Undifferentiated Histology Research Articles

Neuroimaging Characteristics of Nasopharyngeal Carcinoma in Children.

Pediatric nasopharyngeal carcinoma (NPC) is a rare epithelial origin tumor associated with undifferentiated histology, Epstein-Barr virus (EBV) infection, and genetic risk factors. Childhood NPC is usually clinically silent, often presenting with advanced locoregional compromise, including skull base invasion and cervical lymphadenopathy, and has a better prognosis than adult NPC. This article describes computed tomography (CT) and magnetic resonance imaging (MRI) features in a cohort of 28 pediatric NPC patients. A retrospective review was performed among children with histopathology proven NPC diagnoses between 1996 and 2019 for this study. The electronic medical records were reviewed to determine demographics, EBV serology, and World Health Organization (WHO) type. Nasopharyngeal CT and/or MRI at presentation for tumor spread as well as density and/or intensity, lymphadenopathy, postcontrast enhancement and diffusion characteristics before treatment were evaluated. Twenty-eight patients (21 males, 7 females) were included. The mean patient age at diagnosis was 13.3 (range 7 to 17) years. EBV was positive in 71.4% of patients. The majority of patients (78.6%) had a WHO type III tumor, unilateral fossa of Rosenmuller involvement (71.4%). Neuroimaging features were CT isodensity, T1-isointensity, T2-hyperintensity, and heterogeneous postcontrast enhancement for all patients (100%) and restricted diffusion (90%). Although uncommon in pediatric patients, NPC should be in the differential diagnosis of adolescents presenting with a nasopharyngeal mass. Recognizing key imaging characteristics is helpful in the diagnosis of NPC.

Mismatch repair status in Endometrioid type of Endometrial Carcinoma: association with clinicopathological parameters

Introduction: Endometrial carcinoma [EC], particularly the most predominant endometrioid type [EEC] is a major contributor to cancer burden globally, and its molecular classification has gained much importance recently. Aim: This study aimed to determine the immunohistochemical expression of mismatch repair proteins 'MLH1 and MSH2' in relation to clinicopathologic parameters in EEC and to characterize clinicopathologic features of mismatch repair protein (MMRP) deficient EEC. Material and methods: The current work was carried out on 80 cases of EEC retrieved [with clinical data] from the Department of Pathology, Faculty of Medicine, Tanta University in the period from June 2018 to December 2019. HE the MMRP deficient EEC often displays adverse clinicopathological parameters as poorly differentiated or undifferentiated histology, an advanced stage with young age at presentation.

Loss of switch/sucrose non-fermenting complex protein expression in undifferentiated gastrointestinal and pancreatic carcinomas.

Undifferentiated carcinoma refers to an epithelial malignancy that lacks morphological evidence of differentiation. Recent studies have implicated the loss of constitutively expressed switch/sucrose non-fermenting (SWI/SNF) complex subunits in undifferentiated carcinomas of the gastrointestinal tract and other sites. In this study we examine the expression of SWI/SNF and mismatch repair (MMR) proteins in a series of undifferentiated carcinomas from the gastrointestinal tract and the pancreas. We searched pathology databases from four Canadian health centres for primary undifferentiated carcinoma from gastrointestinal and pancreatic resection specimens. Upon review of 31 cases, 19 were confirmed to be undifferentiated carcinomas (eight colonic, six gastric, three pancreatic, one appendiceal and one duodenal). Immunohistochemical analysis of SMARCA4, SMARCA2, SMARCB1, ARID1A, ARID1B, MSH2, MSH6, MLH1 and PMS2 was performed on whole sections. Five of 19 (26%) showed loss of core SWI/SNF proteins (two loss of SMARCA4, one loss of SMARCB1 and two concurrent loss of ARID1A and ARID1B). SMARCA4, SMARCB1, or ARID1A/ARID1B-deficient undifferentiated carcinoma consistently exhibited sheet-like growth pattern, with cellular discohesion and rhabdoid morphology. Nine of 17 undifferentiated carcinomas tested were MMR-deficient by immunohistochemistry. In comparison, none of the 12 poorly differentiated carcinomas that were originally diagnosed as undifferentiated carcinomas showed loss of SMARCA4, SMARCA2, SMARCB1 or ARID1B. Undifferentiated gastrointestinal/pancreatic carcinomas show frequent loss of expression of SWI/SNF complex proteins. The loss of these core components of SWI/SNF complex may contribute to the arrest of cellular differentiation, resulting in the undifferentiated histology and aggressive clinical behaviour.

