The prognostic significance of non-lymphoid immune cells of the tumor microenvironment,including neutrophils,eosinophils, and mast cells in breast carcinomas

Background and objectiveThe prognostic importance of lymphoid cells in the tumor microenvironment and their effect on treatment response have been demonstrated in many cancer types. However, there are limited studies on non-lymphoid immune cells. Conflicting results have been obtained regarding the effects of these cells on prognosis.Materials and methodsA total of 331 patients who underwent surgery for breast cancer were included. Patients that received neoadjuvant chemotherapy and those with distant metastasis were excluded. CD 15 immunohistochemistry was performed to detect tumor-infiltrating neutrophils (TINs) and eosinophils (TIEs), while Toluidine Blue histochemistry was performed to detect tumor-infiltrating mast cells (TIMs).ResultsHigh TINs were statistically associated with low ER expression (p < 0.001), low PR expression (p = 0.001), high Ki-67 proliferation index (p = 0.008), and HER2/TN molecular subtypes (p = 0.001). High TIEs were associated with low ER expression (p = 0.001), high Ki67 proliferation index (p = 0.005), and HER2/TN molecular subtype (p = 0.002). High TIMs were associated with high PR expression (p = 0.024), low Ki-67 proliferation index (p = 0.003), and high survival rate (p = 0.006). TIMs and TIEs were good prognostic factors for overall survival in Luminal A and Luminal B subtypes, while TINs and TIEs were found to be independent risk factors for disease-free survival.ConclusionThe evaluation of components of the tumor microenvironment including TINs, TIEs, and TIMs is easy and practical. High TIMs and TIEs are independent prognostic factors, especially in luminal molecular subtype of invasive breast carcinoma. However, to use this parameter in routine pathology practice, more studies from different centers and standard evaluation are needed.     

The predictive and prognostic value of Foxp3+/CD25+ regulatory T cells and PD-L1 expression in triple negative breast cancer

Recent significant developments in cancer immunotherapy have led to important breakthroughs and paradigm shifts in the treatment of malignancy. Although breast cancer traditionally has been considered less immunogenic, triple-negative breast cancer (TNBC) is the most immunogenic subtype with more stromal tumor-infiltrating lymphocytes (TILs) and higher programmed death-ligand 1 (PD-L1) expression. The goal of this study is to evaluate regulatory T cells (Tregs) and PD-L1 expression in TNBC, as well as their associations with clinicopathologic features and the outcomes. Tissue microarrays (TMA) of biopsy and resection specimens of 43 TNBC patients who underwent breast biopsy, neoadjuvant chemotherapy, and mastectomy were prepared. The number of Foxp3+ Tregs, Foxp3+/CD25+ Tregs, and expression of PD-L1 in tumor cells (PD-L1 TCs) and TILs (PD-L1 TILs) were assessed by immunohistochemistry. PD-L1 expression combined positive score (PD-L1 CPS) was calculated according to the manufacturer's guidelines. PD-L1 expression was detected in 72% of the cases, and it expressed in a higher percentage and higher intensity in TILs than TCs in TNBC (p = 0.006 and 0.0005, respectively). PD-L1 TCs, PD-L1 TILs, and PD-L1 CPS were all positively associated with pathologic complete response (pCR) (p = 0.04, 0.03, and 0.02, respectively). PD-L1 TILs and PD-L1 CPS also correlated with TILs and tumor infiltrating lymphocyte volume (TILV). Foxp3+ Tregs and Foxp3+/CD25+ Tregs had strong positive correlation (r = 0.89), and they were positively associated with TILs, TILV, and PD-L1 expression. Foxp3+/CD25+ Tregs, PD-L1 TCs, and PD-L1 CPS were positively correlated with better overall survival (p = 0.04, 0.04 and 0.01, respectively).     

