Recurrence of oral squamous cell carcinoma in surgically treated patients at Khartoum Teaching Dental Hospital retrospective cross-sectional study.

BACKGROUND: In terms of survival rate, recurrent oral squamous cell carcinoma (OSCC) after primary surgery is considered as a poor prognostic indicator. OBJECTIVE: This study aims to determine the incidence of OSCC recurrence among patients treated at Khartoum Teaching Dental Hospital (KTDH) and possible risk factors associated with it. METHODS: Records of 303 patients with a history of radical surgery were retrieved from the hospital's archives, and the histopathological records were retrieved from the archival specimens of Professor Ahmed Suleiman Oral Pathology Laboratory, Faculty of Dentistry, and University of Khartoum. RESULTS: Advanced stages of OSCC (III, IV) were associated with higher recurrence rates, and the poorly differentiated OSCC was the commonest recurrent type. CONCLUSION: The condition of the surgical margin is a significant predictor of OSCC recurrence and tumor stage. The tumor site, the type of surgical resection, and the tumor differentiation were also identified as significant factors influencing the recurrence of OSCC.

Association of tumor-infiltrating lymphocytes with survival depends on primary tumor sidedness in stage III colon cancers (NCCTG N0147) [Alliance].

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are a robust and independent prognostic variable in localized colon cancer. Given reported differences in molecular features and prognosis of right- versus left-sided tumors, we examined the association of TIL densities with patient survival by primary tumor sidedness in stage III cancers, including clinical low- (T1-3, N1) and high-risk (T4 and/or N2) groups. PATIENTS AND METHODS: In a phase III trial of FOLFOX-based adjuvant chemotherapy, TIL densities were analyzed and dichotomized in colon carcinomas (N = 1532) based on a previously determined cut point optimized for disease-free survival (DFS). Right-sided tumors were defined as proximal to the splenic flexure. Associations of TILs and sidedness with 5-year DFS were examined using Kaplan-Meier methodology along with multivariable modeling and relative contribution analysis by Cox regression. RESULTS: Lower TIL densities were found in left- versus right-sided tumors (P < 0.0001). The association of TIL densities with DFS differed significantly by tumor sidedness (Pinteraction = 0.045). Overall, patient tumors with low (versus high) TILs had significantly poorer DFS in right-sided (hazard ratio 2.02, 95% confidence interval 1.45-2.82; Padj < 0.0001), but not left-sided tumors (Padj = 0.1731). Among clinical low-risk patients, low (versus high) TILs were adversely prognostic only in right-sided tumors (Padj = 0.0058). Among high-risk patients, low TILs were prognostic independent of sidedness (Padj < 0.025). The relative contribution of TILs to DFS was substantially greater in right- versus left-sided tumors (24% versus 1.5%). In high-risk tumors, TILs had the highest relative contribution to DFS (42%) of all variables. In low-risk tumors, the contribution of TILs (16%) to DFS was second to KRAS. CONCLUSIONS: The association of TIL densities with patient survival differed by primary tumor sidedness and clinical risk group, suggesting that TILs should be interpreted in this context among stage III colon cancers. GOV IDENTIFIER: NCT00079274; https://clinicaltrials.gov/ct2/show/NCT00079274.

A validated predictive model for risk of nodal metastasis in node negative oral squamous cell carcinoma of the buccal mucosa and tongue.

BACKGROUND: Lymph node metastasis in oral squamous cell carcinoma (OSCC) is influenced by clinical and histopathological variables. The aim of this study was to develop a simple model to predict nodal metastasis of OSCC in clinically negative necks (cN0). METHODS: Data from patients who underwent surgery for treatment of OSCC of the tongue or buccal mucosa with neck dissection were used for model development and validation. RESULTS: Nodal metastasis was significantly associated with gender, age, tumor size, site, pattern of invasion and depth of invasion on univariate analysis. All the five variables except age were retained at the variable selection step of the model development and were used in the final model because it was not significant at 0.10 significance level after adjusting for other variables. Regression coefficients of the model were used to estimate risks of nodal metastases for each combination of clinicopathological characteristics. A 10-fold cross-validation was used to assess the model. The average of the resultant 10 AUCs (along with its 95% confidence interval estimated using bootstrap) was used as the overall validated measure of the model. A risk chart was produced using probability of nodal metastasis predicted by the model for each combination of five characteristics. The model's ability to identify patients with nodal metastases as assessed by the area under the ROC curve (AUC) was 0.752. CONCLUSION: The model based on established clinicopathological variables has been internally validated on a large cohort of patients and offers practicability for use in OSCCs of the tongue and buccal mucosa.