Increased CD44 Expression and MEK Activity Predict Worse Prognosis in Gastric Adenocarcinoma Patients Undergoing Gastrectomy

PurposeWe have shown that activation of the receptor tyrosine kinase (RTK)-RAS pathway in gastric adenocarcinoma (GA) promotes acquisition of cancer stem-like cell (CSC) phenotypes including metastasis and chemotherapy resistance. Here, we evaluated the prognostic value of the CSC marker CD44 and the RTK-RAS activation marker phosphorylated MEK (p-MEK) in patients with resectable GA. MethodsCD44 and p-MEK were measured in tumors from GA patients who underwent curative-intent gastrectomy at Fujian Medical University Union Hospital (FMUUH, n = 134) and Memorial Sloan Kettering Cancer Center (MSKCC, n = 56). Overall survival (OS) was estimated by the Kaplan-Meier method, and multivariate analysis was performed by Cox proportional hazards regression modeling. ResultsDespite multiple significant differences in clinicopathologic characteristics between the FMUUH and MSKCC cohorts, high CD44 and high p-MEK expression were both independent negative prognostic factors for OS on univariate analysis in both cohorts (p < 0.05). Both factors were also significant on multivariate analysis when the cohorts were combined (p ≤ 0.003). On subgroup analysis, the 5-year OS of patients with both high CD44 and high p-MEK was 39.5–41.6% compared with 55.4–66.4% for patients with low CD44. High CD44 expression was associated with more advanced TNM stage in the FMUUH cohort and larger tumor size and undifferentiated histology in the MSKCC cohort. High p-MEK was associated with undifferentiated histology in the FMUUH cohort and larger tumor size in the MSKCC cohort. ConclusionsIncreased CD44 and p-MEK expression are predictive of worse OS in GA patients. Thus, targeting the RTK-RAS pathway may benefit patients with CD44-positive, RAS-activated GA by inhibiting metastasis and reversing chemotherapy resistance.

Preoperative imaging evaluation of the absolute indication criteria for endoscopic submucosal dissection in early gastric cancer patients.

IntroductionGastric cancer (GC) is a common malignant tumor with a high mortality rate.AimTo determine the accuracy of preoperative imaging information obtained from the combined use of general gastroscopy (GS), endoscopic ultrasonography (EUS), and multi-detector computed tomography (MDCT) regarding absolute indication of endoscopic submucosal dissection (ESD) in early gastric cancer (EGC).Material and methodsThe relationship between clinical features of 794 EGC patients and lymph node metastasis (LNM) was analyzed. Multivariate logistic regression analysis was used to investigate the risk factors for LNM. Additionally, the accuracy of diagnosis of imaging techniques for ESD indications was determined by receiver operating characteristic (ROC) analysis.ResultsData showed that tumor size > 2 cm (p = 0.0071), T1b stage (p < 0.0001), undifferentiated histology (p < 0.0001), and vascular invasion (p = 0.0007) were independent risk factors for LNM in patients with EGC. Indications for ESD have a specificity of 100% for the diagnosis of patients with LNM. Additionally, the diagnostic efficacy of the use of GS, EUS, and MDCT in identifying node positive status, T1a disease, tumor size ≤ 2 cm, and ulceration was found to be moderate with area under the curve (AUC) of receiver operating characteristic curve (ROC) of 0.71, 0.64, 0.72, and 0.68, respectively. Furthermore, the use of imaging techniques for overall indication criteria for ESD had a moderate utility value with an AUC of 0.71.ConclusionsOur data suggested that, based on the combined use of GS, EUS, and MDCT, a high specificity of patient selection for ESD treatment can be achieved.

