Faculty Bibliography

Background: In addition to respiratory distress, GI symptoms have been reported in COVID-19 patients at various stages of the disease. Among the GI symptoms that have been reported, diarrhea, nausea, vomiting, abdominal pain and GI bleeding were often seen. Age and comorbid conditions such as obesity, HTN, DM and/or CAD have been considered as risk factors for COVID-19 patients for severe disease. GI manifestations in COVID-19 patients appeared to act as a sign for a serious condition. The virus has been identified in the stool and in rectal swabs of some infected patients, even after a negative nasopharyngeal test. There is a lack of reports on pathological alterations of the GI tract in COVID-19 infected patients.
Design(s): 16 PCR confirmed COVID-19 patients (11 males and 5 females) were included in the study. Biopsy or resection specimens were taken from the esophagus (4), stomach (6), small intestine (5), appendix (3), colon (5) and gallbladder (3). Clinical information including demographics, comorbidities, GI symptoms, related laboratory tests were collected. Histopathologic evaluation was performed and correlated with clinical properties.
Result(s): The age of the patients ranged from 10 to 84 years old, with an average of 47 years. Eight (50%) patients had at least one comorbid condition, two patients (12.5%) had prior history of cancer, and six patients had no significant medical history. Abdominal pain and GI bleeding were the most common presenting symptoms. Histologically, acute and chronic inflammation was seen in 14 of 16, and 15 of 16 cases, respectively. Eight cases showed severe acute inflammation with ulceration. The mucosal changes included nonspecific reactive change, hypermucinous, atrophic/ischemic changes, and necrosis, were indiscriminately noticed in these cases. Four cases showed intraepithelial lymphocytosis. Viral like inclusions were found in four cases. Microthrombi were identified in 5 cases with an average patient age of 60 years. Notably, microthrombi were seen in about 5 out of 8 (62%) patients with comorbidities. The patients with microthrombi had a higher D dimer test value than those without thrombus. Three patients died shortly after operation, and two of them showed microthrombi in the tissue specimens.
Conclusion(s): Acute and chronic inflammation were indiscriminately seen in these cases. Microthrombi were dominantly found in aging patients with comorbidities, suggesting microthrombi in the GI tract may be a histologic indication for severe COVID-19 patients with GI symptoms

Background: Digestive symptoms are often seen in COVID-19 patients with poor outcomes. The Viral RNA is mostly positive in the stool of these patients, and has a longer delay before viral clearance. However, its diagnostic value and significance for guiding clinical treatment remain unknown. And the pathologic alterations in the GI tract in COVID-19 patients have not been well defined. We evaluated rectal swab SAS-CoV-2 test and histopathologic changes in the small intestine in autopsy patients.
Design(s): 18 autopsy cases with confirmed SAS-CoV2 infection were included. Nasal, bronchial, and rectal swab SARS-CoV-2 PCR were performed at the time of autopsy. Clinical information included demographics, comorbidities, presenting symptoms, related laboratory tests were collected. Histopathologic evaluation was performed and correlated with clinical properties.
Result(s): 83% (15/18) of patients were male. Median age is 50 years. 7/18 (38.9%) patients had diarrhea in addition to cough, fever and other symptoms. Except in one case, all patients had underlying comorbidities of diabetes, hypertension and /or obesity. In the small intestine, acute inflammation was not seen in any cases. 5/18 displayed mild and one showed moderate chronic inflammation. Hypermucinous change was found in six patients but not associated with diarrhea. 3 cases had microthrombi identified in the sections. Notably, obviously increased D dimer in lab tests were noticed in all patients. Postmortem 17/17 (100%) nasal, 18/18 (100%) bronchial and 7/16 (43.8%) rectal swabs showed SARS-CoV-2 PCR positivity. 3 of 7 (42.9%) patients with diarrhea are positive in rectal swab for SARS-CoV-2.
Conclusion(s): There are no specific COVID-19 changes in the small intestine. More investigations are needed, especially on tissues from different locations of the GI tract. Data from rectal swab testing suggests that it is not ideal for diagnosing COVID-19, guiding treatment, or predicting small intestinal pathology