Risk factors for surgical site infection in head and neck cancer.

PURPOSE: Surgical site infection (SSI) frequently occurs in patients with head and neck cancer (HNC) after tumor resection and can lead to death in severe cases. Moreover, there is no definitive conclusion about the risk factors of SSI. Therefore, it is of great clinical significance to study the factors affecting the SSI. METHODS: The HNC patients included in this study were all from the Department of Oral and Maxillofacial Surgery of the Second Xiangya Hospital of Central South University (CSU), and these patients received surgical treatment in the department from January 2018 to December 2019. The cross tabulation with chi-squared testing and multivariate regression analysis were applied to determine the risk factors of SSI. To identify the key risk factors of SSI, the caret package was used to construct three different machine learning models to investigate important features involving 26 SSI-related risk factors. RESULTS: Participants were 632 HNC patients who underwent surgery in our department from January 2018 to December 2019. During the postoperative period, 82 patients suffered from SSI, and surgical site infection rate (SSIR) was about 12.97%. Multivariate logistic regression analysis shows that diabetes mellitus, primary tumor site (floor of mouth), preoperative radiotherapy, flap failure, and neck dissection (bilateral) are risk factors for SSI of HNC. Machine learning indicated that diabetes mellitus, primary tumor site (floor of mouth), and flap failure were consistently ranked the top three in the 26 SSI-related risk factors. CONCLUSION: Diabetes mellitus, primary tumor site (floor of mouth), flap failure, preoperative radiotherapy, and neck dissection (bilateral) are risk factors for SSI of HNC.

The Oncobiome in Gastroenteric and Genitourinary Cancers.

Early evidence suggests a strong association of microorganisms with several human cancers, and great efforts have been made to understand the pathophysiology underlying microbial carcinogenesis. Bacterial dysbiosis causes epithelial barrier failure, immune dysregulation and/or genotoxicity and, consequently, creates a tumor-permissive microenvironment. The majority of the bacteria in our body reside in the gastrointestinal tract, known as gut microbiota, which represents a complex and delicate ecosystem. Gut microbes can reach the pancreas, stomach and colon via the bloodstream. Oral bacterial translocations can also occur. In the stomach, pancreas and colon, low microbial diversity is associated with cancer, in particular with a bad prognosis. The urogenital tract also harbors unique microbiota, distinct from the gut microbiota, which might have a role in the urinary and female/male reproductive cancers' pathogenesis. In healthy women, the majority of bacteria reside in the vagina and cervix and unlike other mucosal sites, the vaginal microbiota exhibits low microbial diversity. Genital dysbiosis might have an active role in the development and/or progression of gynecological malignancies through mechanisms including modulation of oestrogen metabolism. Urinary dysbiosis may influence the pathogenesis of bladder cancer and prostate cancer in males. Modulation of the microbiome via pre, pro and postbiotics, fecal or vaginal microbiota transplantation and engineering bacteria might prove useful in improving cancer treatment response and quality of life. Elucidating the complex host-microbiome interactions will result in prevention and therapeutic efficacy interventions.

The impact of different metastatic patterns on survival in patients with pancreatic cancer.