Abundant CD8+ tumor infiltrating lymphocytes and beta-2-microglobulin are associated with better outcome and response to interleukin-2 therapy in advanced stage clear cell renal cell carcinoma

Studies assessing tumor-infiltrating lymphocytes (TILs) in clear cell renal cell carcinoma (ccRCC) and clinical outcomes have mixed results. Given fundamental interaction of MHC class I with CD8+ T-cells, we hypothesized that expression of MHC class I associated protein, beta-2-microglobulin (B2M), may be an important immunologic marker in RCC. We sought to understand potential implications of CD8 + TILs and tumor B2M expression on overall survival and response to high-dose interleukin-2 (IL-2) therapy, in a cohort of patients with high-stage (clinical stage III and IV) ccRCC. Four tumor regions from 56 patients with ccRCC were retrospectively assessed immunohistochemically. At a median follow-up time of 33 months, 22 (39%) patients had died of disease, 23 (41%) were alive disease, and 11 (20%) had no evidence of disease. Tumors with high CD8 + TILs had a significantly lower death rate [hazard ratio (HR): 0.33, p = 0.02]. CD8 + TILs correlated with B2M expression (p = 0.007). On multivariable analyses, patients with both high B2M and CD8 + TILs had lower death rate (HR: 0.27, p = 0.03). Within the subgroup treated with IL-2 (n = 27, 48%), tumors with high CD8 + TILs were more likely to respond to IL-2 therapy [coefficient (coef): 1.6, p = 0.05]. On multivariable analyses, tumors with a combination of both high B2M expression and high CD8 + TILs also showed trend to responding to IL-2 therapy (coef: 2.5, p = 0.06). In conclusion, abundant CD8+ TILs and high tumor expression of beta-2-microglobulin were good prognostic indicators associated with longer survival in patients with high-stage ccRCC. Abundant CD8+ TILs may predict response to IL-2 therapy.     

Clinicopathological significance of the immunologic signature (PDL1, FOXP3+ Tregs,TILs) in early stage triple-negative breast cancer treated with neoadjuvant chemotherapy

Patients with breast cancer are appropriate candidates for neoadjuvant chemotherapy (NAC) to facilitate conservative surgery. The chemotherapeutic agents may exert their action by inducing the anti-tumor immune response. This study aimed to evaluate the tumor immune microenvironment including PD-L1, Foxp3+ Tregs, and TILs count in early stages TNBC patients (stage T1, T2) before and after neoadjuvant chemotherapy and their correlation with the clinical and pathological response. Fifty patients of TNBC patients were enrolled in this study; all of them received neoadjuvant chemotherapy. TILs count, Foxp3+ Tregs, and PD-L1 immunohistochemical expression were investigated in all cases before NAC and then evaluated in residual masses after surgery. Data on the clinical and pathological response to NAC were collected and then statistically analyzed. PDL1 expression was detected in 24% of all studied cases, all of them were node-positive (P < 0.002); while Foxp3+ Tregs expressed in 50% and high TILs in 28%. Pathological complete response (pCR) was achieved in 40% of patients and was associated with high TILs expression (P < 0.02) and absence of Foxp3+ Tregs and PDL1 (P < 0.001 for each). In conclusion, Pathologic complete response to NAC was associated with the immunological profile of TNBC. High TILs expression with concomitant decreased PD-L1 expression and low FOXP3+ Tregs is associated with favorable tumor prognosis. Combined therapeutic approaches aiming to PD-L1 block and Tregs depletion might improve treatment efficacy in TNBC.     

Pathological complete response and prognosis after neoadjuvant chemotherapy in patients with HER2-low breast cancer

