Iowa Digestive Disease Center

PurposeTo elucidate the clinical significance of peritoneal washing cytology (PWC) in patients with resectable biliary tract cancer (BTC).MethodsClinical data of patients with BTC, who received PWC at curative intent surgery from March 2009 to December 2021, were retrospectively analyzed. Eligible patients were stratified into two groups according to positive or negative PWC. Recurrence-free survival and overall survival were compared between the two groups. Independent factors associated with positive PWC were investigated using multivariate analysis.ResultsAmong the 284 patients analyzed, all 53 patients with ampullary carcinoma showed negative PWC and these patients were excluded. Among the remaining eligible 231 patients, 41 patients had intrahepatic cholangiocarcinoma, 55 had gall bladder carcinoma, 72 had hilar cholangiocarcinoma, and 63 had distal cholangiocarcinoma. Eleven (4.8%) patients had positive PWC, and 220 (95.2%) had negative PWC. The median recurrence-free survival in the positive and negative PWC groups were 12.0 vs. 60.7 months (p = 0.005); the median overall survival times were 17.0 vs. 60.6 months (p = 0.008), respectively. Multivariate analysis revealed that serum carbohydrate antigen 19–9 level over 80 U/mL and multiple lymph node metastasis were independently associated with positive PWC (odds ratio [OR]: 5.84, p = 0.031; OR: 5.28, p = 0.021, respectively).ConclusionPatients with positive PWC exhibited earlier recurrence and shorter survival times compared with those with negative PWC.

Background Protracted conflict has destroyed Syria's health system with severe impacts on the diagnosis and treatment of chronic and high-cost diseases including cancer. Here, we review the type and (where possible) the stage of cancers diagnosed in a pathology laboratory serving Northwest Syria. Methods We retrospectively reviewed all pathology reports which reported a diagnosis of cancer from a pathology department in Northwest Syria from January to December 2020. Results A total of 397 new cancers were diagnosed during 2020 of which 191 were among males (48.1%) and 20 cases were in children aged 17 years or under (5%). The most common cancer in men was bladder cancer (15.7%) and skin cancers (14.7%) followed by cancers in the lymph nodes (includes primary and secondary; 9.9%.) In women, breast cancer (38.3%) followed by skin cancer skin (9.7%) and uterine cancer (8.7%) was the most common. The overall proportion of cancer diagnoses were breast cancer (20.2%), skin cancer (12.1%), cancer affecting lymph nodes (8.8%), and urinary bladder (8.3%) and colorectal cancer (7.3%). Discussion This preliminary analysis is the first report of cancer types and demographics in areas outside of government control in Syria since the onset of the conflict. Despite limitations, it presents some indication of the burden of oncological diagnoses in this area. Further research which aims to describe and address the burden of cancer on populations under ongoing conflict and humanitarian crises remains essential, especially in Northwest Syria given ongoing attacks and severe underfunding. There is a particular need to investigate how best to apply interventions and support health systems and cancer services within conflict settings. More support and resources need to be allocated to cancer centers with long-term health partnership models. The underresourced and understaffed conditions of the hospital are significant limits to a more detailed report.

Background Protracted conflict has destroyed Syria's health system with severe impacts on the diagnosis and treatment of chronic and high-cost diseases including cancer. Here, we review the type and (where possible) the stage of cancers diagnosed in a pathology laboratory serving Northwest Syria.Methods We retrospectively reviewed all pathology reports which reported a diagnosis of cancer from a pathology department in Northwest Syria from January to December 2020.Results A total of 397 new cancers were diagnosed during 2020 of which 191 were among males (48.1%) and 20 cases were in children aged 17 years or under (5%). The most common cancer in men was bladder cancer (15.7%) and skin cancers (14.7%) followed by cancers in the lymph nodes (includes primary and secondary; 9.9%.) In women, breast cancer (38.3%) followed by skin cancer skin (9.7%) and uterine cancer (8.7%) was the most common. The overall proportion of cancer diagnoses were breast cancer (20.2%), skin cancer (12.1%), cancer affecting lymph nodes (8.8%), and urinary bladder (8.3%) and colorectal cancer (7.3%).Discussion This preliminary analysis is the first report of cancer types and demographics in areas outside of government control in Syria since the onset of the conflict. Despite limitations, it presents some indication of the burden of oncological diagnoses in this area. Further research which aims to describe and address the burden of cancer on populations under ongoing conflict and humanitarian crises remains essential, especially in Northwest Syria given ongoing attacks and severe underfunding. There is a particular need to investigate how best to apply interventions and support health systems and cancer services within conflict settings. More support and resources need to be allocated to cancer centers with long-term health partnership models. The underresourced and understaffed conditions of the hospital are significant limits to a more detailed report.