Postoperative Wound Complications in Fungating Extremity Soft Tissue Sarcomas

Background: Among deep extremity soft tissue sarcomas, skin ulceration is infrequent. Fungating sarcomas may lead to infection or clinically significant bleeding. Data regarding management of ulcerating sarcomas is lacking. We sought to evaluate the outcomes of different treatments for these tumors.Patients and methods: A retrospective review of patients treated at two sarcoma referral centers with histologically confirmed extremity soft tissue sarcoma was performed from 2000-2018. Patient demographics, clinicopathologic, and treatment factors were analyzed in terms of method of resection, receipt of radiation, and wound complications.Results: Overall, 22 patients had fungating lesions. Most patients were male with tumors of the distal extremity.Median tumor size was 8 cm. Half had undifferentiated pleomorphic sarcoma histology, followed by myxofibrosarcoma (n=5), leiomyosarcoma (n=3), or other (n=3). Fifteen patients (68%) underwent limb-preserving resection, of which 7 underwent adjuvant radiation. Six patients (27%) developed wound complications, which occurred equally between amputation versus local excision (p = 0.93). Among local excision patients, one who received adjuvant radiation developed a wound complication (14%), which was not significantly different from those who did not undergo radiation (n=3 of 8, 38%; p = 0.31).Conclusions: Similar rates of wound complications were seen between amputation and limb-preserving groups.Among patients who underwent local excision, the administration of adjuvant radiation therapy did not significantly increase wound complication rates.

Gastric endoscopic submucosal dissection: a systematic review and meta-analysis on risk factors for poor short-term outcomes.

Endoscopic submucosal dissection (ESD) is now established as the first option to manage early gastric neoplasms, but its efficacy may vary according to diverse factors. We aimed to systematically identify risk factors for poor short-term outcomes of gastric ESD with the purpose to improve patients' selection and management. Three online databases (MEDLINE, ISI Web of Knowledge and Scopus) were searched (last search on June 2018) for poor outcomes of gastric ESD (deep submucosal invasion, piecemeal/incomplete resection, noncurative resection and local recurrence). One hundred five studies were included referring to 52.126 ESDs. Undifferentiated histology and upper location (vs lower) were associated with submucosal invasion [odds ratio (OR) = 2.42 [95% confidence interval (CI), 1.62-3.61] and OR = 3.20 (1.04-9.86), respectively] and deep submucosal invasion [OR = 2.98 (2.02-4.39) and OR = 2.35 (1.45-3.81), respectively]. Lesion size greater than 30 mm and ulceration were associated with piecemeal resection [OR = 2.78 (1.17-6.60) and OR = 2.76 (1.23, 6.20), respectively]. Lesion size greater than 30 mm, ulceration, upper location and fibrosis were risk factors for incomplete resection [OR = 3.83 (2.68-5.49), OR = 4.06 (1.62-10.16), OR = 3.71 (2.49-5.54) and OR = 4.46 (1.66-11.96), respectively]. A noncurative resection was more often observed for lesions located in the upper third of the stomach [OR = 1.49 (1.24-1.79)], depressed morphology [OR = 1.49 (1.04-2.12)] and those outside standard criteria [OR = 3.56 (2.31-5.48)]. Older age was significantly linked with local recurrence rates [OR = 3.08 (1.13-5.02)]. Several risk factors influence poor efficacy short-term outcomes of gastric ESD that may be used to inform both patients and health providers about the expected efficacy.

Patterns of Care and Survival in Elderly Patients With Locally Advanced Soft Tissue Sarcoma.

The aim of this study was to analyze patterns of care in elderly soft tissue sarcoma (STS) patients and their impact on clinical outcome and treatment-related toxicity. We retrospectively collected data of >65-year-old patients diagnosed with locally advanced STS between 1991 and 2017 in a single institution. The study included 111 patients: 105 (94.6%) patients underwent surgery, associated with preoperative (n=19, 17.1%) or postoperative radiotherapy (n=72, 64.8%). Anthracycline-based chemotherapy was prescribed in 41.4% of patients (n=46). Acute grade ≥3 postoperative radiotherapy-related radiation dermatitis and all grades of chemotherapy-induced neutropenia were significantly correlated to age >80 years (P=0.02) and >70 years (P=0.045), respectively. The mean follow-up was 4.1 years (range, 0.1 to 17.7). Three-year and 5-year local recurrence-free survival were 80.3% and 75.7%, respectively; neither treatment-related nor patient-related characteristics affected local recurrence. Three-year and 5-year distant relapse-free survival were 59.6% and 44.6%, respectively. On multivariate Cox regression, undifferentiated pleomorphic sarcoma histology and Charlson Comorbidity Index >7 were independent factors associated with distant relapse-free survival (P=0.026 and P=0.0001). Overall survival was 62% and 46.6% at 3 and 5 years, respectively. On multivariate Cox regression, surgery and Charlson Comorbidity Index <7 were independent factors associated with overall survival (P=0.006 and P=0.0001). In this study, elderly STS patients receiving a tailored treatment encompassing surgery, radiotherapy, and/or chemotherapy obtained an improved outcome, although caution is advised because of increased toxicity in relation to age. Comorbidities should be considered to offer the best treatment option to this frail patient population.

