Search

Purpose: To analyse the risk of inguinal lymph node (ILN) metastases in T1G2 penile cancer stratified by lymphovascular invasion (LVI), perineural invasion (PNI) and tumour size. Methods: Retrospective study of men with localised T1G2 penile cancer with non-palpable lymph nodes and no local recurrence during follow-up at six European institutional high-volume centres was performed. ILN involvement was defined as cancer detected during ultrasound-guided fine-needle aspiration cytology, core needle biopsy, dynamic sentinel lymph node biopsy, ILN dissection or inguinal recurrence during follow-up. Uni- and multivariable logistic regression analyses were performed. Results: In the cohort of 554 men with T1G2 penile cancer, from 6 European institutions, ILN metastases were observed in 46/554 men (8%, 95% confidence interval (CI) 6–11%). Men with both, LVI- and PNI- primary cancers had the lowest risk of ILN involvement (6%) whereas men with LVI + or PNI + showed ILN metastases in 22% and 30%. In multivariable regression, men with LVI + or PNI + had higher odds for ILN metastases compared to men with LVI- and PNI- (OR 3.9, 95% CI 1.6–9.0, p value < 0.01) Tumour size was not associated with ILN risk (OR 1.01 95% CI 0.99–1.04, p = 0.17). Conclusion: Approximately, one out of ten men with T1G2 overall and one out of four men with either LVI + or PNI + still have ILN metastases despite being clinically node negative. Therefore, invasive ILN staging should strongly be recommended in T1G2 with LVI + or PNI + but importantly, must be discussed in patients with T1G2 with LVI- or PNI-.

Purpose Lymphovascular invasion (LV1) and presence of > 50% embryonal carcinoma (> 50% EC) represent risk factors for progression in patients with clinical stage 1 (CS1) nonseminomatous (NS) testicular germ cell tumours. As serum levels of microRNA-371a-3p (M371) are capable of detecting small amounts of GCT, we evaluated if LV1 and > 50% EC are associated with M371 levels. Methods M371 serum levels were measured postoperatively in 153 NS CS1 patients and both pre- and postoperatively in 131 patients. We registered the following factors: age, tumour size, LV status, > 50% EC, teratoma in primary, preoperative elevation of classical tumour markers. M371 expression was compared among subgroups. The ability of M371 to predict LV1 was calculated by receiver operating characteristics (ROC) curves. Multiple regression analysis was used to look for associations of M371 levels with other factors. Results Postoperatively elevated M371 levels were found in 29.4% of the patients, but were neither associated with LV status nor with > 50% EC. Likewise, relative decrease of M371 was not associated. ROC analysis of postoperative M371 levels revealed an AUC of 0.5 for the ability to predict LV1 while preoperative M371 had an AUC of 0.732. Multiple regression analysis revealed significant associations of preoperative M371 levels with LV status (p = 0.003), tumour size (p = 0.001), > 50% EC (p = 0.004), and teratoma component (p = 0.045). Conclusion Postoperatively elevated M371 levels are not associated with risk factors for progression in NS CS1 patients. However, the significant association of preoperative M371 expression with LV1 deserves further evaluation.

Lymphovascular invasion (LVI) is a factor significantly impacting treatment and outcome of patients with gastric cancer (GC). We aimed to investigate prognostic aspects of a preoperative LVI prediction in GC using radiomics and deep transfer learning (DTL) from contrast-enhanced CT (CECT) imaging. A total of 1062 GC patients (728 training and 334 testing) between Jan 2014 and Dec 2018 undergoing gastrectomy were retrospectively included. Based on CECT imaging, we built two gastric imaging (GI) markers, GI-marker-1 from radiomics and GI-marker-2 from DTL features, to decode LVI status. We then integrated demographics, clinical data, GI markers, radiologic interpretation, and biopsies into a Gastric Cancer Risk (GRISK) model for predicting LVI. The performance of GRISK model was tested and applied to predict survival outcomes in GC patients. Furthermore, the prognosis between LVI (+) and LVI (−) patients was compared in chemotherapy and non-chemotherapy cohorts, respectively. GI-marker-1 and GI-marker-2 yield similar performance in predicting LVI in training and testing dataset. The GRISK model yields the diagnostic performance with AUC of 0.755 (95% CI 0.719–0.790) and 0.725 (95% CI 0.669–0.781) in training and testing dataset. Patients with LVI (+) trend toward lower progression-free survival (PFS) and overall survival (OS). The difference of prognosis between LVI (+) and LVI (−) was more noticeable in non-chemotherapy than that in chemotherapy group. Radiomics and deep transfer learning features on CECT demonstrate potential power for predicting LVI in GC patients. Prospective use of a GRISK model can help to optimize individualized treatment decisions and predict survival outcomes.

CD109 is a glycosylphosphatidylinositol-anchored glycoprotein, whose expression is upregulated in some types of malignant tumors. High levels of CD109 in tumor cells have been reported to correlate with poor prognosis; however, significance of CD109 stromal expression in human malignancy has not been elucidated. In this study, we investigated the tumorigenic properties of CD109 in pancreatic ductal adenocarcinoma (PDAC). Immunohistochemical analysis of 92 PDAC surgical specimens revealed that positive CD109 expression in tumor cells was significantly associated with poor prognosis (disease-free survival, p = 0.003; overall survival, p = 0.002), and was an independent prognostic factor (disease-free survival, p = 0.0173; overall survival, p = 0.0104) in PDAC. Furthermore, CD109 expression was detected in the stroma surrounding tumor cells, similar to that of α-smooth muscle actin, a histological marker of cancer-associated fibroblasts. The stromal CD109 expression significantly correlated with tumor progression in PDAC (TNM stage, p = 0.033; N factor, p = 0.024; lymphatic invasion, p = 0.028). In addition, combined assessment of CD109 in tumor cells and stroma could identify the better prognosis group of patients from the entire patient population. In MIA PaCa-2 PDAC cell line, we demonstrated the involvement of CD109 in tumor cell motility, but not in PANC-1. Taken together, CD109 not only in the tumor cells but also in the stroma is involved in the progression and prognosis of PDAC, and may serve as a useful prognostic marker in PDAC.

The aim of the present study was to clarify an appropriate staging system for patients with locally advanced esophageal squamous cell carcinoma (LAESCC) after neoadjuvant chemotherapy (NAC) prior to surgery. A total of 388 patients with clinical stage II or III LAESCC who had undergone NAC followed by an esophagectomy with three-field lymphadenectomy were retrospectively reviewed. The relapse-free survival (RFS) curves plotted using ypN grading and ypTNM staging both monotonically decreased as the classification number increased, and the groups were more clearly separated than when the Japanese Classification (JC) was applied. A multivariate analysis of relapse free survival (RFS) suggested that ypN (HR = 2.911, P

PURPOSE. Routine use of the Oncotype DX Recurrence Score (RS) in patients with early-stage, estrogen receptor-positive, HER2-negative (ER+/HER2−) breast cancer is limited internationally by cost and availability. We created a supervised machine learning model using clinicopathologic variables to predict RS risk category in patients aged over 50 years. METHODS. From January 2012–December 2018, we identified patients aged over 50 years with T1-2, ER+/HER2−, node-negative tumors. Clinicopathologic data and RS results were randomly split into training and validation cohorts. A random forest model with 500 trees was developed on the training cohort, using age, pathologic tumor size, histology, progesterone receptor (PR) expression, lymphovascular invasion (LVI), and grade as predictors. We predicted risk category (low: RS ≤25, high: RS >25) using the validation cohort. RESULTS. Of the 3880 tumors identified, 1293 tumors comprised the validation cohort in patients of median (IQR) age 62 years (56–68) with median (IQR) tumor size 1.2 cm (0.8–1.7). Most tumors were invasive ductal (80.3%) of low-intermediate grade (80.5%) without LVI (80.9%). PR expression was ≤20% in 27.3% of tumors. Specificity for identifying RS ≤25 was 96.3% (95% CI 95.0–97.4), and the negative predictive value was 92.9% (95% CI 91.2–94.4). Sensitivity and positive predictive value for predicting RS >25 was lower (48.3% and 65.1%, respectively). CONCLUSION. Our model was highly specific for identifying eligible patients aged over 50 years for whom chemotherapy can be omitted. Following external validation, it may be used to triage patients for RS testing, if predicted to be high risk, in resource-limited settings.

