The Role of Lymphocyte Subsets, PD-1, and FAS (CD95) in COVID-19 Cancer Patients.

Lymphocytes are the main orchestrators that regulate the immune response in SARS-COV-2 infection. The exhaustion of T lymphocytes is a contributing factor to lymphopenia, which is responsible for the COVID-19 adverse outcome. However, it is still not demonstrated on a large scale, including cancer patients. Peripheral blood samples were obtained from 83 SARS-CoV2 infected cancer patients, and 29 COVID-19 infected noncancer patients compared to 28 age-matched healthy controls. Lymphocyte subsets were assessed for CD3, CD4, CD8, CD56, PD-1, and CD95 using flow cytometry. The data were correlated to the patients' clinical features, COVID-19 severity and outcomes. Lymphopenia, and decreased CD4+ T cells and CD8+ T cells were significantly observed in COVID-19 cancer and noncancer patients compared to the control group (p < 0.001, for all). There was a significantly increased expression of CD95 and PD-1 on the NK cells, CD4+ T cells, and CD8+ T cells in COVID-19 cancer and noncancer patients in comparison to the control group. The increased expression of CD95 on CD8+ T cells, as well as the increased expression of PD-1 on CD8+ T cells and NK cells are significantly associated with the severity of COVID-19 infection in cancer patients. The increased expression of CD95 and PD-1 on the CD4+ T cells, CD8+ T cells, and NK cells was observed significantly in nonsurviving patients and those who were admitted to the intensive care unit in COVID-19 cancer and noncancer patients. The increased expression of PD-1 and CD95 could be possible prognostic factors for COVID-19 severity and adverse outcomes in COVID-19 cancer and noncancer patients.

Detection of abnormal lymphocytes in the peripheral blood of COVID-19 cancer patients: diagnostic and prognostic possibility.

BACKGROUND: Peripheral morphological abnormalities play important roles in the early diagnosis and prognosis of the COVID-19 infection. The aim of the present study was to assess the morphological alterations in the peripheral blood (PB) cells in patients with COVID-19 infection, with special attention to a different group of atypical lymphocytes that had been observed in the PB of COVID-19 cancer and non-cancer patients. METHODS: The PB cells were examined in 84 COVID-19 positive cancer patients, and 20 COVID-19 positive non-cancer patients, compared to 30 healthy normal controls. The data were correlated to the disease severity, patients' clinicopathological features, and outcomes. RESULTS: There was an increased incidence of giant platelets, neutrophils shifting left, and abnormal monocytes in the COVID-19 positive cancer and non-cancer patients compared to the control group (P < .001, P < .001 and P = .014; respectively). Neutrophils with abnormal toxic granulations, Pseudo Pelger-Heut abnormality, and reactive lymphocytes were significantly increased in COVID-19 cancer patients compared to COVID-19 non-cancer patients and the control group (P = .001, P < .001, and P < .001; respectively). An abnormal form of lymphocytes' morphological changes (Covicytes) was significantly detected in COVID-19 cancer patients [60.7% (51/84)], and in COVID-19 non-cancer patients [55% (11/20)], while it was absent in the normal controls [0.0% (0/30), P < 0.001]. The presence of the Covicytes is associated significantly with a better prognosis in cancer and non-cancer COVID-19 patients. CONCLUSION: Covicytes could be a useful marker supporting the diagnosis of SARS-COV-2 infection, and it is associated with a favorable prognosis.

Could COVID-19 induce remission of acute leukemia?

BACKGROUND: COVID-19 viral pandemic caused many mortalities in cancer patients especially those with hematological malignancies. The immunological response to COVID-19 infection is responsible for the outcome of cases whether mild, severe or critical. CASE PRESENTATION: Two cases presented with moderate COVID-19 viral infection, concomitant with acute myeloid leukemia and T acute lymphoblastic leukemia, respectively. Surprisingly, after the administration of COVID-19 supportive therapy, the cases showed disease remission after a follow-up period of 12 and 5 months, respectively. Additionally, the blast cells dropped to only 3% and 0% in the bone marrow aspirates of those two cases, respectively, after it was 30% in both cases at diagnosis. CONCLUSION: The immune response that emerged against COVID-19 infection could potentially produce anti-tumor immunity in some patients, or the virus may act as an oncolytic virus. However, further investigations are required to explain this phenomenon, which may help in finding a possible new targeted therapy for these cases.

The role of inflammatory indices in the outcome of COVID-19 cancer patients.

