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PURPOSE: The prognostic outcomes of metastasis patterns in patients with de novo metastatic breast cancer (dnMBC) of different ages are unknown. Our study used a large-scale data to investigate the metastasis patterns and prognostic features in dnMBC of different ages. METHODS: Total 24,698 women with dnMBC in the Surveillance, Epidemiology and End Results database (2010-2018) were divided into three groups by age. Chi-squared test was used to compare metastasis patterns and logistic regression was performed to investigate the risk of age and specific organ metastases. Kaplan-Meier survival curves were used to compare the overall survival. RESULTS: In three groups, young group had the largest proportion of liver metastases (35.2% vs. 28.2% vs. 21.1%, p < 0.001), and elderly group had the largest proportion of lung metastases (22.6% vs. 30.0% vs. 35.0%, p < 0.001) and the lowest proportion of bone metastases (65.7% vs. 67.6% vs. 64.4%, p < 0.001). In young group, patients with liver metastases had better prognosis than patients with lung metastases (MST: 34 months vs. 29 months, p = 0.041), but in middle-aged and elderly groups, the prognosis of lung metastases was better than that of liver metastases (MST in middle-aged group: 24 months vs. 20 months, p = 0.002; MST in elderly group: 12 months vs. 6 months, p < 0.001). CONCLUSION: DnMBC patients at different age have distinct metastasis patterns and prognostic features. The findings lend support to consideration of tailored management and surveillance strategies for different age patients.

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INTRODUCTION: The histological grade of a tumor is an important prognostic indicator in both primary breast cancer and metastatic. We aimed to show the distribution of bone metastasis locations across different histological subtypes of breast cancer and how they relate to each. METHODS: The cohort retrospective study comprised 65 patients diagnosed with bone-only metastatic breast cancer, all female. The secondary statistics for 2014 to 2022 were derived from breast cancer registration data collected to determine the relationships between patterns of bone metastases sites and histopathological grading in various histological categories. RESULTS: The average age was 44.28±9.80 years (25-62 years), with 38 patients (58.5%) diagnosed with Invasive Ductal Carcinoma (IDC) and 27 patients (41.5%) with Invasive Lobular Carcinoma (ILC). Grade III were found in 34 patients (50.8%), Grade II in 31 patients (47.7%) and Grade I in one patient (1.5%). The most common sites of bone metastases are costae, followed by femur, vertebrae and pelvic. Vertebrae and costae metastasis are significantly correlated with histological grading and breast cancer pathology (p: 0.027 and 0.033, respectively). CONCLUSION: There is a considerable difference between vertebrae and costae metastasis in terms of histological grading and breast cancer pathology which indicates the higher grade contains a greater variety of bone metastases sites.

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Gastric mixed adenoneuroendocrine carcinomas(G-MANEC)are an infrequent variant of gastrointestinal tumors.Despite their relatively low occurrence,there has been a noticeable upward trend.G-MANEC exhibit a highly invasive nature,frequently leading to lymph-atic and distant metastases,which ultimately result in unfavorable prognosis.Consequently,this condition has garnered considerable in-terest among researchers.G-MANEC are characterized by the presence of adenocarcinoma and neuroendocrine carcinoma components,with each component comprising at least 30%of the tumor.In recent years,a growing body of knowledge regarding G-MANEC has led to a more comprehensive research approach towards this type of carcinoma.Nevertheless,there has been a notable deficiency to date in the ex-amination of lymph node metastatic aspects of G-MANEC,which poses several pressing challenges that demand immediate resolutions.This review aims to systematically analyze previous case reports and studies on mixed neuroendocrine-non-neuroendocrine neoplasms(MiNEN)while incorporating research on gastric cancer.This study focuses on various aspects of G-MANEC,including the epidemiology,biological ori-gin,diagnosis,patterns of lymph node metastasis,relationship with hematogenous metastasis,association between lymphatic and distant metastases,and treatment.The objective is to offer guidance for future research endeavors concerning G-MANEC.