BACKGROUND: The aims of this study were to compare the metastatic patterns of pancreatic ductal adenocarcinoma (PDAC) of head and body/tail and to determine the prognostic factors. METHODS: Data of metastatic PDAC (MPC) between 2004 and 2015 from the Surveillance, Epidemiology and End Results (SEER) database was extracted and analyzed. The correlation analyses of metastatic patterns were also conducted. Multivariate Cox regression analyses were used to analyze prognosis. RESULTS: A total of 27470 eligible MPC patients were collected from SEER database. Patients in the head group had a higher proportion of single-metastasis while those in the body/tail group had a higher proportion of two-site metastases. Similar distributions of metastatic sites were observed in cases with single-metastasis between two groups. Patients with liver and peritoneum metastases in the head group had significantly higher overall survival (OS) rates than those in the body/tail group. Also, the OS rates stratified by varied tumor sites did not differ significantly in patients with bone, brain, and lung metastases. Chemotherapy could prolong survival in almost all MPC patients while radiotherapy or surgery could only benefit certain types of metastases. Tumor site, therapy and vascular invasion were independent prognostic factors of OS in MPC patients. CONCLUSIONS: MPC of the head and body/tail presented with different metastatic patterns. Chemotherapy benefited patients with metastases while surgery and radiotherapy could only prolong survival in patients with liver and peritoneum metastases. Our findings may provide more details for the precise management of patients with MPC in clinical practice.

Tumor primary site as a prognostic factor for Merkel cell carcinoma disease-specific death.

BACKGROUND: Merkel cell carcinoma (MCC) primary site has not been fully investigated as a potential prognostic factor. OBJECTIVE: To determine the incidence by tumor primary site of death due to MCC. METHODS: We undertook a retrospective analysis of the Survival, Epidemiology, and End Results database. MCC patients treated between 1973 and 2016 were grouped by tumor primary site and a competing risks analysis was performed to test the impact of primary site on disease-specific death. Cumulative incidence of Merkel cell carcinoma-specific mortality (CMMI) at 5 years was estimated for each primary site. RESULTS: Of 9407 MCC patients identified, 6305 (67.0%) had localized disease, 2397 (25.5%) had regional metastasis, and 705 (7.5%) had distant metastasis. Tumor primary site was predictive of CMMI and varied by stage at diagnosis. Tumors involving the scalp/neck carried the highest CMMI among localized MCC (26.0%). Tumors involving the lip had the highest CMMI among MCC with regional metastasis (56.7%) and distant metastasis (82.1%). LIMITATIONS: Tumor size data were missing for a large proportion of patients, precluding stratification by stage according to current American Joint Committee on Cancer guidelines. CONCLUSIONS: Probability of MCC disease-specific death varies by primary site. The primary site of the tumor may be useful as a prognostic indicator for MCC.

Immune-related genes LAMA2 and IL1R1 correlate with tumor sites and predict poor survival in pancreatic adenocarcinoma.

Aims: The aim of this study was to identify the immune- and locus-associated genes in pancreatic ductal adenocarcinoma and evaluate their value in prognosis. Methods: The pancreatic ductal adenocarcinoma stromal and immune scores were calculated with the estimation of stromal and immune cells in malignant tumor tissues using expression data algorithm. The authors screened the differentially expressed genes to generate immune- and stromal-related differentially expressed genes. Next, the authors conducted weighted correlation network analysis to find the gene sets related to tumor sites. Results: IL1R1 and LAMA2 were identified as the site- and immune-related genes in pancreatic ductal adenocarcinoma, and their high expression in pancreatic head cancer exhibited high immune scores and predicted unfavorable prognosis. Conclusion: The authors identified IL1R1 and LAMA2 as immune- and locus-associated genes, and their high expression predicted a poor prognosis.

Lay abstract The prognosis of pancreatic cancer is poor, and pancreatic head carcinoma is different from pancreatic body/tail carcinoma in many respects. In recent years, the role of the immune microenvironment in tumors has been increasingly revealed. The authors wanted to find ways to improve the diagnosis and treatment of patients with pancreatic cancer by analyzing the key genes associated with different immune scores and pancreatic cancer sites. In the authors' study, IL1R1 and LAMA2 were identified as immune- and locus-associated genes, and their high expression predicted a poor prognosis, especially in pancreatic body/tail cancer. Early identification of high IL1R1 expression in pancreatic body/tail carcinoma may improve tumor prognosis.

Epidemiology and prognosis of lymphoepithelioma-like carcinoma: a comprehensive analysis of surveillance, epidemiology, and end results (SEER) database.