To assess the prognostic role of different inflammatory indices on the outcome of cancer patients with COVID-19. Sixty-two adults and 22 pediatric cancer patients with COVID-19 infection were assessed for the prognostic value of certain inflammatory indices including the neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio (PLR), derived NLR (dNLR), systemic inflammation index (SII), mean platelet volume to platelet ratio (MPR), C-reactive protein to lymphocyte ratio (CRP/L), aggregate index of systemic inflammation (AISI), systemic inflammation response index (SIRI), and neutrophil to lymphocyte, platelet ratio (NLPR). Data were correlated to patients' outcome regarding ICU admission, and incidence of mortality. Increased CRP/L ratio in adult COVID-19 cancer patients was significantly associated with inferior survival [152 (19-2253) in non-survivors, compared to 27.4 (0.8-681) in survivors (P = 0.033)]. It achieved a sensitivity (60%) and a specificity (90.2%) at a cut-off 152, while it achieved a sensitivity of 60% and specificity 95.1% at a cut-off 252 (AUC 0.795, P = 0.033). When combining both CRP/L and NLPR for the prediction of poor outcome in adult cancer patients with COVID19, the sensitivity increased to 80% and the specificity was 70.7% (AUC 0.805, P = 0.027). Increased incidence of ICU admission in pediatric cancer patients associated significantly with the severity of covid19 infection, decreased mean corpuscular hemoglobin (MCH) < 28.3, increased red cell distribution width (RDW) > 16, lymphopenia < 1.04, pseudo Pelger-Huet appearance, and PLR < 196.4 (P = 0.004, P = 0.040, P = 0.029, P = 0. 0.039, P = 0.050, and P = 0.040; respectively). The mean corpuscular volume (MCV), MCH, and RDW could be useful prognostic markers for poor outcome in COVID-19 pediatric cancer patients (P < 0.05 for all). Increased both CRP/L and NLPR associated significantly with poor survival in adult COVID-19 cancer patients, while PLR associated significantly with ICU admission in pediatric COVID-19 cancer patients.

Biological and molecular studies on specific immune cells treated with checkpoint inhibitors for the thera-personal approach of breast cancer patients (ex-vivo study).

Immunotherapy becomes a promising line of treatment for breast cancer (BC) however, its success rate is still limited. Methods: The study was designed to optimize the condition for producing an effective dendritic cell (DCs) based immunotherapy by using DCs and T lymphocytes together with tumor-infiltrating lymphocytes (TILs) and tumor-infiltrating DCs (TIDCs), treated with anti-PD1 and anti-CTLA4 monoclonal antibodies. This mixture of immune cells was co-cultured with autologous breast cancer cells (BCCs) isolated from 26 BC females. Results: There was a significant upregulation of CD86 and CD83 on DCs (p = 0.001 and 0.017, respectively), similarly upregulation of CD8, CD4 and CD103 on T cells (p = 0.031, 0.027, and 0.011, respectively). While there was a significant downregulation of FOXP3 and combined CD25.CD8 expression on regulatory T cells (p = 0.014 for both). Increased CD8/Foxp3 ratio (p < 0.001) was also observed. CD133, CD34 and CD44 were downregulated on BCCs (p = 0.01, 0.021, and 0.015, respectively). There was a significant increase in interferon-γ (IFN-γ, p < 0.001), lactate dehydrogenase (LDH, p = 0.02), and a significant decrease in vascular endothelial growth factor (VEGF, p < 0.001) protein levels. Gene expression of FOXP3 and Programmed cell death ligand 1 (PDL-1) were downregulated in BCCs (p < 0.001, for both), similarly cytotoxic T lymphocyte antigen-4 (CTLA4, p = 0.02), Programmed cell death 1 (PD-1, p < 0.001) and FOXP3 (p < 0.001) were significantly downregulated in T cells. Conclusion: Ex-vivo activation of immune cells (DCs, T cells, TIDCs, and TILs) with immune checkpoint inhibitors could produce a potent and effective BC immunotherapy. However, these data should be validated on an experimental animal model to be transferred to the clinical setting.

Pelvic exenteration and composite sacral resection in the surgical treatment of locally recurrent rectal cancer.

