Terms Of Clinicopathological Features Research Articles

Significance of Preoperative Modified Nutritional Risk Index in Patients With Gastric Cancer After Curative Resection.

A new modified nutritional risk index (mNRI), calculated using serum albumin (g/l)+body mass index (BMI) [weight (kg_/height2 (m2)], is a good predictor of postoperative complications and cancer survival. However, no study has used this index in patients with gastric cancer (GC). Therefore, we aimed to investigate the clinical significance of the preoperative mNRI values in patients with GC who underwent curative resection. We examined 449 patients who underwent curative resection for GC at Kanagawa Cancer Center between 2013 and 2017. The mNRI cutoff value obtained using a receiver operating characteristic analysis was 23.31. Patients were divided into high and low mNRI groups according to the cutoff value, and the clinicopathological characteristics and outcomes were compared between the two groups. In terms of clinicopathological characteristics, the high mNRI group had a higher proportion of men, higher BMI, and a higher proportion of patients with American Society of Anesthesiologists physical status class 2/3 compared with the low mNRI group; the low mNRI group had significantly worse 5-year recurrence-free survival (RFS) and overall survival (OS) than the high mNRI group (OS, p=0.005) (OS, p=0.006; RFS, p=0.018) did. In the multivariate analysis, a low mNRI was an independent predictor of OS (p=0.006) and RFS (p=0.013). Preoperative mNRI may be a useful recurrence and prognostic biomarker in patients with GC who have undergone curative resection.

Effect of Pap Smear Cytology, HPV Genotyping on the Concordance of Colposcopy and Conization Results.

To evaluate the conization results performed due to human papillomavirus (HPV), smear, colposcopy results or clinician's decision and determine the factors that predict ≥CIN2. Retrospective comparative study. Place and Duration of the Study: Department of Gynaecology and Obstetrics, Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey, between January 2011 and December 2021. Women with known HPV results who underwent conization in the Gynaecology clinic were retrospectively included. Age, HPV genotypes, conization, and colposcopy results of the patients were recorded. Patients were divided into two groups as those with and without ≥CIN2 and compared in terms of clinicopathological features. Four hundred and twenty eight (82.8%) of the 517 patients were premenopausal and perimenopausal, and 89 (17.2%) of the patients with a median age of 42 years (range: 30-65 years) were postmenopausal. While 374 were HPV 16/18 positive, 143 were non-16/18 HPV positive. Conization result was normal in 202 (39.1%) patients, CIN1 in 129 (25.0%) patients, and CIN 2-3 in 186 (36.0%) patients. In the HPV 16/18 positive group, conization result was normal in 38.2% of patients, CIN1 in 20.9%, and CIN 2-3 in 40.9%; these rates were 41.3%, 35.7%, and 23.1% in the HPV-other group, respectively (p <0.001). In the logistic regression model, age, HPV type (16/18), and smear cytology results (≥ASC-US) were tested as independent factors predicting ≥CIN2. HPV 16/18 positivity and smear cytology result (≥ASC-US) were the factors predicting ≥CIN2. Smear and HPV genotyping can make an important contribution to detecting false <NIC2 results as a result of colposcopy. CIN, Colposcopy, Conization, Cervix, Cervical cancer, Neoplasia, HPV.

Comparison of clinicopathological characteristics and long-term survival between patients with gallbladder adenosquamous carcinoma and pure gallbladder adenocarcinoma after curative-intent surgery: a single-center experience in China and a meta-analysis.

The aim of the study was to evaluate the similarities and differences between gallbladder adenosquamous carcinoma (GBASC) and pure gallbladder adenocarcinoma (GBAC). Patients with GBASC and GBAC from 2010 to 2020 were analyzed in terms of clinicopathological features and long-term survival. Moreover, a meta-analysis was also performed for further validation. Our experience: A total of 304 patients with resected GBC were identified, including 34 patients with GBASC and 270 patients with GBAC. Patients with GBASC had a significantly higher preoperative CA199 level (P <0.0001), a significantly higher incidence of liver invasion (P <0.0001), a relatively larger tumor size (P = 0.060), and a significantly higher proportion of patients with T3-4 (P <0.0001) or III-IV disease (P = 0.003). A comparable R0 rate was obtained between two groups (P = 0.328). A significantly worse overall survival (OS) (P = 0.0002) or disease-free survival (DFS) (P = 0.0002) was observed in the GBASC. After propensity score matching, comparable OS (P = 0.9093) and DFS (P = 0.1494) were obtained. Clear margin (P = 0.001), node metastasis (P <0.0001), T stage (P <0.0001), and postoperative adjuvant chemoradiotherapy (P <0.0001) were independent prognostic factors for OS for the entire cohort. Adjuvant chemoradiotherapy had a survival benefit for patients with GBAC, while the survival benefit was still being validated in patients with GBASC. Meta-analysis: With our cohort incorporated, a total of seven studies involving 1,434 patients with GBASC/squamous carcinoma (SC) were identified. GBASC/SC shared a worse prognosis (P <0.00001) and more aggressive tumor biological features than GBAC. GBASC/SC shared more aggressive tumor biological features and a much worse prognosis than those with pure GBAC.

