Efficacies of prokinetics and rifaximin on the positivity of a glucose breath test in patients with functional dyspepsia: a randomized trial.

BACKGROUND AND AIM: prokinetics could eradicate small intestinal bacterial overgrowth. This study aimed to evaluate the efficacy of mosapride, rifaximin and a combination of mosapride and rifaximin for the treatment of small intestinal bacterial overgrowth. METHODS: we randomly assigned patients with functional dyspepsia diagnosed with small intestinal bacterial overgrowth in a 1:1:1 ratio to receive mosapride, rifaximin or a combination of both for two weeks. The hydrogen-methane glucose breath test and symptom questionnaire were surveyed before and after the treatment. Primary outcome was eradication rate of small intestinal bacterial overgrowth. Secondary outcomes were changes in the gas concentration, symptoms and safety. RESULTS: the eradication rates were 17.2 % (5/29) for mosapride, 32.1 % (9/28) for rifaximin, and 34.6 % (9/26) for the combined groups, with no significant differences among the three groups. Total hydrogen concentration during the glucose breath test significantly decreased in the rifaximin group (p = 0.001). Total methane concentration significantly decreased in the rifaximin and combined groups (p = 0.005). Significant symptomatic improvements were observed in chest and abdominal discomfort with mosapride, in flatulence with rifaximin, and in chest discomfort with the combined groups. Adverse events were similar between the groups. CONCLUSIONS: rifaximin has an advantage of reducing gas, whereas mosapride can help to decrease breath hydrogen concentration. Certain intestinal symptoms improved with mosapride alone or combined with rifaximin.

Effect of prophylactic clip application for the prevention of postpolypectomy bleeding of large pedunculated colonic polyps: a randomized controlled trial.

BACKGROUND AND AIMS: Prophylactic application of a hemoclip has been suggested as an alternative to the use of an endoloop for the prevention of postpolypectomy bleeding (PPB) when resecting large, pedunculated colorectal polyps. Therefore, this multicenter, randomized controlled trial investigated the efficacy of prophylactic hemoclip application to reduce PPB during the resection of large pedunculated polyps. METHODS: Large pedunculated polyps (≥10 mm in head diameter) were eligible for inclusion. Polyps were randomized into a study arm (where clips were applied before resection) and a control arm (without pretreatment). The primary outcome was the rate of PPB in each group. PPB included immediate PPB (IPPB) and delayed PPB (DPPB). IPPB was defined as blood oozing (≥1 minute) or active spurting occurring immediately after polyp resection. DPPB was defined as rectal bleeding, occurring after completion of the colonoscopy. RESULTS: In total, 238 polyps from 204 patients were randomized into the clip arm (119 polyps) or the control arm (119 polyps). Overall bleeding adverse events were observed in 20 cases (IPPB, 16; DPPB, 4). The rate of overall PPB, IPPB, and DPPB was 8.4%, 6.7%, and 1.7%, respectively, for all polyps. The rate of overall PPB (clip 4.2% vs control 12.6%, P = .033) and IPPB (clip 2.5% vs control 10.9%, P = .017) was significantly lower in the clip arm than the control arm. CONCLUSIONS: Prophylactic clipping before resecting large pedunculated polyps can reduce overall PPB and IPPB compared with no prior treatment. Therefore, prophylactic clipping may be considered before resection of large pedunculated polyps. (Clinical trial registration number: NCT02156193.).

Unilateral versus bilateral Y-type stent-in-stent metal stent insertions in inoperable malignant hilar biliary strictures: A multicenter retrospective study.