Accelerated perineural invasion in colitis-associated cancer: A retrospective cohort study.

Perineural invasion (PNI) is a prognostic factor in patients with colorectal cancer. Neurotrophic factors, molecular determinants of PNI, are altered in their expression levels in patients with ulcerative colitis. In this study, we evaluated the frequency of PNI in colitis-associated cancer (CAC) and sporadic cancer.We retrospectively reviewed 778 colorectal cancers with pathological T3-T4 in 761 patients all of whom were surgically resected without preoperative treatment. The lesions were classified into either CAC or sporadic cancer based on the clinical information. Clinicopathological findings including PNI were compared between CACs and sporadic cancers. Moreover, we analyzed the risk factors for positive PNI by multivariate analysis using a logistic regression model.Ten of the cancers (1.3%) were diagnosed as CACs, and the remaining 768 as sporadic cancers. CACs were characterized by being nonobstructive and predominantly located in the rectum. The CACs had a larger size and more frequent undifferentiated histology than sporadic cancers. PNI was observed more frequently in CACs (90%) than in sporadic cancers without obstruction (45%, P = .007). On multivariate analysis, CAC was one of the significant factors associated with PNI (odds ratio: 9.05, P = .040).Our results suggest that CAC was more likely to exhibit PNI than sporadic colorectal cancer.

WiNTRLINC1/ASCL2/c-Myc Axis Characteristics of Colon Cancer with Differentiated Histology at Young Onset and Essential for Cell Viability.

WiNTRLINC1 is a long non-coding RNA (lncRNA) that positively regulates the Wnt pathway via achaete-scute complex homolog 2 (ASCL2) in colorectal cancer. ASCL2 was recently reported to play a critical role in chemoresistance, however clinical relevance of the WiNTRLINC1/ASCL2 axis remains obscure in colon cancer. WiNTRLINC1/ASCL2 expression was investigated at messenger RNA (mRNA) level in 40 primary colon cancer tissues and the corresponding normal mucosa tissues, together with Wnt-related genes (c-Myc/PRL-3) and other lncRNAs (H19, HOTAIR, and MALAT1). Knock-down experiments of WiNTRLINC1 clarified its role in their expression and chemoresistance. Real-time quantitative reverse transcriptase-polymerase chain reaction confirmed definite overexpression of WiNTRLINC1 mRNA in primary colon cancer compared with the corresponding normal colon mucosa tissues (p = 0.0005), such as ASCL2, c-Myc, and PRL-3 (p < 0.0001). The four gene expression signatures were tightly associated in the center of the ASCL2 gene (r = 0.72, p < 0.0001) in clinical samples. WiNTRLINC1 was not significantly associated with prognostic factors in colon cancer and other lncRNAs, while the WiNTRLINC1/ASCL2/c-Myc signatures were unique to young-onset colon cancer with differentiated histology. On the other hand, undifferentiated histology was significantly associated with H19 expression. Knockdown of the WiNTRLINC1 gene reduced the expression of ASCL2/c-Myc, but rather augmented PRL-3 at mRNA level, and robustly affected cell viability in colon cancer cell lines. The enhanced WiNTRLINC1/ASCL2/c-Myc axis involved in Wnt pathway activation is a common pathway essential for differentiated colon tumorigenesis, especially with young onset, and may be essential for a viable phenotype of colon cancer.

Does Preoperative Hypofractionated Radiation Therapy for Soft Tissue Sarcoma Impact Post-operative Wound Complications?