Lymph node yield is an important factor to ensure adequate staging in rectal cancer. In rectal cancer after neoadjuvant treatment, the nodal yield decreases. However, many studies showed better outcomes for those patients with lesser nodal yield. This is a retrospective study from a prospectively maintained database, assessing factors affecting nodal yield in rectal cancer after neoadjuvant therapy and its prognostic implications with regard to disease recurrence. Patients who underwent curative resection of rectal cancer after neoadjuvant therapy from 2016 to 2018 were included. Nodal yield was calculated, and relevant clinical factors were collected and analysed. Patients were then followed up for assessing oncological outcomes. A total of 501 consecutive patients were included in the study period of 3 years. 87.9% of patients had pre-op neoadjuvant chemoradiation (NACRT). Mean nodal yield was 12.3 nodes with a range of 5–42. On multivariate analysis, nodal yield significantly increased with increasing pathological stage (p = 0.002) and positive lymphovascular invasion (p = 0.021). After a median follow-up of 24 months, disease-free survival probability at 3 years was 84.1% for those with less than or equal to 12 nodes vs 83% for more than12 nodes (p = 0.253). This trend was more so among those who attained pathological complete response (pCR) (96.1% vs 92.9%; p = 0.677). Presence of lymphovascular invasion significantly increases nodal yield. Pathological complete response was significantly associated with lesser nodal yield. Thereby, lesser nodes harvested after surgery may be a surrogate marker of better responses to radiation and thereby may indicate a better prognosis.

Previous studies have shown a relationship between the occurrence and recurrence of prostate cancer; however, this relationship remains controversial. We investigated the relationship between obesity and biochemical recurrence in patients with prostate cancer. Clinicopathological factors were analyzed after dividing the patient population according to the Asian population-specific body mass index (BMI) criteria for “normal” (

To compare the disease-free survival (DFS) and overall survival (OS) at 3 years and 5 years in patients undergoing treatment for early-stage cervical cancer with either robotic (RRH) or open radical hysterectomy (ORH). This retrospective study compared all patients with stage IA1 (lymphovascular invasion), IA2, IB1, IB2 and II A cervical cancer in accordance with International Federation of Gynaecology and Obstetrics staging (FIGO 2009) of cancer of the cervix uteri. Patients who underwent Radical Hysterectomy at our centre from January 2011 till January 2018 were included in the study. One hundred and eighty-nine patients ( ORH = 67, RRH = 122) were included. The median follow-up time was 46.3 months in RRH group and 70.0 months in the ORH group. The 3-year DFS was comparable in both the arms, 91.5% in RRH and 91.6% in ORH. The 5-year DFS was 88.9% and 85.9% in robotic and open approaches, respectively (P = 0.258), hazard ratio (HR) 0.616 (CI = 0.266-1.427). The 3-year overall survival for robotic approach was 93.4% and for open was 95%, whereas 5-year overall survival was 84.7% and 87.4% in robotic and open approaches, respectively (P = 0.813). The median estimated blood loss for robotics was lower (100 ml vs 300 ml, P

In 2020, the WHO published a new system for classifying invasive endocervical adenocarcinoma based on histological features and high-risk human papillomavirus (HPV) infection. However, immunophenotypes of each histological subtype require further investigation. We immunohistochemically analyzed 66 invasive endocervical adenocarcinomas using three cell-lineage–specific markers: claudin 18 (CLDN18) for gastric, cadherin 17 (CDH17) for intestinal, and PAX8 for Mullerian epithelial cells. We identified five immunophenotypes of endocervical adenocarcinoma: gastric (21%); intestinal (14%); gastrointestinal (11%); Mullerian (35%); and not otherwise specified (NOS) (20%). Adenocarcinomas with gastric immunophenotype, characterized by aging (p = 0.0050), infrequent HPV infection (p

Background The present systematic review aimed to compare survival outcomes of invasive intraductal papillary mucinous neoplasms (IIPMNs) treated with adjuvant chemotherapy versus surgery alone and to identify pathologic features that may predict survival benefit from adjuvant chemotherapy. Method A systematic search of MEDLINE, PubMed, Scopus, and EMBASE was performed using the PRISMA framework. Studies comparing adjuvant chemotherapy and surgery alone for patients with IIPMNs were included. Primary endpoint was overall survival (OS). A narrative synthesis was performed to identify pathologic features that predicted survival benefits from adjuvant chemotherapy. Results Eleven studies and 3393 patients with IIPMNs were included in the meta-analysis. Adjuvant chemotherapy significantly reduced the risk of death in the overall cohort (HR 0.57, 95% CI 0.38–0.87, p = 0.009) and node-positive patients (HR 0.29, 95% CI 0.13–0.64, p = 0.002). Weighted median survival difference between adjuvant chemotherapy and surgery alone in node-positive patients was 11.6 months (95% CI 3.83–19.38, p = 0.003) favouring chemotherapy. Adjuvant chemotherapy had no impact on OS in node-negative patients (HR 0.53, 95% CI 0.20–1.43, p = 0.209). High heterogeneity (I2 > 75%) was observed in pooled estimates of hazard ratios. Improved OS following adjuvant chemotherapy was reported for patients with stage III/IV disease, tumour size > 2 cm, node-positive status, grade 3 tumour differentiation, positive margin status, tubular carcinoma subtype, and presence of perineural or lymphovascular invasion. Conclusion Adjuvant chemotherapy was associated with improved OS in node-positive IIPMNs. However, the findings were limited by marked heterogeneity. Future large multicentre prospective studies are needed to confirm these findings and explore additional predictors of improved OS to guide patient selection for adjuvant chemotherapy.

Sonographic features are associated with pathological and immunohistochemical characteristics of triple-negative breast cancer (TNBC). To predict the biological property of TNBC, the performance using quantitative high-throughput sonographic feature analysis was compared with that using qualitative feature assessment. We retrospectively reviewed ultrasound images, clinical, pathological, and immunohistochemical (IHC) data of 252 female TNBC patients. All patients were subgrouped according to the histological grade, Ki67 expression level, and human epidermal growth factor receptor 2 (HER2) score. Qualitative sonographic feature assessment included shape, margin, posterior acoustic pattern, and calcification referring to the Breast Imaging Reporting and Data System (BI-RADS). Quantitative sonographic features were acquired based on the computer-aided radiomics analysis. Breast cancer masses were manually segmented from the surrounding breast tissues. For each ultrasound image, 1688 radiomics features of 7 feature classes were extracted. The principal component analysis (PCA), least absolute shrinkage and selection operator (LASSO), and support vector machine (SVM) were used to determine the high-throughput radiomics features that were highly correlated to biological properties. The performance using both quantitative and qualitative sonographic features to predict biological properties of TNBC was represented by the area under the receiver operating characteristic curve (AUC). In the qualitative assessment, regular tumor shape, no angular or spiculated margin, posterior acoustic enhancement, and no calcification were used as the independent sonographic features for TNBC. Using the combination of these four features to predict the histological grade, Ki67, HER2, axillary lymph node metastasis (ALNM), and lymphovascular invasion (LVI), the AUC was 0.673, 0.680, 0.651, 0.587, and 0.566, respectively. The number of high-throughput features that closely correlated with biological properties was 34 for histological grade (AUC 0.942), 27 for Ki67 (AUC 0.732), 25 for HER2 (AUC 0.730), 34 for ALNM (AUC 0.804), and 34 for LVI (AUC 0.795). High-throughput quantitative sonographic features are superior to traditional qualitative ultrasound features in predicting the biological behavior of TNBC. • Sonographic appearances of TNBCs showed a great variety in accordance with its biological and clinical characteristics. • Both qualitative and quantitative sonographic features of TNBCs are associated with tumor biological characteristics. • The quantitative high-throughput feature analysis is superior to two-dimensional sonographic feature assessment in predicting tumor biological property.