BACKGROUND: To date, there is controversy regarding unilateral versus bilateral stent placement in patients with malignant hilar biliary strictures (MHBSs). The aim of this study was to compare the clinical outcomes and complications of unilateral and bilateral (stent-in-stent method) stent placements for these patients. METHODS: We conducted a multicenter retrospective analysis of patients with inoperable MHBS who underwent endoscopic self-expandable metal stent (SEMS) placement from January 2009 to December 2019. Two groups classified according to the stent procedure method were compared for demographic, procedural, and postprocedure factors. Survival analysis for patency loss and overall survival was also conducted. RESULTS: A total of 236 subjects were included. A superior technical success rate was found in the unilateral stent group (98.8% vs. 82.5%, P < 0.001), whereas the clinical success rate was higher in the bilateral group (85.7% vs. 70.5%, P = 0.028). There was no significant difference with respect to complications or patency loss, and the bilateral group had better overall survival (P < 0.01). In the Cox proportional hazard model, MHBSs from lymph node compression were associated with a higher risk of death (HR = 9.803, P = 0.003). In contrast, bilateral SEMS insertion showed reduced postprocedural mortality (HR = 0.316, P = 0.001). CONCLUSIONS: Y-type stent-in-stent bilateral SEMSs are technically difficult but demonstrated more favorable overall survival for palliative bile drainage of inoperable MHBS patients compared to unilateral insertions.

Hemosuccus pancreaticus with a variant of separate orifices in the duodenal papilla treated with a covered self-expandable metal stent.

This is the peculiar report of endoscopic treatment with metal stent in a patient with hemosuccus pancreaticus by pancreatic cancer, who refused surgical treatment due to old age and patient's intention. Reports of endoscopic hemostasis in hemosuccus pancreaticus are very rare. Moreover our case showed variant location of separate orifices in major duodenal papilla. This rare variant should be handled with importance because late recognition could result in unnecessary manipulation and treatment failure.

The characteristics of small intestinal bacterial overgrowth in patients with gallstone diseases.

BACKGROUND AND AIM: Small intestinal bacterial overgrowth (SIBO) might be prevalent in gallstone disease, including cases involving cholecystectomy and gallstones. The study aimed to investigate the prevalence and characteristics of SIBO in patients with gallstone disease. METHODS: This prospective study evaluated 265 patients for gallstone disease (200, gallstones; 65, cholecystectomy) and 39 healthy controls. Laboratory data, abdominal ultrasonography, and glucose breath test (GBT) with bowel symptom questionnaire were performed. RESULTS: Glucose breath test positivity (+) in patients with gallstone disease (36.6%) was significantly higher than that in controls (20.5%). GBT+ in the gallstone group (40.5%) was significantly higher than that in the control or cholecystectomy group (24.6%). The number of patients with gallstone, tend to be higher in the GBT (H2 )+, (CH4 )+, and (mixed)+ groups (56 [28.0%], 11 [5.5%], and 14 [7.00%]), respectively. Gallbladder disease was independently associated with fatty liver, metabolic syndrome, and SIBO. Of 97 GBT+ patients, 70 (72.1%), 12 (12.4%), and 15 (15.5%) were in the GBT (H2 )+, (CH4 )+, and (mixed)+ groups, respectively. GBT (CH4 )+ or GBT (mixed)+ were significantly associated with the gallstone group compared with the cholecystectomy group. The GBT (mixed)+ group had higher total symptom scores than the GBT- group for hard stool and urgency tendency, or the GBT (H2 )+ group in hard stool and loose stool tendency. Gallstone was the only independent factor for SIBO in patients with gallstone diseases. CONCLUSIONS: Small intestinal bacterial overgrowth is common among patients with gallstone. Especially, CH4 or mixed-type SIBO seems to be prevalent and to worsen intestinal symptoms.

90Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin's lymphoma.

