Ductal hamartoma of the pancreas: A clinicopathologic study.

BACKGROUND: Benign ductular proliferative lesions that resemble hepatic von-Meyenburg Complexes(VMC)/bile duct hamartomas have been noted to occur in the pancreas, but their incidence, clinicopathologic features and pathogenesis remains unknown. We present herein 3 patients that presented as cysts and call them pancreatic ductal hamartomas (PDH). METHODS: Three cases of PDH were identified form a multi-institutional collaborative group, and their clinicopathological were reviewed. In addition, we also examined 115 consecutive pancreatic resections at our institutions for the presence of incidental PDHs. RESULTS: The lesions were detected in each case during imaging for abdominal symptoms or grossing. The clinical suspicion was intra-ductal pancreatic mucinous cystic neoplasm (IPMN) in each case that led to pancreatectomy. The cyst fluid CEA was elevated in 2 of the patients tested. The patient age and gender were 73/M (case1), 68/F (case2) and 73/M (case3). In case1 besides the larger cystic lesion, numerous tiny lesions (0.1-0.3 cm) were seen throughout the pancreas. In case2 this was the only lesion, while in case3 there was another gastric-type IPMN with high-grade dysplasia. PDH were identified in 5(4.3%) of 115 consecutive pancreatectomy specimens. The PDHs measured 0.1-2.3 cm, and the histology is characterized by proliferation of irregular ductal structures lined by bland flattened to low columnar epithelium, variable cystic change and inspissated luminal secretions. The lining epithelium varied from non-mucinous pancreatico-biliary type to mucinous gastric foveolar-type, with occasional squamous metaplasia. SUMMARY: PDH are seen in 4.5% of all pancreatectomy specimens and detected incidentally, but occasionally may become large and/or cystic enough leading to pancreatectomy. Their relationship to pancreatic carcinoma or IPMN remains currently unknown.

Polypoid Kaposi Sarcoma Involving the Lower Gastrointestinal Tract: Clinicopathologic Study of 15 Cases.

CONTEXT.­: Gastrointestinal manifestations of Kaposi sarcoma are rare but may cause morbidity. Lower gastrointestinal involvement is particularly rare and lesions may resemble conventional bowel polyps. OBJECTIVE.­: To study 15 patients who presented with lower gastrointestinal tract Kaposi sarcoma with polypoid architecture. DESIGN.­: The surgical pathology files of the departments of pathology at multiple institutions were searched for cases of Kaposi sarcoma forming polyps in the lower gastrointestinal tract (jejunum, colon, rectum); 15 cases with such features were identified. Clinicopathologic information was extracted from the medical record and documented by reviewing individual hematoxylin-eosin stained slides. RESULTS.­: The patients were 13 men and 2 women aged 26-80 years (median = 44 years). Gastrointestinal tract involvement was multifocal in 11 cases and unifocal in 4. The tumors involved the rectum, recto-sigmoid junction, cecum, ascending colon, transverse colon, and descending colon and presented as polypoid lesions measuring 0.2-2.1 cm. Six patients had upper gastrointestinal tract involvement in addition to lower gastrointestinal lesions. Histologically the tumors were characterized in 6 cases by a dense spindle cell proliferation in the lamina propria; however, the remaining cases showed only a subtle fascicular spindle cell proliferation in the lamina propria that did not form an expansile mass. CONCLUSIONS.­: Biopsies of gastrointestinal polyps showing absence of the common features of hyperplastic or adenomatous polyps, particularly in immunocompromised patients, should be carefully examined for the presence of a stromal spindle cell proliferation. Use of immunohistochemical stains, particularly human herpesvirus-8, can help in establishing the correct diagnosis.

Spleen shear wave elastography measurements do not correlate with histological grading of liver fibrosis in Fontan physiology: a preliminary investigation.

