Impact of reflux esophagitis on the esophageal function before and after laparoscopic fundoplication

Background

High-resolution manometry (HRM), which is breakthrough testing equipment to evaluate esophageal motor function, was developed in Europe and United State and has garnered attention. Moreover, multichannel intraluminal impedance pH (MII-pH) testing has allowed us to grasp all liquid/gas reflux including not only acid but also non-acid reflux. We examined the impact of the presence of reflux esophagitis (RE) on esophageal motor function before and after laparoscopic fundoplication.

Materials and methods

The subjects included 100 patients (male: 63 patients, mean age: 54.1?±?15.8) among 145 patients who underwent laparoscopic fundoplication for GERD associated diseases during a 4-year period from October 2012 to September 2016, excluding 6 patients who underwent further surgery, 32 patients on whom HRM was not performed, 3 patients who had technical errors during testing, and 4 patients for whom the status of RE was unknown. Regarding HRM, Mano Scan from Given Imaging Ltd. was used, and for the analysis, Mano View version 3.0 from the same company was used, after which data was calculated based on the Chicago Classification advocated by Pandolfino et al. Moreover, for the MII-pH testing, Sleuth manufactured by Sandhill Scientific. Inc. was used and automatic analysis was conducted by a computer. Postoperative assessments were conducted 3 months following surgery for all. Data was described in the median value and inter-quartile range, with a statistically significant difference defined as p?<?0.05 by Chi square, Mann–Whitney, and Wilcoxon tests.

Results

RE+?group (Los Angeles classification A:B:C:D?=?7:9:16:12 patients) included 44 patients (44%), of older age compared to the RE? group (62 vs. 50 years, p?=?0.012) and a higher Body Mass Index value (24.0 vs. 22.5, p?=?0.045); however, no differences were observed in terms of gender and duration of symptoms. In the preoperative findings on MII-pH, the RE+?group demonstrated significantly longer acid reflux time (4.7 vs. 1.3%, p?=?0.005), while in the HRM findings, the RE? group demonstrated a significantly longer abdominal esophagus (0 vs. 0.4 cm, p?=?0.049) and maintained esophageal body motor function (DCI: 1054 vs. 1407 mmHg s cm, p?=?0.021, Intact peristalsis ratio: 90 vs. 100%, p?=?0.037). As to the comparison of the treatment effect before and after laparoscopic fundoplication (Toupet fundoplication for all), significant improvements were observed in both groups in various parameters regarding reflux including acid reflux time, total number of liquid reflux episodes and total number of reflux episodes. Moreover, for both groups, the total length of the lower esophageal sphincter (LES) (RE+?group: 2.7 vs. 3.2 cm, p?=?0.001, RE? group: 3.0 vs. 3.4 cm, p?=?0.003) and the total length of the abdominal esophagus (RE+?group: 0 vs. 1.6 cm, p?<?0.001, RE? group: 0 vs. 1.8 cm, p?=?0.001) were significantly extended following surgery; however, no change was observed in DCI before and after surgery.

Conclusions

Regardless of the presence of RE, cardiac function and LES function were improved following laparoscopic Toupet fundoplication, but no changes were observed in esophageal body motor function.

     

Direct demonstration of the cross-bridge recovery stroke in muscle thick filaments in aqueous solution by using the hydration chamber

Despite >50 years of research work since the discovery of sliding filament mechanism in muscle contraction, structural details of the coupling of cyclic cross-bridge movement to ATP hydrolysis are not yet fully understood. An example would be whether lever arm tilting on the myosin filament backbone will occur in the absence of actin. The most direct way to elucidate such movement is to record ATP-induced cross-bridge movement in hydrated thick filaments. Using the hydration chamber, with which biological specimens can be kept in an aqueous environment in an electron microscope, we have succeeded in recording ATP-induced cross-bridge movement in hydrated thick filaments consisting of rabbit skeletal muscle myosin, with gold position markers attached to the cross-bridges. The position of individual cross-bridges did not change appreciably with time in the absence of ATP, indicating stability of time-averaged cross-bridge mean position. On application of ATP, individual cross-bridges moved nearly parallel to the filament long axis. The amplitude of the ATP-induced cross-bridge movement showed a peak at 5–7.5 nm. At both sides of the filament bare region, across which the cross-bridge polarity was reversed, the cross-bridges were found to move away from, but not toward, the bare region. Application of ADP produced no appreciable cross-bridge movement. Because ATP reacts rapidly with the cross-bridges (M) to form complex (M·ADP·Pi) with an average lifetime >10 s, the observed cross-bridge movement is associated with reaction, M + ATP → M·ADP·Pi. The cross-bridges were observed to return to their initial position after exhaustion of ATP. These results constitute direct demonstration of the cross-bridge recovery stroke.     