Standard treatment for soft tissue sarcoma (STS) includes conventionally fractionated radiotherapy at 1.8-2 Gy/fx followed by surgical resection resulting in wound complication rates of 35% (O’Sullivan et al., Lancet 2002). STS has a low α/β ratio suggesting higher doses per fraction should lead to improved tumor control with a similar side effect profile. This single arm phase 2 clinical trial assessed the safety of preoperative hypofractionated radiotherapy in patients with STS. Patients with newly diagnosed and histologically confirmed Stage I-III STS of the extremity or chest wall were enrolled on this protocol at one institution. Patients were deemed resectable with negative margins and treated with radiotherapy to 3500 cGy in 5 fractions administered every other day prior to undergoing resection 4 to 6 weeks after completion of treatment. The primary outcome was wound complications assessed using the NCIC definition. Secondary outcomes included local control, disease free survival, and overall survival. Twenty-six patients enrolled with 24 completing surgical resection. Of these patients, 14 were male and 10 female and the median age was 66. Median tumor size was 9.5 cm. The vast majority of patients had undifferentiated histology (n=11, 46%) followed by liposarcoma/leiomyosarcoma (n=6, 25%), myxofibrosarcoma (n=5, 21%), and other (n=2, 8%). Tumor anatomic location was proximal lower extremity/buttock, upper extremity, distal lower extremity, and chest wall in 71%, 13%, 8%, and 8%, respectively. Most patients presented with stage III disease (79%) followed by I (13%) and II (8%). Histologic grade was high, low, and intermediate in 79%, 13%, and 8%, respectively. Two patients (8.3%) had positive margins on surgical specimens and plastic surgery was involved in 9 of the operations (38%). Median RT elapsed days was 9.5 and the median time from initiation of RT to time of surgery was 50.5 days. At a median follow-up time of 19.8 months, 6 patients (25%) experienced a post-operative wound complication. Local control was 100%. Five patients developed distant metastatic disease (20.8%) with a median time to distant metastases of 15.4 months. Two patients (8%) died of metastatic disease. Results of preoperative hypofractionated radiotherapy for treatment of patients with STS of the extremity and trunk demonstrates post-operative wound complication rates comparable to historical rates using conventionally fractionated RT. Although local control was optimal at 100%, further follow-up is needed to corroborate these findings.

Clinical Significance of NADPH Oxidase 5 in Human Colon Cancer.

Recent studies have reported the involvement of NADPH oxidases (NOXs) in tumor progression. However, the role of NOX5 in colon cancer is unclear. We examined the clinical significance of NOX5 expression in colon cancer. NOX5 expression was evaluated by immunohistochemistry in 119 patients with stage II or III colon cancer, and the relationship between NOX5 expression and clinicopathological data was analyzed. Of all tissues, 39.5% were negative and 60.5% were positive for NOX5 expression. Positive expression was significantly associated with undifferentiated histology (p=0.037) and lymph node metastasis (p=0.023). The 5-year progression-free survival rate of NOX5-positive patients was significantly worse than that of NOX5-negative patients (p=0.046). The rates of local recurrence observed in NOX5-positive patients were higher than that in NOX5-negative patients. NOX5 expression may be related to poor prognostic factors and could be useful as a prognostic biomarker.

P53 expression status is associated with cancer-specific survival in stage III and high-risk stage II colorectal cancer patients treated with oxaliplatin-based adjuvant chemotherapy

BackgroundWe attempted to elucidate whether p53 expression or TP53 mutation status was associated with cancer-specific survival in adjuvant FOLFOX-treated patients with stage III or high-risk stage II colorectal cancer (CRC).MethodsWe analysed CRCs (N = 621) for the presence of TP53 alterations and for p53 expression, using targeted resequencing and immunohistochemistry. CRCs were grouped into four subsets according to the p53 expression status, which included p53-no, mild, moderate and strong expression.ResultsThe distributions of CRCs were 19.85, 11.05, 17.7% and 51.5% in the p53-no, mild, moderate and strong expression groups, respectively. Cases in the p53-mild to moderate expression group were associated with a more frequent proximal location, undifferentiated histology, lower N category, extraglandular mucin production, microsatellite instability, CIMP-P1, CK7 expression and decreased CDX2 expression compared with those of cases of the p53-no expression and p53-strong expression groups. According to survival analysis, the p53-mild expression group showed a poor 5-year relapse-free survival (hazard ratio (HR): 2.71, 95% confidence interval (CI) = 1.60–4.60, P < 0.001) and poor 5-year cancer-specific survival (HR: 2.90, 95% CI = 1.28–6.57, P = 0.011).Conclusionsp53-mild expression status was found to be an independent prognostic marker in adjuvant FOLFOX-treated patients with stage III and high-risk stage II CRC.