Despite advances in neoadjuvant systemic therapy (NST), some patients with aggressive T4 breast cancers do not respond. The efficacy of ‘heroic’ mastectomy in maintaining local control is unclear. In consecutive patients with primary or recurrent T4 cancers with < 50% shrinkage on NST who underwent mastectomy from 2007 to 2017, clinicopathologic characteristics and locoregional recurrence (LRR) were examined. Among 104 patients, 59 (57%) had primary T4M0, 12 (12%) had locally recurrent T4M0, and 33 (32%) had T4M1 disease. Median age was 58.5 years and the majority had high-grade (74%) ductal cancers (85%); 45 (44%) were estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2−), 26 (25%) were HER2 positive (HER2+), and 31 (30%) were triple negative (TN). Postoperative complications developed in 41 (39%) patients. At a median follow-up of 37 months, 42 (40%) patients developed LRR. TN (hazard ratio [HR] 7.5) and HER2+ (HR 2.67) subtypes, lymphovascular invasion (LVI; HR 3.80), and positive margins (HR 4.09) were predictive of LRR. The 3-year LRR rate was highest and overall survival (OS) was lowest among patients with TN cancers, at 66% (95% confidence interval [CI] 48–83%) and 30% (95% CI 14–47%), respectively. After heroic mastectomy, postoperative complications were frequent and LRR occurred in 40% of patients despite a median OS of 3.8 years. Among TN patients, the 3-year LRR rate of 66% and 3-year OS of 30% suggest limited surgery benefit. Careful patient selection is prudent when considering heroic mastectomy.

To determine the prognostic value of sarcopenia measurements done on staging 2-[18F] FDG PET/CT together with metabolic activity of the tumor in patients with adenocarcinoma esophagogastric cancer with surgical treatment. Patients with early-stage, surgically treated esophageal adenocarcinoma and available pre-treatment 2-[18F] FDG PET/CT were included. The standard uptake value (SUV) and SUV normalized by lean body mass (SUL) were recorded. Skeletal muscle index (SMI) was measured at the L3 level on the CT component of the PET/CT. Sarcopenia was defined as SMI

The feasibility and oncological safety of non-curative endoscopic submucosal dissection (ESD) prior to additional gastrectomy for early gastric cancer (EGC) are still unclear. The aim of this study was to evaluate the impact of non-curative ESD on short- and long-term outcomes of subsequent laparoscopic gastrectomy (LG) for pathological T1 (pT1) EGC. We retrospectively investigated 422 patients who underwent LG for pT1 EGC between January 2007 and December 2017 at our center. Eighty-five of these patients underwent ESD with curative intent before surgery. Using propensity-score matching for sex, age, body mass index, American society of anesthesiologists score, history of previous abdominal surgery, tumor location, mucosal/submucosal infiltration, histology, lymph node metastasis, extent of lymph node dissection, operative method, lymphatic invasion, and venous invasion, the clinicopathologic and survival data of these patients were compared. The median follow-up period was 60 (range 2–168) months. Using propensity-score matching from a total of 422 patients, 75 patients were selected in the Non-ESD and the ESD cohorts each. There were no significant differences in terms of characteristics and clinicopathological findings between the two groups. Furthermore, there were no significant differences in postoperative morbidity (13.3% vs. 17.3%; P = 0.497) and mortality (1.3% vs. 0%; P = 0.316). Both the 5-year overall survival ratio (88.8% vs. 86.9%; P = 0.757) and 5-year disease-specific survival ratio (97.1% vs. 98.4%; P = 0.333) were similar in the two groups. Short- and long-term outcomes of LG in patients with pT1 EGC are not related to preoperative ESD history. Even for non-curative resections, ESD prior to surgery is feasible in terms of oncological and surgical outcomes in pT1 EGC.

Following publication of the AMAROS trial, we sought to optimize axillary lymph node dissection (ALND) or postmastectomy radiation therapy (PMRT) + axillary radiation (AxRT) utilization in cT1-2N0 patients with 1–2 positive sentinel lymph nodes (SLNs) after mastectomy. In November 2015, our multidisciplinary group implemented a protocol to omit intraoperative SLN evaluation for mastectomy patients with cT1-2N0 breast cancer likely to be recommended PMRT if found to have 1–2 positive SLNs (age ≤ 60 years and/or high-risk features defined as estrogen receptor-negative and/or positive for lymphovascular invasion). We prospectively evaluated axillary management, short-term complications, and oncologic outcomes in patients with 1–2 positive SLNs. From November 2015 to December 2018, 479 of 560 (85%) cT1-2N0 breast cancers treated with mastectomy were potential candidates for PMRT. Intraoperative SLN evaluation was omitted in 344 (72%), thus following the protocol. Overall, 121 cases had 1–2 positive SLNs: 17 (14%) were managed with observation, 5 (4%) PMRT alone, 59 (49%) PMRT + AxRT, 16 (13%) ALND alone, and 24 (20%) ALND + PMRT. Protocol compliance resulted in less ALND (8% vs. 24%) and less ALND + PMRT (9% vs. 41%, p

The aim of this article is to summarize the MRI features of each sarcoma subtype and to correlate them with its pathological findings. Literature review through PubMed/Medline database to identify relevant articles on uterine sarcomas, with a special emphasis on their MRI findings and pathological features. While several, more generalistic, MRI findings of a uterine tumour should raise suspicion for malignancy (including irregular contour, intra-tumoral necrosis/hemorrhage and low ADC values), some particular features may suggest their specific histological subtype such as the gross lymphovascular invasion associated with endometrial stromal sarcomas, the "bag of worms" appearance of the low-grade endometrial stromal sarcoma and the "lattice-like" aspect of adenosarcomas which results from the mixed composition of solid and multiseptated cystic components. Knowledge of the different histological uterine sarcoma subtypes, their specific MRI features and comprehension of their pathological background allows for a more confident diagnosis and may indicate the correct histological subtype.

Endoscopic management of early gastric cancer is limited by the risk of lymph node metastasis. We aimed to examine the incidence and predictors of nodal metastasis in early gastric adenocarcinoma in a large national US cohort. Cases were abstracted from the National Cancer Database from 2004 to 2016. The incidence and predictors of lymph node involvement for patients with Tis, T1a, and T1b tumors were examined. A total of 202,216 cases of gastric adenocarcinoma were identified in the NCDB. Cases with unknown patient or tumor characteristics, presence of other cancers, and prior neoadjuvant chemotherapy or radiotherapy were excluded. 1839 cases of Tis, T1a, and T1b tumors were identified. Lymph node metastases were present in 18.1% of patients. Lymphovascular invasion (LVI), high-grade histology, stage T1b, and larger size (> 3 cm) were independently associated with an increased risk of nodal metastasis on multivariate analysis (P

INTRODUCTION: Approximately 20–25% of human breast tumors are found within an adipose, rather than fibrous, stroma. Adipose stroma is associated with an increased risk of lymph node metastasis, but the causal association between adipose stroma and metastatic progression in human breast cancer remains unclear. METHODS: We used micropatterned type I collagen gels to engineer ~3-mm-long microscale human breast tumors within a stroma that contains adipocytes and adipose-derived stem cells (ASCs) (collectively, "adipose cells"). Invasion and escape of human breast cancer cells into an empty 120-μm-diameter lymphatic-like cavity was used to model interstitial invasion and vascular escape in the presence of adipose cell-derived factors for up to 16 days. RESULTS: We found that adipose cells hasten invasion and escape by 1–2 days and 2–3 days, respectively. These effects were mediated by soluble factors secreted by the adipose cells, and these factors acted directly on tumor cells. Surprisingly, tumor invasion and escape were more strongly induced by ASCs than by adipocytes. CONCLUSIONS: This work reveals that both adipocytes and ASCs accelerate the interstitial invasion and escape of human breast cancer cells, and sheds light on the link between adipose stroma and lymphatic metastasis in human breast cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12195-021-00697-6.