Despite significant advances in the treatment of Hodgkin's lymphoma (HL), a significant proportion of patients will not respond or will subsequently relapse. We identified CD25, the IL-2 receptor alpha subunit, as a favorable target for systemic radioimmunotherapy of HL. The scientific basis for the clinical trial was that, although most normal cells with exception of Treg cells do not express CD25, it is expressed by a minority of Reed-Sternberg cells and by most polyclonal T cells rosetting around Reed-Sternberg cells. Forty-six patients with refractory and relapsed HL were evaluated with up to seven i.v. infusions of the radiolabeled anti-CD25 antibody (90)Y-daclizumab. (90)Y provides strong ß emissions that kill tumor cells at a distance by a crossfire effect. In 46 evaluable HL patients treated with (90)Y-daclizumab there were 14 complete responses and nine partial responses; 14 patients had stable disease, and nine progressed. Responses were observed both in patients whose Reed-Sternberg cells expressed CD25 and in those whose neoplastic cells were CD25(-) provided that associated rosetting T cells expressed CD25. As assessed using phosphorylated H2AX (γ-H2AX) as a bioindicator of the effects of radiation exposure, predominantly nonmalignant cells in the tumor microenvironment manifested DNA damage, as reflected by increased expression of γ-H2AX. Toxicities were transient bone-marrow suppression and myelodysplastic syndrome in six patients who had not been evaluated with bone-marrow karyotype analyses before therapy. In conclusion, repeated (90)Y-daclizumab infusions directed predominantly toward nonmalignant T cells rosetting around Reed-Sternberg cells provided meaningful therapy for select HL patients.

The association between a positive lactulose methane breath test and rectocele in constipated patients.

OBJECTIVES: Rectocele with constipation might be related to methane (CH4) producing intestinal bacteria. We investigated the breath CH4 levels and the clinical characteristics of colorectal motility in constipated patients with rectocele. METHODS: A database of consecutive female outpatients was reviewed for the evaluation of constipation according to the Rome III criteria. The patients underwent the lactulose CH4 breath test (LMBT), colon marker study, anorectal manometry, defecography and bowel symptom questionnaire. The profiles of the lactulose breath test (LBT) in 33 patients with rectocele (with size ≥ 2 cm) and 26 patients with functional constipation (FC) were compared with the breath test results of 30 healthy control subjects. RESULTS: The mean size of rectocele was 3.52 ± 1.06 cm. The rate of a positive LMBT (LMBT+) was significantly higher in patients with rectocele (33.3%) than in those with FC (23.1%) or healthy controls (6.7%) (p = 0.04). Breath CH4 concentration was positively correlated with rectosigmoid colon transit time in rectocele patients (γ = 0.481, p < 0.01). A maximum high pressure zone pressure > 155 mmHg was a significant independent factor of LMBT+ in rectocele patients (OR = 8.93, 95% CI = 1.14-71.4, p = 0.04). CONCLUSIONS: LMBT+ might be expected in constipated patients with rectocele. Moreover, increased rectosigmoid colonic transit or high anorectal pressure might be associated with CH4 breath levels. Breath CH4 could be an important therapeutic target for managing constipated patients with rectocele.

Discordance in lymphoid tissue recovery following stem cell transplantation in rhesus macaques: an in vivo imaging study.

Ionizing irradiation is used routinely to induce myeloablation and immunosuppression. However, it has not been possible to evaluate the extent of ablation without invasive biopsy. For lymphoid recovery, peripheral blood (PB) lymphocytes (PBLs) have been used for analysis, but they represent <2% of cells in lymphoid tissues (LTs). Using a combination of single-photon emission computed tomography imaging and a radiotracer ((99m)Tc-labeled rhesus immunoglobulin G1 anti-CD4R1 (Fab')2), we sequentially imaged CD4(+) cell recovery in rhesus macaques following total body irradiation (TBI) and reinfusion of vector-transduced, autologous CD34(+) cells. Our results present for the first time a sequential, real-time, noninvasive method to evaluate CD4(+) cell recovery. Importantly, despite myeloablation of circulating leukocytes following TBI, total depletion of CD4(+) lymphocytes in LTs such as the spleen is not achieved. The impact of TBI on LTs and PBLs is discordant, in which as few as 32.4% of CD4(+) cells were depleted from the spleen. In addition, despite full lymphocyte recovery in the spleen and PB, lymph nodes have suboptimal recovery. This highlights concerns about residual disease, endogenous contributions to recovery, and residual LT damage following ionizing irradiation. Such methodologies also have direct application to immunosuppressive therapy and other immunosuppressive disorders, such as those associated with viral monitoring.