BackgroundThe development of novel human epidermal growth factor receptor 2 (HER2) antibody drug conjugates brings encouraging opportunities for the treatment of HER2-low breast cancer. In this study, we investigated the clinical factors and prognosis of HER2-low breast cancer after neoadjuvant chemotherapy (NAC).MethodsData from patients diagnosed with HER2-zero or HER2-low breast cancer at a single center between January 2017 and December 2021 who underwent NAC followed by surgery were retrospectively reviewed. HER2 status was detected by immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH), and classified as HER2-zero (IHC 0), HER2-low (IHC 1+ or IHC 2+ and FISH–), and HER2-positive (IHC 3+ or IHC 2+ and FISH+). Baseline characteristics were analyzed and compared between the HER2-low and HER2-zero groups. Survival outcomes were analyzed using the Kaplan–Meier method with the log-rank test and Cox proportional-hazards regression analysis.ResultsThe sample comprised 132 patients with HER2-zero [n = 62 (47.0 %)] and HER2-low [n = 70 (53.0 %)] breast cancer. Relative to the HER2-zero group, the HER2-low group contained larger proportions of patients with hormone receptor (HR) positivity (37.1 % vs. 75.7 %, P < 0.001) and low nuclear grades and Ki-67 indices (both P < 0.05). The pathological complete response (pCR) rate was significantly lower in the HER2-low group than in the HER2-zero group (20.0 % vs. 37.1 %, P = 0.03). At the final follow-up [median 20 (range 4–66) months], patients with HER2-low status had significantly favorable disease-free survival (DFS) and overall survival (OS) outcomes relative to those with HER2-zero status (87.1 % vs. 71.0 %, P = 0.02 and 94.3 % vs. 82.3 %, P = 0.02, respectively). HER2-low status and pCR were independent prognostic factors for DFS [hazard ratio (HR) = 0.31, 95 % confidence interval (CI) 0.13–0.75, P = 0.009 and HR = 0.08, 95 % CI 0.01–0.67, P = 0.02, respectively].ConclusionThis analysis revealed that HER2-low status is associated significantly with HR positivity and low nuclear grades, Ki-67 indices, and pCR rate. It is also associated with favorable DFS and OS outcomes after NAC. HER2-low status and pCR are independent prognostic factors for DFS.     

The expression of programmed death-ligand 1 and programmed death-ligand 2 in endometrial carcinosarcoma: Correlation with mismatch repair protein expression status,tumor-infiltrating lymphocyte infiltration,and clinical outcomes

BackgroundEndometrial carcinosarcomas have high malignant potential with a high recurrence rate and poor prognosis. Immunotherapy may be a promising treatment option. The aim of this study is to evaluate the expression of PD-L1/PD-L2 and its relationship to mismatch repair (MMR) protein status and tumor-infiltrating lymphocyte (TIL) density.MethodsWe performed immunohistochemical analyses of PD-L1 (clone 22C3), PD-L2 (clone TY25), MSH-2, MSH-6, PMS-2, and MLH-1 in 77 tumors. We count TILs using CD8 antibody. Clinicopathologic features were recorded and statistically correlated with immunohistochemical results. Kaplan-Meier analyses were used to analyze the prognosis.ResultsWhile PD-L1 positivity was seen more commonly in MMR protein deficient tumors (p = 0.010), PD-L2 positivity was seen more commonly in MMR protein proficient tumors (p = 0.003). PD-L1 positivity was also found to be more common in carcinosarcoma with high TIL infiltration. PD-L2 positivity was associated with decreased overall survival (OS) rates (p = 0.043, p = 0.043, respectively), whereas the PD-L1 positivity and TIL density were not significantly associated with OS rate. The OS rate of patients with MMR protein proficient tumors was significantly lower compared with those with MMR protein deficient tumors (p = 0.042). The lower TILs infiltration was associated with a shorter disease-free survival (DFS) rate. PD-L1 and PD-L2 positivity did not affect the DFS rate.ConclusionsPD-L1/PD-L2 might be a better target for immunotherapy in endometrial carcinosarcoma. PD-L2 positivity was also associated with a worse clinical outcome in patients with endometrial carcinosarcoma, suggesting that PD-L2 status can be used to predict clinical behavior. Further studies are needed to elucidate the relationship between PD-L1/PD-L2 expression and therapeutic response.     

Impact of chemokine receptor CXCR3 on tumor-infiltrating lymphocyte recruitment associated with favorable prognosis in advanced gastric cancer

Chemokine receptor CXCR3 has been proved to play an important role in tumorigenesis and tumor progression in many malignancies, but its precise efficacy on gastric cancer (GC) has not been evaluated yet. The present study was aimed to explore the correlation of chemokine receptor CXCR3 with tumor-infiltrating lymphocytes (TILs) and prognosis in advanced gastric cancer (GC). Expression of CXCR3 and CD4+, CD8+ TILs was conducted in 192 advanced GC specimens and 48 corresponding paracancerous tissues by immunohistochemical (IHC) analysis. CXCR3 expression in GC tissues was significantly higher than that in paracancerous tissues (P<0.001) and CD8+, CD4+ TILs infiltration increased with high CXCR3 expression (P=0.032 and P<0.001, respectively). Our study showed significantly lower CXCR3 expression in patients with greater tumor invasion depth and lymph node metastasis compared with patients with lesser tumor invasion depth and without lymph node metastasis (P=0.002 and P=0.001, respectively). Univariate analysis indicated that patients with high CXCR3 expression and high CD8+ TILs infiltration had longer overall survival (OS) (log-rank test, P<0.001 and P=0.002, respectively). Univariate and multivariate analyses indicated that CXCR3 expression was an independent prognostic factor for OS (P=0.002). The present study suggested that CXCR3 expression was upregulated in advanced GC and was associated with increased CD4+, CD8+ TILs infiltration and improved OS. Therefore, CXCR3 overexpression is implicated as a favorable prognostic biomarker in human advanced GC.     