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BACKGROUND: Few studies compared the oncological and biological characteristics between ampullary carcinoma (AC) and cancer of the second portion of the duodenum (DC-II), although both tumors arise from anatomically close locations. AIM: To elucidate differences in clinicopathological characteristics, especially the patterns of lymph node metastasis (LNM), between AC and DC-II. METHODS: This was a retrospective cohort study of 80 patients with AC and 27 patients with DC-II who underwent pancreaticoduodenectomy between January 1998 and December 2018 in two institutions. Clinicopathological factors, LNM patterns, and prognosis were compared between the two groups. RESULTS: The patients with AC and DC-II did not exhibit significant differences in 5-year overall survival (66.0% and 67.1%, respectively) and 5-year relapse-free survival (63.5% and 62.2%, respectively). Compared to the patients with DC-II, the rate of preoperative biliary drainage was higher (P = 0.042) and the rates of digestive symptoms (P = 0.0158), ulcerative-type cancer (P < 0.0001), large tumor diameter (P < 0.0001), and advanced tumor stage (P = 0.0019) were lower in the patients with AC. The LNM rates were 27.5% and 40.7% in patients with AC and DC-II, respectively, without significant difference (P = 0.23). The rates of LNM to hepatic nodes (N-He) and pyloric nodes (N-Py) were significantly higher in patients with DC-II than in those with AC (metastasis to N-HE: 18.5% and 5% in patients with DC-II and AC, respectively; P = 0.0432; metastasis to N-Py: 11.1% and 0% in patients with DC-II and AC, respectively; P = 0.0186). CONCLUSION: Although there were no significant differences in the prognosis and recurrence rates between the two groups, metastases to N-He and N-Py were more frequent in patients with DC-II than in those with AC.

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Background: The extent of a neck dissection for patients with metastasis of cutaneous squamous cell carcinoma of the head and neck (HNcSCC) is still subject to debate and clear guidelines are lacking. Tumor characteristics like size, differentiation and tumor location are known risk factors for lymph node metastasis (LNM). There is some evidence that, depending on tumor location, LNM follows a specific pattern. This study aims to identify which tumor characteristics can predict the pattern and extent of LNM. Method: In this cohort study 80 patients were included, who underwent a primary neck dissection for LNM of HNcSCC between 2003 and 2018 at the University Medical Center Groningen, the Netherlands. Retrospective data was collected for primary tumor characteristics and LNM and included surgical and follow-up data. Influence of tumor characteristics on the extent of LNM was analyzed using non-parametric tests. Logistic regression analysis were used to identify a metastasis pattern based on the primary tumor location. Results: Only primary tumor location was associated with the pattern of LNM. HNcSCC of the ear metastasized to level II (OR = 2.6) and the parotid gland (OR = 3.6). Cutaneous lip carcinoma metastasized to ipsilateral and contralateral level I (OR = 5.3). Posterior scalp tumors showed a metastasis pattern to level II (OR = 5.6); level III (OR = 11.2), level IV (OR = 4.7) and the parotid gland (OR = 10.8). Ear canal tumors showed a low risk of LNM for all levels. The extent of LNM was not related to age or any tumor characteristics i.e. tumor diameter, infiltration depth, differentiation grade, perineural growth and vascular invasion. Conclusion: Primary tumor location determines the LNM pattern. Whereas known unfavorable tumor characteristics did not relate to the extent of LNM. Location guided limited neck dissection combined with parotidectomy will treat most patients adequately.