AIM: Lymphoepithelioma-like carcinoma (LELC) is a rare histological types of solid tumors. The present study aims to comprehensively describe the demographic and clinical features of LELC using surveillance, epidemiology, and end results (SEER) database, with an emphasis on the prognostic difference according to primary tumor sites of LELC. MATERIALS AND METHODS: A population cohort with histologically diagnosed LELC were identified from SEER database between 1973 and 2016. Age-adjusted incidence rates and cancer-specific survival (CSS) were determined. Cox-regression proportional hazards model was used for both univariate and multivariate analyses. RESULTS: In total, 2106 patients with LELC were identified, with the most common diagnosed primary tumor site of nasopharyngeal LELC (56.22%), followed by non-nasopharyngeal head and neck LELC (21.32%) and respiratory system (7.83%). The overall age-adjusted incidence of LELC was 0.091 per 100,000. The CSS rates of LELC patients at 5, 10, 15, and 20 years were 76%, 69%, 65%, and 61%, respectively. A tendency of decreasing incidence of LELC was observed in the past decade. Univariate analysis indicated that sex [hazard ratio (HR) 1.21, p = 0.031], year of diagnosis (HR 0.60 and 0.63, p < 0.001), race (HR 1.29, p = 0.0021), age (HR 1.25, p = 0.0072), summary tumor stage (HR 1.97, and 4.57, both p < 0.001), number of positive LN(HR2.21, p < 0.001), surgery (HR 0.58, p = 0.0033), chemotherapy (HR 1.19, p = 0.037) and primary tumor site (p < 0.001) were significant factors associated with prognosis of LELC. In multivariate analysis, age (HR 1.75, p = 0.03), distant stage (HR 6.57, p = 0.0001), number of positive LN (HR 2.63, p = 0.0015) and non-nasopharyngeal head and neck LELC (HR 0.37, p = 0.0031) were significantly independent predictors for CSS of LELC. In sub-group analysis, radiotherapy significantly improves CSS for nasopharyngeal LELC (HR 0.57, p = 0.0002), while surgery significantly improve CSS for non-nasopharyngeal LELC (HR 0.33, p < 0.0001). CONCLUSION: Based on SEER data analysis, age older than 50 years, distant stage and more than three positive LN are significantly associated with worse CSS for LELC, while the prognosis of non-nasopharyngeal head and neck LELC is significantly better than nasopharyngeal LELC. Local treatments for LELC could be recommended according to primary tumor sites.

Do breast quadrants explain racial disparities in breast cancer outcomes?

PURPOSE: Tumors of the inner quadrants of the breast are associated with poorer survival than those of the upper-outer quadrant. It is unknown whether racial differences in breast cancer outcomes are modified by breast quadrant, in addition to comparisons among Asian subgroups. METHODS: Using the Surveillance, Epidemiology, and End Results database, we analyzed data among women diagnosed with non-metastatic invasive breast cancer between 1990 and 2014. We performed Cox proportional hazards regression models to assess the associations of race with breast cancer-specific survival and overall survival, stratified by breast quadrants. The models were adjusted for age, year of the diagnosis, tumor size, grade, histological type, tumor laterality, lymph node, estrogen receptor, progesterone receptor, and treatments. RESULTS: Among 454,154 patients (73.0% White, 10.0% Black, 7.8% Asian/PI, and 9.2% Hispanic), 54.3% had tumors diagnosed in the upper-outer quadrant of the breast. Asian/PI women were more likely than White to have tumors diagnosed in the nipple/central portion of the breast and were less likely to have diagnosed in the upper-outer quadrant (P < 0.001), despite a similar distribution of breast quadrant between Black, Hispanic, and White women. Compared with White women, the multivariable-adjusted hazard ratios of breast cancer-specific mortality were 1.41 (95% CI 1.37-1.44) in Black women, 0.82 (95% CI 0.79-0.85) in Asian women, and 1.05 (95% CI 1.02-1.09) in Hispanic women. Among Asian subgroups, Japanese American women had a lower risk of breast cancer-specific mortality (HR = 0.68, 95% CI 0.62-0.74) compared with White women. Overall survival was similar to breast cancer-specific survival in each race group. The race-associated risks did not vary significantly by breast quadrants for breast cancer-specific mortality and all-cause mortality. CONCLUSIONS: Differences in breast cancer survival by race could not be attributed to tumor locations. Understanding the cultural, biological, and lifestyle factors that vary between White, African American, and ethnic subgroups of Asian American women may help explain these survival differences.