Comparison between laparoscopic versus open appendectomy in morbid obese patients

Purpose To evaluate the laparoscopic approach advantages for the management of acute appendicitis in morbidly obese patients. Methods A prospective study included all morbidly obese patients who had presented to the emergency department at Sohag University Hospitals and were diagnosed with acute appendicitis between the 1st of June 2022 and the 31st of January 2023. All those patients were invited to participate in the research by randomization. The authors informed patients and their first-degree relatives about both techniques, signed a consent form for participation in the study. The authors categorized them into two groups; laparoscopic approach (group I) and open approach (group II). Comparisons were based on operative time, intraoperative complications, length of hospital stay, postoperative complications, and time until return to normal daily activities. Results The study enrolled 64 patients: 33 had a laparoscopic appendectomy, and 31 had an open appendectomy. The groups were similar in terms of clinicopathologic characteristics. The operating time was significantly shorter for Group I patients than Group II (Group I, 49.09±16.21 min vs. Group II, 68.03±15.78 min; P value less than 0.05). Regarding the length of hospital stay, twenty-six patients (78.8%) were discharged within the 1st 24 h in the laparoscopic group versus 17 patients (54.8%) in the open group (P value 0.041). The time until return to the routine daily work was significantly shorter in the laparoscopic group (11.27±2.6 days) than in the open group (17.23±4.8 days) (P value less 0.05). Four postoperative complications were reported in the study population: wound complications (infection, seroma formation), residual abdominal abscess, paralytic ileus, and thromboembolic complications (Deep venous thrombosis and pulmonary embolism). Group II had a statistically significant higher complication rate (32.3%) than Group I (9.09%) (P value 0.007). Conclusion Laparoscopic appendectomy had superior clinical outcomes than an open appendectomy in morbidly obese patients. In addition to minimal invasiveness and better cosmetic results, it has a great advantage as a diagnostic and therapeutic tool in morbidly obese patients with suspected appendicitis. It is also a safe and feasible approach with a low rate of complications with a well-trained expert surgeon.

Perioperative Complications and Oncologic Outcomes of Nephrectomy Following Immune Checkpoint Inhibitor Therapy: A Multicenter Collaborative Study

BackgroundImmune checkpoint inhibitors (ICIs) are now a mainstay of metastatic renal cell carcinoma (RCC) management with five current Food and Drug Administration–approved regimens. However, data regarding nephrectomy outcomes following an ICI are limited. ObjectiveTo evaluate the safety and outcomes of nephrectomy following an ICI. Design, setting, and participantsA retrospective review was performed of patients with primary locally advanced or metastatic RCC undergoing nephrectomy following an ICI in five US academic centers between January 2011 and September 2021. Outcome measurements and statistical analysisClinical data, perioperative outcomes, and 90-d complications/readmissions were recorded and evaluated by univariate and logistic regression models. Recurrence-free and overall survival probabilities were estimated by the Kaplan-Meier method. Results and limitationsA total of 113 patients with a median (interquartile range) age of 63 (56–69) yr were included. The main ICI regimens were nivolumab ± ipilimumab (n = 85) and pembrolizumab ± axitinib (n = 24). Risk groups included 95% intermediate- and 5% poor-risk patients. Surgical procedures were 109 radical and four partial nephrectomies, including 60 open, 38 robotic, and 14 laparoscopic with five (10%) conversions. Two intraoperative complications were reported (bowel and pancreatic injury). The median operative time, estimated blood loss, and hospital stay were 3 h, 250 ml, and 3 d, respectively. A complete pathologic response (ypT0N0) was noted in six (5%) patients. The 90-d complication rate was 24%, with 12 (11%) patients requiring readmission. On a multivariable analysis, two or more risk factors (odds ratio [OR] 2.91, 95% confidence interval [CI]: 1.09, 7.42) and pathologic T stage ≥T3 (OR 4.21, 95% CI: 1.13–15.8) were independently associated with a higher 90-d complication rate. The 3-yr estimated overall survival and recurrence-free survival rates were 82% and 47%, respectively. Limitations include the retrospective nature and heterogeneous cohort in terms of clinicopathologic characteristics and ICI regimens received. ConclusionsNephrectomy following ICI therapy is feasible and a potential consolidative therapy option in select patients. Further research in the neoadjuvant setting is also warranted. Patient summaryThis study evaluates the outcomes of kidney surgery following immune checkpoint inhibitor therapy (mainly nivolumab and ipilimumab or pembrolizumab and axitinib) for patients with advanced kidney cancer. We utilized data from five academic centers across the USA and found that surgery in this setting did not have more complications or returns to the hospital than similar surgeries, indicating that it is a safe and feasible procedure at this time.