Endoscopic resection (ER) is performed for early esophageal squamous cell carcinoma (ESCC) cases. Additional esophagectomy or chemoradiotherapy is recommended for non-curative resection (NCR) even with pathologically negative vertical margins (pVM0); however, their clinical outcomes remain unknown. We examined the long-term clinical outcomes of NCR for ESCCs according to additional treatments.We retrospectively analyzed the data of patients who underwent ER for cT1N0M0 ESCC between 2009 and 2017 judged to have NCR, which defined when pathologically diagnosed as invading the submucosa (SM) or muscularis mucosae (MM) involving lymphovascular invasion (LVI), pVM0, and endoscopically judged as negative horizontal margin. Additional esophagectomy (involving three-field lymphadenectomy), chemoradiotherapy [mainly cisplatin and 5-fluorouracil with concurrent radiotherapy (41.4 Gy)], or observation was undertaken. Thereafter, computed tomography was performed every 6-12 months. The cumulative recurrence (CRR) and recurrence-free survival (RFS) rates were evaluated.Eighty-nine patients were included. Among them, 14 had pathologically diagnosed pMM with LVI; 9 and 6, and 32 and 28 patients had pSM1 and pSM2 without and with LVI. Twenty-one patients underwent observation, whereas 18 and 50 underwent esophagectomy and chemoradiotherapy. During the 60.6-month median follow-up period, nine patients had recurrence; among them, six patients had occurrence at 4 years after ER. The 5-year CRR/RFS rates were 35.7%/48.1%, 13.4%/80.4%, and 0.0%/98.0% in the observation, esophagectomy, and chemoradiotherapy groups, respectively (observation vs. chemoradiotherapy; P 0.001).Additional treatments showed better long-term outcomes than observation for patients with NCR. As recurrence may occur at 4 years after ER, careful long-term follow-up examinations are needed.

Only a few countries of the world have a population more than Bihar, but due to the lack of a cancer registry, authentic research, and publications, data regarding the clinicopathological characteristics of breast cancer patients from this state are scarce. The present study was aimed to report the clinicopathological characteristics of breast cancer patients at a tertiary care center in Bihar, India. This is a retrospective review of a prospectively maintained database of patients of breast cancer treated between January-2018 and March-2020. One hundred fifteen patients with breast carcinoma were included of which 112 (97.4%) were women. The mean age was 47.28 ± 11.62 years and 54.5% of women were postmenopausal. Most patients had a clinical stage of II or III (44.5% each) while 8.7% of patients had stage IV disease. Invasive ductal carcinoma no special type (IDC-NST) was the most common histology (85.2%). The majority of tumors were grade II (55.6%), lymphovascular invasion was seen in 45.6%, and perineural invasion in 18.4%. Estrogen receptor was found in 41.8%, progesterone receptor was positive in 47.3%, and human epidermal growth factor receptor-2 (HER-2/Neu) overexpression was observed in 39.8%. Triple-negative breast cancer was found in 26.2% of patients. The majority underwent mastectomy (71.3%) while breast conservation was done in 26%. All except one patient underwent axillary lymph node dissection for axillary staging. 43.5% patients received neoadjuvant chemotherapy, 52.9% received adjuvant chemotherapy, while 3.5% patients received palliative chemotherapy. The clinicopathological profile of breast cancer patients from Bihar is similar to that reported from other parts of India except for a lower rate of distant metastasis.

Radiomics (or texture analysis) is a new imaging analysis technique that allows calculating the distribution of texture features of pixel and voxel values depend on the type of ROI (3D or 2D), their relationships in the image. Depending on the software, up to several thousand texture elements can be obtained. Radiomics opens up wide opportunities for differential diagnosis and prognosis of pancreatic neoplasias. The aim of this review was to highlight the main diagnostic advantages of texture analysis in different pancreatic tumors. The review describes the diagnostic performance of radiomics in different pancreatic tumor types, application methods, and problems. Texture analysis in PDAC is able to predict tumor grade and associates with lymphovascular invasion and postoperative margin status. In pancreatic neuroendocrine tumors, texture features strongly correlate with differentiation grade and allows distinguishing it from the intrapancreatic accessory spleen. In pancreatic cystic lesions, radiomics is able to accurately differentiate MCN from SCN and distinguish clinically insignificant lesions from IPMNs with advanced neoplasia. In conclusion, the use of the CT radiomics approach provides a higher diagnostic performance of CT imaging in pancreatic tumors differentiation and prognosis. Future studies should be carried out to improve accuracy and facilitate radiomics workflow in pancreatic imaging.

Meckel’s diverticulum (MD) is a congenital abnormality of the gastrointestinal tract occurring in 2% of the general population, and is rarely symptomatic. MD can present with gastrointestinal bleeding, perforation, bowel obstruction or intussusception. We present a rare case of a 16-year-old male who presented with small bowel intussusception. The patient required an emergency laparotomy with small bowel resection. He recovered well and was discharged 5 days postoperatively. The histopathology revealed ulcerated Meckel’s diverticulum with well-differentiated neuroendocrine tumour (grade 1), without any lymphovascular invasion. There were no lymph nodes seen in the mesentery. His pathology was discussed at the gastrointestinal multi-disciplinary team meeting. The recommendation was to follow up 6 monthly with urinary 5HIAA and serum CgA, with consideration for colonoscopy when the patient turns 18 years old. Neuroendocrine tumours (NETs) remain a rare finding within MD with a reported incidence of 2.1% following Meckel’s diverticulectomy. These tumours are rarely symptomatic and often present at advanced stage. While emerging research suggests that radical oncological resection of NETs in adults is recommended regardless of tumour size, level of invasion, or differentiation to prevent regional and distant spread, limited consensus is available on management of NETs in children.

We aimed to investigate the prognostic factors affecting disease-free survival in patients with triple-negative breast cancer (TNBC), especially to reveal the prognostic value of Ki-67 and which cutoff value should be used. The medical records of the 180 patients who underwent surgery for invasive breast cancer were retrospectively reviewed. Potential prognostic factors that could affect the disease-free survival (DFS) in TNBC such as age (

BackgroundB7 homolog 4 (B7-H4) is a negative regulator of immune responses, but its immunoregulatory role in the tumor microenvironment of upper urinary tract urothelial carcinoma (UTUC) remains unclear.MethodsWe measured the immunohistochemical expression of B7-H4, CD8 and T cell intracellular antigen 1 (TIA-1), a marker of activated CD8, in 133 patients with UTUC who underwent nephroureterectomy. We also studied the relationship between B7-H4, CD8 and TIA-1 expression and clinicopathological characteristics.ResultsB7-H4 was mainly expressed on the surface in tumor cells, while CD8 and TIA-1 were often expressed in tumor-infiltrating lymphocytes. Elevated expression of B7-H4 in tumor cells was associated with a poorer histological grade, higher pT stage, regional lymph node metastasis, lymphovascular invasion, poorer response of recurrent metastatic lesions to systemic chemotherapy and shorter overall survival. Expression of CD-8 or TIA-1 alone did not correlate directly with clinicopathological characteristics, but among the patients with higher B7-H4 expression in the primary tumors, those with higher CD8 or TIA-1 expression had a better response to systemic chemotherapy, and longer survival, than these with lower CD8 or TIA-1 expression. Cox multivariate regression analysis revealed that higher expression of B7-H4 was associated with shorter overall survival.ConclusionsThese findings suggest that B7-H4 expression in the tumor microenvironment influences the progression of UTUC through cancer immunity and metabolic activity. Tumor cell-associated B7-H4 might be a potential target for cancer immunotherapies.

Esophagectomy is recommended after endoscopic resection (ER) for early esophageal squamous cell carcinoma (ESCC) when histopathological factors indicate a risk of nodal metastasis and incomplete resection. We aimed to analyze the outcomes of surgery management in this clinical setting and evaluate risk factors for residual disease after ER. We conducted a retrospective review of cT1N0M0 ESCC patients with noncurative ER and additional esophagectomy (2009–2019, eight centers). Noncurative ER was defined as positive resected margins on pathology, lymphovascular invasion (LVI), poor differentiation, or submucosal invasion. The pathology after ER and esophagectomy was analyzed to identify predictors of nodal metastasis and residual tumor. The study enrolled 128 patients. Primary residual tumor and nodal metastasis were confirmed in 25 (19.5%) and 15 (11.7%) patients, respectively. On multivariate analysis, nodal metastasis was independently associated with submucosal invasion [odds ratio (OR), 9.9; 95% CI, 1.1–96.1], LVI (OR, 20.9; 95% CI, 2.9–150.5), and tumor size ≥ 2 cm (OR, 8.1; 95% CI, 1.4–48.2) (all P 999; P < 0.001). Additional esophagectomy after noncurative ER allowed the resection of residual tumor and nodal metastasis, with favorable outcomes. Close follow-up may be feasible for a positive horizontal margin alone or poor differentiation alone, whereas intensive treatment should be considered for patients with submucosal invasion, LVI, and a positive vertical margin, especially when combined with tumor size ≥ 2 cm. Prospective research is needed to confirm the optimal management after ER.