Artifacts of the common bile duct caused by duodenal metallic hemoclip on magnetic resonance cholangiopancreatography.

Magnetic resonance cholangiography (MRCP) is a non-invasive and highly sensitive diagnostic modality for pancreatobiliay lesions, which can replace the role of Endoscopic Retrograde Cholangiopancreatography (ERCP). However metallic components can lead to misinterpretation of the images of MRCP. Here we present a case of a duodenal metal hemoclip, producing a susceptibility artifact of pathologic lesion in the common bile duct on MRCP.

A recurrence of pancreatic non-functioning neuroendocrine tumor mimicking splenosis.

There have been a number of case reports where intra-abdominal splenosis or accessory spleens have mimicked metastatic cancer. However, to the best of our knowledge, this to be the first report of a Tc-99m phytate scintigraphy study in English literature showed the uptake in the metastatic mass of pancreatic NET which had been resected for 19 years ago. Although a nuclear scintigraphy is useful method to differentiate between abdominal splenosis and metastatic cancer, the histopathological confirmation should be considered.

Breath hydrogen and methane are associated with intestinal symptoms in patients with chronic pancreatitis.

BACKGROUNDS: The bacterial overgrowth might be associated with chronic pancreatitis. This study was to evaluate the prevalence and characteristics of small intestinal bacterial overgrowth (SIBO) in patients with chronic pancreatitis. METHODS: 36 patients with chronic pancreatitis and 49 healthy controls undergoing the hydrogen (H2)-methane (CH4) lactulose breath test (LBT) were reviewed. The LBT positivity (+) indicating the presence of SIBO, gas types, bowel symptom questionnaire, laboratory and radiologic results were surveyed. The LBT+ was (1) an increase in the breath H2 (≥20 ppm) or CH4 (≥10 ppm) over the baseline or (2) a baseline H2 (≥20 ppm) or CH4 (≥10 ppm) within 90 min after lactulose load. RESULTS: LBT+ was significantly higher in the patients (17/36) than in controls (13/49) (47.2% vs. 26.5%, P < 0.05). During LBT, the H2 levels between 0 and 105 min were significantly higher in patients than in controls. Among LBT+ patients, 11 (64.7%), 1 (5.9%), 5 (29.4%) were in the LBT (H2)+, (CH4)+, (mixed)+ groups, respectively. The LBT+ group had significantly higher scores of flatus than those of the LBT- group. Considering the subtypes of LBT, the LBT (mixed)+ group had higher symptom scores of significance or tendency in hard stool, strain, urgency, and flatus than LBT- group The laboratory and radiologic features were not significantly different between LBT+ and LBT- groups. CONCLUSIONS: SIBO is common in patients in chronic pancreatitis. Especially, excretions of mixed H2 and CH4 appear to be related with deterioration of intestinal symptoms.

Impact of C4'-O-Alkyl Linker on in Vivo Pharmacokinetics of Near-Infrared Cyanine/Monoclonal Antibody Conjugates.