Clinicopathologic Profile, Management and Outcome of Sinonasal Ameloblastoma-A Systematic Review.

Sinonasal ameloblastoma (SNA) is considered to be a subtype of ameloblastoma. It differs from gnathic ameloblastoma in terms of clinicopathologic features, management and prognosis. Thus, the objective of the present review was to study the complications, survival, recurrence rate and outcomes following the management of SNA. The electronic search process was conducted on PubMed-Medline, Embase, and Scopus. Google Scholar was used to search grey literature. Quality assessment of the case reports (CR) and case series (CS) was done based on CARE guidelines. The initial search resulted in 2111 articles. 15 studies (13 CR and 2 CS) were found to meet the eligibility criteria. The majority of the studies described histological features of SNA, which were consistent with ameloblastomas of gnathic origin. There were no SNA-related deaths reported in the included studies. Five studies described endoscopic surgeries to remove SNAs, and three SNAs were treated with post-surgery radiotherapy. Data from included studies suggest that sinonasal ameloblastomas are histologically similar to gnathic ameloblastomas, but their clinical presentation is different. They may cause complete or partial obstruction of the nasal cavity and the sinus. They appear to affect an older demographic, and their resection may be accompanied by the excision of a large portion of the maxilla, necessitating maxillofacial prosthetic rehabilitation.

Radioiodine adjuvant therapy in differentiated thyroid cancer: An update and reconsideration.

Radioiodine (131I) therapy (RAI) has been utilized for treating differentiated thyroid cancer (DTC) for decades, and its uses can be characterized as remnant ablation, adjuvant therapy (RAT) or treatment for known diseases. Compared with the definite 131I treatment targets for remnant ablation and known disease, 131I adjuvant therapy (RAT) aims to reduce the risk of recurrence by destroying potential subclinical disease. Since it is merely given as a risk with no imaging confirmation of persistence/recurrence/metastases, the evidence is uncertain. With limited knowledge and substance, the indication for RAT remains poorly defined for everyday clinical practice, and the benefits of RAT remain controversial. This ambiguity results in a puzzle for clinicians seeking clarity on whether patients should receive RAT, and whether patients are at risk of recurrence/death from undertreatment or adverse events from overtreatment. Herein, we clarified the RAT indications in terms of clinicopathological features, postoperative disease status and response to therapy evaluation, and retrospectively examined the clinical outcomes of RAT as reported in current studies and guidelines. Furthermore, given the evolution of nuclear medicine imaging techniques, it can be expected that the future of RAT may be advanced by nuclear medicine theranostics (i.e., 131I whole-body scan, PET/CT) by accurately revealing the biological behaviors, as well as the underlying molecular background.

Can HER2 1+ Breast Cancer Be Considered as HER2-Low Tumor? A Comparison of Clinicopathological Features, Quantitative HER2 mRNA Levels, and Prognosis among HER2-Negative Breast Cancer.