Gastrointestinal (GI) symptoms of SARS-CoV-2/COVID-19 in the form of anorexia, nausea, vomiting, abdominal pain and diarrhea are usually preceded by respiratory manifestations and are associated with a poor prognosis. Hematochezia is an uncommon clinical presentation of COVID-19, and we hypothesize that older patients with significant comorbidities (obesity and cardiovascular) and prolonged hospitalization are susceptible to ischemic injury to the bowel. We reviewed the clinical course, key laboratory data including acute-phase reactants, and drug/medication history in 2 elderly male patients admitted for COVID-19 respiratory failure. Both patients had a complicated clinical course and suffered from hematochezia, acute blood loss, and anemia which led to hemodynamic instability requiring blood transfusion around day 40 of their hospitalization. Colonoscopic impressions were correlated with the histopathological findings in the colonic biopsies that included changes compatible with ischemia and nonspecific acute inflammation, edema, and increased eosinophils in the lamina propria. Both patients were hemodynamically stable, on prophylactic anticoagulants, multiple antibiotics, and antifungal agents due to respiratory infections at the time of lower GI bleeding. Hematochezia resolved spontaneously with supportive care. Both patients eventually recovered and were discharged. Elderly patients with significant comorbid conditions are uniquely at risk for ischemic injury to the bowel. This case report highlights hematochezia as an uncommon GI manifestation of spectrum of COVID-19 complications. The causes of bleeding in these COVID-19 associated cases are likely multifactorial and can be attributed to concomitant etiologies based on their age, multiple comorbid conditions, prolonged hospitalization compounded by lung injury, and hypoxia precipitated by the virus. We hypothesize that rather than a direct viral cytopathic effect, ischemia and hypoperfusion may be unleashed due to the cytokine storm orchestrated by the virus that leads to abnormal coagulation profile. Additional factors that may contribute to ischemic injury are prophylactic use of anticoagulants and polypharmacy. There were no other causes to explain the brisk lower GI bleeding. Presentation of hematochezia was followed by hemodynamic instability that may further increase the mortality and morbidity of COVID-19 patients, and prompt consultation and management by gastroenterology is therefore warranted.

AIMS/OBJECTIVE:Neuroendocrine neoplasms (NN)s range from well to poorly differentiated and indolent to highly aggressive. The site of origin in metastatic NNs has therapeutic and prognostic implications. SATB2 is a transcriptional regulator involved in osteoblastic and neuronal differentiation and a sensitive and specific marker of colorectal epithelium. This study aimed to evaluate the expression of SATB2 in NNs from various primary sites and its utility as a marker in determining the site of origin of these neoplasms. METHODS AND RESULTS/RESULTS:SATB2 immunohistochemistry was performed on 266 NNs, including lung small cell carcinomas (N=39) and carcinoids (N=30); bladder (N=21) and prostate (N=31) small cell carcinomas; and gastrointestinal (GI)/pancreatic NNs of various primary sites (N=145) consisting of well differentiated neuroendocrine tumors (WDNET)s (N=124) and poorly differentiated neuroendocrine carcinomas (PDNEC)s (N=21). SATB2 was expressed in prostatic (10/31, 32%) and bladder (8/21, 38%) small carcinomas, and lung carcinoid tumors (1/30, 3%) and small cell carcinomas (8/39, 21%). Among primary GI NNs, SATB2 was expressed in 37/124 (30%) WDNETs and 4/21 (19%) PDNECs. Of the former, 15/15 (100%) rectal/rectosigmoid and 22/22 (100%) appendiceal neoplasms expressed SATB2. By receiver operator characteristic analysis, SATB2 was a sensitive and specific marker for rectal (100.0%; 80.0%) and appendiceal (100.0%; 84.5%) WDNETs, respectively. CONCLUSIONS:In summary, SATB2 is a sensitive and specific marker for rectal/rectosigmoid and appendiceal WDNETs and may represent a useful diagnostic tool when these sites of origin are considered in the differential diagnosis.

BACKGROUND:A surgical pulmonary artery band (PAB) is used to control excessive pulmonary blood flow for certain congenital heart diseases. Previous attempts have been made to develop a transcatheter, implantable pulmonary flow restrictor (PFR) without great success. We modified a microvascular plug (MVP) to be used as a PFR. The objectives of this study were to demonstrate feasibility of transcatheter implantation and retrieval of the modified MVP as a PFR, and compare PA growth while using the PFR versus PAB. METHODS AND RESULTS/RESULTS:The PFR was implanted in eight newborn piglets in bilateral branch pulmonary arteries (PAs). Immediately post-PFR implantation, the right ventricular systolic pressure increased from a median of 20-51 mmHg. Transcatheter retrieval of PFR was 100% successful at 3, 6, and 9 weeks and 50% at 12-weeks post-implant. A left PAB was placed via thoracotomy in four other newborn piglets. Debanding was performed 6-weeks later via balloon angioplasty. On follow-up, the proximal left PA diameters in the PFR and the PAB groups were similar (median 8 vs. 7.1 mm; p = 0.11); albeit the surgical band sites required repeat balloon angioplasty secondary to recurrent stenosis. By histopathology, there was grade II vessel injury in two pigs immediately post-retrieval of PFR that healed by 12 weeks. CONCLUSIONS:Transcatheter implantation and retrieval of the MVP as a PFR is feasible. PA growth is comparable to surgical PAB, which is likely to require reinterventions. The use of the MVP as a PFR in humans has to be trialed before recommending its routine use.