Differential expression of HER2 and downstream proteins in prediction of advanced tumor phenotypes and overall survival of patients with Epstein-Barr virus-positive vs. negative gastric cancers

This study evaluated the associations of HER2 protein, HER2 gene amplification, and positivity for p-AKT, p-ERK, and p-PLCγ proteins with clinicopathological status and overall survival (OS) of patients who had Epstein-Barr virus-associated gastric cancer (EBVaGC; n = 58) or EBV-negative GC (EBVnGC; n = 329). Tissue samples were subjected to immunohistochemistry and fluorescence in situ hybridization (FISH). Results showed that EBVaGC less expressed HER2 and amplified HER2 gene. p-AKT (p = 0.035) and p-ERK (p = 0.001) were inhibited in EBVaGC than in EBVnGC, while p-PLCγ (p = 0.034) was upregulated. Among EBVaGC patients, p-ERK positivity was associated with Lauren classification (p = 0.023), and p-PLCγ positivity was inversely associated with TNM stage (p = 0.041) and lymph node metastasis (p = 0.041). In contrast, among EBVnGC patients, HER2 expression was associated with distant metastasis (p = 0.043) and p-AKT positivity was associated with intestinal subtype (p < 0.004), lymph node metastasis (p = 0.031), distant metastasis (p < 0.001), and elder age (>60y, p < 0.004). Overall analysis showed that EBVaGC patients presented better OS than EBVnGC patients (p = 0.044). Among EBVaGC patients, p-AKT positivity (p = 0.008) was associated with worse OS; as well as, HER2 high expression (p < 0.001), p-AKT positivity (p = 0.010), and p-PLCγ (p < 0.001) were associated with worse OS in EBVnGC patients. Multivariate analysis showed that distant metastasis (95% CI: 1.559 to 4.028, p < 0.001), HER2 high expression (95% CI: 1.058 to 2.454, p = 0.026), and p-PLCγ positivity (95% CI: 1.056 to 2.435, p = 0.027) were independent prognostic predictors of OS in EBVnGC patients. Our results indicated that p-AKT positive patients presented worse OS than p-AKT negative ones in EBVaGC, as well as, HER2, p-AKT, and p-PLCγ are prognostic biomarkers for OS in EBVnGC patients.     

Grading system for medullary thyroid carcinoma; an institutional experience

ObjectiveMedullary thyroid carcinoma (MTC) is a rare type of thyroid malignancy. Recently, a two-tier grading system (GS) for MTC has been suggested. We conducted this study to evaluate the generalizability, as well as application of recently proposed GS to our cohort of Medullary thyroid carcinoma (MTC) cases.MethodsWe assigned grades to MTC cases and divided them into two groups by using morphologic criteria only as suggested by recent studies: low-grade (LG, <5 mitosis per 2 mm², and no necrosis) and high-grade (HG, ≥5 mitosis per 2mm² or necrosis).ResultsA total of 59 MTC cases were evaluated and of those 52 (88 %) were LG and 7 (12 %) were HG. Vascular invasion (VI) (p = 0.017), distant metastasis (DM) (p < 0.0001), nuclear pleomorphism (NP) (p = 0.017) and prominent nucleoli (p = 0.03) were prominently noted in the HG group. After controlling for demographics using multivariate cox regression, tumor grade and necrosis remained significantly associated with the overall survival (HR = 22.7, p < 0.01 and HR = 11.1, p = 0.008, respectively). Upon comparing the cases with and without nodal disease, we found that nodal disease is more strongly associated with NP (p = 0.029), tumor fibrosis (p = 0.0001), VI (p = 0.001) and DM (p = 0.005).ConclusionsWe applied the two-tier GS for MTC to our cohort of cases and found statistically significant differences in the overall survival among the two groups. Adding the grading to the pathology report communicates additional information regarding risk stratification in MTC.     