Simple SummaryHER2-low breast cancer is a new entity featuring low HER2 expression (HER2 1+ or HER2 2+/FISH−) and can potentially benefit from novel antibody-drug conjugates. A precise estimation of HER2-low expression is warranted. Here, we found that HER2 1+ and HER2 0 tumors shared similar clinicopathologic features and HER2 mRNA expression, significantly different from HER2 2+/FISH− tumors. A poor concordance rate was found between IHC/FISH and qRT-PCR for the estimation of HER2 expression in HER2-negative tumors. This study suggests that the current definition of HER2-low expression with the lower boundary of HER2 IHC 1+ may be inaccurate. IHC and qRT-PCR were not optimal to quantify HER2-low expression, especially for HER2 1+ patients.Background: Human epidermal growth factor receptor 2 (HER2)-low tumor is a new entity defined as HER2 immunohistochemistry (IHC) 1+ or 2+/fluorescence in situ hybridization (FISH)-negative. We aimed to evaluate whether HER2 mRNA levels tested by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) could better define HER2-low tumors. Patients and methods: Consecutive breast cancer patients with hormonal receptor-positive, HER2-negative diseases, and HER2 mRNA results were included. Clinicopathologic features, HER2 mRNA expression level, and prognosis were compared among HER2 0, 1+ and 2+/FISH− groups. Concordance of the HER2 category between qRT-PCR and IHC/FISH was analyzed for each group. Results: 2296 patients were included: 368 (16.0%) HER2 0, 911 (39.7%) 1+, and 1017 (44.3%) 2+/FISH− tumors. HER2 1+ cases shared similarities with HER2 0 tumors in terms of clinicopathologic features (all p > 0.05), whereas IHC 2+/FISH− cases were less often non-IDC (p = 0.045), node-negative (p = 0.044), and Ki-67 < 14% (p <0.001). The mRNA expression was similar between HER2 0 and 1+ cases (p = 0.063), and both were lower than 2+/FISH− cases (p < 0.001). A poor concordance rate was found between IHC/FISH and qRT-PCR for HER2 0 and HER2-low cases (Cohen’s kappa 0.126, p < 0.001). No survival difference was observed among these groups, whether stratified by HER2 IHC/FISH status or mRNA level (all p > 0.05). Conclusions: HER2 1+ cases had similar clinicopathological features to HER2 0 breast cancers, and both were different from HER2 2+/FISH− cases. HER2 mRNA levels were comparable between HER2 0 and 1+ tumors, and both were significantly lower than IHC 2+/FISH− tumors. Neither IHC nor qRT-PCR may be optimal to quantify HER2-low expression, especially for HER2 1+ patients.

Clinical outcomes of immunohistochemistry of the p53 Staining pattern in high-grade serous ovarian carcinoma.

ObjectiveTo investigate the prevalence of p53 mutations and associated factors between immunohistochemistry (IHC) and p53 staining patterns among patients with high-grade serous ovarian carcinoma (HGSOC).MethodsThis study is a retrospective review. A total of 62 patients with HGSOC underwent surgery at Srinagarind Hospital between January 2016 and December 2020. Histological examination was performed based on a combination of morphology and IHC staining with p53. The p53 immunostaining pattern was interpreted as a missense mutation, nonsense mutation, or a wild-type pattern. Missense (p53 overexpression pattern) and nonsense (null expression p53 pattern) mutations were considered p53 mutations. A wild-type pattern was defined as a p53 non-mutation.Resultsp53 mutations were identified in 93.6% of the patients. Subgroup analysis of the p53 mutation group between the p53 overexpression pattern and the p53 null expression pattern in terms of clinicopathological characteristics and initial treatment was performed. Patients with the p53 overexpression pattern had significantly more omental metastases than those with the p53 null expression pattern (87.8% vs. 64.7%, P=0.042). There were no statistically significant differences in median progression-free survival (PFS) (9 vs. 10 months, P=0.813) or median overall survival (OS) (12 vs. 17 months, P=0.526) between the two groups.ConclusionThe prevalence of p53 mutations in HGSOC patients in this study was 93.6%. Omental metastasis is a significant pathological factor in predicting overexpression p53 pattern in HGSC. However, IHC analysis of the p53 staining pattern did not affect OS or PFS among patients with HGSOC.

Fusobacterium nucleatum load in MSI colorectal cancer subtypes.

Fusobacterium nucleatum (F. nucleatum) infection may lead to colorectal cancer (CRC) development in the context of microsatellite instability (MSI). To date, however, the relationship between F. nucleatum load and MSI CRC subtypes has not been clarified. One hundred seventy-nine consecutive patients with CRC were enrolled in the present study. In 94 patients with MSI CRC, 32 had hereditary MSI CRC from Lynch syndrome, 62 had sporadic MSI CRC, while the remaining 85 had microsatellite stable (MSS) CRC. The association of the F. nucleatum load with each CRC subtype and the patients' clinicopathological characteristics was examined. Of the 179 patients with CRC, 158 (88.3%) were F. nucleatum-positive. A high F. nucleatum load was found in 84.4% (27/32), 96.8% (60/62), and 83.5% (71/85) of the patients with hereditary MSI CRC, sporadic MSI CRC, and MSS CRC, respectively (P = 0.024). In terms of clinicopathological features, a high F. nucleatum load was significantly associated with female, right-sided CRC, BRAF V600E, CpG island methylator phenotype-positive CRC, and MSI CRC (P = 0.008, P = 0.015, P = 0.007, P = 0.006, and P < 0.001, respectively). However, the clinicopathological characteristics did not differ significantly by F. nucleatum load between hereditary and sporadic MSI CRCs without tumor depth. The F. nucleatum load was higher in hereditary MSI CRC than in MSS CRC as well as sporadic MSI CRC. These findings may contribute to preventing CRC in hereditary MSI CRC through appropriate intervention.