The number of involved lymph nodes negatively affects prognosis in breast cancer patients. Nevertheless, current staging and treatment recommendations do not distinguish between patients with single versus multiple lymphatic micrometastases. In this study, we aim to better characterize these patients. The National Cancer Database was retrospectively queried to identify 486,800 women with stage I–III, estrogen receptor-positive/progesterone receptor-positive/human epidermal growth factor receptor 2-negative (ER+/PR+/HER2−) breast cancer and nodal status of N0, N1mi with 1 (Nmic1) or more (Nmic > 1) involved nodes, and N1 with 1 involved node (N1.1), from 2010 to 2016. Patients with different nodal statuses were compared regarding treatment characteristics, survival, and benefit from chemotherapy by their 21-gene recurrence score (RS). Of the 23,072 N1mi patients, 88.3% were Nmic1 and 11.7% were Nmic > 1. Nmic > 1 patients were younger, had larger and higher-grade tumors, with more lymphovascular invasion, and were more commonly treated by axillary dissection, radiation, and chemotherapy than Nmic1 patients. In that, they were comparable with N1.1 patients. Five-year survival of Nmic > 1 patients (88.1%) was worse than Nmic1 patients (90.1%; p = 0.02), but similar to N1.1 patients (87.9%). Nmic1, Nmic > 1, and N1.1 patients with RS 11–25 exhibited a 25, Nmic > 1 patients showed a 3.5% benefit, similar to Nmic1 (4.8%) and lower than N1.1 (10.9%) patients. Nmic > 1 breast cancer patients have worse prognoses than Nmic1 patients, similar to N1.1 patients. Our data suggest those patients with RS 11–25 have minimal benefit from chemotherapy. These findings should be taken into account when discussing prognosis and considering chemotherapy in patients with lymphatic micrometastases.

Background The role of surgery for circumscribed synchronous hepatic lesions of the pancreatic ductal adenocarcinoma (PDAC) remains controversial. Thus, the aim of our study was to compare survival outcome (OS) after surgery of patients with hepatic metastases (M1surg) to patients with only localized disease. Methods Correlation analysis of clinicopathological data and OS after resection of M1surg patients and patients with localized PDACs (M0) was performed. Patients were included for survival analysis only if a complete staging including perineural, venous and lymphatic invasion was available. Results Out of the study collective, 35 patients received extended surgery (M1surg), whereas 131 patients received standardized surgery for localized disease (M0). Length of hospitalization and mortality was similar in both groups. FOLFIRNOX as an adjuvant treatment regime was administered in ~ 23 and ~ 8% of M1surg and M0 patients, respectively. In subgroup analysis of R0 resected patients and in multivariate analysis of the total cohort, there was no difference in overall survival between both groups. Only the resection status (R1 vs R0) and venous invasion (V1) were identified as independent prognostic factors. Site of recurrence in R0 resected M1surg patients and in M0 patients were homogenously distributed. Conclusion This is the first study demonstrating a survival benefit after extended surgery for synchronously hepatic-metastasized PDACs. We found no difference in survival outcome of metastasized patients when compared to patients with localized disease. FOLFIRINOX as an adjuvant treatment regime for resected M1surg presumably is worthwhile. Larger multicenter studies are still needed to validate our results.

Luminal A breast cancers are generally associated with low metastatic potential and good prognosis. However, there is a proportion of patients, who present with metastases in lymph nodes. The aim of our study was to determine the association between the number of positive lymph nodes and infiltrates of tumor-associated cytotoxic CD8 + (CTLs), regulatory FOXP3 + T cells (Tregs), as well as other prognostic factors. Immunohistochemistry (IHC) for CD8 + and FOXP3 + was performed in 87 formalin-fixed paraffin-embedded primary breast cancer tissues, and cell infiltrate was assessed under light microscope. We observed that node-positive cases were associated with higher numbers of Treg cells and lower CTL/Treg ratio. There was also an inverse correlation between the CTL/Treg ratio and the number of metastatic lymph nodes. Similar relationships were found between the number of metastatic lymph nodes and Treg density or CTL/Treg ratio in pT1 BC. An elevated intratumoral CTL/Treg ratio was associated with pN0 stage. The relationship between lymphovascular invasion (LVI) and Treg density was also noted in node-negative tumors. In addition, more advanced nodal stage was related to LVI, higher pT, and lower PR expression. The numbers of CD8 + and FOXP3 + were also associated with tumor size, histologic grade, PR expression, and mitotic index. The results of our study suggested that the levels of tumor-infiltrating regulatory and cytotoxic cells as well as the balance between them play a role in lymphovascular spread of luminal A breast cancers.

To evaluate the association between preoperative serum human epididymis protein 4 (HE4) levels and survival outcomes in endometrial cancer (EC) patients. A retrospective cohort study was conducted of EC patients who were scheduled for surgery between September 2013 and May 2014 at Rajavithi Hospital. Association between preoperative serum HE4 levels and clinicopathological characteristics were evaluated. Cox proportional-hazards model was used to compare overall survival (OS) and recurrence-free survival (RFS) between EC patients who had high serum HE4 levels and those who did not. A total of 86 EC patients were enrolled. Serum HE4 levels was significantly associated with older age (p

Lymphatic vascular invasion (LVI) is a poor prognostic factor for hypopharyngeal squamous cell carcinoma (HPSCC), but the risk factors of LVI and its relationship with clinicopathological of HPSCC remain unclear. This study aims to explore these issues. We retrospectively analyzed the clinicopathological data of 170 patients with HPSCC from January 2011 to December 2015. The relationship between LVI and clinicopathologic was analyzed by Chi-square test or Fisher’s exact test. The risk factors of LVI were examined using a logistic regression model, while risk factors of survival rate were carried out using the Cox regression model. LVI occurred in 59 cases (34.7%). In multivariate analysis, T3–4 stage (HR = 2.877; 95% CI: 1.379–6.004; p = 0.005), N2–3 stage (HR = 2.325; 95% CI: 1.120–4.824; p = 0.024), and poor differentiation (HR = 2.983; 95% CI: 1.229–7.242; p = 0.016) were independent risk factors for LVI; positive LVI was an independent risk factor for local recurrence (HR = 2.488; 95% CI: 1.150–5.383; p = 0.021), poor 5-year OS (HR = 0.375; 95% CI: 0.232–0.606; p

Although patients with early gastric cancer have good prognosis, recurrence after treatment may occur. Lymphovascular invasion (LVI) in gastric cancer has long been suggested as a poor prognostic indicator. This study sought to evaluate the prognostic effect of LVI in patients with early gastric cancer. From 2005 to 2016, 6516 patients with early gastric cancer who underwent radical gastrectomy were analyzed. The patients were categorized according to LVI and lymph node (LN) status. LVI was present in 853 patients (13.1%). Patients with LVI or LN metastasis had more aggressive tumor characteristics than patients without both LVI and LN metastasis. The overall and relapse-free survival in patients with LVI were significantly worse than in patients without LVI. When we compared the survival rate of patients stratified by LVI and LN status, there was a significant overall and relapse-free survival difference between patients without both LVI and LN metastasis compared with those with LVI but without LN metastasis (p < 0.001). The overall and relapse-free survival of patients with LVI but without LN metastasis were similar to those without LVI but with LN metastasis (p = 0.818). Patients with LVI or LN metastasis showed a high frequency of recurrence (p < 0.001). Multivariate analysis showed that LVI and LN status were independent risk factors for relapse-free survival of early gastric cancer patients. Early gastric cancer with LVI is associated with poor prognosis and frequent recurrence. When predicting the prognosis of patients with early gastric cancer, LVI should be considered.