Survival outcomes in patients with undifferentiated endometrial carcinoma

Objective: The aim of this study was to investigate the clinicopathological features and survival of patients with undifferentiated endometrial carcinoma (UEC). Methods: Patients who were operated between 2006 and 2014 for endometrial cancer (EC) in the same center were retrospectively reviewed from the clinical archive. Data were obtained from patient files. Survival curves and rates were calculated using the Kaplan-Meier method, and differences in survival were evaluated using the Log-Rank test. Results: In this study, 774 patients with EC were screened. According to the pathology report, 14 (1.8%) had undifferentiated type histology. The mean age, parity and body mass index (BMI) of the patients were 58.6 year (range 40-73); 3.28 (range 0-6) and 32.1 kg/m2 (range 22.8-41.7), respectively. Of the patients, 64% (n=9) had deep myometrial invasion, 93% (n=13) had lymphovascular space invasion, and 57% (n=8) had cervical involvement. Tumor size was greater than 5 cm in 64% (n=9) of the patients. Thirty five percent (n=5) of the patients were stage 1A, 21% (n=3) were stage 1B, 14% (n=2) were stage 2, 14% were stage 3C, and 14% were stage 4. As adjuvant therapy, 21% (n=3) of the patients received chemotherapy only, 14% (n=2) received radiotherapy only, and 57% (n=8) received chemotherapy and radiotherapy together. The mean follow-up duration was 36 months (range 4-104). In this period, survival rates were 77% for early-stage (FIGO 1-2) and 0% for advanced-stage (FIGO 3-4). The mean survival duration was 81 months in the early stage; 6.8 months in advanced stage (Log Rank test P value= 0.001). Conclusion: According to this study, UEC is highly associated with pathological poor prognostic factors such as deep myometrial invasion, lymphovascular space invasion, cervical involvement and large tumor size. Patients with advanced stage do not have the chance to survive. Long-term survival is possible if the diagnosis and treatment of the disease is achieved while the tumor is limited to the uterus.

Lymphocyte-C-reactive Protein Ratio as Promising New Marker for Predicting Surgical and Oncological Outcomes in Colorectal Cancer.

Systemic inflammation via host-tumor interactions is currently recognized as a hallmark of cancer. The aim of this study was to evaluate the prognostic value of various combinations of inflammatory factors using preoperative blood, and to assess the clinical significance of our newly developed inflammatory score in colorectal cancer (CRC) patients. In total 477 CRC patients from the discovery and validation cohorts were enrolled in this study. We assessed the predictive impact for recurrence using a combination of nine inflammatory markers in the discovery set, and focused on lymphocyte-C-reactive protein ratio (LCR) to elucidate its prognostic and predictive value for peri-operative risk in both cohorts. A combination of lymphocytic count along with C-reactive protein levels demonstrated the highest correlation with recurrence compared with other parameters in CRC patients. Lower levels of preoperative LCR significantly correlated with undifferentiated histology, advanced T stage, presence of lymph node metastasis, distant metastasis, and advanced stage classification. Decreased preoperative LCR (using an optimal cut-off threshold of 6000) was an independent prognostic factor for both disease-free survival and overall survival, and emerged as an independent risk factor for postoperative complications and surgical-site infections in CRC patients. Finally, we assessed the clinical feasibility of LCR in an independent validation cohort, and confirmed that decreased preoperative LCR was an independent prognostic factor for both disease-free survival and overall survival, and was an independent predictor for postoperative complications and surgical-site infections in CRC patients. Preoperative LCR is a useful marker for perioperative and postoperative management of CRC patients.

The efficacy of splenic hilar lymph node dissection in advanced gastric cancer.