Cytoproliferative activity in colorectal poorly differentiated clusters: Biological significance in tumor setting

BackgroundPoorly differentiated clusters (PDCs) have gained a significant prognostic role in colorectal carcinomas (CRCs) being associated to high risk of lymph node metastasis, shorter survival time and poor prognosis. The knowledge in PDC biology is not completely clear.Materials and methodsWe assessed Ki-67 LI in 45 CRCs showing ≥10 PDCs. We distinguished PDCs at the periphery of the tumor masses (pPDCs) from those within the tumor masses (cPDCs). We chose 3 cut-offs of Ki-67 labeling index (Ki-67 LI): <10%, 10–50%, and >50% of the labeled cells.ResultsKi-67 LI in pPDCs was<10% in 37 cases (82%), 10–50% in 6 cases (13%) and >50%in 2 cases (5%); Ki-67 LI in cPDCs was<10% in 4 cases (23.5%), 10–50% in 4 (23.5%) and >50% in 9 (54%). Ki-67 LI in tumor budding foci (TBs) was <10% in 8 cases (32%), 10–50% in 8 (32%) and >50% in 9 (36%). The difference of Ki-67 LI reaches the statistical significance (p < 0.005). Ki-67 LI <10% in the pPDCs was associated with nodal metastases (pN+) (p < 0.0001), pTNM stage III and IV(p < 0.0001) and TB (p < 0.001). Ki-67 LI > 50% in cPDC was significantly associated withpT3-pT4 and advanced pTNM stages (p < 0.0001), N+ (p = 0.0001) and LVI (p < 0.05).ConclusionDifferent Ki-67 LI detected between cPDCs and pPDCs suggesting a biological difference in PDCs. An actively proliferating central tumor areas can be distinguished from the peripheral portion of the tumors in which the cells interact with the stroma acquiring invasive and metastatic potential.     

Microbiological features,clinical characteristics and outcomes of infective endocarditis in adults with and without hemodialysis: A 10-year retrospective study in Northern Taiwan

Background/purposesInfective endocarditis (IE) is an important cause of morbidity and mortality in hemodialysis (HD) patients. Data on the differences in the microbiological features as well as clinical characteristics and outcomes of HD and non-HD patients with IE are limited.MethodsMedical records of patients (aged over 20 years) with IE were retrospectively reviewed from January 2008 to June 2017 in a tertiary care center in Northern Taiwan. Those with definite or possible IE were included in the study. The clinical characteristics, microbiological results, echocardiographic findings and outcomes of patients were analyzed.ResultsOf the 183 patients with definite or possible IE, 47 had undergone HD and 136 had not. Advanced age (67.3 vs. 61.5 years, p = 0.027), more female gender (51.1% vs. 33.8%, p = 0.036), comorbidities (a high Charlson comorbidity index, 8.17 vs. 4.21, p < 0.001), diabetes mellitus (68.1% vs. 35.3%, p < 0.001), and hypertension (85.1% vs. 53.7%, p < 0.001) were commonly observed in HD patients than in non-HD patients. The yield rate of the blood cultures was higher in HD group than in non-HD group (89.4% vs. 72.8%, p = 0.02). The proportion of methicillin-resistant Staphylococcus aureus was significantly higher in HD group than in non-HD group (31.9% vs. 5.9%, p < 0.001). HD patients versus non-HD patients had higher cardiac complication rates (38.3% vs. 14%, p < 0.001).ConclusionAdvanced age, sex (female), comorbidities, diabetes mellitus, and hypertension were more common in HD patients than in non-HD patients with IE. HD patients had higher proportion of methicillin-resistant S. aureus and cardiac complication rates than non-HD patients with IE. Culture-negative IE was more common in non-HD patients.     