Primary Angiosarcoma of the Breast: A Single-Center Retrospective Study in Korea.

Due to the rarity of primary angiosarcoma of the breast, optimal management is based on expert opinion. The aim of this study was to review all primary angiosarcomas of the breast obtained from a single center in terms of clinicopathologic characteristics, treatment, and survival outcomes. From 1997 to 2020, 15 patients with primary angiosarcoma of the breast underwent either mastectomy or wide excision. We analyzed the clinicopathologic data to assess disease-free survival and overall survival. Fifteen women with primary angiosarcoma of the breast were identified. The mean age at diagnosis was 33 years (range: 14–63 years). The overall mean tumor size was 7.7 cm (range 3.5–20 cm). Upon histological grading, there were three cases of low grade, five intermediate grade, six high grade, and one unidentified grade. The five-year disease-free survival rate was 24.4%, and the five-year survival rate was 37.2%. The survival rate of the low-grade patient group was statistically higher than that of the intermediate- or high-grade patient groups (p = 0.024). Primary angiosarcoma of the breast is a rare aggressive tumor characterized by high grade and poor outcome. Histologic grade appears to be a reliable predictor of survival. There are no standard treatment guidelines; thus, optimal R0 surgical resection remains the best approach. The roles of neoadjuvant, adjuvant chemotherapy, and radiotherapy remain unclear.

Genomic landscape of sporadic pediatric differentiated thyroid cancers: a systematic review and meta-analysis.

Differentiated thyroid cancers (DTCs) in the paediatric population differ from that of their adult counterparts in terms of clinicopathological characteristics and treatment outcomes. This systematic review and meta-analysis was conducted to comprehensively evaluate the prevalence of various genetic alterations underlying the pathogenesis of sporadic paediatric DTCs. This study followed the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Systematic searches were made on the PubMed and Embase databases using relevant keywords, and articles published until October 15, 2021 were selected. Data on the prevalence of various genetic alterations were extracted from the individual articles. Random-effects model was employed for meta-analysis to generate pooled estimates and their 95% confidence intervals (95% CIs). Thirty-three articles comprising 1,380 paediatric patients were included. RET rearrangement (pooled prevalence: 24.4%, 95% CI: 19.1-30.1) was observed to be the most common genetic alteration in sporadic paediatric DTCs, closely followed by BRAF point mutation (pooled prevalence: 21.2%, 95% CI: 17.2-25.5). Other common alterations included: NTRK rearrangement (pooled prevalence: 13.5%, 95% CI: 9.5-17.9) and DICER1 mutation (pooled prevalence: 12.5%, 95% CI: 3.6-25.7). RAS and TERT mutations were observed to be relatively uncommon (pooled prevalence: 5.7%, 95% CI: 2.9-9.3, and 2.2%, 95% CI: 0.4-5.5, respectively). There was no evidence of publication bias. Fusion oncogenes are noted to be the major oncogenic drivers in sporadic paediatric DTCs and underlie their unique behaviour. However, despite the relatively lower frequency of BRAF point mutation compared to adults, it remains a major player in childhood DTCs.