BACKGROUND: Elevated spleen stiffness may be seen in patients with portal hypertension due to cirrhosis. In patients with Fontan physiology, elevated liver stiffness has been shown to correlate poorly with liver fibrosis. It is unknown whether spleen stiffness may instead serve as a surrogate marker of liver fibrosis in these patients. OBJECTIVE: To compare spleen stiffness determined by shear wave elastography (SWE) with histological findings of an ultrasound-guided liver biopsy in patients who had undergone Fontan palliation as a potential surrogate for Fontan-associated liver disease. MATERIALS AND METHODS: This was an IRB-approved single-center, retrospective study. Patients with Fontan palliation who had undergone both a spleen SWE study and a percutaneous liver biopsy between 2016 and 2020 were included. Biopsy, performed during cardiac catheterization, within 3 months of the SWE was required for inclusion. Using Kruskal-Wallis tests, spleen stiffness was compared with three liver biopsy scoring methods: Ishak, METAVIR, and congestive hepatic fibrosis score (CHFS). When available, Pearson's correlation was also used to compare collagen deposition determined using Sirius Red stain (%SR) with SWE values. A P-value < 0.05 was considered statistically significant. RESULTS: Twenty-two patients (15 males) were included in the study, with a median age of 17 years (IQR is 14.8-20.5 years; age range: 7 years to 30.2 years). The median spleen stiffness was 2.94 m/s (IQR: 2.57-3.61 m/s; range: 1.48-4.27 m/s). The median Fontan pressure was 11 mm Hg (IQR: 10-13.3 mm Hg; range: 7-19 mm Hg) obtained within a median of 10 days (IQR: 1-41 days) of SWE. Splenic stiffness did not correlate with the extent of fibrosis determined by histology (all P > 0.05). There was also no statistically significant correlation between the %SR staining and SWE-determined spleen stiffness (Pearson's correlation of 0.165, P = 0.59, n = 13). CONCLUSIONS: In this preliminary study, SWE spleen stiffness values did not correlate with biopsy-determined scoring of liver fibrosis in patients with Fontan physiology.

Clinicopathologic Characterization of Invasive Fungal Intestinal Infections in Pediatric Patients.

BACKGROUND: Invasive fungal intestinal infections are rare in pediatric patients with limited studies reported to date. METHODS: Retrospective study of invasive intestinal fungal infections in pediatric patients. For fungal specification, 18S rRNA gene PCR was performed using formalin-fixed paraffin-embedded tissues. RESULTS: A total of 19 cases from 18 patients were included (13 males, 72%) with a median age of 20 days (8 days-14 years). About 13 patients (72%) presented within 67 days of birth and 11 patients (61%) were premature and 14 patients (78%) had a significant medical history. The most common location was the jejunum/ileum (56%) followed by the right colon and terminal ileum (22%). In 10 patients, the fungal elements were seen in the mucosa with 3 extending into the submucosa, and only 3 patients showed full-thickness involvement. Tissue necrosis and angioinvasion were seen in 13 (72%) and 8 (44%) patients, respectively. Morphologically, organisms consistent with Candida spp. were seen in 17 patients and with a mucoraceous mold in 1 patient. A 18S rRNA gene sequencing performed in 18 cases identified Candida dubliniensis in 16 cases and Candida spp. in 2 cases. During the study follow-up period, 56% of the patients died. CONCLUSION: In our experience, most cases were due to Candida spp. and predominantly in premature infants and associated with poor outcomes.

Breastfeeding in women with HIV infection: A qualitative study of barriers and facilitators.