CK20 and Ki-67 as significant prognostic factors in human bladder carcinoma

Aberrant expression of CK20 and Ki-67 has been documented in many kinds of primary tumors and has proved useful as an ancillary diagnostic aid for those tumors. The aim of this study was to analyze the expression patterns of CK20 and Ki-67 in human bladder carcinomas (BCa) and to evaluate their clinical significance in the progression of BCa. CK20 and Ki-67 expression in BCa and normal bladder tissues were detected by immunohistochemical staining. The Spearman correlation was calculated between the expression of CK20 and Ki-67 in BCa tissues. The correlation of CK20 and Ki-67 expression with the clinicopathological characteristics and the prognosis of BCa were subsequently assessed. CK20 expression was positively expressed in 103/154 (66.9%) of BCa and 2/30 (6.67%) of normal bladder tissues, respectively. The positive expression rate of Ki-67 in BCa tissues was also significantly higher than those in normal bladder tissues (81.8 vs. 10%, p < 0.01). The Spearman analysis indicated that the expression level of CK20 has a significant positive correlation with that of Ki-67 (rs = 0.86, p = 0.02). Pathologic findings demonstrated that the intensity of CK20 and Ki-67 staining in cancerous tissues was associated significantly with tumor grades (p = 0.03, p < 0.01), distant metastasis (both p < 0.01) and TNM grades (p = 0.01, p = 0.03) of BCa. The progression-free survival of the patients with CK20 (+)/Ki-67 (+) expression was poorest (p < 0.01). The results suggest that the expression of CK20 and Ki-67 may be an important feature of BCa, and the detection of their co-expression may benefit the prediction of BCa prognosis.     

Risk factors and prognoses of invasive Candida infection in surgical critical ill patients with perforated peptic ulcer

BackgroundThe risk of invasive Candida infection (ICI) is high in patients with perforated peptic ulcer (PPU) who received laparotomy or laparoscopic surgery, but the risk factors and predictors of morbidity outcomes remain uncertain. This study aims to identify the risk factors of ICI in surgical critically ill PPU patients and to evaluate the impact on patient's outcomes.MethodsThis is a single-center, retrospective study, with a total of 170 surgical critically ill PPU patients. Thirty-seven patients were ICI present and 133 were ICI absent subjects. The differences in pulmonary complications according to invasive candidiasis were determined by the Mann–Whitney U test. Evaluation of predictors contributing to ICI and 90-day mortality was conducted by using multivariate logistic regression analysis.ResultsCandida albicans was the primary pathogen of ICI (74.29%). The infected patients had higher incidence of bacteremia (p < 0.001), longer intensive care unit (p < 0.001) and hospital (p < 0.001) stay, longer ventilator duration (p < 0.001) and increased hospital mortality (p = 0.02). In the multivariate analysis, serum lactate level measured at hospital admission was independently associated with the occurrence of ICI (p = 0.03). Liver cirrhosis (p = 0.03) and Sequential Organ Failure Assessment (SOFA) score (p = 0.007) were independently associated with the 90-day mortality.ConclusionsBlood lactate level measured at hospital admission could be a predictor of ICI and the surgical critically ill PPU patients with liver cirrhosis and higher SOFA score are associated with poor outcomes.     

Clinicopathological features and lymph node metastasis risk in early gastric cancer with WHO criteria in China: 304 cases analysis

AimsThe aim of this research was to identify the clinicopathological characteristics of early gastric cancer (EGC) based on the WHO criteria, and to analyze predictors for lymph node metastasis (LNM) in EGC in a Chinese study population.MethodsWe retrospectively collected data of 304 Chinese EGC patients, including 265 patients undergoing radical gastrectomy and 39 patients undergoing endoscopic resection. Histological features were accessed by three experienced pathologists. Univariate analysis and multivariate analysis were used to identify the correlation between clinicopathological features and LNM.ResultsAmong the 304 cases with EGC, the rate of well differentiated tubular adenocarcinoma was 11.2%, significantly lower than that of Japanese and South Korean, which was 24.8% and 19.9% respectively (p<0.001 and p = 0.006), but similar to that of a Western result, which was 11.9% (p = 0.860). Among the 265 patients who underwent gastrectomy, 18.5% of the patients had LNM. Univariate analysis showed that macroscopic type, differentiation degree, invasion depth, infiltration pattern (INF), lymphovascular invasion and ulceration were related to LNM. Multivariate analysis revealed that lymphovascular invasion (p < 0.001, OR = 6.549), ulceration (p = 0.035, OR = 2.527) and INF c (p = 0.042, OR = 3.424) were the independent risk factors of LNM in EGC.ConclusionsThe pathological diagnosis standard of well differentiated tubular adenocarcinoma in China significantly differs from that in Japan and South Korea, but is similar to western countries. LNM is more likely to occur in EGCs with lymphovascular invasion, ulceration and INF c.     