Inhibition of growth and induction of apoptosis by all-trans retinoic acid in lymphoid cell lines transfected with the PML/RARα fusion gene

The interaction of an exogenous PML/RARα fusion gene associated with acute promyelocytic leukaemia, with all- trans retinoic acid (ATRA) was examined in two lymphoid cell lines. L1210 and MOLT-4 cells were transfected with PML/RARα cDNA in the expression vector pGD and stable transformants (L1210 PML/RAR α and MOLT-4 PML/RAR α) were selected with G418. ATRA inhibited the growth of these stable transformants, as assessed by [³H]thymidine incorporation, in a dose-dependent manner, but had no effect on the growth of control cells stably transformed with neomycin resistant gene alone. ATRA also induced apoptosis, as assessed by fragmentation of genomic DNA, in L1210 PML/RAR α and MOLT-4 PML/RAR α cells but not in control cells. The exogenous PML/RARα fusion gene therefore probably mediates the effects of ATRA on cell growth and apoptosis in these cell lines.     

Delayed esophageal perforation after laparoscopic fundoplication in a patient with diabetes mellitus: a case report

A 55-year-old man on hemodialysis for diabetic nephropathy suffered from vomiting and hematoemesis. He was diagnosed to have reflux esophagitis with Los Angeles classification grade D, which was accompanied by a shortened esophagus and stricture. His reflux esophagitis was proton pump inhibitor resistant. Therefore, we performed laparoscopic Toupet fundoplication. Delayed esophageal perforation occurred on the ninth day postoperatively, for which he had to be reoperated. To our knowledge, there is no previous report of delayed esophageal perforation after laparoscopic fundoplication. Esophageal perforation might have been caused by denudation or attenuation of the abdominal esophagus.     

Effect of Alcohol Drinking on Gene Expression of Hepatic O6-Methylguanine DNA Methyltransferase in Chronic Liver Diseases

O⁶-methylguanine DNA methyltransferase (MGMT) is a repair protein that transfers methyl groups from O⁶-methylguanine to a cysteine acceptor in its own molecule, and restores DNA to its undamaged state. If left unrepaired, O⁶-methylguanine can pair with either a thymine or a cytosine, causing a C-G to T-A transition, which is considered to be one of the molecular mechanisms of both mutagenesis and carcinogenesis. The expression of MGMT mRNA in liver tissue was quantitatively assessed by the competitive reverse transcrip-tion-polymerase chain reaction method in patients with chronic liver diseases with or without alcohol drinking. MGMT mRNA expression was 1.4 ± 0.9 pg/μg RNA in control livers. Its expression in chronic hepatitis was 3.8 ± 0.7 in alcoholics and 2.7 ± 0.8 in nonalcoholics, which were not statistically different. MGMT mRNA expression in liver cirrhosis was significantly low, compared with that in chronic hepatitis, and 0.8 ± 0.3 in alcoholics and 0.5 ± 0.1 in nonalcoholics, which also were not significantly different. The present study shows that MGMT mRNA was not decreased in patients with chronic liver diseases with alcohol drinking, compared with those without alcohol drinking.     