BACKGROUND: Until recently, breastfeeding has been contraindicated for women living with HIV (WHIV) in the U.S. However, given the numerous health benefits of breastfeeding, recommendations have changed to support parental choice to breastfeed through shared decision-making. Although specific guidelines for managing the care of these women and their infants are not yet available, various approaches have been successful without infants acquiring HIV from their virologically suppressed mothers, thus, establishing breastfeeding as a viable option for the rising number of interested WHIV. This descriptive qualitative study aimed to identify factors influencing infant feeding choices decisions among WHIV in a multiethnic and multicultural population. METHODS AND FINDINGS: A qualitative description design was used. WHIV who had given birth within 6 months were recruited using purposeful sampling. Data were collected using a semistructured interview guide in the participant's preferred language. Content analysis was used, and barriers and facilitators were separated and used to generate the themes and categories. In total, 20 participants were interviewed, and from these interviews, 11 barriers and 14 facilitators that influenced the decision to breastfeed were identified. Major barriers were related to the interference with daily activities, fear of transmission, lack of a standardized approach to education, and maternal concerns. Key facilitators included the benefits and advantages of breastmilk, access to more scientific research information on breastfeeding in the context of HIV, advice from a lactation consultant, emotional connection and attachment with the child, support from family and partners, empowering and supporting autonomy and decision-making about infant feeding, providing feeding choices, access to the lived experiences of women who have successfully breastfed their infants, and collaborative relationship with the physician and other healthcare providers. CONCLUSION: The study identified barriers and facilitators to breastfeeding among WHIV that may influence their infant feeding decision-making process. More research is needed to guide the standardization of institutional policies and develop strategies to support breastfeeding in this population.

The Effect of Photodynamic Therapy on Enterococcus spp. and Its Application in Dentistry: A Scoping Review.

Enterococci spp. are Gram-positive bacteria that cause mild to severe infections, many associated with the oral cavity, such as periapical infections and healthcare-associated infections (HAIs). Many of these infections become serious diseases that are difficult to resolve, specifically when multidrug-resistant (MDR) strains cause them. In recent years, the number of MDR strains of Enterococcus spp. has increased significantly. This increased prevalence of MDR strains produces significant pressure to generate more antimicrobial therapies, but there is a decline in the production of new antibiotics, driving the development of complementary therapies, such as photodynamic therapy (PDT). PDT combines a photosensitizer agent (PS), light, and oxygen to cause photooxidative stress in bacterial cells. PDT can eradicate Enterococcus spp. contaminations, improve the classic cleaning processes, and eradicate the bacteria in dental pieces. PDT's effectiveness can be improved with nanoparticles that function as carriers. Our work aims to describe the advances in PDT against Enterococcus spp. as a complement to antibiotic therapy, focusing on infections by Enterococcus faecium and Enterococcus faecalis, dental hygiene, and using nanoparticles to improve the antimicrobial effect. A systematic bibliographic search without a meta-analysis was conducted on various databases, using inclusion and exclusion criteria to identify the most relevant research. Of the 193 non-redundant articles found, 65 were selected for a systematic review, from which a summary table was created and a manual description was made. Photodynamic therapy for treating E. faecium and E. faecalis is a widely studied area, with promising results concerning bactericidal effectiveness and reductions in biofilm formation, particularly in regard to dental hygiene. Because most of the studies were conducted in vitro or ex vivo, the results indicated that there were not sufficient data to initiate clinical trials for safety and efficacy studies on humans.

Clinicopathologic Features of Gastrointestinal Tract Langerhans Cell Histiocytosis.

Gastrointestinal (GI) tract involvement by Langerhans cell histiocytosis (LCH) is rare and its clinicopathologic characteristics have only been described in case reports and small series. We reviewed hematoxylin and eosin and CD1a, S100, and Langerin immunohistochemical-stained slides from 47 patients with well-documented demographic and clinical findings. Our cases included 8 children and 39 adults, with a mean follow-up of 63 months. All pediatric patients had concurrent multisystem LCH, presented with GI symptoms, and showed nonpolypoid lesions. Seven (88%) showed multifocal GI disease, including 5 with multiple GI organ involvement. All sampled lesions from children exhibited infiltrative growth. More than half had died of the disease or manifested persistent LCH at last follow-up. Twenty-five of 39 (64%) adults had LCH involving only the GI tract (single system), with the remaining 14 (36%) exhibiting multisystem disease. Adult single-system GI LCH was typically encountered incidentally on screening/surveillance endoscopy (72%). Most exhibited isolated colorectal involvement (88%) as a solitary polyp (92%), with a well-demarcated/noninfiltrative growth pattern (70%), and excellent prognosis (100%). In comparison, adult patients with multisystem LCH more frequently presented with GI symptoms (92%, P < .001), noncolorectal GI site involvement (50%, P = .02), multifocal GI lesions (43%, P = .005), nonpolypoid lesions (71%, P < .001), infiltrative histologic growth pattern (78%, P = .04), and persistent disease (57%, P < .001). Adult patients with multisystem LCH appear to exhibit similar clinicopathologic features to those of pediatric patients. These results demonstrated that adults with single-system LCH involving the GI tract have an excellent prognosis, whereas multisystem LCH occurring at any age carries an unfavorable prognosis. High-risk features of GI LCH include pediatric age, GI symptomatology, noncolorectal GI involvement, multifocal GI disease, nonpolypoid lesions, and infiltrative growth pattern.