Cell of Origin Based on Hans’ Algorithm as Prognostic Factor in Diffuse Large B-Cell Lymphoma: A Clinicopathologic and Survival Study

Background: Diffuse Large B-Cell Lymphoma (DLBCL) has been classified based on Cell of Origin (COO) into Germinal Center B-cell (GCB) and Non-Germinal Center B-cell (Non-GCB). The practical application of this concept by immunohistochemistry (IHC)-based subtyping with Hans’ algorithm and its role as a prognostic factor has been widely investigated with conflicting results. Moreover, the recent deeper molecular characterizations of DLBCL have been another challenges for this approach to remain as a prognostic factor. Objective: To determine the prognostic value of COO by IHC-based subtyping with Hans’ algorithm for DLBCL. Materials and Methods: This was a single-center retrospective analysis including DLBCL cases diagnosed in 2014-2019 from Dr. Sardjito Hospital, Yogyakarta, Indonesia. Hans’ algorithm with CD10, BCL6, and MUM1 were used. The two subtypes were compared in terms of clinicopathological features and 3 years overall survival. Results: Seventy patients were included in this study. Non-GCB was predominant than GCB 74.3% vs 25.7%, with the ratio of 2.8:1. No statistical difference in the clinicopathological features from both subtypes in terms of age, gender, Ann Arbor stadium, ECOG performance status, extra-nodal involvement, and LDH level. Ann Arbor stadium and ECOG showed significant prognostic value for patients outcome with multivariate analysis (OR 3.64; 95%CI 0.18-0.61; p=0.001) and (OR 2.68; 95%CI 0.11-0.77; p=0.009). Survival analysis based on COO did not show significant difference between GCB and non-GCB subtypes (log rank=0.46). Further analysis based on COO and the use of rituximab showed better OS in the two subtypes than without rituximab although not significant (log rank=0.67). Conclusion: The role of COO with Hans’ algorithm as prognostic factor in DLBCL is not confirmed in this study. Some related factors may be the addition of rituximab and the recent molecular characterization of DLBCL which covered a more subtle classification of the disease beyond GCB and non-GCB subtypes.

Prognostic significance of splenectomy during completion total gastrectomy in patients with remnant gastric cancer: propensity score matching analysis.

Splenectomy for patients with remnant gastric cancer has been controversial. The purpose of this study is to identify the impact of splenectomy in the treatment of remnant gastric cancer. We retrospectively analyzed 285 patients with remnant gastric cancer who underwent completion total gastrectomy with or without splenectomy in Samsung Medical Center, between September 1996 and December 2017. We used a 1:1 propensity score matching method for the analysis. The matching factors were age, sex, and pathologic stage. After the matching process, we compared the 5-year overall survival (OS) and the disease-free survival (DFS) between patients with and without splenectomy during completion total gastrectomy. The median duration of follow-up was 58.0 months (range, 0-132 months). After propensity score matching, there were no statistically significant differences between the splenectomy group (n=77) and no splenectomy group (n=77) in terms of clinicopathological features. The 5-year OS rate between the no splenectomy and splenectomy group were not significantly different. There was no significant difference between 5-year DFS of the matched groups. Multivariate analysis revealed that splenectomy is not a significant prognostic factor in terms of 5-year OS (no splenectomy vs. splenectomy; 61.5% vs. 60.2%, P=0.884) or DFS (74.9% vs. 69.8%, P=0.880). Splenectomy has no impact on the OS and DFS in patients with remnant gastric cancer. Splenectomy during completion total gastrectomy may not be necessary.

Construction of a novel immune-related lncRNA signature and its potential to predict the immune status of patients with hepatocellular carcinoma

BackgroundThe accuracy of existing biomarkers for predicting the prognosis of hepatocellular carcinoma (HCC) is not satisfactory. It is necessary to explore biomarkers that can accurately predict the prognosis of HCC.MethodsIn this study, original transcriptome data were downloaded from The Cancer Genome Atlas (TCGA) database. Immune-related long noncoding ribonucleic acids (irlncRNAs) were identified by coexpression analysis, and differentially expressed irlncRNA (DEirlncRNA) pairs were distinguished by univariate analysis. In addition, the least absolute shrinkage and selection operator (LASSO) penalized regression was modified. Next, the cutoff point was determined based on the area under the curve (AUC) and Akaike information criterion (AIC) values of the 5-year receiver operating characteristic (ROC) curve to establish an optimal model for identifying high-risk and low-risk groups of HCC patients. The model was then reassessed in terms of clinicopathological features, survival rate, tumor-infiltrating immune cells, immunosuppressive markers, and chemotherapy efficacy.ResultsA total of 1009 pairs of DEirlncRNAs were recognized in this study, 30 of these pairs were included in the Cox regression model for subsequent analysis. After regrouping according to the cutoff point, we could more effectively identify factors such as aggressive clinicopathological features, poor survival outcomes, specific immune cell infiltration status of tumors, high expression level of immunosuppressive biomarkers, and low sensitivity to chemotherapy drugs in HCC patients.ConclusionsThe nonspecific expression level signature involved with irlncRNAs shows promising clinical value in predicting the prognosis of HCC patients.