Recent trials have explored surveillance of ductal carcinoma in situ (DCIS) without complete excision, but it is difficult to fully exclude an associated, unsampled invasive focus. Tumor microenvironment, including tumor-associated macrophages, may play a role in the transition from in situ to invasive carcinoma, and the presence of CD163-positive cells with DCIS has been associated with increased risk of progression to invasive carcinoma. We aimed to evaluate the role of DCIS-associated CD163-positive cells on biopsy in predicting associated invasion on excision. Immunohistochemistry for CD163 was performed on 57 total biopsy cases of DCIS of low (n = 13), intermediate (n = 21), and high (n = 23) nuclear grade, 27 (47%) of which showed invasion on the subsequent excision specimen. Positive intratumoral and stromal cells were quantified independently by 2 observers based on the percentage of cells staining. Intratumoral CD163 scores ranged from 0 to 2 (mean, 0.7). Stromal CD163 scores ranged from 0 to 3 (mean, 1.3). Intratumoral and stromal CD163 levels were not significantly associated with the presence of subsequent invasion when evaluated as a whole group (P = .36 and P = .47) or when subdivided into low (P = .36 and P = .17), intermediate (P = .82 and P = .82), or high (P = .09 and P = .68) nuclear grades. There was no correlation between intratumoral CD163 content and DCIS grade (P = .257). A trend for higher stromal CD163 expression was seen with higher-grade DCIS, although not statistically significant (P = .178). In conclusion, CD163 on breast core biopsy does not help select patients who may safely forgo excision of DCIS.

Objectives/UNASSIGNED:Immunohistochemistry (IHC) staining of core biopsy sections often plays an essential role in the diagnosis of acute megakaryoblastic leukemia (AMKL). The goal of this study was to define the relative sensitivities of commonly used stains for markers of megakaryocytic differentiation. Methods/UNASSIGNED:The sensitivities of IHC stains for CD42b, CD61, and von Willebrand factor (vWF) were compared in 32 cases of pediatric AMKL. Results/UNASSIGNED:The sensitivities of CD42b, CD61, and vWF were 90.6%, 78.1% and 62.5%, respectively. When CD42b and CD61 were used together, the combined sensitivity increased to 93.6%. There were no cases in which vWF was positive when both CD42b and CD61 were negative. Conclusions/UNASSIGNED:CD42b can reliably be used as a solitary first-line marker for blasts of megakaryocytic lineage, whereas CD61 may be reserved for infrequent cases that are CD42b negative. There is no role for the routine use of vWF when CD42b and CD61 are available.

Studies in adult HT have demonstrated improved cardiac function in the recipient following administration of T3 to the donor. The purpose of this experiment was to assess the effects of T3 on the function of the immature donor heart following HT in a piglet model. A total of 32 piglets were divided into 16 donors and 16 recipients. Following creation of brain death, half of the donor piglets were randomized to receive three doses of T3 (0.2 μg/kg) along with hydrocortisone (1 mg/kg). The donor hearts were then transplanted into the recipient piglets on CPB. Duration of survival off CPB, inotrope score, and EF of heart following CPB were evaluated. There were no differences between the two groups in age, weight, pre-brain death EF, T3 levels, and CPB times. Post-CPB survival times were inversely related to the ischemic times in both groups (Pearson r=-0.80, P<.001), and this relationship was not influenced by T3. There was no difference in inotrope score, EF, or biochemical assessment between the two groups. Administration of T3 in combination with hydrocortisone to the brain-dead donor confers no beneficial effect on myocardial function or survival following HT in a piglet model.

OBJECTIVES/OBJECTIVE:The primary objective of this study was to demonstrate that pulmonary artery (PA) debanding via cardiac catheterization using balloon angioplasty is feasible and safe in swine. The secondary objectives were to determine the acute and long-term effects of this therapy. DESIGN/METHODS:This is a chronic survival experimental study in newborn swine. BACKGROUND:PA bands are used in infants for transient palliation of congenital heart defects with excessive pulmonary blood flow. Although rare, if these defects should close spontaneously or become hemodynamically insignificant, a sternotomy and occasionally cardiopulmonary bypass may still be required for band removal. Alternatively, debanding could be accomplished through less invasive methods. INTERVENTIONS/METHODS:The main pulmonary artery was banded in three piglets, and the left pulmonary artery in five piglets via mini-thoracotomy at a mean weight of 2.5 kg. Following a threefold increase in weight, the piglets underwent PA debanding via balloon angioplasty. Four piglets were sacrificed to evaluate the acute effects. The remainder were followed to evaluate long-term effects. Histopathology was performed on all piglets. OUTCOME MEASURES/METHODS:Reintervention rates. Histopathologic consequences of high pressure balloon angioplasty used for PA debanding acutely and after reinterventions. RESULTS:Debanding was performed at a mean weight of 8.1 ± 2.23 kg. The median preintervention gradient across the band was 18 mm Hg. Debanding was successful in all piglets. The median postintervention gradient was 3.5 mm Hg. All piglets in the long-term model required re-interventions for recurrent stenosis at mean weights of 26 ± 1.6 and 61 ± 3.2 kg. Histopathology demonstrated vessel wall injury in only one piglet. CONCLUSIONS:Endovascular PA debanding can be safely achieved in a swine model. Angioplasty following debanding may be necessary for recurrent stenosis. This catheter-based therapy may provide a less-invasive alternative to surgery.