112 Background: Total gastrectomy with splenectomy for splenic hilar lymph node (No.10 LN) dissection had been a standard treatment for proximal advanced gastric cancer in Japan. The efficacy of No. 10 LN dissection with splenectomy for advanced gastric cancer without the greater curvature invasion was denied by a randomized controlled trial, JCOG0110. However, JCOG0110 did not include the patients with greater curvature invasion. Therefore, we aimed to clarify the role of No. 10 LN dissection in patients with proximal advanced gastric cancer invading the greater curvature. Methods: A total of 273 patients with proximal advanced gastric cancer who underwent curative total gastrectomy with splenectomy from 2002 to 2013 were included. We reviewed esophagogastroduodenoscopy and upper gastrointestinal series for evaluation of clinical tumor localization and classified the patients into with greater curvature invasion group (G group, n = 108) or without invasion group (NG group, n = 165). The incidence and therapeutic value index (TVI) of No. 10 LN were compared between the groups. Results: Patients in the G group had more advanced T stage, undifferentiated histology, and larger tumor size than those in the NG group. However, there was no difference in survival between the groups; 5-year overall survival (5-OS) was 66.3% in the G group and 69.1% in the NG group (p = 0.570). The incidence of No.10 LN metastasis was significantly higher in the G group (10.2%) than that in the NG group (3.0%) (p = 0.028). TVI for No.10 LN dissection was higher in the G group (5.6) than that in the NG group (0.6). The survival of the patients with No.10 LN metastasis tended to be better in the G group, although it did not reach statistical significance (5-OS: 54.5% in G group vs. 20.0% in NG group, p = 0.336). Conclusions: It is suggested that splenic hilar LN dissection has a favorable effect on survival in patients with proximal gastric cancer invading the greater curvature.

Long-term clinical outcomes of endoscopic vs. surgical resection for early gastric cancer with undifferentiated histology.

The efficacy of endoscopic submucosal dissection (ESD) for undifferentiated early gastric cancer (UD EGC) is controversial due to the relatively high risk of lymph node metastasis. We compared long-term clinical outcomes of UD EGC between ESD and surgical resection groups. We retrospectively reviewed the medical records of patients with UD EGC treated by either ESD or surgical resection between January 2007 and December 2014. Long-term clinical outcomes were compared between the two groups in terms of survival. A total of 1147 patients were enrolled with median follow-up duration of 59.1 months. ESD and surgical resections were performed in 126 and 1021 patients respectively. Additional surgery was performed in 22 patients after ESD. There were no significant differences in overall survival [total, p = 0.641; propensity score matching (PSM), p = 0.330; expanded criteria, p = 0.512]. Although the disease-free survival rate was lower in ESD group because of the higher rate of metachronous cancer development (total, p < 0.001; PSM, p = 0.001), the difference was not significant in the group within expanded criteria (p = 0.071). ESD could be a comparable treatment option with surgical resection for UD EGC within expanded criteria in terms of long-term survival. It is mandatory to establish a meticulous indication of ESD for UD EGC considering the risk of lymph node metastasis.

Clinicopathological features and prognostic impact of splenic hilar lymph node metastasis in proximal gastric carcinoma

BackgroundLymph nodes (LNs) at the splenic hilum (no. 10) are treated as regional LNs in proximal gastric carcinoma. However, patients with no.10 LN metastasis show a poor prognosis after curative surgery. This study aimed to investigate the prognostic impact of no.10 LN metastasis in proximal gastric carcinoma. MethodsWe retrospective reviewed 665 proximal gastric carcinoma patients who underwent total gastrectomy and D2 LN dissection. Clinicopathological features were compared between patients with and without no.10 LN metastasis. The prognostic value of no.10 LN metastasis was examined using Cox prognostic model. ResultsThere were 63 (9.5%) patients with no. 10 LN metastasis. No. 10 LN metastasis only existed in stage III/IV, and was significantly associated with greater curvature/circumferential tumor location, larger tumor size, B4 gross type, undifferentiated histology, lymphovascular invasion. The 5-year survival of no.10 LN metastasis group was 26%, which was significantly lower than those without no.10 LN metastasis (79%, p < 0.001). Patients with no. 10 LN metastasis also showed a significantly worse survival than those without in each tumor stage (stage III = 45% vs. 66%, p = 0.044, stage IV = 13% vs. 33%, p = 0.024). In the multivariate cox model, no.10 LN metastasis was an independent poor prognostic factor when adjusting for TNM stage and other prognostic factors. ConclusionThe prognosis of no.10 LN metastasis is as poor as that of distant metastasis. This suggests that no. 10 LN should rather be considered as non-regional LNs in the treatment of proximal gastric carcinoma.