Clinical characteristics and risk factors for children with norovirus gastroenteritis in Taiwan

BackgroundNorovirus is a common acute gastroenteritis (AGE) pathogen across all age groups worldwide, which is difficult to differentiate from other pathogens. This study aimed to understand the clinical characteristics and risk factors of norovirus gastroenteritis among children in Taiwan.MethodsA prospective AGE surveillance study was conducted in children aged ≤5 years who were hospitalized in 10 major hospitals in Taiwan between 2014 and 2017. The non-AGE control group included healthy children who were matched based on age, gender, season, and geographic area.ResultsOverall, 674 norovirus gastroenteritis patients were enrolled. Fever (p < 0.001), mucoid stool (p < 0.001), and bloody stool (p < 0.001) occurred less frequently among norovirus gastroenteritis patients. Norovirus gastroenteritis patients yielded lower CRP values on admission (21.78 ± 36.81 vs. 46.26 ± 58.12 mg/L, p < 0.001) than non-norovirus controls. Norovirus gastroenteritis patients were associated with higher direct contact rates with AGE patients within 1 week (30.5% vs. 0.97%, p < 0.001), lower hand wash rates before meals (21.6% vs. 15.4%, p = 0.001), lower human milk (15.8% vs. 19.8%, p = 0.045) and guava consumption rates (17.8% vs. 24.3%, p = 0.002) than non-AGE participants.ConclusionsBody temperature, stool characteristics, and CRP value can help distinguish the norovirus from other pathogens. The major risk factor of norovirus AGE is contact with AGE patient. Higher frequency of hand wash, human milk, and guava intake may be protective against norovirus gastroenteritis.     

Prognostic significance of intrahepatic lymphatic invasion in colorectal liver metastases

BackgroundIntrahepatic lymphatic invasion is an adverse prognostic factor after hepatectomy for colorectal liver metastases (CLMs). However, most patients in previous reports had liver resection before the era of FOLFOX/FIRI-based chemotherapy.MethodsForty-six patients who underwent hepatectomy for CLMs from 2004 to 2020 were evaluated. We histologically evaluated portal invasion, intrahepatic lymphatic invasion, and biliary invasion on hematoxylin-eosin slides. We also collected the following clinicopathologic factors: gender, age, timing, the number and maximum size of CLMs, preoperative tumor markers, neutrophil/lymphocyte ratio, location, and lymph node metastases of primary cancer, and chemotherapy after hepatectomy. A multivariate Cox proportional hazard model was used to define the relationship between overall (OS) or disease-free survival (DFS) and clinicopathologic factors.ResultsHistological invasions were portal invasion in 8 (17.4 %), intrahepatic lymphatic invasion in 6 (13.0 %), and biliary invasion in 5 (10.9 %). Chemotherapy for recurrence after hepatectomy (n = 29) was performed in 22 and 14 of those who received FOLFOX/FIRI-based chemotherapy. By multivariate analysis, the number of CLMs (p < 0. 01) and presence of intrahepatic lymphatic invasion (p = 0.02) were independent predictors of recurrence. The number of CLMs (p = 0.02) and prehepatectomy carcinoembryonic antigen level (p = 0.02), but not intrahepatic lymphatic invasion (p = 0.18), were independent predictors of survival using multivariate analysis.ConclusionsThe presence of intrahepatic lymphatic invasion adversely affected patient's DFS, but not OS in patients with CLMs in the era of FOLFOX/FIRI chemotherapy. FOLFOX/FIRI-based chemotherapy might improve OS, even in patients with positive intrahepatic lymphatic invasion.     