Age dependency of primary tumor sites and metastases in patients with Ewing sarcoma.

BACKGROUND: The median age of patients with Ewing sarcoma (EwS) at diagnosis is around 14-15 years. Older age is associated with a worse outcome. The correlation of age at diagnosis on sites of disease has not been fully described. OBJECTIVE: The goal of this study was to evaluate the differences in sites of primary tumor and metastatic tumor involvement according to age groups. DESIGN/METHOD: EwS data from the Gesellschaft für Pädiatrische Onkologie und Hämatology (GPOH) database of the Cooperative Ewing Sarcoma Study (CESS) 81/86 and the European Intergroup Cooperative Ewing's Sarcoma Study EICESS 92 and the EUROpean Ewing tumor Working Initiative of National Groups-99-Protocol (EURO-E.W.I.N.G.-99) study were analyzed. Patient and tumor characteristics were evaluated statistically using chi square tests. RESULTS: The study population included 2,635 patients with bone EwS. Sites of primary and metastatic tumors differed according to the age groups of young children (0-9 years), early adolescence (10-14 years), late adolescence (15-19 years), young adults (20-24 years), and adults (more than 24 years). Young children demonstrated the most striking differences in site of disease with a lower proportion of pelvic primary and axial tumors. They presented less often with metastatic disease at diagnosis. CONCLUSIONS: Site of primary and metastatic tumor involvement in EwS differs according to patient age. The biological and developmental etiology for these differences requires further investigations.

Intraoperative Identification of Colonic Tumor Sites Using a Near-Infrared Fluorescence Endoscopic Imaging System and Indocyanine Green.

BACKGROUND: This study aimed to investigate the feasibility of the PINPOINT® Endoscopic Fluorescence Imaging System (PINPOINT) for intraoperative identification of colonic tumor sites during laparoscopic colorectal surgery. METHODS: Eighty consecutive patients with colorectal cancer were prospectively enrolled. Preoperatively, 0.5 mL of indocyanine green (ICG; 2.5 mg/mL) was injected into the submucosal space only at the distal side of the tumor under colonoscopy. Intraoperatively, we identified the tumor site on a PINPOINT image in which near-infrared fluorescence was superimposed in pseudocolor on a white light image. We estimated the intraoperative visibility rate of the tumor site and safety of ICG injection and assessed the interobserver variability of visibility grade between 2 surgeons. RESULTS: The intraoperative visibility rate of the tumor site was 93.8% (75/80). The visibility rate at an interval between injection and surgery of <7 days was significantly better than that at an interval of ≥10 days (p < 0.001). The kappa value between 2 observers was 0.827 (95% CI 0.635-1.019) with an agreement rate of 92.5%. There were no preoperative adverse reactions to ICG or intraoperative complications. CONCLUSIONS: Using ICG with the PINPOINT for identifying colonic tumor sites was feasible without any adverse effects during laparoscopic colorectal surgery.

Primary tumor location as a predictor of the benefit of palliative resection for colorectal cancer with unresectable metastasis.

BACKGROUND: It is still under debate that whether stage IV colorectal cancer patients with unresectable metastasis can benefit from primary tumor resection, especially for asymptomatic colorectal cancer patients. Retrospective studies have shown controversial results concerning the benefit from surgery. This retrospective study aims to evaluate whether the site of primary tumor is a predictor of palliative resection in asymptomatic stage IV colorectal cancer patients. METHODS: One hundred ninety-four patients with unresectable metastatic colorectal cancer were selected from Sun Yat-sen University Cancer Center Database in the period between January 2007 and December 2013. All information was carefully reviewed and collected, including the treatment, age, sex, carcinoembryonic antigen, site of tumor, histology, cancer antigen 199, number of liver metastases, and largest diameter of liver metastasis. The univariate and multivariate analyses were used to detect the relationship between primary tumor resection and overall survival of unresectable stage IV colorectal cancer patients. RESULTS: One hundred twenty-five received palliative resection, and 69 received only chemotherapy. Multivariate analysis indicated that primary tumor site was one of the independent factors (RR 0.569, P = 0.007) that influenced overall survival. For left-side colon cancer patients, primary tumor resection prolonged the median overall survival time for 8 months (palliative resection vs. no palliative resection: 22 vs. 14 months, P = 0.009); however, for right-side colon cancer patients, palliative resection showed no benefit (12 vs. 10 months, P = 0.910). CONCLUSIONS: This study showed that left-side colon cancer patients might benefit from the primary tumor resection in terms of overall survival. This result should be further explored in a prospective study.