Near-infrared (NIR) fluorophores have several advantages over visible-light fluorophores, including superior tissue penetration and lower autofluorescence. We recently accessed a new class of readily synthesized NIR cyanines containing a novel C4'-O-alkyl linker, which provides both high chemical stability and excellent optical properties. In this study, we provide the first in vivo analysis of this new class of compounds, represented by the tetrasulfonate FNIR-774 (Frederick NIR 774). Monoclonal antibody (mAb) conjugates of FNIR-774 were compared to conjugates of the commercially available dye (IRDye800CW (IR800)), one of the most widely used NIR fluorophores for clinical translation. Both dyes were conjugated to panitumumab (pan) or cetuximab (cet) with ratios of 1:2 or 1:5. Conjugates of both dyes demonstrated similar quenching capacity, stability, and brightness in target cells in vitro. In contrast, in vivo imaging in mice showed different pharmacokinetics between pan-FNIR-774 (1:5) and pan-IR800 (1:5), or cet-FNIR-774 (1:5) and cet-IR800 (1:5). Particularly at the higher labeling density, mAb-FNIR-774 conjugates showed superior specific accumulation in tumors compared with mAb-IR800 conjugates. Thus, FNIR-774 conjugates showed superior in vivo pharmacokinetics compared with IR800 conjugates, independent of the mAb. These results suggest that FNIR-774 is a promising fluorescent probe for NIR optical imaging.

Glypican-3 targeted human heavy chain antibody as a drug carrier for hepatocellular carcinoma therapy.

Glypican-3 (GPC3) represents an attractive target for hepatocellular carcinoma (HCC) therapy because it is highly expressed in HCC but not in adult normal tissue. Recently, high affinity anti-GPC3 antibodies have been developed; however, full antibodies may not penetrate evenly into tumor parenchyma, reducing their effectiveness. In this study, we compared a whole IgG antibody, anti-GPC3 YP7, with an anti-GPC3 human heavy chain antibody, HN3, with regard to their relative therapeutic effects. Both YP7 and HN3 bound to GPC3-positive A431/G1 cells and were internalized by the cells by in vitro evaluation with (125)I- and (111)In-radiolabeling antibodies. In vivo biodistribution and tumor accumulation was performed with (111)In-labeled antibodies, and intratumoral microdistribution was evaluated using fluorescently labeled antibodies (IR700). HN3 showed similar high tumor accumulation but superior homogeneity within the tumor compared with YP7. Using the same IR700 conjugated antibodies photoimmunotherapy (PIT) was performed in vitro and in a tumor-bearing mouse model in vivo. PIT with IR700-HN3 and IR700-YP7 demonstrated that comparable results could be achieved despite of low reaccumulation 24 h after the first NIR light exposure. These results indicated that a heavy-chain antibody, HN3, showed more favorable characteristics than YP7, a conventional IgG, as a therapeutic antibody platform for designing molecularly targeted agents against HCC.

Clinical significance of the glucose breath test in patients with inflammatory bowel disease.

BACKGROUND AND AIM: Small intestinal bacterial overgrowth which has recently been diagnosed with the glucose breath test is characterized by excessive colonic bacteria in the small bowel, and results in gastrointestinal symptoms that mimic symptoms of inflammatory bowel disease. This study aimed to estimate the positivity of the glucose breath test and investigate its clinical role in inflammatory bowel disease. METHODS: Patients aged > 18 years with inflammatory bowel disease were enrolled. All patients completed symptom questionnaires. Fecal calprotectin level was measured to evaluate the disease activity. Thirty historical healthy controls were used to determine normal glucose breath test values. RESULTS: A total of 107 patients, 64 with ulcerative colitis and 43 with Crohn's disease, were included. Twenty-two patients (20.6%) were positive for the glucose breath test (30.2%, Crohn's disease; 14.1%, ulcerative colitis). Positive rate of the glucose breath test was significantly higher in patients with Crohn's disease than in healthy controls (30.2% vs 6.7%, P=0.014). Bloating, flatus, and satiety were higher in glucose breath test-positive patients than glucose breath test-negative patients (P=0.021, 0.014, and 0.049, respectively). The positivity was not correlated with the fecal calprotectin level. CONCLUSIONS: The positive rate of the glucose breath test was higher in patients with inflammatory bowel disease, especially Crohn's disease than in healthy controls; gastrointestinal symptoms of patients with inflammatory bowel disease were correlated with this positivity. Glucose breath test can be used to manage intestinal symptoms of patients with inflammatory bowel disease.