Clinicopathological and prognostic significance of p53, Ki-67, and Bcl-2 expression in Tunisian gastric adenocarcinomas

Gastric carcinoma (GC) is a highly aggressive malignancy with poor prognosis. It is widely accepted that malignancy results from abnormal cell growth due to dysregulation of the balance between cell proliferation and apoptosis. Our study aimed to investigate the clinicopathological and prognostic significance of p53, Ki-67, and Bcl-2 in Tunisian GC patients by immunohistochemistry. It was observed that the older patients showed p53 overexpression compared with the younger patients (p < 0.05). There was higher p53 expression in the intestinal-type compared with the diffuse-type (p < 0.05), and in well/moderate differentiated than in poor differentiated tumors. The expression of Ki-67 was positively associated with tumor size and venous invasion (p < 0.05). Bcl2 expression occurred in male patients and correlated with depth of invasion (p = 0.02). A Kaplan–Meier analysis indicated an inverse correlation between p53 and Ki-67 expression and the overall survival. Multivariate analysis revealed that the tumor site, Ki-67 and p53 expression were independent prognostic factors for gastric carcinomas (p < 0.05). Finally, combined expression of p53, Ki-67 and Bcl-2 showed that the group of patients with tumors p53+/Ki-67+/Bcl2− had aggressive behavior and poor prognosis (p log rank = 0.000). In summary, our data indicated that the expression of p53, Ki-67, and Bcl-2 may provide useful information for identifying patients with aggressive behavior and poor prognosis of GC.     

Specifying the effects of physician's communication on patients’ outcomes: A randomised controlled trial

ObjectiveTo experimentally test the effects of physician's affect-oriented communication and inducing expectations on outcomes in patients with menstrual pain.MethodsUsing a 2 × 2 RCT design, four videotaped simulated medical consultations were used, depicting a physician and a patient with menstrual pain. In the videos, two elements of physician's communication were manipulated: (1) affect-oriented communication (positive: warm, emphatic; versus negative: cold, formal), and (2) outcome expectation induction (positive versus uncertain). Participants (293 women with menstrual pain), acting as analogue patients, viewed one of the four videos. Pre- and post video participants’ outcomes (anxiety, mood, self-efficacy, outcome expectations, and satisfaction) were assessed.ResultsPositive affect-oriented communication reduced anxiety (p < 0.001), negative mood (p = 0.001), and increased satisfaction (p < 0.001) compared to negative affect-oriented communication. Positive expectations increased feelings of self-efficacy (p < 0.001) and outcome expectancies (p < 0.001), compared to uncertain expectations, but did not reduce anxiety. The combination of positive affect-oriented communication and a positive expectation reduced anxiety (p = 0.02), increased outcome expectancies (p = 0.01) and satisfaction (p = 0.001).ConclusionBeing empathic and inducing positive expectations have distinct and combined effects, demonstrating that both are needed to influence patients’ outcomes for the best.Practice implicationsContinued medical training is needed to harness placebo-effects of medical communication into practice.     

Cardiac function in adolescents and young adults with 22q11.2 deletion syndrome without congenital heart disease

BackgroundDiagnosis and treatment of 22q11.2 deletion syndrome (22q11.2DS) have led to improved life expectancy and achievement of adulthood. Limited data on long-term outcomes reported an increased risk of premature death for cardiovascular causes, even without congenital heart disease (CHD). The aim of this study was to assess the cardiac function in adolescents and young adults with 22q11.2DS without CHDs.MethodsA total of 32 patients (20M, 12F; mean age 26.00 ± 8.08 years) and a healthy control group underwent transthoracic echocardiography, including Tissue Doppler Imaging (TDI) and 2-dimensional Speckle Tracking Echocardiography (2D-STE).ResultsCompared to controls, 22q11.2DS patients showed a significant increase of the left ventricle (LV) diastolic and systolic diameters (p = 0.029 and p = 0.035 respectively), interventricular septum thickness (p = 0.005), LV mass index (p < 0.001) and aortic root size (p < 0.001). 2D-STE analysis revealed a significant reduction of LV global longitudinal strain (p < 0.001) in 22q11.2DS than controls. Moreover, several LV diastolic parameters were significantly different between groups.ConclusionsOur results suggest that an echocardiographic follow-up in 22q11.2DS patients without CHDs can help to identify subclinical impairment of the LV and evaluate a potential progression of aortic root dilation over time, improving outcomes, reducing long-term complications and allowing for a better prognosis.