Immune checkpoint markers and tumour mutation burden in Wilms tumour: a study of 59 cases.

Wilms tumour (WT) is the most common renal tumour in children, and studies of immune checkpoint inhibitors (ICIs) treatment and markers are limited in number. In this study we investigated the ICIs' related immune landscape by examining the expression of PD-L1, PD-1, CD8 and DNA mismatch repair (MMR) proteins by immunohistochemistry (IHC), tumour mutation burden (TMB), and correlations with histology and clinical outcome. Positive PD-L1 (SP263) expression was defined as modified combined positive score (CPS) ≥1. A total of 59 WTs (from 2000 to 2017), including eight (14.0%) with anaplasia, from 46 patients were analysed (45 primary and 14 metastatic). Thirteen WTs (13/59, 22%) were positive for PD-L1 (8 primary, 5 metastatic; CPS 1.11-3.42). Positive PD-L1 expression was associated with diffuse anaplasia (p<0.05) and significantly shorter progression-free survival (p<0.05) among WTs with favourable histology (n=39). CD8+ lymphocytes were present in all analysed WTs. A subset of CD8+ cells co-expressed PD-1, which was associated with favourable histology and treatment. MMR IHC stains identified two (2/18, 11%) WTs with isolated PMS2 loss. All six WTs analysed for TMB showed low mutation burden. We found CD8+ lymphocytes in all analysed WTs and identified a fraction of WT (17.8% of primary and 35.8% of metastatic) with positive PD-L1 CPS, suggesting potential response to ICIs in some patients.

Extraskeletal Ewing Sarcoma of the Gastrointestinal and Hepatobiliary Tract: Deceptive Immunophenotype Commonly Leads to Misdiagnosis.

Ewing sarcoma (ES) is an uncommon mesenchymal neoplasm that typically develops as a bone mass, although up to 30% arise in extraskeletal sites. ES of the gastrointestinal (GI) and hepatobiliary tract is rare and may be misdiagnosed as other, more common neoplasms that occur in these sites. However, the correct classification of extraskeletal ES is important for timely clinical management and prognostication. We reviewed our experience of ES in the GI and hepatobiliary tract in order to further highlight the clinicopathologic features of these neoplasms and document the potential for misdiagnosis in this setting. The archives and consultation files of 6 academic institutions were retrospectively queried for cases of ES occurring in the GI and hepatobiliary tract. The histologic slides and ancillary studies were reviewed and clinical data were retrieved for each case through the electronic medical records, when available. Twenty-three patients with ES in the GI and/or hepatobiliary tract were identified from 2000 to 2022. Of these, 11 were women and 12 were men with a median age of 38 years (range, 2 to 64). Tumor locations included the pancreas (n=5), liver (n=2), stomach (n=3), colorectum (n=3), and small intestine (n=5), as well as tumors involving multiple organs, pelvis and retroperitoneum (n=5). Tumor size varied between 2 cm and 18 cm. Twenty were primary and 3 were metastases. Of the 23 cases, only 17% were initially diagnosed as ES. The most common misdiagnoses involved various forms of neuroendocrine neoplasia due to expression of synaptophysin and other neuroendocrine markers (22%). A wide variety of diagnoses including GI stromal tumor was considered due to aberrant CD117 expression (4%). The diagnosis of ES was ultimately confirmed by detection of the EWSR1 rearrangement in 22 cases. The remaining case was diagnosed using traditional immunohistochemistry. Follow-up information was available in 20 cases, with follow-up time varying between 2 and 256 months. Six patients with follow-up died of disease between 6 and 60 months following initial presentation. Our data indicate ES in the GI and hepatobiliary tract is commonly misdiagnosed leading to a delay in therapy. In light of the attendant therapeutic and prognostic implications, ES should be considered in the differential diagnosis of any GI or hepatobiliary tumor with epithelioid and/or small round cell morphology.