(99m)Tc-labeled porphyrin-lipid nanovesicles.

Porphyrin-lipid nanovesicles (PLN) have been developed with intrinsic capabilities as activatable multimodal photonic contrast agents. Radiolabeling of PLN encapsulating drugs could eventually be able to provide quantitative in vivo information for diagnosing and treating diseases. In this study, we developed (99m)Tc-labeled porphyrin-lipid nanovesicles ((99m)Tc-PLN) as a cargo-encapsulated formulation without significant impact on liposome integrity and encapsulation stability. 50 mM calcein was encapsulated into PLN by probe sonication. The size of the PLN was about 150 nm. The PLN were then reacted with (99m)Tc using SnCl2 dissolved in 1 mM HCl as a reducing agent and incubated for 10 min at 22 °C. The radiolabeling efficiency and stability of (99m)Tc-PLN were evaluated by instant thin-layer chromatography and low-pressure liquid chromatography (LPLC). (99m)Tc labeling was successful with a >92% labeling efficiency. LPLC showed that the liposomal elution peaks of the porphyrin-lipid and the calcein overlapped with the radioactivity elution peak of (99m)Tc-labeled PLN. The (99m)Tc-labeling procedure did not change the size of PLN. Encapsulated calcein remained inert inside PLN. Thus, this work lays out a simple and effective radiolabeling method using SnCl2 in HCl in the preparation of (99m)Tc-PLN.

Ezetimibe prevents the formation of oestrogen-induced cholesterol gallstones in mice.

BACKGROUND: Oestrogen is an important risk factor for cholesterol cholelithiasis not only in women of childbearing age taking oral contraceptives and postmenopausal women undergoing hormone replacement therapy, but also in male patients receiving oestrogen therapy for prostatic cancer. In women, hormonal changes occurring during pregnancy markedly increase the risk of developing gallstones. We investigated whether the potent cholesterol absorption inhibitor ezetimibe could prevent the formation of oestrogen-induced cholesterol gallstones in mice. DESIGN: Following ovariectomy, female AKR mice were implanted subcutaneously with pellets releasing 17ß-estradiol at 6 µg/day and fed a lithogenic diet supplemented with ezetimibe in doses of 0 or 8 mg/kg/day for 8 weeks. Cholesterol crystallization and gallstone prevalence, lipid concentrations and composition in bile, and biliary lipid output were analysed by physical-chemical methods. Intestinal cholesterol absorption efficiency was determined by faecal dual-isotope ratio methods. RESULTS: Ezetimibe inhibited intestinal cholesterol absorption, while significantly reducing hepatic secretion of biliary cholesterol. Consequently, bile was desaturated through the formation of numerous unsaturated micelles and gallstones were prevented by ezetimibe in mice exposed to high doses of oestrogen and fed the lithogenic diet. Ezetimibe did not influence mRNA levels of the classical oestrogen receptors α (ERα) and ERß, as well as a novel oestrogen receptor the G protein-coupled receptor 30 (GPR30) in the liver. CONCLUSIONS: Ezetimibe protects against the oestrogen-mediated lithogenic actions on gallstone formation in mice. Our finding may provide an efficacious novel strategy for the prevention of cholesterol gallstones in high-risk subjects, especially those exposed to high levels of oestrogen.

Immuno-PET imaging of tumor endothelial marker 8 (TEM8).