Introduction: Glepaglutide (ZP1848, glepaglutide1-39, Zealand Pharma) is a potent long-acting glucagon-like peptide-2 (GLP-2) analogue, comprised of 39 L-amino acids, and currently in phase-3 development for the treatment of short bowel syndrome Following subcutaneous (s.c.) injection of glepaglutide, 2 functionally active metabolites are formed (M1: glepaglutide1-34 and M2: glepaglutide1-35). As such, the clinical efficacy should be evaluated as the composite effect of all 3 compounds. A clinical phase-1 trial was conducted to characterize the pharmacokinetic (PK) and pharmacodynamics (PD) profile of glepaglutide in human. Methods: Fifteen healthy subjects (10 males), aged 25-58 years and with BMI of 20-30 kg/m2 received 10 mg glepaglutide s.c. once-weekly for 6 consecutive weeks. Blood samples were collected throughout the 6-week period. PK samples were analyzed for glepaglutide, M1 and M2 using a GLP-validated LC/MS/MS assay. The levels of citrulline, a circulating plasma PD marker for intestinal mucosal cell mass, were monitored. Compound exposure is expressed as area under the curve (AUC) and by the half-life (T1/2, both within the dosing interval). Values were computed for M1 and the constructed analyte “glepaglutide-total” = glepaglutide + M1 + M2, using a non-compartmental approach. As such “glepaglutide-total” represents the combined efficacy of glepaglutide and its 2 main metabolites. Safety and tolerability were assessed. Results: Glepaglutide, M1 and M2 were detected in plasma. All 3 compounds are potent GLP-2 receptor (GLP-2R) agonists. M1 was the main metabolite, accounting for 91% of “glepaglutide-total” based on AUC. The mean effective T1/2 for “glepaglutide-total” was 53±21 hours. Citrulline mean levels increased by 20±16 µM above baseline levels after 6 weeks dosing. Glepaglutide was well tolerated and no serious adverse events were reported. Conclusion: Following once-weekly s.c. dosing of 10 mg glepaglutide, the parent compound and 2 functionally active metabolites were detected. All 3 are potent agonists at the GLP-2R. Thus, the overall efficacy of glepaglutide is a composite of the 3 compounds with a T1/2 of 53 hours. Together data suggest 10 mg glepaglutide once-weekly could be an efficacious intestinotrophic therapy option.

症例は56歳の男性で，右下腹部痛を主訴に当院紹介となった．血液検査所見では炎症反応の上昇を認め，CTでは周囲脂肪織濃度上昇を伴う虫垂腫大に加え，虫垂根部の造影効果と周囲の囊胞状低吸収域を認めることから虫垂粘液産生腫瘍を否定できず，まずは抗菌薬にて保存的加療を行った．1か月後，炎症反応は改善したもののCTでも虫垂根部の造影効果と周囲の囊胞状低吸収域は変わらず，虫垂腫瘍の可能性を考えて待機的に腹腔鏡下回盲部切除術，D3郭清を行った．術中所見で虫垂の硬結，後腹膜への硬い癒着を認め，後腹膜下筋膜および右精巣動静脈の合併切除を行った．病理組織学的検査では黄色肉芽腫と診断され，悪性所見は認めなかった．以後，無症状，無再発で経過している．黄色肉芽腫性炎症は比較的まれな慢性炎症の1特殊型であり，臓器では胆囊や腎臓に好発とされる．虫垂に発生した例はまれであり，文献的考察を加えて報告する．

Purpose:To provide an outline of the timeline from acute care admission to inpatient rehabilitation facility discharge and describe the functional progress and tolerance of 2 individuals who were hospitalized but not intubated because of COVID-19.Method:Retrospective data were collected from the electronic medical record to describe the rehabilitation course of the first 2 consecutive patients admitted to the rehabilitation facility who were recovering from COVID-19. Both patients were octogenarian men who experienced functional decline while hospitalized for symptoms of COVID-19 and were recommended for further inpatient rehabilitation services. Progress during inpatient rehabilitation was tracked using the following outcome measures: Centers for Medicare & Medicaid Services Quality Indicators (QI), 6-Minute Walk Test, 10-Meter Walk Test, Timed Up and Go, and Berg Balance Scale.Results:Patient 1 had an 18-day acute care stay, a 13-day inpatient rehabilitation facility stay, and was discharged to home. Patient 2 had an interrupted 19-day acute care stay, a 15-day inpatient rehabilitation facility stay, and was discharged to a skilled nursing facility. Patient 1 improved 160.98 m in the 6-Minute Walk Test, 0.08 m/s in self-selected walking speed, and 85 points in the total Quality Indicators score. Patient 2 improved 115.22 m in the 6-Minute Walk Test, 0.14 m/s in self-selected walking speed, and 39 points in the total Quality Indicators score.Conclusion:The patients made clinically meaningful improvements in each outcome measure during their length of stay for inpatient rehabilitation. This reveals the positive rehabilitation potential of 2 older adult patients with COVID-19 and demonstrates the patients' ability to maintain inpatient rehabilitation facility level of activity. With individualized care and discharge planning, similar patients may make significant gains in function despite advanced age and comorbid conditions.