Liver manifestation of patients with celiac disease: A single center experience.

OBJECTIVES: Characterize the clinicopathologic features of liver biopsies from patients with celiac disease (CD). METHODS: Single center, retrospective search for liver biopsies from patients with CD. RESULTS: 36 unique patients were included, median age of 46 years (range: 2-75), including 5 pediatric patients, with an overall female predominance (25, 69 %) but in in children a male predominance was seen (p = 0.023). Most cases (75 %) had an underlying condition including autoimmune hepatitis (AIH) (11 %), AIH/primary biliary cholangitis (PBC) overlap (3 %) and PBC (3 %). The median body mass index was 28, with 4 (11 %) underweight and 22 (61 %) overweight/obese patients. The most common histologic pattern was steatosis (18, 50 %), considered severe in 5 (14 %) and in 7 (19 %) regarded as steatohepatitis. The other histologic patterns included a nonspecific portal and/or lobular inflammation ("celiac hepatitis") in 9 cases (25 %), autoimmune hepatitis (3, 8 %), chronic cholestatic pattern (3, 8 %), chronic hepatitis (1, 3 %), acute lobular hepatitis (1, 3 %) and stablished cirrhosis (1, 3 %). Additionally, 2 of the cases with steatosis show cirrhosis. CONCLUSIONS: The biopsy findings from patients with CD are heterogenous and in most represent a concomitant underlying disease, particularly metabolic dysfunction-associated steatotic liver disease. Additionally, CD injury should remain in the differential diagnosis in liver biopsies with a nonspecific portal and/or lobular inflammation.

Characteristics, clinical laboratory, histopathology, and outcomes of glycogenic hepatopathy in children.

Introduction: Glycogenic hepatopathy (GH) is a rare complication of type I diabetes mellitus (DM1), resulting in abnormal deposition of glycogen in the liver due to poor glycemic control. Clinical characteristics and natural history of GH are not completely understood in children. In this study, we investigated clinical, biochemical, histologic parameters and outcomes in children with GH. Method: This was a retrospective review of patients less than 18 years old diagnosed with GH and DM. GH was confirmed on liver biopsy. Medical records were reviewed for clinical presentation, laboratory tests, and clinical outcomes. Liver biopsy findings were reviewed by a pediatric pathologist (I. A. G.). Results: Nine children were diagnosed with GH and type 1 DM. The median age at diagnosis of GH was 16 (IQR 14.5-17) years. Duration of diagnosis of DM until GH diagnosis was 7 (IQR 5-11) years. The median frequency of diabetic ketoacidosis before GH diagnosis was three times (IQR 2-5.25). Peak Aspartate transaminase (AST) and Alanine transaminase (ALT) ranged from 115 to 797, and 83-389 units/L, respectively. Only two children had mild fibrosis. Seven of nine had steatosis without steatohepatitis. There was no correlation between glycosylated hemoglobin (HbA1c), or other laboratory tests and liver fibrosis on biopsy. HbA1c was 11.2 (IQR 10.2-12.8) at GH diagnosis and 9.8 (IQR 9.5-10.8) with normalization of liver enzymes. Conclusion: GH appears to be related to poor glycemic control in teenagers with long-term diabetes. GH presents with high to very high aminotransferase especially AST > ALT and resolves with modestly improved glycemic control. Diffuse hepatocyte swelling, steatosis, minimal fibrosis without hepatocyte ballooning or lobular inflammation are most common histological features.

Granulomas in Pediatric Liver Biopsies: Single Center Experience.