Tumor endothelial marker 8 (TEM8) is a cell surface receptor that is highly expressed in a variety of human tumors and promotes tumor angiogenesis and cell growth. Antibodies targeting TEM8 block tumor angiogenesis in a manner distinct from the VEGF receptor pathway. Development of a TEM8 imaging agent could aid in patient selection for specific antiangiogenic therapies and for response monitoring. In these studies, L2, a therapeutic anti-TEM8 monoclonal IgG antibody (L2mAb), was labeled with (89)Zr and evaluated in vitro and in vivo in TEM8 expressing cells and mouse xenografts (NCI-H460, DLD-1) as a potential TEM8 immuno-PET imaging agent. (89)Zr-df-L2mAb was synthesized using a desferioxamine-L2mAb conjugate (df-L2mAb); (125)I-L2mAb was labeled directly. In vitro binding studies were performed using human derived cell lines with high, moderate, and low/undetectable TEM8 expression. (89)Zr-df-L2mAb in vitro autoradiography studies and CD31 IHC staining were performed with cryosections from human tumor xenografts (NCI-H460, DLD-1, MKN-45, U87-MG, T-47D, and A-431). Confirmatory TEM8 Western blots were performed with the same tumor types and cells. (89)Zr-df-L2mAb biodistribution and PET imaging studies were performed in NCI-H460 and DLD-1 xenografts in nude mice. (125)I-L2mAb and (89)Zr-df-L2mAb exhibited specific and high affinity binding to TEM8 that was consistent with TEM8 expression levels. In NCI-H460 and DLD-1 mouse xenografts nontarget tissue uptake of (89)Zr-df-L2mAb was similar; the liver and spleen exhibited the highest uptake at all time points. (89)Zr-L2mAb was highly retained in NCI-H460 tumors with <10% losses from day 1 to day 3 with the highest tumor to muscle ratios (T:M) occurring at day 3. DLD-1 tumors exhibited similar pharmacokinetics, but tumor uptake and T:M ratios were reduced ∼2-fold in comparison to NCI-H460 at all time points. NCI-H460 and DLD-1 tumors were easily visualized in PET imaging studies despite low in vitro TEM8 expression in DLD-1 cells indicating that in vivo expression might be higher in DLD-1 tumors. From in vitro autoradiography studies (89)Zr-df-L2mAb specific binding was found in 6 tumor types (U87-MG, NCI-H460, T-47D MKN-45, A-431, and DLD-1) which highly correlated to vessel density (CD31 IHC). Westerns blots confirmed the presence of TEM8 in the 6 tumor types but found undetectable TEM8 levels in DLD-1 and MKN-45 cells. This data would indicate that TEM8 is associated with the tumor vasculature rather than the tumor tissue, thus explaining the increased TEM8 expression in DLD-1 tumors compared to DLD-1 cell cultures. (89)Zr-df-L2mAb specifically targeted TEM8 in vitro and in vivo although the in vitro expression was not necessarily predictive of in vivo expression which seemed to be associated with the tumor vasculature. In mouse models, (89)Zr-df-L2mAb tumor uptakes and T:M ratios were sufficient for visualization during PET imaging. These results would suggest that a TEM8 targeted PET imaging agent, such as (89)Zr-df-L2mAb, may have potential clinical, diagnostic, and prognostic applications by providing a quantitative measure of tumor angiogenesis and patient selection for future TEM8 directed therapies.

Cholesterol cholelithiasis in pregnant women: pathogenesis, prevention and treatment.

Epidemiological and clinical studies have found that gallstone prevalence is twice as high in women as in men at all ages in every population studied. Hormonal changes occurring during pregnancy put women at higher risk. The incidence rates of biliary sludge (a precursor to gallstones) and gallstones are up to 30 and 12%, respectively, during pregnancy and postpartum, and 1-3% of pregnant women undergo cholecystectomy due to clinical symptoms or complications within the first year postpartum. Increased estrogen levels during pregnancy induce significant metabolic changes in the hepatobiliary system, including the formation of cholesterol-supersaturated bile and sluggish gallbladder motility, two factors enhancing cholelithogenesis. The therapeutic approaches are conservative during pregnancy because of the controversial frequency of biliary disorders. In the majority of pregnant women, biliary sludge and gallstones tend to dissolve spontaneously after parturition. In some situations, however, the conditions persist and require costly therapeutic interventions. When necessary, invasive procedures such as laparoscopic cholecystectomy are relatively well tolerated, preferably during the second trimester of pregnancy or postpartum. Although laparoscopic operation is recommended for its safety, the use of drugs such as ursodeoxycholic acid (UDCA) and the novel lipid-lowering compound, ezetimibe would also be considered. In this paper, we systematically review the incidence and natural history of pregnancy-related biliary sludge and gallstone formation and carefully discuss the molecular mechanisms underlying the lithogenic effect of estrogen on gallstone formation during pregnancy. We also summarize recent progress in the necessary strategies recommended for the prevention and the treatment of gallstones in pregnant women.