The purpose is to delineate the clinico-pathologic features of papillary thyroid carcinoma (PTC) occurring in a background of Hashimoto's thyroiditis (HT). A retrospective analysis of consecutive PTC patients who underwent surgery at an academic center between Jan. 2010 and Jan. 2020 was performed. The primary end point was to assess whether a background of HT implied a higher likelihood for postoperatively determined high-risk histopathologic features. Accordingly, its implication on initial surgical planning. Tumor high-risk features included aggressive histologic variants, lymphovascular invasion, extrathyroidal extension, multifocality, and positive nodal metastasis. To achieve the primary outcome of interest, a two group-designation was followed: group A (none-HT-group) and group B (HT-group). The two groups were also compared regarding postoperative complications as a secondary outcome of interest. In the specified period, 331 patients were found to have a histologically proven diagnosis of PTC. Group A accounted for 80% (265/331) of the study cohort, while group B accounted for the remainder 20%. PTC was significantly more prevalent in the absence of HT (p 0.0001). Both groups were comparable in mean-patient-age. However, Group B demonstrated a considerably higher male:female ratio (1:10 vs. 1:3; p = 0.01). All postoperatively determined high-risk histopathologic features were comparable in both groups (p 0.05). Nevertheless, transient hypoparathyroidism was considerably higher in group B (12% vs. 23%; p = 0.02). A background of HT does not seem to reflect a more aggressive cancerous biologic behavior. Therefore, it should not preclude the conservative surgical strategy adopted by the most recent clinical practice guidelines.

To compare perioperative and long-term oncological outcomes and recurrence patterns between robot-assisted radical cystectomy with intra-corporeal urinary diversion (iRARC) and open radical cystectomy (ORC). We retrospectively analyzed 177 bladder cancer patients who received iRARC or ORC at Fujita Health University between 2008 and 2020. Our primary endpoint was long-term oncological outcomes. As a secondary endpoint, we examined perioperative outcomes, complications, and recurrence patterns. These outcome measures were compared between the propensity score (PS)-matched cohorts. PS-matched analysis resulted in 60 matched pairs from iRARC and ORC groups. The iRARC cohort was associated with significantly longer operative time (p = 0.02), lower estimated blood loss (p

We aimed to determine the parameters that affect the mortality of patients operated on for gastric cancer and to investigate whether fibrinogen affects mortality or not. This retrospective clinical study included patients who underwent surgery due to gastric adenocarcinoma between January 2011 and January 2014. Patients’ demographic data, laboratory values, (hemogram parameters, fibrinogen, albumin, and tumor markers), operations, lymph node dissections, parameters of histopathology reports, stages, mortality/survival status, metastasis status at follow-up, and admission/operation/follow-up were obtained from the hospital automation system and recorded using the statistical software. Patients were divided into two groups: deceased and survivors. Analyses were carried out to determine whether the parameters of the patients, including fibrinogen, affected survival. A total of 130 patients were included in the study. Of the patients, 91 were men and 39 were women. The mean age of the patients was 63.99 SD 11.22 years. The results of the analysis of the patients’ parameters revealed that the presence of lymphatic invasion, lymph node positivity, high metastatic lymph node ratio, and advanced stage were statistically significantly correlated with low survival (p

Endoscopic treatment is one of the options for superficial esophageal cancer, but additional therapy such as esophagectomy or chemoradiotherapy (CRT) is sometimes needed due to noncurative resection. However, the outcome of additional therapy after endoscopic treatment has not been fully evaluated. In 160 patients with superficial esophageal cancer, including 37 patients who underwent esophagectomy and 123 patients who underwent CRT after noncurative endoscopic resection, outcomes were investigated. The CRT group included more elderly patients than the surgery group, although there were no significant differences in tumor depth or lymphovascular invasion between the two groups. Overall survival was significantly better in the surgery group than in the CRT group (5-year overall survival: 94.3% vs. 79.9%; p = 0.039). Two (5.4%) patients in the surgery group who developed lymph node recurrence achieved complete response by chemotherapy or CRT, and 9 of 16 patients (13.0%) in the CRT group who developed recurrence underwent salvage esophagectomy or lymphadenectomy. As a result, the 5-year cause-specific survival was 100% in the surgery group and 92.8% in the CRT group. SM2 invasion (≥ SM2) was significantly associated with recurrence after CRT, while lymphatic invasion was associated with lymph node metastasis in the surgery group. Endoscopic treatment combined with esophagectomy or CRT can be a curative treatment option in patients with superficial esophageal cancer. However, esophagectomy rather than CRT should be recommended for patients with massive submucosal tumor invasion due to the risk of recurrence after CRT.

Operative complications affect recurrence in non-breast malignancies. Rising rates of mastectomy with immediate reconstruction and their increased post-operative complications fuel concerns for poorer outcome in breast cancer (BC). We sought to determine the effect of complications on recurrence in BC patients. A single-institution retrospective review was conducted of incident BC treated with mastectomy and immediate reconstruction. Overall survival and recurrence were compared between patients with complications to those without. Of 201 patients (350 mastectomies, 86 nipple-sparing), 62 (30.8%) had a surgical complication. Patients with complications were older, but groups were similar for type of reconstruction, tobacco use, hormone receptor status, HER2, lymphovascular invasion, and pathologic stage (all p > 0.05). Twenty-two complications (10.9%) were infection, 5 (2.5%) dehiscence, 14 flap necrosis (7%), 21 hematomas (10.4%), and 8 nipple necroses (9%). Recurrence occurred in 18 (8.9%) patients: 4 local, 2 regional, and 12 distant. After 8.9 years of median follow-up, patients with complications trended towards higher recurrence (hazard ratio (HR) 2.23, log-rank p = 0.08, Cox regression p = 0.05), particularly with nipple necrosis (HR 3.28, log-rank p = 0.09, regression p = 0.06). Patients with other complications had similar recurrence-free survival to those without (all p > 0.05). Higher stage (HR 13.66, log-rank p = 0.03) and adjuvant radiation (HR 2.78, log-rank p = 0.04) cases were more likely to recur. Patients with complications had similar overall survival to those without (log-rank p > 0.05). BC patients with surgical complications do not have lower overall survival. This finding may be due to the improved prognosis compared to non-breast malignancies.

Purpose The value of bladder cancer (BC) substaging into macroscopic (pT3b) and microscopic (pT3a) perivesical fat extension in lymph node (Ln)-negative patients is controversially discussed and limited evidence for prognostic relevance of additional histopathological factors in pT3 BC exists. We evaluated the prognostic value of pT3 substaging and established pathological and clinical parameters with focus on tumor invasive front (TIF) and tumor size. Methods Specimens of 52 patients treated with radical cystectomy (RC) for pT3 a/b muscle-invasive BC were reviewed and re-evaluated by a pathologist specialized in uropathology. Clinical variables and standard histopathologic characteristics were assessed including TIF and tumor size. Their value as prognosticators for overall survival (OS) and recurrence-free survival (RFS) was evaluated. Results Mean age of patients was 67.55 years. Tumors were staged pT3a in 28 patients (53.8%) and pT3b in 24 (46.8%). Median OS was 34.51 months. Median tumor size was 3.2 cm, median TIF was 11.0 mm. Differences in OS between pT3a and pT3b were not significant (p = 0.45). Carcinoma in situ (CIS) and lymphovascular invasion (LVI) were significantly associated with pT3b tumors. Univariate analysis could not identify pathological prognosticators like TIF or tumor size for OS and RFS (p for all > 0.05). Conclusion No significant differences in OS or RFS were observed comparing Ln-negative pT3 BC following radical cystectomy. Additional pathologic variables like TIF could not be identified as prognosticator. Relevance of pT3 BC substaging needs reevaluation in larger prospective cohorts.

We sought to investigate whether preoperative dual-phase 2-[18F]FDG PET-CT identify predictors for poor survival in patients with ampullary carcinoma receiving pancreaticoduodenectomy. The preoperative PET-CT images of patients with resected ampullary carcinoma from June 2007 to July 2017 were analyzed. Survival curves were analyzed using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazard model was used to identify potential prognostic factors associated with disease-free survival (DFS) and overall survival (OS). Fifty-four subjects (26 men, 28 women) were enrolled with a median tumor size of 20 mm. All patients were followed for a median period of 36.9 months with 3- and 5-year DFS of 50.3% and 44.2%, and OS of 77.0% and 68.2%, respectively. Parameters associated with DFS in multivariate analysis were lymphovascular invasion (hazard ratio [HR]: 9.45, p < 0.001), involved margin in pathology (HR: 7.67, p < 0.001), and tumor retention index (RI) from the dual-phase PET (HR: 2.41, p = 0.03), whereas involved margin (HR: 13.14, p < 0.001), post-recurrence chemotherapy (HR: 0.10, p < 0.001), and metabolic tumor volume (MTV) (HR: 4.62, p = 0.009) emerged as independent prognostic factors for OS. Preoperative 2-[18F]FDG PET-CT offered independent prognostic biomarkers in patients with ampullary carcinoma receiving standard surgical resection. • 2-[ 18 F]FDG PET-CT offers good survival prediction before operation in primary malignant neoplasms at ampulla of Vater. • Dual-phase PET scan with bowel distention can better delineate Ampulla of Vater and characterize tumor physiology. • Preoperative risk stratification might aid in better treatment planning.