BACKGROUND: Granulomas in pediatric liver biopsies (GPLB) are rare with the largest pediatric cohort reported over 25 years ago. METHODS: Single-center retrospective study of GPLB. RESULTS: Seventeen liver biopsies from 16 patients with granulomas were identified (9 boys, 56%) with a median age of 13 years (range: 1-18) for which the most common indication was the presence of a nodule/mass (47%). Significant comorbidities were seen in 13 patients (81%) and included: liver transplant (25%), history of a neoplasm (25%), autoimmune hepatitis (6%), Crohn disease (6%), bipolar disorder (6%), severe combined immunodeficiency (6%), and sickle cell disease (6%). Eleven patients were taking multiple medications at the time of biopsy. Granulomas were more commonly pan-acinar (11 cases) followed by subcapsular (4 cases), portal (1 case), and periportal (1 case). Necrosis was seen in 10 cases (59%). GMS stain was positive in 2 cases for Histoplasma-like yeast; microbiological cultures were negative in all cases (no: 4). A 18S and 16S rRNA gene sequencing performed in 15 cases revealed only 1 with a pathogenic microorganism, Mycobacterium angelicum. CONCLUSION: In our experience, GPLB are heterogenous with only 3 cases having an identifiable infectious etiology and many of the remaining cases being associated to multiple medications, suggesting drug-induced liver injury as possible etiology.

Incidental findings during donor liver assessment: Single center experience.

Intraoperative consultation of donor liver is an important part of transplant evaluation and determination of liver eligibility. In this study, we describe incidental pathologic findings discovered during the pretransplant evaluation of liver donors in our Institution from 1/2010 to 12/2022. During this 13-year period 369 intraoperative consultations from 262 liver donors were performed. Of those cases, incidental findings were identified in 22 cases (5.9 %) from 19 donors (7.3 %); two donors had more than one lesion. The median age of this subset of patients was 53 years (range: 18-70) and females predominated (63 %). Sixteen of the donors had abnormal findings in the liver: 6 bile duct hamartoma (BDH), 5 hyalinized nodule with Histoplasma capsulatum, 5 focal nodular hyperplasia (FNH), 2 bile duct adenomas (BDA), 1 biliary cyst and 1 hemangioma. One donor had both FNH and a BDH. One BDH and 1 BDA case was misdiagnosed as malignancy during the frozen section evaluation. Three donors had extrahepatic pathologies: a pancreatic tail schwannoma, a low-grade appendiceal mucinous neoplasm, and a lymph node with metastatic endometrial endometrioid adenocarcinoma. Of the 19 livers, the final organ disposition was available for 9: 6 were transplanted (67 %) and 3 were discarded (33 %). Two of the 3 discarded organs were misdiagnosed BDH and BDA cases, and one was incorrectly reported as having 90 % microvesicular steatosis during the frozen assessment. We present the clinicopathologic characteristics of liver donors with incidental findings during the pre-transplant evaluation which could lead to unwarranted graft dismissal if misdiagnosed. Additionally, incidental fungal infections can have implications for immunosuppressive therapy and the decision to use or reject the graft.

Gastrointestinal Tract Granular Cell Tumor in the Pediatric Population: A Multicenter Experience.

BACKGROUND: Pediatric granular cell tumors (GCT) involving the gastrointestinal tract (GIT) are rare with limited case report/series reported to date. METHODS: Multicenter retrospective study of pediatric GIT GCT. RESULTS: A total of 10 cases were included in the study with a median age of 13.5 years (range: 7-18 years) and were predominantly female patients (60%). In half of the patients no significant medical history was present with the remaining 5 having Crohn disease (10%), eosinophilic esophagitis (EoE) (10%), Crohn disease and EoE (10%), growth hormone deficiency (10%), and aplasia cutis congenita (10%). The GCT median size was 1.3 cm (range: 1-1.6 cm) and were more commonly located in the esophagus (70%) followed by the stomach (20%) and rectum (10%). Most of the cases showed round/polygonal tumor cells with abundant granular cytoplasm, and none of the cases had nuclear atypia, increased mitotic activity, or tumor cell necrosis. None of our cases received specific therapy for GCT other than clinical follow-up, and none of the patients had evidence of local recurrence or metastatic disease. CONCLUSION: We present our multicenter experience with GIT GCT, all cases had a benign course. Interestingly, 4 of the esophageal GCT cases (including 2 patients with EoE) showed an eosinophil-rich esophagitis in the underlying mucosa.