Clinicopathological characteristics and survival outcomes of bladder neuroendocrine carcinomas: a population-based study.

BackgroundBladder neuroendocrine carcinomas (BNECs) are relatively a rare type of tumor. The aim of this study was to examine the clinicopathological characteristics and predictors of survival outcomes of patients with BNECs based on the analysis of the national Surveillance, Epidemiology, and End Results (SEER) database.Materials and methodsKaplan–Meier analysis with log-rank test was used for survival comparisons. Multivariate Cox regression model was employed to analyze the effect of different treatments on overall survival (OS) and cancer-specific survival (CSS).ResultsA total of 910 patients were identified between 2004 and 2014. Overall, 648 (71.2%) patients had small cell neuroendocrine carcinoma (SCNEC), 35 (3.8%) had large cell neuroendocrine carcinoma (LCNEC), 10 (1.1%) had carcinoid tumor (well-differentiated neuroendocrine tumor), 16 (1.8%) had paraganglioma/pheochromocytoma (PGL/PHEO), 619 (68.0%) had a poorly differentiated or undifferentiated histology grade, 214 (23.5%) presented with metastatic disease, 586 (64.4%) underwent transurethral ablation/destruction for bladder tumor, and 245 (26.9%) had partial/total cystectomy. Cystectomy+chemotherapy+radiotherapy (CCR) has the highest long-term survival rate among various treatments. The 1-, 3-, and 5-years CSS of CCR were 56%, 56%, and 56%, respectively. By using multivariable Cox proportional hazard model, age, histology, N stage, SEER stage, tumor size, radiotherapy, chemotherapy, and local treatment of the primary site were identified as independent predictors for OS and CSS; all P<0.05.ConclusionIn BNEC, SCNEC has an absolute advantage in number. SCNEC/LCNEC tend to be older men. PGL/PHEO and carcinoid tumors have younger mean ages, earlier tumor stages, and better prognosis than SCNEC/LCNEC. Surgery, radiotherapy and chemotherapy are better than conservative treatment. However, whatever cystectomy or bladder sparing, chemotherapy should be a major component of treatment.

Increase in PD-L1 expression after pre-operative radiotherapy for soft tissue sarcoma

ABSTRACTSoft tissue sarcomas (STS) have minimal expression of PD-L1, a biomarker for PD-1 therapy efficacy. Radiotherapy (RT) has been shown to increase PD-L1 expression pre-clinically. We examined the expression of PD-L1, pre- and post-RT, in 46 Stage II-III STS patients treated with pre-operative RT (50–50.4 Gy in 25–28 fractions) followed by resection. Five additional patients who did not receive RT were utilized as controls. PD-L1 expression on biopsy and resection samples was evaluated by immunochemistry using the anti PD-L1 monoclonal antibody (E1L3 N clone; Cell Signaling). Greater than 1% membranous staining was considered positive PD-L1 expression. Changes in PD-L1 expression were analyzed via the Fisher exact test. Kaplan-Meier statistics were used to correlate PD-L1 expression to distant metastases (DM) rate. The majority of STS were T2b (87.0%), high-grade (80.4%), undifferentiated pleomorphic histology (71.7%), and originated from the extremities (84.6%). Zero patients demonstrated PD-L1 tumor expression pre-RT. Post-RT, 5 patients (10.9%) demonstrated PD-L1 tumor expression (p = 0.056). Tumor associated macrophages (TAM) expression of PD-L1 increased after RT: 15.2% to 45.7% (p = 0.003). Samples from controls demonstrated no baseline (0%) or change in tumor PD-L1 expression. Freedom from DM was lower for patients with PD-L1 TAM expression post-RT (3 years: 49.7% vs. 87.8%, log-rank p = 0.006); TAM PD-L1 positivity remained an independent predictor for DM on multivariate analyses (Hazard ratio – 0.16, 95% confidence interval: 0.034–0.721, p = 0.042). PD-L1 expression on human STS tumor and TAM appears to elevate after pre-operative RT. Expression of PD-L1 on TAM after RT was associated with a higher rate of DM.