Five to 10% of patients with stage IA, grade 1 or 2, endometrioid adenocarcinoma subsequently develop locoregional or distant recurrence. These patients have significantly reduced 5-year survival rates and salvage therapy success rates as low as 40%. The aim of this review is to highlight knowledge gaps that could further refine the risk categories of endometrial carcinoma (EC) and guide future randomized trials of adjuvant therapy for low-risk EC. A systematic search of the literature on PubMed and Medline was conducted using the following search terms: endometrial cancer, endometrial adenocarcinoma, endometrioid adenocarcinoma, low grade, early stage, stage IA, low risk, locoregional recurrence, and relapse. Relevant primary studies were extracted and included in this review. Risk factors for recurrence of low-risk EC were epidemiological (age, body mass index, ethnicity), molecular (DNA MMR, MSI, TP53 mutation and P53 defect, CTNNB1 mutation, PTEN and POLE mutation, L1CAM expression), pathological (positive peritoneal cytology, lymphovascular invasion, tumor size), and others like Ki67-percentage, micro-RNA expression, and hormonal receptor expression. CTNNB1 mutation, L1CAM expression, lymphovascular invasion, and tumor size were identified as significant risk factors for recurrence in low-risk EC. There are subsets of low-risk EC patients at high risk of recurrence and should be suspected when having the following risk factors: positive molecular markers, large tumor size, and lymphovascular invasion. A novel scoring system and randomized controlled trials should be conducted to identify these patients who will benefit most from adjuvant therapy to avoid recurrence.

e21509 Background: Immunosuppression (IS) is not currently considered in staging for Merkel cell carcinoma (MCC). We performed an analysis of the National Cancer Database (NCDB) to investigate immune status as an independent predictor of overall survival (OS) for patients with MCC and describe the relationship between immune status and other prognostic factors. Methods: The NCDB was queried for patients diagnosed with MCC from 2010 to 2016 with known immune status. Multivariable Cox proportional hazards models were used to define factors associated with OS. Adjuvant radiation and chemotherapy were treated as time-dependent predictors to limit immortal time bias. Secondary models were constructed to assess the association between IS etiology and OS. Multivariable logistic regression models were used to characterize relationships between immune status and other factors. Multiple imputation was used to minimize missing data bias. Results: The overall cohort included 3,882 patients (3,470 patients with known immunocompetence and 412 patients with known immunosuppression). Etiologies for profound IS included chronic lymphocytic leukemia (CLL, n = 118), Other including HIV/AIDS (n = 116), solid-organ transplant (n = 106), and Non-Hodgkin Lymphoma (NHL, n = 72). 2,864 patients (73.8%) underwent surgical nodal examination. The median follow-up time was 33 months (Interquartile Range: 18 to 55 months). The 3-year OS was lower for patients with IS (44.6%, CI 39.8-49.9%) compared to immunocompetent (IC) patients (68.7%, CI 67.1-70.4%, p < .0001). IS was associated with increased adjusted mortality hazard (HR 2.36, 95% CI 2.03-2.75). Etiology of IS was associated with OS ( p = .0015) with lowest 3-year OS (32.7%, CI 24.6%-43.5%) for patients with solid-organ transplantation. IS was associated with increased odds of greater nodal burden (OR 1.70, CI 1.37-2.11) and lymphovascular invasion (OR 1.58, CI 1.23-2.03). Conclusions: Immune status was independently prognostic for OS for patients with localized MCC. Etiology of IS may be associated with differential survival outcomes. Multiple adverse prognostic factors were associated with increased likelihood of IS. Immune status and potentially etiology of IS may be useful prognostic factors to consider for future MCC staging systems.

The non-invasive nature of the preoperative axillary ultrasound (AUS) fits the current trend of increasingly conservative axillary management. Recent publications suggest that early disease patients with clinically and radiologically negative axillae do not require sentinel lymph node biopsy (SLNB). This study aims to determine the true extent of axillary node disease in negative preoperative AUS patients. A 10-year breast cancer registry was reviewed to identify women with pathologically confirmed T1-2 invasive breast cancer and a negative preoperative AUS. Patients who received neoadjuvant chemotherapy were excluded. Combined positive lymph node count of SLNB ± ALND was used to determine total nodal burden (TNB). Axillae were classified into low nodal burden (LNB) defined as 1–2 positive nodes and high nodal burden (HNB) defined as ≥ 3 positive nodes. 762 patients with negative AUS were included. There were 46.9% and 53.0% T1 and T2 tumours, respectively. 76.9% were node negative (0 LN +), 18.9% had LNB (1–2 LN +) and 4.2% had HNB (≥ 3LN +). Specifically, HNB disease was seen in 2% of T1 tumours and 6.2 % of T2 tumours with a negative AUS. In multivariate analysis, T2 strongly associated with ≥ 3 positive ALNs (OR 2.66 CI 1.09–6.51 p = 0.03) as did lymphovascular invasion (OR 3.56 CI 1.52–8.30 p =

This study aimed to investigate the relationship between the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the systemic immune-inflammation index (SII) with the clinical and pathological parameters of 118 laryngeal cancer patients, as well as their effects on the survival of the disease. For the calculation of SII, PLR, and NLR, hemogram tests were conducted before treatment. Receiver-operating characteristic (ROC) analysis was used to calculate the cut-off value of SII, NLR, and PLR for overall survival (OS) and disease-free survival (DFS). A statistically significant relationship was found between SII and lymphovascular invasion and between NLR and local recurrence, and lymphovascular invasion. In a univariate analysis, SII (p

It remains unclear whether laparoscopic conversation to open gastrectomy causes higher morbidity and has an adverse effect on the long-term survival outcomes of patients with gastric cancer. This study was designed to evaluate the impact of the conversion on short and long-term outcomes of patients with locally advanced gastric cancer (AGC). We retrospectively investigated 871 patients who initially underwent laparoscopic gastrectomy (LG) for pathologically confirmed diagnosis of AGC between February 2009 and April 2018. The patients were grouped as the conversion (CONV) group and completed laparoscopic (LAP) group. The 1:2 propensity score matching was performed to reduce the effect of bias due to the imbalanced baseline features between the two groups. Multivariate analyses were performed to identify risk factors for conversion and poor survival. After propensity-score matching, 168 patients (56 in the CONV group and 112 in the LAP group) were studied. The CONV group was associated with significantly longer operation time (252.4 vs. 216.7 min, P < 0.001) and greater estimated blood loss (234.8 vs. 171.2 ml, P < 0.001) as compared with the LAP group. The time to first flatus (3.8 vs. 3.3 days, P = 0.043), time to start a liquid diet (4.1 vs. 3.5 days, P = 0.021), and postoperative hospital stay (8.7 vs. 7.6 days, P = 0.020) were significantly longer in the CONV group than that in the LAP group. The overall complication rate did not differ significantly between the CONV group and the LAP group (16.1% vs. 12.5%, P = 0.692). Both 5-year overall survival (OS) and 5-year disease-free survival (DFS) did not differ significantly between the CONV group and the LAP group (P = 0.805, P = 0.945, respectively). Multivariate analysis showed that lymphovascular invasion and stage III were independent prognostic factors for poor OS and DFS, whereas conversion was not. The conversion from laparoscopic to open gastrectomy had no negative impact on morbidity and long-term survival outcomes for patients with locally AGC.