Introduction: Determining the best treatment for persistent diarrhea can be challenging due to the many potential etiologies. A test that measures multiple analytes may be useful to aid in diagnosis or to guide further testing in patients with persistent diarrhea. We investigated a new test panel that measures analytes associated with common causes of persistent diarrhea including pathogenic organisms and inflammatory as well as immunologic biomarkers. Additionally, a new serum assay of 7a-hydroxy-4-cholesten-3-one (7C4) by mass spectrometry for assessment of bile acid diarrhea was included. We conducted a prospective, multi-center study of this panel in a real world cohort of patients with persistent diarrhea to assess the ability of the test to differentiate causes of diarrhea. Methods: 395 evaluable adult patients with diarrhea of at least four weeks of duration provided both blood and stool specimens. Diagnoses were determined via standard of care methods at the enrolling sites by gastroenterologists blinded to the study test results. Patients’ specimens were analyzed by the test at a central laboratory using the manufacturer’s clinical cut-off for each analyte. The analytes tested are listed in Table 2. Results: Demographics are shown in Table 1. 177 (44.8%) patients tested positive in one or more of the tests as summarized by analyte in Table 2. The most commonly positive tests were 7C4, FCP, CRP and C. difficile (Table 2). Table 3 summarizes the performance of these analytes according to the most common clinical diagnoses made by a gastroenterologist blinded to the study test results. Conclusion: Use of a multi-test approach provided important information for diagnosis and/or guiding further investigation in patients with persistent diarrhea. E.g., the inflammatory markers FCP and CRP were one or both elevated in 28 IBS-D patients, suggesting that undetected inflammation was active in 15% of these patients. This result may be useful in prompting further search for inflammatory etiologies or co-morbidities in patients with apparently functional diarrhea. Similarly, 7C4 was positive in 22% of IBS-D patients and 19% of the undiagnosed, suggesting that bile acid malabsorption may play a role in many diarrhea patients. This panel approach of testing for common causes of persistent or chronic diarrhea may prove useful for early diagnosis of patients with diarrhea and in the management of patients with persistent symptoms.445_A Figure 1 No Caption available.445_B Figure 2 No Caption available.445_C Figure 3 No Caption available.

Polarized epithelial cells line diverse surfaces throughout the body forming selective barriers between the external environment and the internal milieu. To cross these epithelial barriers, large solutes and other cargoes must undergo transcytosis, an endocytic pathway unique to polarized cell types, and significant for the development of cell polarity, uptake of viral and bacterial pathogens, transepithelial signaling, and immunoglobulin transport. Here, we review recent advances in our knowledge of the transcytotic pathway for proteins and lipids. We also discuss briefly the promise of harnessing the molecules that undergo transcytosis as vehicles for clinical applications in drug delivery.

Probe-based confocal laser endomicroscopy (pCLE) is a promising new imaging technique enabling in-vivo analysis of tissues at the cellular level, in real time. The aim of the present study was to prospectively evaluate the feasibility and accuracy of indocyanine green-aided pCLE for the diagnosis of malignant liver nodules. From October 2014 to July 2015, liver specimens from 30 consecutive patients were analyzed ex vivo using pCLE directly after resection, with indocyanine green as contrast agent. The final diagnosis was obtained histologically, as per standard of care. In phase 1, a pathologist and a physicist established pCLE image criteria to distinguish normal parenchyma, malignant nodules, and metastases that had completely responded to chemotherapy. In phase 2, a pathologist and a surgeon reviewed selected videos retrospectively to assess the effectiveness of these. In phase 1, the healthy nodules were characterized by fluorescent hepatocytes with nonfluorescent nuclei and the malignant nodules were identified as strongly fluorescent, irregular cancer-cell clusters. The extracellular matrix was substantially less fluorescent compared with the cancerous clusters of cells. After chemotherapy, a very dense and strongly fluorescent fibrosis replaced tubular structures of cancerous cells. The retrospective evaluation in phase 2 resulted in 78 and 100% sensitivity, 100 and 89% specificity, 90 and 100% positive predictive value, and 90 and 100% negative predictive value for the surgeon and the pathologist, respectively, for the detection of malignant nodules. This series emphasized that characterization of liver metastases is possible with pCLE, with high performance results.