Role of nitric oxide and endothelin-1 in a portal hypertensive rat model

BACKGROUND: Portal hypertension is often accompanied by a hyperdynamic circulation state. Some reports have suggested that nitric oxide (NO) plays an important role in this hyperdynamic state. On the other hand, although endothelin (ET)-1, a powerful vasoconstrictor, was recently identified, little is known about its role in portal hypertension or about the interaction between NO and ET-1. The aim of this study was therefore to investigate whether or not the inhibitor of NO synthase (NOS) might improve portal hypertension, and also to clarify the relationship between NO and ET-1. METHODS: Portal hypertensive (PHT) rats, in which hypertension was induced by a two-step ligation of the portal vein (PVL), were used. The mean arterial pressure (MAP), portal pressure (PP), visceral blood flow volume (BFV), and serum levels of NO and ET-1 were determined in PVL rats treated with two NOS inhibitors with different functions: N(G)-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine (AG). Control (CTR) rats. treated by a sham operation (SO), were also studied. RESULTS: Two-step PVL treatment induced a significant increase in the serum level of NO3-and ET-1 in the portal vein. L-NAME and AG administration significantly decreased PP at doses of 50 mg/kg in PHT rats after 60 min administration, while no inhibitor effected any modification in the CTBR rats. Both NOS inhibitors increased MAP and decreased PP and BFV in the portal vein, gastric mucosa, and spleen, in addition to decreasing the serum levels of NO3- and ET-1 in the PHT rats, while neither blockade modified any parameters in the CTR rats. In PHT rats, L-arginine, a NO substance, reversed the effect of L-NAME, while it did not induce any recovery from the AG effect. CONCLUSIONS: In PHT rats, NO seems to contribute to portal hypertension. PVL increases not only the serum level of NO3-, but also that of ET-1 in the portal vein. Both L-NAME and AG reduce PP and BFV of the portal vein, spleen, gastric mucosa. and liver. In addition, the inhibition of NOS diminishes the serum level not only of NO, but also of ET-1. Use of an appropriate NOS inhibitor may therefore positively affect the hyperdynamic state in portal hypertension.     

Developmental and evolutionary significance of the mandibular arch and prechordal/premandibular cranium in vertebrates: revising the heterotopy scenario of gnathostome jaw evolution

The cephalic neural crest produces streams of migrating cells that populate pharyngeal arches and a more rostral, premandibular domain, to give rise to an extensive ectomesenchyme in the embryonic vertebrate head. The crest cells forming the trigeminal stream are the major source of the craniofacial skeleton; however, there is no clear distinction between the mandibular arch and the premandibular domain in this ectomesenchyme. The question regarding the evolution of the gnathostome jaw is, in part, a question about the differentiation of the mandibular arch, the rostralmost component of the pharynx, and in part a question about the developmental fate of the premandibular domain. We address the developmental definition of the mandibular arch in connection with the developmental origin of the trabeculae, paired cartilaginous elements generally believed to develop in the premandibular domain, and also of enigmatic cartilaginous elements called polar cartilages. Based on comparative embryology, we propose that the mandibular arch ectomesenchyme in gnathostomes can be defined as a Dlx1-positive domain, and that the polar cartilages, which develop from the Dlx1-negative premandibular ectomesenchyme, would represent merely posterior parts of the trabeculae. We also show, in the lamprey embryo, early migration of mandibular arch mesenchyme into the premandibular domain, and propose an updated version of the heterotopy theory on the origin of the jaw.     

A national surveillance study of the current status of reirradiation using brachytherapy in Japan

PurposeThis study aimed to explore the current status and pattern of practice for reirradiation using brachytherapy (ReRT-BT) through a survey in Japan.Materials and MethodsWe distributed an e-mail-based questionnaire to 153 institutions equipped with high-dose-rate brachytherapy facilities.ResultsWe received responses from 76 institutions (49.7%). Forty-three of these institutions performed ReRT-BT and 42 institutions (55%) performed ReRT-BT during 2009–2018. However, 29 of the 42 institutions (69%) reported difficulty in obtaining ReRT-BT case information from their respective databases. Almost all the institutions encountered insufficient database system to extract details about the ReRT-BT cases. Responses from 33 institutions included the number of ReRT-BT cases; this increased from 90 in the period 2009–2013 (institution median = 0.5; 0–16) to 172 in the period 2014–2018 (institution median = 2; 0–26). Nine institutions had to perform ReRT-BT for more than one case per year. The major location for cancer treatment was the pelvis (94%), followed by the head and neck (5%) and others (1%). In six site-specific scenarios, barring uterine corpus cancer recurrence, more than 90% of radiation oncologists agreed to perform ReRT-BT, whereas other areas (head and neck, prostate, and rectal cancer) gained 16–37% agreement.ConclusionsThis decade saw an increase in the number of ReRT-BT cases in Japan and radiation oncologists’ interest in ReRT-BT as a viable therapeutic option. However, scarce availability, immature education system, and insufficient database system are barriers to further consensus building.