Surgical resection for elderly patients with gastric cancer is controversial. This study aims to evaluate the preoperative features and postoperative short- and long-term outcomes of elderly patients following surgical resection for gastric adenocarcinoma. Between January 2000 and May 2018, a total of 177 consecutive patients underwent curative gastrectomy for gastric adenocarcinoma was retrospectively reviewed. Propensity score matching (PSM) analysis was used to balance confounding covariates between the elderly and non-elderly groups. Clinicopathological characteristics, intraoperative characteristics, postoperative complications and long-term survival outcomes including overall survival (OS) and Disease Specific Survival (DSS) were compared and analysed using the Kaplan-Meier log-rank test. Multivariate cox proportional hazards regression analysis of clinicopathological factors influencing survival were evaluated. There were 50 patients in the elderly group (age ≥ 75 years) and 127 patients in the non-elderly group (age

Chemokines are major regulators of cell trafficking and adhesion. The chemokine CXCL12 and its receptors, CXCR4 and CXCR7, have been reported as biomarkers in various cancers, including esophageal cancer; however, there are few studies in esophageal adenocarcinoma (EAC). In this study, we investigated the relationship between expression of CXCL12, CXCR4, and CXCR7, and prognosis in patients with EAC. This study examined 55 patients with EAC who were treated in Toronto General Hospital from 2001 to 2010. Tissue microarray immunohistochemistry was used to evaluate the expression of CXCL12, CXCR4, and CXCR7. Evaluation of immunohistochemistry was performed by a pathologist without knowledge of patients’ information and results were compared with the patients’ clinicopathological features and survival. High CXCR7 expression was significantly associated with lymphatic invasion (present vs absent, P = 0.005) and higher number of lymph node metastases (pN0-1 vs pN2-3, P = 0.0014). Patients with high CXCR7 expression (n = 23) were associated with worse overall (OS) and disease-free survival (DFS) (P = 0.0221, P = 0.0090, respectively), and patients with high CXCL12 (n = 24) tended to have worse OS and DFS (P = 0.1091, P = 0.1477, respectively). High expression of both CXCR7 and CXCL12 was an independent prognostic factor for OS and DFS on multivariate analysis (HR = 0.3, 95% CI: 0.1–0.9, P = 0.0246, HR = 0.3, 95% CI: 0.1–0.8, P = 0.0134, respectively). High CXCR7 expression was associated with poor prognosis in patients with EAC, and high expression of CXCR7 with its ligand CXCL12 had a stronger association with prognosis. Further study of this potential biomarker using whole tissue samples and a larger sample size is warranted.

Although multidisciplinary treatments including the use of adjuvant therapy (AT) have been adopted for biliary tract cancers, patients with distal cholangiocarcinoma (DCC) can still experience recurrence. We sought to characterize the incidence and predictors of early recurrence (ER) that occurred within 12 months following surgery for DCC. Patients who underwent resection for DCC between 2000 and 2015 were identified from the US multi-institutional database. Cox regression analysis was used to identify clinicopathological factors to develop an ER risk score, and the predictive model was validated in an external dataset. Among 245 patients included in the analysis, 67 patients (27.3%) developed ER. No difference was noted in ER rates between patients who did and did not receive AT (28.7% vs. 25.0%, p = 0.55). Multivariable analysis revealed that neutrophil-to-lymphocyte ratio (NLR), peak total bilirubin (T-Bil), major vascular resection (MVR), lymphovascular invasion, and R1 surgical margin status were associated with a higher ER risk. A DIstal Cholangiocarcinoma Early Recurrence Score was developed according to each factor available prior to surgery [NLR > 9.0 (2 points); peak T-bil > 1.5 mg/dL (1 points); MVR (2 points)]. Cumulative ER rates incrementally increased among patients who were low (0 points; 10.6%), intermediate (1–2 points; 26.8%), or high (3–5 points; 57.6%) risk (p < 0.001) in the training dataset, as well as in the validation dataset [low (0 points); 3.4%, intermediate (1–2 points); 32.7%, or high risk (3–5 points); 55.6% (p < 0.001)]. Among patients undergoing resection for DCC, 1 in 4 patients experienced an ER. Alternative treatment strategies such as neoadjuvant chemotherapy may be considered especially among individuals deemed to be at high risk for ER.

Anti-HER2 therapy delivered in the adjuvant setting for breast cancer is given in conjunction with cytotoxic chemotherapy. For HER2-positive (HER2+) patients who cannot tolerate chemotherapy, there is no randomized data regarding the role of anti-HER2 therapy without chemotherapy. The National Cancer Database (NCDB) was queried for non-metastatic breast cancer patients with estrogen receptor-positive (ER+) and HER2+ breast cancer who received surgery and endocrine therapy, without chemotherapy from 2013 to 2016. Outcomes were compared between endocrine therapy alone (ET) or endocrine therapy with anti-HER2 therapy (ET + aHER2). Univariate and multivariate Cox-proportional hazards models were used to analyze the association between clinical characteristics and survival outcomes between groups. Propensity score matching (PSM) was performed to account for differences between the two groups. Of all patients with non-metastatic ER+/HER2+ breast cancer, we identified 9458 (20.5%) who did not receive chemotherapy. Of the 6741 patients who received ET, 17.2% also received aHER2 therapy. Median follow-up was 31.7 months (IQR 21.1–42.1). In the aHER2 group (vs. ET), there were more patients with older age, higher stage, node positivity, poorly or undifferentiated disease, lymphovascular invasion, lobular cancer, and Medicare insurance. Compared to the ET cohort, ET + aHER2 was not significantly associated with improved OS on multivariate analysis (HR 0.88 95% CI 0.68–1.15) or after propensity score matching (HR 0.80 95% CI 0.57–1.11). There is no significant difference in survival with the addition of HER2 therapy to endocrine therapy in ER+/HER2+ non-metastatic breast cancer patients who do not receive chemotherapy. To our knowledge, this is the largest series investigating this question.

The effect of postmastectomy radiotherapy (PMRT) on patient outcomes after neoadjuvant chemotherapy (NAC) remains controversial. We aimed to establish a model to identify the subsets benefiting from PMRT and to examine the effect of PMRT according to molecular subtype. We retrospectively analyzed 1118 cT1-4cN0-3M0 breast cancer patients treated with NAC and mastectomy. A nomogram predicting locoregional recurrence (LRR) was established based on 418 unirradiated patients, and X-tile analysis was performed to divide the patients into two risk groups. The effect of PMRT on LRR, distant recurrence (DR), and breast cancer mortality (BCM) was estimated for patients with different molecular subtypes in two risk groups. A nomogram predicting LRR was developed using six factors: histologic classification, lymphovascular invasion, ypT stage, ypN stage, estrogen receptor status, and Ki-67 expression. Our study found that PMRT correlated with lower 5-year LRR, DR, and BCM rates for the high-risk group; however, no significant improvement in these endpoints was observed in the low-risk group. Among patients with high risk, subgroup analysis showed that LRR control was improved after PMRT for the human epidermal growth factor receptor 2 (HER2)-negative/hormone receptor (HR)-positive (HER2−/HR+), HER2-positive (HER2+)/HR+, and HER2−/HR-negative (HR−) subtypes, with hazard ratios of 0.113 (95% confidence [CI] 0.034–0.379; p

Medullary thyroid carcinoma (MTC) displays a wide variety of histopathological features, and several histological variants have been described. In follicular cell-derived thyroid carcinomas, there is a good correlation between genotype and phenotype. In this study, we investigated whether such a correlation is also present in MTC. The histopathological features were evaluated in a series of 66 molecularly characterised tumours and correlated with the clinical characteristics. Most MTC exhibited the classical variant (83.3%). Other variants included spindle cell (6.1%), pseudopapillary (4.5%), paraganglioma-like (3.0%), angiosarcoma-like (1.5%), and oncocytic follicular (1.5%). Tumours were classified into four groups: group 1, with somatic p.Met918Thr and p.Ala883Phe RET mutations; group 2, with other RET mutations; group 3, with RAS mutations; and group 4, without RET or RAS mutations. Tumours from groups 1 and 4 were typically associated with the classical variant, with abundant fibrosis, lymphovascular invasion, extrathyroidal extension, and more advanced stages of disease, whereas group 2 included histological variants other than the classical variant (namely, pseudopapillary and paraganglioma-like), with tumours that were highly cellular, less invasive, and with a better overall prognosis. In tumours from group 4, amyloid deposition was characteristically absent or low. The spindle cell variant appeared only in tumours from group 3, which had high cellularity and a degree of invasion and prognosis intermediate between groups 1 and 2, but better than group 4. The grade of fibrosis correlated directly with the clinical outcome. Our results support the idea that a genotype–phenotype correlation does, indeed, exist in MTC. However, further studies are warranted to confirm these findings in a larger sample size.