Clinicopathologic Characterization of Lymphocytic Colitis in the Pediatric Population.

BACKGROUND: Lymphocytic colitis (LC) in the pediatric population has been associated with immune dysregulation. METHODS: Single-center retrospective study of pediatric LC. RESULTS: 50 patients (35 female, 70%) with a median age of 12 years at diagnosis (interquartile range: 5.7-15.8) of LC were identified. At presentation, 11 patients (22%) had malnutrition, 16 (32%) had a known underlying immune dysregulation, 4 (8%) had celiac disease (CD), and none had a diagnosis of inflammatory bowel disease. The most common medications prior to diagnosis were non-steroidal anti-inflammatory drugs, proton pump inhibitor, and selective serotonin reuptake inhibitors (10% each). Colonic biopsies showed a median number of intraepithelial lymphocytes (IELs)/100 epithelial cells of 48 (range: 25-85), and only 10% of cases had neutrophilic cryptitis. Upper gastrointestinal tract findings included lymphocytic esophagitis (4%), and duodenal IELs without and with villous blunting (9% each) (n: 47). Ten patients (23%) had increased IELs in the terminal ileum (n: 43). Treatments including 5-ASA, budesonide, prednisone, and gluten-free diet improved symptoms in <50% of patients (n: 42), and all follow-up colonoscopies showed persistent LC (n: 13). CONCLUSION: Our study supports the association of LC with immune-mediated conditions, most commonly celiac disease. Symptomatic improvement was seen in <50% of patients with none of the patients with repeat colonoscopy showing histologic improvement.

Solid-Tubulocystic carcinoma: A new variant of intrahepatic cholangiocarcinoma.

A new variant of intrahepatic cholangiocarcinoma (iCCA) has been recognized in recent years presenting predominantly as a large hepatic mass in young woman with the characteristic expression of inhibin by immunohistochemistry. This variant iCCA was originally termed as cholangioblastic variant of iCCA, and subsequently proposed to be renamed as inhibin-positive hepatic carcinoma or solid-tubulocystic variant of iCCA to better reflect its immunohistochemical profile or morphologic spectrum. The tumor histologically is composed of small to medium sized cells with scant to moderate amount of eosinophilic cytoplasm heterogeneously organized in solid, tubular, and cystic growth patterns. The tumor cells are positive for biliary markers, inhibin and albumin, and have a novel recurrent gene fusion, NIPBL::NACC1. Awareness of this new iCCA variant and its clinicopathologic features will aid in the diagnostic work-up and avoid confusion with other primary and metastatic hepatic neoplasms.

Brain MRI segmentation of Zika-Exposed normocephalic infants shows smaller amygdala volumes.

BACKGROUND: Infants with congenital Zika syndrome (CZS) are known to exhibit characteristic brain abnormalities. However, the brain anatomy of Zika virus (ZIKV)-exposed infants, born to ZIKV-positive pregnant mothers, who have normal-appearing head characteristics at birth, has not been evaluated in detail. The aim of this prospective study is, therefore, to compare the cortical and subcortical brain structural volume measures of ZIKV-exposed normocephalic infants to age-matched healthy controls. METHODS AND FINDINGS: We acquired T2-MRI of the whole brain of 18 ZIKV-exposed infants and 8 normal controls on a 3T MRI scanner. The MR images were auto-segmented into eight tissue types and anatomical regions including the white matter, cortical grey matter, deep nuclear grey matter, corticospinal fluid, amygdala, hippocampus, cerebellum, and brainstem. We determined the volumes of these regions and calculated the total intracranial volume (TICV) and head circumference (HC). We compared these measurements between the two groups, controlling for infant age at scan, by first comparing results for all subjects in each group and secondly performing a subgroup analysis for subjects below 8 weeks of postnatal age at scan. ZIKV-exposed infants demonstrated a significant decrease in amygdala volume compared to the control group in both the group and subgroup comparisons (p<0.05, corrected for multiple comparisons using FDR). No significant volume differences were observed in TICV, HC, or any specific brain tissue structures or regions. Study limitations include small sample size, which was due to abrupt cessation of extramural funding as the ZIKV epidemic waned. CONCLUSION: ZIKV-exposed infants exhibited smaller volumes in the amygdala, a brain region primarily involved in emotional and behavioral processing. This brain MRI finding may lead to poorer behavioral outcomes and warrants long-term monitoring of pediatric cases of infants with gestational exposure to Zika virus as well as other neurotropic viruses.