BACKGROUND: The incidence of rectal cancer recurrence after surgery is 5-45%. Extended pelvic resection which entails En-bloc resection of the tumor and adjacent involved organs provides the only true possible curative option for patients with locally recurrent rectal cancer. AIM: To evaluate the surgical and oncological outcome of such treatment. PATIENTS AND METHODS: Between 2006 and 2012 a consecutive series of 40 patients with locally recurrent rectal cancer underwent abdominosacral resection (ASR) in 18 patients, total pelvic exenteration with sacral resection in 10 patients and extended pelvic exenteration in 12 patients. Patients with sacral resection were 28, with the level of sacral division at S2-3 interface in 10 patients, at S3-4 in 15 patients and S4-5 in 3 patients. RESULTS: Forty patients, male to female ratio 1.7:1, median age 45 years (range 25-65 years) underwent extended pelvic resection in the form of pelvic exenteration and abdominosacral resection. Morbidity, re-admission and mortality rates were 55%, 37.5%, and 5%, respectively. Mortality occurred in 2 patients due to perineal flap sepsis and massive myocardial infarction. A R0 and R1 sacral resection were achieved in 62.5% and 37.5%, respectively. The 5-year overall survival rate was 22.6% and the 4-year recurrence free survival was 31.8%. CONCLUSION: Extended pelvic resection as pelvic exenteration and sacral resection for locally recurrent rectal cancer are effective procedures with tolerable mortality rate and acceptable outcome. The associated morbidity remains high and deserves vigilant follow up.

Comparing a combination of penicillin G and gentamicin to a combination of clindamycin and amikacin as prophylactic antibiotic regimens in prevention of clean contaminated wound infections in cancer surgery.

BACKGROUND AND AIM: Appropriate antibiotic selection and timing of administration for prophylaxis are crucial to reduce the likelihood of surgical site infection (SSI) after a clean contaminated cancer surgery. Our aim is to compare the use of two prophylactic antibiotic (PA) regimens as regards efficacy, timing, and cost. PATIENTS AND METHODS: Two hundred patients with gastric, bladder, or colorectal cancer were randomized to receive preoperative PA, group A received penicillin G sodium and gentamicin and group B received clindamycin and amikacin intravenously. The demographic data of patients were collected, and they were observed for wound infections. RESULTS: Infected wounds occurred in 19 patients with a rate of 9.5%. Highest incidence of SSI was among bladder cancer patients (14.2%); p=0.044. The rate of SSI was 11% in group A, and 8% in group B, p=0.469. The cost of PA administered in group A was significantly less than that of group B (21.96±3.22LE versus 117.05±12.74LE, respectively; p<0.001). SSI tended to be higher among those who had longer time for antibiotic and incision (≥30min) than those who had shorter time interval (<30min), (13% vs. 6.5%, respectively). CONCLUSION: Both penicillin+gentamicin and clindamycin+amikacin are safe and effective for the prevention of SSI in clean contaminated operative procedures. In a resource limited hospital, a regimen including penicillin+gentamicin is a cost-effective alternative for the more expensive and broader coverage of clindamycin+amikacin. Timing of PA is effective in preventing SSIs when administered 30min before the start of surgery.

Distribution of axillary lymph node metastases in different levels and groups in breast cancer, a pathological study.

BACKGROUND: It was observed during dissection of heavy deposits of axillary lymph nodes (LNs) in breast cancer that there were grossly positive LNs outside the confines of classical axillary dissection. AIM OF STUDY: To know the extent of LN metastases in these new basins by dissecting and labeling them separately, for pathological examination and proper staging of those patients. PATIENTS AND METHODS: From 2005 to 2009, 59 private patients with breast cancer who had positive axillary LNs were subjected to axillary dissection with accurate leveling according to its relation to pectoralis minor. In addition to the classical three levels, the brachial, thoracoacromial, humeral, scapular and Rotter's lymph nodes were dissected. RESULTS: Levels I, II and III axillary LNs were involved in 91.5%, 62.7%, and 52.5%, respectively. Skip metastases (without the involvement of level one) were found in 5/59 patients (8.4%). Brachial, acromiothoracic, humeral and Rotter's LNs were involved in 10.1%, 15.2%, 5% and 1.7%, respectively, with no metastatic deposits encountered in scapular LNs. In our patients, lymphedema of the ipsilateral upper limb was nearly of the same incidence as after classical axillary dissection. CONCLUSION: In addition to the classic complete axillary lymph node dissection (ALND) indicated in patients with breast cancer with axillary LNs metastases, dissection of the brachial, acromiothoracic, humeral, Rotter's and scapular LNs, is recommended for proper staging.

