cases and 741 deaths in Myanmar (case fatality rate of 2.18%). The first wave in Myanmar from March to July was linked to overseas travel, and then a second wave started from Rakhine State, a western border state, leading to the second wave spreading countrywide in Myanmar from August to December 2020. The estimated effective reproductive number (R_t) nationwide reached 6–8 at the beginning of each wave and gradually decreased as the epidemic spread to the community. The whole-genome analysis of 10 Myanmar SARS-CoV-2 strains together with 31 previously registered strains showed that the first wave was caused by GISAID clade O or PANGOLIN lineage B.6 and the second wave was changed to clade GH or lineage B.1.36.16 with a close genetic relationship with other South Asian strains. Constant monitoring of epidemiological situations combined with SARS-CoV-2 genome analysis is important for adjusting public health measures to mitigate the community transmissions of COVID-19.     

Use of sismotherapy during pregnancy for severe depression

Electroconvulsive therapy (ECT), also known as electroshock, is a treatment option for patients with severe depression. It involves inducing a comitial crisis under short general anesthesia with curarization. Its use during pregnancy is a rare event and a poorly studied one. A primigravida with a prior bipolar disorder presented a major depressive episode during the second trimester, slightly improved by medical treatment. Electroshocks were performed (10 sessions planned from 26 to 30 weeks of amenorrhea [WA]), with the agreement of the patient. A marked improvement in her condition was recorded in the early sessions. Following a threat of premature birth, the last session was not carried out. She received antidepressant medical treatment in the months preceding childbirth. At 36 WA, the birth was natural and fast to a healthy child (3120 g, Apgar 10-10-10). The mother-child relationship was good. Even if publications are reassuring, the case of a child with multiple cerebral infarctions in a preeclamptic patient was recently reported. The occurrence of any superimposed obstetrical pathology (preeclampsia, premature delivery) should revise this treatment. Given the possible complications, it requires strict supervision of the pregnancy in a hospital setting.     

Targeting the K-Ras - JNK axis eliminates cancer stem-like cells and prevents pancreatic tumor formation

Cancer cells with self-renewal and tumor-initiating capacity, either quiescent (cancer stem cells, CSCs) or proliferating (cancer stem-like cells, CSLCs), are now deemed responsible for the pervasive therapy resistance of pancreatic cancer, one of the deadliest human cancers characterized by high prevalence of K-Ras mutation. However, to date, much remains unknown how pancreatic CSCs/CSLCs are regulated. Here we show that the K-Ras – JNK axis plays a pivotal role in the maintenance of pancreatic CSCs/CSLCs. In vitro inhibition of JNK, either pharmacological or genetic, caused loss of the self-renewal and tumor-initiating capacity of pancreatic CSLCs. Importantly, JNK inhibition in vivo via systemic JNK inhibitor administration, which had no discernible effect on the general health status of mice, efficiently depleted the CSC/CSLC population within pre-established pancreatic tumor xenografts. Furthermore, knockdown of K-Ras in pancreatic CSLCs with K-Ras mutation led to downregulation of the JNK pathway as well as in loss of self-renewal and tumor-initiating capacity. Together, our findings suggest that pancreatic CSCs/CSLCs are dependent on K-Ras activation of JNK and also suggest that the K-Ras – JNK axis could be a potential target in CSC/CSLC-directed therapies against pancreatic cancer.     

Cyclodextrin-induced release of drug-entrapping liposomes associated with the solation of liposome gels

In this work, we demonstrate that liposome gels in which liposomes are connected by polyethylene glycol terminated by cholesterol groups at both ends can store hydrophilic and hydrophobic drugs in the gel interiors, inner aqueous phases, and lipid membranes. The addition of cyclodextrins (CDxs) as extrinsic stimuli led to the release of drug-entrapping liposomes due to the interactions between CDxs and cholesteryl groups and/or the alkyl chains of lipids. The addition of aqueous solutions of β-CDx, dimethyl-β-CDx, trimethyl-β-CDx, and γ-CDx (final concentration: 7.5 mM) induced the solation of liposome gels and the release of liposomes accompanying the solation. Furthermore, the addition of β-CDx led to the partial release of hydrophilic drugs encapsulated in the liposomes, although the drug release was scarcely observed in other CDxs. In particular, the addition of trimethyl-β-CDx, which has low cytotoxicity, accelerated solation, and cationic liposomes released from the gels were effectively taken up by murine colon cancer (Colon26) cells. Thus, we propose that liposomes released from liposome gels can function as drug carriers.

The solation of liposome gels owing to the addition of trimethyl-β-cyclodextrin (TMe-β-CDx) and the uptake of cationic liposomes released from liposome gels by Colon26 cells are demonstrated.     

New prenylated anthraquinones and xanthones from Vismia guineensis

From the roots of Vismia guineensis 23 structurally related compounds were isolated and identified. Ten of them are new constituents, namely 3-O-(2-hydroxy-3-methylbut-3-enyl)-emodin (1); 3-O-(2-methoxy-3-methylbut-3-enyl)-emodin (2); 1, 8-dihydroxy-3-(2-methoxy-3-methylbut-3-enyloxy)-6-methylx anthone (3); 1,8-dihydroxy-3-geranyloxy-6-methylxanthone (4); 1, 8-dihydroxy-3-isoprenyloxy-6-methylxanthone (5); 1,8-dihydroxy-3-(3, 7-dimethyl-7-methoxyoct-2-enyloxy)-6-methylxanthone (6); 3-O-(E-3-hydroxymethylbut-2-enyl)-emodin (7); 3-O-(3-hydroxymethyl-4-hydroxybut-2-enyl)-emodin (8); 1, 8-dihydroxy-3-(E-3-hydroxymethylbut-2-enyloxy)-6-methylxa nthone (9); and 1, 8-dihydroxy-3-(3-hydroxymethyl-4-hydroxybut-2-enyloxy)-6- methylxantho ne (10). Their structures were established by means of EIMS and a combination of homonuclear and heteronuclear 2D NMR techniques. Furthermore, an in vitro preliminary screening of antimitotic activity of all the isolated compounds was also evaluated.     

Counting gross fetal movement using a fetal movement acceleration measurement recorder in two fetuses with gastroschisis

We used the fetal movement acceleration measurement recorder to count gross fetal movement in two fetuses with gastroschisis. In conclusion, both fetuses moved as much as normal fetuses, which suggested that normal fetal movement could indicate reassuring status also in fetuses with malformation when they have normal neurological developments.