The impact of oral rehabilitation on oral health-related quality of life in patients receiving radiotherapy for the treatment of head and neck cancer.

OBJECTIVES: To analyze the influence of dental treatment on oral health-related quality of life (OHRQoL) in head and neck cancer patients. MATERIALS AND METHODS: This study included the data of 116 patients who underwent radiotherapy (RT) because of head and neck cancer. For each patient, the variables age, sex, tumor site, irradiation technique, dose on the spared parotid gland, concomitant chemotherapy, and denture status were documented. OHRQoL was determined using the OHIP-G14 questionnaire. Patients were divided into subgroups according to denture status: none or fixed partial dentures (none/FPD), removable partial dentures (RPD), and full dentures (CD). OHIP summary scores were determined and tested for clinical relevant differences with respect to the different variables. The association between OHRQol and the variables was assessed using linear regression. RESULTS: No clinically relevant influence on OHRQoL was found for gender, irradiation technique, and chemotherapy. Patients with tumors located in the oral cavity had a significantly higher OHIP score than patients with other tumor sites (p < 0.001). None/FPD and RPD patients had higher values than those found in a normal population, but did not differ significantly from each other (p = 0.387). CONCLUSIONS: In contrast to tumor site, teeth and type of denture seem to have a limited effect on OHRQoL in head and neck cancer patients. CLINICAL SIGNIFICANCE: Prosthetic treatment in head and neck cancer patients do not lead to the same improvement in OHRQoL as found in the normal population. This might be taken into account especially if extensive dental treatment is intended.

Primary tumor site is a useful predictor of cetuximab efficacy in the third-line or salvage treatment of KRAS wild-type (exon 2 non-mutant) metastatic colorectal cancer: a nationwide cohort study.

BACKGROUND: Previous studies have shown left-sided colorectal cancer (LCRC) and right-sided colorectal cancer (RCRC) exhibit different molecular and clinicopathological features. We explored the association between the primary tumor site and cetuximab efficacy in KRAS wild-type colorectal cancer (CRC). METHODS: This study enrolled a cohort of patients, who had received cetuximab treatment after two or more lines of chemotherapy for KRAS wild-type (exon 2 nonmutant) metastatic CRC, from the databases of Taiwan Cancer Registry (2004-2010) and National Health Insurance (2004-2011). Survival data were obtained from the National Death Registry. Time to treatment discontinuation (TTD) and overall survival (OS) after the start of cetuximab treatment were compared between patients with LCRC (splenic flexure to rectum) and RCRC (cecum to hepatic flexure). RESULTS: A total of 969 CRC patients were enrolled. Among them, 765 (78.9 %) and 136 (14.0 %) patients had LCRC and RCRC, respectively. Patients with LCRC, compared to patients with RCRC, had longer TTD (median, 4.59 vs. 2.75 months, P = .0005) and OS (median, 12.62 vs. 8.07 months, P < .0001) after the start of cetuximab treatment. Multivariate analysis revealed a right-sided primary tumor site was an independent predictor of shorter TTD (adjusted hazard ratio [HR] = 1.32, using the LCRC group as a reference, 95 % confidence interval: 1.08-1.61, P = .0072) and OS (adjusted HR = 1.45, 95 % CI: 1.18-1.78, P = .0003). CONCLUSION: Our findings demonstrate that a left-sided primary tumor site is a useful predictor of improved cetuximab efficacy in the third-line or salvage treatment of KRAS wild-type (exon 2 nonmutant) metastatic CRC.

Prognostic significance of promyelocytic leukemia expression in gastrointestinal stromal tumor; integrated proteomic and transcriptomic analysis.

