Gastric IgG4-Related Autoimmune Fibrosclerosing Pseudotumour: A Novel Location

We describe the first reported case of an IgG4-related autoimmune fibrosclerosing pseudotumour located in the stomach of a 75-year old woman presenting with weight loss and vomiting. A lesion was detected in the gastric body at endoscopy. Subsequent characterisation by CT was suggestive of a gastrointestinal stromal tumour. Following laparoscopic resection, the patient recovered uneventfully. Histological examination of the resected specimen revealed an IgG4-related fibrosclerosing pseudotumour, a novel location for this histopathological entity

A comparison of transhepatic versus transperitoneal cholecystostomy for acute calculous cholecystitis: a 5-year experience.

Percutaneous cholecystostomy is a treatment for acute calculous cholecystitis used in patients where surgery is high risk or challenging either to allow for surgical optimisation or as definitive treatment. In this case series we compare the outcomes of a transhepatic versus transperitoneal approach in patients undergoing percutaneous cholecystostomy for acute calculous cholecystitis. A retrospective review of patients from 2014 to 2019 was conducted and included demographics, percutaneous cholecystostomy route, complications and outcome. Fifty-one patients were included. Percutaneous cholecystostomy was placed transhepatically in 15 cases; transperitoneal in 30 cases; 6 cases had undetermined route. The transhepatic cohort had 43.5% fewer readmissions due to biliary sepsis, 32.5% fewer drain-related complications, and were less likely to require further treatment (32.5% reduction) compared to the transperitoneal cohort. In our experience, the transhepatic route is preferred due to fewer complications, fewer readmissions and a reduction in the need for further treatment

Juvenile polyposis syndrome affecting the stomach: A case report

<p>Abstract</p> <p>Introduction</p> <p>Juvenile polyposis syndrome(JPS) is a rare autosomal dominant inherited condition. Hamartomatous polyps can affect the entire gastrointestinal tract but usually predominate in the colon. In this case report we present an unusual case of JPS that presented with massive gastric polyposis requiring a total gastrectomy.</p> <p>Case presentation</p> <p>A 51-year-old man presented with symptoms of gastric outlet obstruction and upper gastrointestinal bleeding. Gastroscopy showed massive gastric polyposis with a large antral polyp that had prolapsed through the pylorus causing gastric outlet obstruction. Initially endoscopic polypectomy was performed, but due to progressive symptoms a total gastrectomy was then performed. Histology confirmed massive gastric juvenile polyposis.</p> <p>Conclusion</p> <p>Massive gastric polyposis is an uncommon manifestation of juvenile polyposis syndrome. This case illustrates important principles in managing this condition.</p

Ceftriaxone-Resistant Salmonella Infection Acquired by a Child from Cattle

Background The emergence of resistance to antimicrobial agents within the salmonellae is a worldwide problem that has been associated with the use of antibiotics in livestock. Resistance to ceftriaxone and the fluoroquinolones, which are used to treat invasive salmonella infections, is rare in the United States. We analyzed the molecular characteristics of a ceftriaxone-resistant strain of Salmonella enterica serotype typhimurium isolated from a 12-year-old boy with fever, abdominal pain, and diarrhea. Methods We used pulsed-field gel electrophoresis and analysis of plasmids and β-lactamases to compare the ceftriaxone-resistant S. enterica serotype typhimurium from the child with four isolates of this strain obtained from cattle during a local outbreak of salmonellosis. Results The ceftriaxone-resistant isolate from the child was indistinguishable from one of the isolates from cattle, which was also resistant to ceftriaxone. Both ceftriaxone-resistant isolates were resistant to 13 antimicrobial agents; all but one of the resistance determinants were on a conjugative plasmid of 160 kb that encoded the functional group 1 β-lactamase CMY-2. Both ceftriaxone-resistant isolates were closely related to the three other salmonella isolates obtained from cattle, all of which were susceptible to ceftriaxone. Conclusions This study provides additional evidence that antibiotic-resistant strains of salmonella in the United States evolve primarily in livestock. Resistance to ceftriaxone, the drug of choice for invasive salmonella disease, is a public health concern, especially with respect to children, since fluoroquinolones, which can also be used to treat this disease, are not approved for use in children

Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma

Abstract: The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy

A comparative analysis of whole genome sequencing of esophageal adenocarcinoma pre- and post-chemotherapy

The scientific community has avoided using tissue samples from patients that have been exposed to systemic chemotherapy to infer the genomic landscape of a given cancer. Esophageal adenocarcinoma is a heterogeneous, chemoresistant tumor for which the availability and size of pretreatment endoscopic samples are limiting. This study compares whole-genome sequencing data obtained from chemo-naive and chemo-treated samples. The quality of whole-genomic sequencing data is comparable across all samples regardless of chemotherapy status. Inclusion of samples collected post-chemotherapy increased the proportion of late-stage tumors. When comparing matched pre- and post-chemotherapy samples from 10 cases, the mutational signatures, copy number, and SNV mutational profiles reflect the expected heterogeneity in this disease. Analysis of SNVs in relation to allele-specific copy-number changes pinpoints the common ancestor to a point prior to chemotherapy. For cases in which pre- and post-chemotherapy samples do show substantial differences, the timing of the divergence is near-synchronous with endoreduplication. Comparison across a large prospective cohort (62 treatment-naive, 58 chemotherapy-treated samples) reveals no significant differences in the overall mutation rate, mutation signatures, specific recurrent point mutations, or copy-number events in respect to chemotherapy status. In conclusion, whole-genome sequencing of samples obtained following neoadjuvant chemotherapy is representative of the genomic landscape of esophageal adenocarcinoma. Excluding these samples reduces the material available for cataloging and introduces a bias toward the earlier stages of cancer.This study was partly funded by a project grant from Cancer Research UK. R.C.F. is funded by an NIHR Professorship and receives core funding from the Medical Research Council and infrastructure support from the Biomedical Research Centre and the Experimental Cancer Medicine Centre. We acknowledge the support of The University of Cambridge, Cancer Research UK (C14303/A17197) and Hutchison Whampoa Limited

Immunotherapy of colorectal cancer using bispecific antibodies

In clinical trials a low affinity monclonal antibody (17.1A) to Ep-CAM, a tumour associated antigen found on colorectal cancer cells, has demonstrated a significant survival advantage as adjuvant therapy in Duke’s C colorectal carcinoma. Bispecific antibodies (BsAbb) are single antibody molecules engineered with two different antigen specificities. In this work I have constructed a F(ab’)2 BsAb from a higher (40x greater than 17.1A) affinity antibody (323A3) to Ep-CAM. The other arm of the BsAb binds to CD3 on cytotoxic T Lymphcyte (CTL), thus targeting them to kill tumour cells. Using CD3 allows recruitment of a large range of CTLs irrespective of their antigen specificity. In vitro this BsAb, 323A3xCD3, successfully killed human colorectal cancer cells (HT-29) and transfected murine tumours bearing human Ep-CAM. Using the same BsAb, successful immunotherapy in vivo has been achieved in an immunocompetent mouse tumour model. Groups of C57/Blk mice were given B16C215 syngeneic tumour cells expressing human E-CAM on their surface. To model minimal residual disease tumour was given intravenously and animals were either called on day 21 and pulmonary surface tumour was given intravenously and animals were either culled on day 21 and pulmonary surface metastases counted, or survival recorded. To model local growth, tumour was given subcutaneously and tumour appearance, growth survival were recorded. In both these models BsAb was given for 10 days starting 24 hours after tumour administration. With intravenous tumour, BsAb treatment reduced mean pulmonary metastases: [4.6 cf. 208.5 (control); p&lt;0.001] and prolonged survival [median 56 days cf. 32 (control); p&lt;0.01]; low affinity 17.1A IgG and high affinity 323A3 IgG had no significant effect. In the local tumour model, 323A3xCD3 therapy retarded tumour appearance [median 25.5 days cf. 16 (control); p&lt;0.0001] and growth [mean volume 51.6mm3 cf. 1036mm3 (control) on day 18; p&lt;0.01]; and prolonged survival [median 37 days cf. 23 (control); p&lt;0.0001]; 17.1A IgG and 323A3 IgG had no significant effect.</p

Immunotherapy of colorectal cancer using bispecific antibodies

EThOS - Electronic Theses Online ServiceGBUnited Kingdo