Impaired T-cell and antibody immunity after COVID-19 infection in chronically immunosuppressed transplant recipients

Assessment of T-cell immunity to the COVID-19 coronavirus requires reliable assays and is of great interest, given the uncertain longevity of the antibody response. Some recent reports have used immunodominant spike (S) antigenic peptides and anti-CD28 co-stimulation in varying combinations to assess T-cell immunity to SARS-CoV-2. These assays may cause T-cell hyperstimulation and could overestimate antiviral immunity in chronically immunosuppressed transplant recipients, who are predisposed to infections and vaccination failures. Here, we evaluate CD154-expressing T-cells induced by unselected S antigenic peptides in 204 subjects-103 COVID-19 patients and 101 healthy unexposed subjects. Subjects included 72 transplanted and 130 non-transplanted subjects. S-reactive CD154+T-cells co-express and can thus substitute for IFN{gamma} (n=3). Assay reproducibility in a variety of conditions was acceptable with coefficient of variation of 2-10.6%. S-reactive CD154+T-cell frequencies were a) higher in 42 healthy unexposed transplant recipients who were sampled pre-pandemic, compared with 59 healthy non-transplanted subjects (p=0.02), b) lower in Tr COVID-19 patients compared with healthy transplant patients (p<0.0001), c) lower in Tr patients with severe COVID-19 (p<0.0001), or COVID-19 requiring hospitalization (p<0.05), compared with healthy Tr recipients. S-reactive T-cells were not significantly different between the various COVID-19 disease categories in NT recipients. Among transplant recipients with COVID-19, cytomegalovirus co-infection occurred in 34%; further, CMV-specific T-cells (p<0.001) and incidence of anti-receptor-binding-domain IgG (p=0.011) were lower compared with non-transplanted COVID-19 patients. Healthy unexposed transplant recipients exhibit pre-existing T-cell immunity to SARS-CoV-2. COVID-19 infection leads to impaired T-cell and antibody responses to SARS-CoV-2 and increased risk of CMV co-infection in transplant recipients.

Pediatric liver transplantation for hepatocellular cancer and rare liver malignancies: US multicenter and single-center experience (1981-2015).

A tenth of all pediatric liver transplantations (LTs) are performed for unresectable liver malignancies, especially the more common hepatoblastoma (HBL). Less understood are outcomes after LT for the rare hepatocellular carcinoma, nonhepatoblastoma embryonal tumors (EMBs), and slow growing metastatic neuroendocrine tumors of childhood. Pediatric LT is increasingly performed for rare unresectable liver malignancies other than HBL. We performed a retrospective review of outcomes after LT for malignancy in the multicenter US Scientific Registry of Transplant Recipients (SRTR; n = 677; 1987-2015). We then reviewed the Children's Hospital of Pittsburgh (CHP; n = 74; 1981-2014) experience focusing on LT for unresectable hepatocellular cancer (HCC), EMBs, and metastatic liver tumors (METS). HBL was included to provide reference statistics. In the SRTR database, LT for HCC and HBL increased over time (P < 0.001). Compared with other malignancies, the 149 HCC cases received fewer segmental grafts (P < 0.001) and also experienced 10-year patient survival similar to 15,710 adult HCC LT recipients (51.6% versus 49.6%; P = 0.848, not significant [NS], log-rank test). For 22 of 149 cases with incidental HCC, 10-year patient survival was higher than 127 primary HCC cases (85% [95% confidence interval (CI), 70.6%-100%] versus 48.3% [95% CI, 38%-61%]; P = 0.168, NS) and similar to 3392 biliary atresia cases (89.9%; 95% CI, 88.7%-91%). Actuarial 10-year patient survival for 17 EMBs, 10 METS, and 6 leiomyosarcoma patients exceeded 60%. These survival outcomes were similar to those seen for HBL. At CHP, posttransplant recurrence-free and overall survival among 25 HCC, 17 (68%) of whom had preexisting liver disease, was 16/25 or 64%, and 9/25 or 36%, respectively. All 10 patients with incidental HCC and tumor-node-metastasis stage I and II HCC survived recurrence-free. Only vascular invasion predicted poor survival in multivariate analysis (P < 0.0001). A total of 4 of 5 EMB patients (80%) and all patients with METS (neuroendocrine-2, pseudopapillary pancreatic-1) also survived recurrence-free. Among children, LT can be curative for unresectable HCC confined to the liver and without vascular invasion, incidental HCC, embryonal tumors, and metastatic neuroendocrine tumors. Liver Transplantation 23 1577-1588 2017 AASLD.

Incidental intraoperative discovery of colonic growth in a patient with esophageal carcinoma- lessons learnt!

Presentation of more than one malignancy at the intial time of diagnosis is rare. Recently we encountered a patient who was diagnosed with carcinoma esophagus found to have another incidental growth in his right colon at the time of surgery. When managed appropriately such patients do well depending on the stage of their malignancy. Here in this article we have reviewed the literature pertaining to multiple primary malignancy.

Aggressive surgical approach for patients with T4 gastric carcinoma: promise or myth?

BACKGROUND: Surgical outcomes of multiorgan resection (MOR) for T4 gastric carcinoma reported in the literature are widely variable. We herein report a large surgical series of T4 gastric carcinoma. METHODS: One hundred seventy-nine patients with cT4 gastric carcinoma were recruited onto the study. Patient characteristics, surgical strategy and related complications, long-term survival, and prognostic factors of T4 gastric carcinoma were analyzed. RESULTS: Of 179 cT4 gastric carcinoma, there were 57 cT4 (pT3) with MOR, 91 pT4 with MOR, and 31 cT4 without MOR. pT4 with MOR were more likely to be associated with nodal metastasis, cellular dedifferentiation, and lymphoperineural infiltration compared to those of pT0-3 (P < 0.01 for all). For 91 pT4 with MOR, their surgical mortality and morbidity rates were 4.4 and 28.6%, respectively; their 1-, 3-, and 5-year overall survival rates were 55.2, 22.4, and 12.2%, respectively. The long-term survival of cT4 (pT3) with MOR was superior to pT4 with MOR (P = 0.006) and cT4 without MOR (P = 0.004). There was a striking difference between pT4 with MOR, R0 and pT4 with MOR, and R1 or R2 (P = 0.007). By means of multivariate analysis, lymph node status, liver invasion, and positive surgical margin were independent prognostic factors. CONCLUSIONS: Aggressive surgical management of pT4 gastric carcinoma should be limited to patients without adverse prognostic factors such as advanced nodal involvement and pancreatic invasion.

Fibrous hamartoma of infancy.

Fibrous hamartoma of infancy (FHI) is a rare, benign tumor of the subcutis and lower dermis, which usually occurs within the first 2 years of life. Ninety one percent of the tumors occur in the first year of life. The histogenesis of FHI is unclear. The clinical course is typically benign and prognosis excellent. The physical characteristics of the subcutaneous mass in a child may suggest a malignant process; however, FHI should be included in the differential diagnosis. The prognosis of FHI is excellent with local surgical excision and it rarely recurs.