Expression of pro- and anti-inflammatory cytokines in relation to apoptotic genes in Egyptian liver disease patients associated with HCV-genotype-4.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide strongly linked to hepatitis C virus (HCV) infection. However, the exact pathogenetic mechanisms are still unclear. METHODS: We assessed the expression of apoptosis genes (GSK3-B, AKT-1, Bcl-2), inflammatory cytokines (TNFalpha, TNF-RI, TNF-RII, IL-6, IL-6R), anti-inflammatory IL-10, CRP and alphaFP by reverse transcription-polymerase chain reaction (RT-PCR) in 33 HCC, 25 chronic hepatitis and 16 asymptomatic HCV carrier positive for HCV subjects. Also, pooled normal liver tissues and HepG2 cells were used as controls. RESULTS: Hepatocellular carcinoma and liver disease (LD) showed reduced expression of GSK-3beta, TNFalpha, TNF-R I, TNF-RII, IL-10 and overexpression of IL-6R and CRP with no significant difference between the two groups. AFP was expressed in HCC only (33%). AKT, BCL2 and IL-6 showed normal, reduced and overexpression in studied patients with a significant difference between AFP, AKT overexpression (67% and 30%), BCL2 overexpression (49% and 10%) and reduced IL-6 in between HCC and LD. The morphologically normal tissues adjacent to tumors showed aberrant expression of AKT, IL-6, CRP, TNFalpha and TNFRI. A significant relation was observed between cirrhosis and GSK-3beta, AKT and IL-6 (P = 0.0018, P = 0.018, P = 0.0001; respectively). CONCLUSIONS: Aberrant expressions of AKT, GSK3-B, and BCL2 are common events in HCV-associated LD and HCC. AKT, GSK3-B and IL-6 are significantly associated with cirrhosis and could be used as biomarkers for both early detection and molecular target therapy for the prevention of HCC development. TNFRII, GSK3-B and s-AFP could be used as prognostic factors that can predict the clinical outcome of HCC patients.

Ileocaecal vs ileal neobladder after radical cystectomy in patients with bladder cancer: a comparative study.

OBJECTIVE: To compare an ileocaecal orthotopic bladder, (which has been the standard procedure in Egypt for >30 years) with the ileal neobladder, as there is no ideal continent orthotopic bladder replacement for patients after cystectomy for bladder cancer. PATIENTS AND METHODS: Between June 1999 and December 2001, 60 patients with invasive bladder cancer were randomized into two groups. Group A comprised 29 patients who had radical cystectomy and reconstruction with an ileal neobladder (median age 50 years, 27 men and two women) and group B included 31 who had an ileocaecal bladder substitution after radical cystectomy (median age 51 years, 28 men and three women). RESULTS: The complication rate after surgery in group A was 17%, with two deaths, one from acute myocardial infarction and the other from haematemesis. In group B, the complication rate was 13%, with two deaths, one from a massive pulmonary embolism and the other from liver cell failure. Daytime continence was achieved in 93% of patients in group A and 90% in group B. The mean (sd) postvoid residual urine volume was larger in group A than group B, at 90 (72) vs 12 (20) mL. Acidosis and hyponatraemia were evident in the patients in group A but in none in group B (P < 0.05). The pelvicalyceal systems were preserved in 85% of patients in group A and 93% in group B during the 2-year follow-up. The mean (sd) renal cortical thickness was less in group A than in group B, at 1.8 (0.5) and 1.9 (0.2) cm, respectively. Although the cystometric capacity was greater and the basal pressure less in group A than B, these were not reflected in the degree of diurnal and nocturnal continence or back pressure on the renal units. CONCLUSION: Continence in both pouches was similar but the renal units were preserved better in the ileocaecal than in the ileal neobladder. Residual urine volume was greater in the ileal neobladder, with its potential complications of infection and stone formation, and acidosis was more evident.

Fasciocutaneous free flaps for hypopharyngeal reconstruction.

Considerable controversy persists regarding the optimal technique for hypopharyngeal reconstruction. The ideal procedure should provide low mortality and morbidity, short hospitalization, a high success rate, few complications, and the greatest potential for neopharyngeal speech and deglutition. In this study, a variety of fasciocutaneous free flaps were used for reconstruction of the hypopharynx. Over a two-year period, fasciocutaneous flaps were used for reconstruction of pharyngoesophageal segments following total laryngopharyngectomies in 16 patients at The National Cancer Institute, Cairo University, Cairo, Egypt. Flap survival, recipient vessels used, and complications were examined. The ultimate functional and cosmetic outcomes of free flaps were compared. Of the 16 patients included in this study, nine were males, and seven were females. Free flaps used for reconstruction included the radial forearm (8), lateral arm (2), anterolateral thigh (3), and posterolateral thigh (3) flaps. Free flaps were successful in 15 patients. One patient had total flap loss. Salvage surgery was successful for one flap that developed venous congestion. Eleven patients received adjuvant radiation therapy. The commonly used recipient vessels were the small arteries of the neck and the external jugular vein. Five patients developed minor pharyngocutaneous fistulas that healed spontaneously. Six patients developed anastomotic line stricture. Donor-site morbidity was more significant with the radial forearm flap, compared to other flaps. Fasciocutaneous free flaps have a definite place in pharyngoesophageal reconstruction. The flap should be selected with reference to the type of the defect and patient obesity; however, donor-site morbidity should also be considered.