Effect of Trimebutine and Rifaximin on Breath Hydrogen and Methane by Glucose Breath Test in Patients With Functional Bloating: A Randomized Double-blind Clinical Trial.

Background/Aims: Drugs that stabilize intestinal motility may improve the efficacy of nonabsorbable antibiotics, such as rifaximin, against small intestinal bacterial overgrowth (SIBO). We compared the efficacy of rifaximin alone with that of its combination with trimebutine maleate against SIBO. Methods: We performed a randomized double-blind placebo-controlled trial (https://cris.nih.go.kr, no. KCT0004836) that included patients with functional bloating, no constipation, and SIBO using the hydrogen (H2)-methane (CH4) glucose breath test (GBT). Patients were randomized into 2 groups in a 1:1 ratio, namely rifaximin (1200 mg/day) + trimebutine maleate (600 mg/day) group and rifaximin + placebo group, for 2 weeks. Patients completed a symptom questionnaire and underwent a GBT at baseline and at 1 month after treatment withdrawal. The primary outcome was SIBO eradication. The secondary outcomes included changes in the concentrations of exhaled gases, symptoms, and presence of adverse events. Results: The complete eradication rate of SIBO was 35.9% (14/39) in the rifaximin group, and 34.1% (14/41) in the combined group with no significant differences. In both groups, no significant differences were observed in GBT profiles before and after the treatment, respectively. However total breath H2 and CH4 concentration were conspicuously decreased in the combined group after treatment. The combined group exhibited substantial relief of bloating. The adverse events were similar in the 2 groups. Conclusion: While the combination therapy was not superior over rifaximin alone for SIBO eradication, it improves the symptom of bloating with numerically reducing the concentration of breath H2/CH4.

Tracking incidentally discovered pancreatic cysts smaller than 30 mm: Natural course and predictors of malignancy.

BACKGROUND AND AIMS: The aim of this study was to assess the natural course and predictors of malignancy in incidentally detected small pancreatic cysts (PCs). METHOD: We retrospectively included patients with PCs smaller than 30 mm followed up with the same cross-sectional imaging modality at least 12 months apart between January 2010 and December 2019 in three academic institutions. Cyst growth, pancreatic cancer incidence, and associated factors associated with pancreatic cancer were analyzed. RESULTS: A total of 1109 patients were followed up for a median of 34 months (range, 12‒118 months). Cyst growth and rapid cyst growth (≥ 5 mm/2 years) during follow-up were observed in 20.7% and 8.3%, respectively, both with higher rates for 15‒30 mm sized PCs. Eight patients were diagnosed with pancreatic cancer. The standardized incidence ratio for pancreatic cancer in small PCs was calculated as 5.2 [95% Confidence interval (CI): 1.3‒20.5].  The development of pancreatic cancer was associated with rapid growth [hazard ratio (HR): 8.1, 95% CI: 1.5‒43.4, p = 0.015] and newly developed worrisome features (HR: 11.7, 95% CI: 1.7‒79.6, p = 0.012) in competing risk analysis. CONCLUSIONS: One-fifth of small incidentally detected PCs increased in size. Rapid growth and newly developed worrisome features were predictors of malignancy.