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Background: Patients with advanced-stage lung adenocarcinoma (LADC) often develop distant metastases in the skeletal system. Yet, the bone-specific metastasis pattern is still controversial. We, therefore, aimed to examine how the primary tumor location affects bone specificity and survival in LADC patients diagnosed with skeletal metastases. Methods: In total, 209 bone-metastatic Caucasian LADC patients from two thoracic centers were included in this study. Focusing on the specific location of primary tumors and bone metastatic sites, clinicopathological variables were included in a common database and analyzed retrospectively. Skeletal metastases were diagnosed according to the contemporary diagnostic guidelines and confirmed by bone scintigraphy. Besides region- and side-specific localization, primary tumors were also classified as central or peripheral tumors based on their bronchoscopic visibility. Results: The most common sites for metastasis were the spine (n = 103) and the ribs (n = 60), followed by the pelvis (n = 36) and the femur (n = 22). Importantly, femoral (p = 0.022) and rib (p = 0.012) metastases were more frequently associated with peripheral tumors, whereas centrally located LADCs were associated with humeral metastases (p = 0.018). Moreover, we deduced that left-sided tumors give rise to skull metastases more often than right-sided primary tumors (p = 0.018). Of note, however, the localization of the primary tumor did not significantly influence the type of affected bones. Multivariate Cox regression analysis adjusted for clinical parameters demonstrated that central localization of the primary tumor was an independent negative prognostic factor for overall survival (OS). Additionally, as expected, both chemotherapy and bisphosphonate therapy conferred a significant benefit for OS. Conclusion: The present study demonstrates unique bone-specific metastasis patterns concerning primary tumor location. Peripherally located LADCs are associated with rib and femoral metastases and improved survival outcomes. Our findings might contribute to the development of individualized follow-up strategies in bone-metastatic LADC patients and warrant further clinical investigations on a larger sample size.

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BACKGROUND: Early metastasis is a hallmark of small cell lung cancer (SCLC). However, the mechanisms and resulting patterns of SCLC dissemination are unclear. Our aim was thus to investigate the organ specificity and timing of blood-borne metastases in a comprehensive large cohort of SCLC patients. METHODS: In this retrospective non-interventional cross-sectional study of 1009 Caucasian SCLC patients, we investigated the correlation between the distinct locations of the primary tumor and metastatic sites. RESULTS: The onset of bone (p < 0.001), brain (p < 0.001), and pericardial (p = 0.02) metastases were late events, whereas adrenal gland (p = 0.005) and liver (p < 0.001) metastases occurred earlier. No significant difference was found in the distribution of early versus late metastases when comparing central and peripheral primary tumors. Patients with bone metastases had a higher than expected likelihood of having liver metastases, while brain metastases tended to appear together with adrenal gland metastases. Pleural and both lung and pericardial metastases also tended to co-metastasize together more frequently than expected if metastatic events occurred independently. Notably, patients with central primary tumors had decreased median overall survival (OS) compared to those with peripheral tumors, although this tendency does not appear to be significant (p = 0.072). CONCLUSION: Our results are suggestive for particular site- and sequence-specific metastasis patterns in human SCLC. SCLC bone metastases tend to appear together with liver metastases, while brain metastases occur together with adrenal gland metastases. Better understanding of metastasis distribution patterns might help to improve the diagnosis and therapeutic decision-making in SCLC patients.

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The aim of the present study was to investigate the prognostic impact of RT on patients with extensive stage small cell lung cancer (ES-SCLC) and distant metastasis. Using the Surveillance Epidemiology and End Results (SEER) database, 8,595 patients with ES-SCLC exhibiting distant metastasis treated between 2010 and 2013 were identified. Patient baseline characteristics were compared using the χ2 test. The Kaplan-Meier test was used to analyze subgroup cancer-specific survival (CSS) rate, and differences were compared using a log-rank test. Univariate and multivariate Cox regression models were used to analyze the prognostic variables on CSS. RT was determined to be an independent prognostic factor for patient CSS (P<0.001). In addition, RT could improve the CSS of patients with ES-SCLC with one metastatic lesion (hazard ratio, 0.63; 95% confidence interval, 0.59-0.68; P<0.001), including the bone, brain, liver and lung metastatic sites. However, for patients with two metastatic sites, RT did not improve CSS regardless of metastasis pattern (all P>0.05). To conclude, RT may improve the survival rate of patients with ES-SCLC with distant metastasis, particularly in those with only one metastatic site.