Potential role of immune cell genetic variants associated with tumor microenvironment response in laryngeal squamous cell carcinoma (LSCC) in terms of clinicopathological features

Immunomodulatory signals regulate the self-tolerance, activation, priming and survival processes of T cells. Programmed cell death protein 1 (PD1), Programmed death-ligand 1 (PD-L1) inhibitory signals and CD27, CD28 costimulators have been detected for many solid organ cancers in tumor-infiltrating T cells. It was aimed to investigate the immune cell-based regulatory genetic variants in laryngeal squamous cell carcinoma (LSCC) in terms of clinicopathological features. Genotyping was performed by PCR-RFLP method for PD-1 rs2227981, PD-L1 rs2890658, CD28 rs3116496, CD27 rs2267966 genetic variants from genomic DNAs extracted from peripheral blood samples in One Hundred Thirty-Six individuals (Sixty-one LSCC and seventy-five controls). Analysis of SNPs was carried out according to multiple inheritance models (co-dominant, dominant, recessive, over-dominant and log-additive). There was no difference between LSCC and control groups in genotype/allele distribution for PD-1 and PD-L1 (p > 0.05). In the PD-1 overdominant model, the CT genotype was found to be high (p = 0.036) in those without a family history. The frequency of C allele (AC+CC) in the PD-L1 dominant model was higher in alcohol users and those with reflux (p = 0.024; p = 0.001 respectively). In the Dominant model for PD-L1, the AA genotype was lower in moderately and well-differentiated tumors than in poorly differentiated tumors (p = 0.02). CD27 AT and CD28 CT genotypes were found to be higher in LSCC patients compared to the control group (p = 0.009; p = 0.01 respectively), while linkage disequilibrium (LD) was detected between CD27 and CD28 (p = 0.02). In the CD28 dominant model, C allele (CT+CC) carriage was found to be high in those with family history and in those without reflux and perineural invasion (p = 0.01; p = 0.01; p = 0.03 respectively). In LSCC, PD-L1 rather than PD-1 has a prognostic effect in terms of clinicopathology, and the LD and clinicopathological relationships detected between CD28 and CD27 genotypes suggest that the hereditary immune checkpoint-dependent T cell traffic may be pathophysiologically important.

Geographic Variability of Nodular Lymphocyte-Predominant Hodgkin Lymphoma.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) differs from classic Hodgkin lymphoma (CHL) in terms of clinicopathologic features, including Epstein-Barr virus (EBV) association. CHL geographic variability is well known, with higher frequencies of mixed-cellularity subtype and EBV positivity in low/middle-income countries (LMICs), but there are few well-characterized series of NLPHL from LMICs. We detail clinicopathologic findings of 21 NLPHL cases received in consultation from Kenya and summarize reports of NLPHL with EBV testing published since 2000. Median age of consultation cases was 36 years, and male/female ratio was 3.2. All cases involved peripheral lymph nodes and showed at least some B-cell-rich nodular immunoarchitecture, with prominent extranodular lymphocyte-predominant (LP) cells and T-cell-rich variant patterns most commonly seen. LP cells expressed pan-B-cell markers, including strong OCT2; lacked CD30 and CD15 expression in most cases; and were in a background of expanded/disrupted follicular dendritic cell meshworks and increased T-follicular helper cells. LP cells were EBV negative in 18 cases. Historical cases showed a low rate of EBV positivity with no significant difference between LMICs and high-income countries. Unlike CHL, NLPHL shows few geographic differences in terms of clinicopathologic features and EBV association. These findings have implications for diagnosis, prognostication, and treatment of patients with NLPHL in LMICs.

Hepatic vascular anomalies during totally laparoscopic pancreaticoduodenectomy: challenging the challenge.

The presence of hepatic vascular anomalies may add challenges to an already difficult surgery such as pancreatoduodenectomy, particularly when performed laparoscopically. Thus, our aim was to assess the impact of an aberrant right hepatic artery (aRHA) on postoperative outcomes during laparoscopic pancreatoduodenectomy (LPD) . Data of patients who underwent LPD were prospectively gathered and retrospectively analyzed. Patients with types III, IV, VI, VII, VIII, and IX anomalies according to Michels' classification were included in the aRHA group and were compared with the remaining patients (nRHA group). 72 patients underwent LPD; 14 of these had an aRHA (19.4%). Except for BMI (p = 0.021), the two groups did not differ in terms of clinico-pathological characteristics. The two groups had similar postoperative complications (p = 0.123), pancreatic fistula (p = 0.790), biliary leakage (p = 0.209), postpancreatectomy hemorrhage (p = 0.790), reoperations (p = 0.416), and mortality (p = 0.312). The median number of lymph nodes harvested was higher in aRHA group (p = 0.032), while R0 resection rate was similar between groups (p = 0.635). At the multivariate analysis, only moderate/high FRS (OR 3.95, p = 0.039) was an independent predictor of postoperative complications. This study suggests that aRHA has no negative impact on surgical and oncological outcomes in patients undergoing LPD.