Prognostic markers are urgently needed to optimize the postoperative treatment strategies for gastrointestinal stromal tumors (GIST). GIST of the small intestine (I-GIST) show more aggressive behavior than those of the stomach (S-GIST), and the molecular background of the malignancy in I-GIST may include potential prognostic biomarkers. We conducted integrated proteomic and transcriptomic analysis to identify genes showing differential expressions according to the tumor site. We generated protein expression profiles for four cases each of surgically resected I-GIST and S-GIST using label-free proteomic analysis. For proteins showing differential expressions, global mRNA expression was compared between 9 I-GIST and 23 S-GIST. Among the 2555 genes analyzed, we found that promyelocytic leukemia (PML), a tumor suppressor gene, was significantly downregulated in I-GIST at both the protein and mRNA levels (P < 0.01; fold difference ≥2.0). Immunohistochemistry of 254 additional cases from multiple clinical facilities showed that PML-negative cases were significantly frequent in the I-GIST group (P < 0.001). The 5-year recurrence-free survival rate was significantly lower in the PML-negative than in the PML-positive cases (60.1% vs 91.7%; P < 0.001). Multivariate analysis revealed that downregulation of PML was an independent unfavorable prognostic factor (hazard ratio = 2.739; P = 0.001). Our study indicated that prognostication based on PML expression may have potential for optimizing the treatment strategy for GIST patients. Further validation studies of PML for clinical application, and investigation for the mechanistic significance of PML to clarify the molecular backgrounds of malignancy in GIST are warranted.

Tumor microenvironment: bone marrow-mesenchymal stem cells as key players.

Tumor progression is a multistep phenomenon in which tumor-associated stromal cells perform an intricate cross-talk with tumor cells, supplying appropriate signals that may promote tumor aggressiveness. Among several cell types that constitute the tumor stroma, the discovery that bone marrow-derived mesenchymal stem cells (BM-MSC) have a strong tropism for tumors has achieved notoriety in recent years. Not only are the BM-MSC recruited, but they can also engraft at tumor sites and transdifferentiate into cells such as activated fibroblasts, perivascular cells and macrophages, which will perform a key role in tumor progression. Whether the BM-MSC and their derived cells promote or suppress the tumor progression is a controversial issue. Recently, it has been proposed that proinflammatory stimuli can be decisive in driving BM-MSC polarization into cells with either tumor-supportive or tumor-repressive phenotypes (MSC1/MSC2). These considerations are extremely important both to an understanding of tumor biology and to the putative use of BM-MSC as "magic bullets" against tumors. In this review, we discuss the role of BM-MSC in many steps in tumor progression, focusing on the factors that attract BM-MSC to tumors, BM-MSC differentiation ability, the role of BM-MSC in tumor support or inhibition, the immunomodulation promoted by BM-MSC and metastatic niche formation by these cells.

Cutaneous extranodal natural killer/T-cell lymphoma: a comparative clinicohistopathologic and survival outcome analysis of 45 cases according to the primary tumor site.

BACKGROUND: Differences in survival outcomes and prognostic factors of cutaneous extranodal natural killer/T-cell lymphoma (ENKTL) depending on primary tumor site are currently unknown. OBJECTIVE: We sought to analyze the clinicopathological features and survival outcomes of cutaneous ENKTL according to primary tumor site. METHODS: In all, 45 patients with cutaneous ENKTL were classified with: (1) primary cutaneous ENKTL, or (2) nasal ENKTL with cutaneous involvement. Clinicopathologic features, survival outcomes, and prognostic factors were analyzed using patient's medical records. Survival outcomes were analyzed using the Kaplan-Meier method and compared using the log rank test. The Student t test, Fisher exact test, and linear by linear association test were used to analyze clinicopathologic differences between groups. RESULTS: Clinical manifestations of cutaneous ENKTL included solitary or multiple subcutaneous nodules and cellulitis or abscess-like lesions. Primary cutaneous ENKTL demonstrated a less aggressive clinical course and better survival outcomes. The extent of cutaneous lesions demonstrated a significant effect on the prognosis of primary cutaneous ENKTL, but not on nasal ENKTL with cutaneous involvement. The presence of nasal lesions in primary cutaneous ENKTL was associated with poor prognosis. LIMITATIONS: This study used a retrospective design and included a small sample size. CONCLUSION: Although the clinicopathological features were similar regardless of subgroup, survival outcomes and prognostic factors differed depending on the primary tumor site of cutaneous ENKTL.