Clinicopathologic characterization of gallbladder graft-versus-host disease in the pediatric population.

Graft-versus-host disease (GVHD) is a common and important complication of allogenic hematopoietic cell transplantation. The cardinal histologic feature of GVHD in the gastrointestinal tract is the presence of apoptotic bodies. To date, no study has evaluated the pathologic characteristics of gallbladder GVHD (GB-GVHD). In this study, we sought to describe their clinicopathologic features in a cohort of pediatric patients and compared them to a control group composed of 10 and 15 recent cases of acute and chronic cholecystitis, respectively. A total of 6 GB-GVHD cases were included, 5 cholecystectomies and 1 autopsy case(s), presenting in 2 boys and 4 girls, with a mean age of 6.7 years (1.5-18.6). The median days post-transplant to presentation was 261 (40-699), and all cases had GVHD involving other organs. GB-GVHD compared to the control groups was significantly associated with a younger age (P = .019), presence of apoptotic bodies and higher number of apoptotic bodies in 10 continuous mucosal folds and in 100 and 500 epithelial cells (all P < .001), and increased number of intraepithelial lymphocytes per 100 epithelial cells (P < .001). All patients were treated for GVHD with half of them achieving treatment response. Besides the autopsy case, all patients are alive with a median follow-up time of 45 months (4-212). The cause of death for the autopsy case was sepsis due to Pseudomonas aeruginosa. In our experience, the presence of both increased apoptotic bodies and intraepithelial lymphocytes in the gallbladder of hematopoietic cell transplantation patients should raise concern for GB-GVHD.

Synergistic effect of Ru(II)-based type II photodynamic therapy with cefotaxime on clinical isolates of ESBL-producing Klebsiella pneumoniae.

Multidrug-resistant bacteria, such as ESBL producing-Klebsiella pneumoniae, have increased substantially, encouraging the development of complementary therapies such as photodynamic inactivation (PDI). PDI uses photosensitizer (PS) compounds that kill bacteria using light to produce reactive oxygen species. We test Ru-based PS to inhibit K. pneumoniae and advance in the characterization of the mode of action. The PDI activity of PSRu-L2, and PSRu-L3, was determined by serial micro dilutions exposing K. pneumoniae to 0.612 J/cm 2 of light dose. PS interaction with cefotaxime was determined on a collection of 118 clinical isolates of K. pneumoniae. To characterize the mode of action of PDI, the bacterial response to oxidative stress was measured by RT-qPCR. Also, the cytotoxicity on mammalian cells was assessed by trypan blue exclusion. Over clinical isolates, the compounds are bactericidal, at doses of 8 µg/mL PSRu-L2 and 4 µg/mL PSRu-L3, inhibit bacterial growth by 3 log10 (>99.9%) with a lethality of 30 min. A remarkable synergistic effect of the PSRu-L2 and PSRu-L3 compounds with cefotaxime increased the bactericidal effect in a subpopulation of 66 ESBL-clinical isolates to > 6 log10 with an FIC-value of 0.16 and 0.17, respectively. The bacterial transcription response suggests that the mode of action occurs through Type II oxidative stress. The upregulation of the extracytoplasmic virulence factors mrkD, magA, and rmpA accompanied this response. Also, the compounds show little or no toxicity in vitro on HEp-2 and HEK293T cells. Through the type II effect, PSs compounds are bactericidal, synergistic on K. pneumoniae, and have low cytotoxicity in mammals.