The temporal evaluation of RAS and BRAF mutation by liquid biopsy at progression after bevacizumab combinations in patients with metastatic colorectal cancer (mCRC).

e15587 Background: Expanded RAS analysis is essential for the selection of biologic agents in mCRC. RAS mutations indicates anti-EGFR unresponsiveness. In this study, we aimed to investigate RAS and BRAF mutations by liquid biopsy at progression in patients with RAS mutant mCRC. Methods: Sixty patients with mCRC who harbored tissue RAS mutations were prospectively analyzed between July 2019 and April 2020. All the patients treated with chemotherapy plus bevacizumab combinations . The plasma samples of the patients were analyzed after progression of bevacizumab combinations. RAS mutation profile was evaluated in plasma using Idylla PCR-based molecular diagnostics method, which enables rapid detection of common mutations in RAS and BRAF genes in circulating tumor DNA (ctDNA). Kaplan-Meier method was used for survival analysis and log-rank test was performed for comparison of groups. Results: The median age of the patients was 60 years (IQR:35-83 years) and female was (n=23, 38.3%). Primary tumor was located in the left colon in 81.7% of all patients. There were 95.0% KRAS and 5% NRAS mutations in baseline tissue biopsy. As a result of liquid biopsy after progression, 55.0% of the patients had KRAS, 3.3% NRAS and 3.3% had BRAF mutations. The RAS mutation detected in 58.3% of the patients. While there was no significant difference in terms of clinicopathological features between wild type (RAS/BRAF) and mutant type (RAS/BRAF) determined by liquid biopsy, the overall survival (OS) of the wild type group was significantly longer than mutant group (43.8 vs. 20.4 months, p= 0.002). Conclusions: This study demonstrated that there may be changes in RAS/BRAF mutation from plasma analysis after progression in patients with mCRC. Since better survival in the patient group with wild type was detected compared to the RAS concordance group, the evaluation of RAS mutation status at the time of progression may be important in terms of disease prognosis and treatment options.

Surgery for Bismuth-Corlette Type 4 Perihilar Cholangiocarcinoma: Results from a Western Multicenter Collaborative Group

BackgroundAlthough Bismuth-Corlette (BC) type 4 perihilar cholangiocarcinoma (pCCA) is no longer considered a contraindication for curative surgery, few data are available from Western series to indicate the outcomes for these patients. This study aimed to compare the short- and long-term outcomes for patients with BC type 4 versus BC types 2 and 3 pCCA undergoing surgical resection using a multi-institutional international database.MethodsUni- and multivariable analyses of patients undergoing surgery at 20 Western centers for BC types 2 and 3 pCCA and BC type 4 pCCA.ResultsAmong 1138 pCCA patients included in the study, 826 (73%) had BC type 2 or 3 disease and 312 (27%) had type 4 disease. The two groups demonstrated significant differences in terms of clinicopathologic characteristics (i.e., portal vein embolization, extended hepatectomy, and positive margin). The incidence of severe complications was 46% for the BC types 2 and 3 patients and 51% for the BC type 4 patients (p = 0.1). Moreover, the 90-day mortality was 13% for the BC types 2 and 3 patients and 12% for the BC type 4 patients (p = 0.57). Lymph-node metastasis (N1; hazard-ratio [HR], 1.62), positive margins (R1; HR, 1.36), perineural invasion (HR, 1.53), and poor grade of differentiation (HR, 1.25) were predictors of survival (all p ≤0.004), but BC type was not associated with prognosis. Among the N0 and R0 patients, the 5-year overall survival was 43% for the patients with BC types 2 and 3 pCCA and 41% for those with BC type 4 pCCA (p = 0.60).ConclusionsIn this analysis of a large Western multi-institutional cohort, resection was shown to be an acceptable curative treatment option for selected patients with BC type 4 pCCA although a more technically challenging surgical approach was required.