The prognostic significance of primary tumor site in vulvar cancer: a population-based cohort study.

OBJECTIVE: To investigate the association of primary tumor site with prognosis in vulvar cancer, stratified by vulvar squamous cell carcinoma (SCC) and non-SCC histological types. METHODS: This population-based retrospective study enrolled patients with vulvar cancer from the Surveillance, Epidemiology, and End Results database between January 2000 and December 2018. The primary outcome was cancer-specific survival (CSS). The prognostic difference between labium majus, labium minus and clitoris groups was investigated using Kaplan-Meier analyses and Cox proportional hazards regression analyses. RESULTS: A total of 3,465 eligible patients with vulvar cancer were included with a mean age of 54.5 years. Among the 1,076 (31.1%) patients with non-SCC, the multivariate Cox regression analyses showed that labium minus-sited disease (hazard ratio [HR]=1.85; 95% confidence interval [CI]=1.27-2.71; p=0.001) and clitoris-sited disease (HR=2.37; 95% CI=1.47-3.85; p<0.001) were significantly associated with worse CSS, compared with labium majus-sited disease. However, among the 2,389 (68.9%) patients with SCC, no significant association of primary tumor site with CSS was found (p>0.05). Kaplan-Meier analyses also showed that the primary tumor site had a significant prognostic effect in vulvar non-SCC (p<0.001) but not in vulvar SCC (p=0.330). CONCLUSION: Among vulvar non-SCC, patients with labium minus-sited disease had a significantly worse prognosis than those with labium majus-sited disease, and a significantly better prognosis than those with clitoris-sited disease. Gynecologic oncologists should consider the prognostic effect of primary tumor site in vulvar non-SCC, and make optimal, personalized treatment and surveillance strategies based on different primary tumor sites.

Epidemiological trends of synovial sarcoma by primary tumor sites in the US from 2000 to 2020.

BACKGROUND: Synovial sarcoma (SS) is a rare soft-tissue cancer. Existing literature encompasses Surveillance, Epidemiology, and End Results (SEER) data-based research on SS explaining the incidence-prevalence in general, by subtypes, and by age at diagnosis. Therefore, this study aimed to fill in the gap of knowledge about measures of disease occurrence and burden of SS by tumor site using the SEER database. METHODS: In this cross-sectional study, primary SS patients were selected from SEER 17 Registries, Nov. 2021 (2000-2020) using ICD-O-3 codes 9040, 9041, 9042, and 9043. Patients with additional cancers were excluded. The primary tumor site was categorized into (1) head/neck, (2) internal thorax, (3) abdomen/pelvis, (4) upper extremity, and (5) lower extremity using ICD-10CM codes. Five outcomes were analyzed: age-adjusted incidence rate, 5-year limited-duration prevalence rate, incidence-based mortality, case-fatality rate, and overall survival. RESULTS: From 2000-2020, the overall age-adjusted incidence rate was 0.15 per 100,000; the 5-year limited duration prevalence rate was 0.56 per 100,000; and the incidence-based mortality rate was 0.06 per 100,000 people. The case-fatality and 5-year OS rates were 39.2 % and 62.9 %, respectively. Lower extremity had the highest incidence of 0.07 (estimated 1166 cases), prevalence of 0.36 (estimated 224 cases), and mortality rate of 0.025 (estimated 429 deaths) per 100,000. The other four locations had much closer rates with each other. Intrathoracic SS had the highest case-fatality rate of 71.5 % (148/207) and lowest 5-year OS of 26.0 % (95 % CI: 19.6 %, 32.9 %) than other sites. CONCLUSION: Based on the measures of disease frequency, the most common primary tumor site is the lower extremity, followed by the upper extremity, abdomen/pelvis, internal thorax, and head/neck. The least favorable primary location is the internal thorax. Those with a primary location of the upper extremity have the longest overall survival, followed by the head/neck, lower extremity, abdomen/pelvis, and internal thorax.