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BACKGROUND: Metastasis sites and breast cancer subtypes are important for breast cancer patients. This study aimed to assess possible relationships between them and their influence on prognosis in male breast cancer (MBC) patients. METHODS: We collected data on 2,983 patients with MBC from the Surveillance, Epidemiology, and End Results database, including 250 patients with M1 stage disease. Information on metastatic patterns was provided for bone, brain, liver, and lung metastases. MBC was classified into four subtypes: Her2-/HR+, Her2+/HR+, Her2+/HR-, and triple negative (TN). Univariate and multivariate logistic regression analysis were used to analyze the association, and Cox regression analyses were used to analyze prognosis. RESULTS: The bone was the most common metastatic site and the brain was the least common metastatic site. Patients with the Her2-/HR+ subtype had the highest proportion of metastatic disease, and Her2+/HR- patients had the lowest proportion. Univariate and multivariate logistic regression analyses showed that there were significant differences in distant metastasis patterns in patients with different subtypes. Men with the Her2+/HR+ or Her2-/HR+ subtypes with bone metastasis had better cancer specific survival (CSS), and those with the TN subtype had the worst CSS in all metastatic patterns. CONCLUSIONS: MBC subtypes are associated with different metastasis patterns and can have different effects on prognosis. This study might provide insights into a better understanding of MBC.

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In addition to hepatocellular carcinoma, metastatic liver cancer (MLC) is another focus of hepatic surgeon. Good outcome of patients with liver metastasis (LM) from colorectal cancer or neuroendocrine tumor have been achieved. Ovarian cancer liver metastasis (OCLM) has its unique oncological characteristics and a variety of metastasis patterns, which brings a challenge to hepatic surgeon. Hepatic surgeons hold different views and techniques from gynecologists, which makes differences in the evaluation and treatment of the disease. We reviewed recent studies and, in combination with our own clinical experience, attempted to introduce the progress of surgical treatment of liver metastases from OC. In our experience, both preoperative imaging and surgical procedures are based on the assurance of R0 resection. R0 cytoreductive surgery (CRS) is the most favorable determinant for the prognosis of OC patients, and R0 liver resection (LR) is a component of R0 CRS. Gynecologists and hepatic surgeons should do their own preoperative and intraoperative evaluation for the extrahepatic and intrahepatic metastasis respectively. During the operation, regardless of the miliary nodules dissemination between the right hemidiaphragm and liver capsule, liver parenchymal infiltration (LPI) or liver parenchymal metastasis (LPM), 1-2 cm resection margin should be emphasized. For patients with liver portal lymph node metastasis (LPLNM), hepatic portal skeletonization should be performed, rather than portal lymph node dissection. The operation should be as radical as possible to ensure the patients to achieve good prognosis.

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BACKGROUND: Papillary thyroid microcarcinomas (PTMCs) often demonstrate lateral lymph node (LN) metastasis. The purpose of this study was to assess whether the size of primary tumor should be considered in deciding lateral neck dissection extent. METHODS: We conducted a retrospective comparison of patients with PTMC and papillary thyroid carcinoma (PTC) larger than 1 cm who received lateral LN dissection from 2009 to 2015. RESULTS: PTMC group had more frequent metachronous metastasis, multifocality, less involvement of lower third thyroid, lower metastatic central LN counts and ratio, and lower metastatic total LN ratio. The two groups showed no difference in lateral LN metastatic pattern. Male and lymphovascular invasion were more often found in PTMCs with synchronous lateral LN metastatic events than metachronous presentations. CONCLUSIONS: Relying on the size of the tumor to determine lateral neck dissection extent could be unreliable, because there is no observed difference in lateral neck metastatic count and pattern between PTC and PTMCs.

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The aim of the present study was to explore the pattern of lymph node metastasis (LNM) in poorly-differentiated esophageal squamous cell carcinoma (pdESCC) and the implication of postoperative irradiation. A total of 690 patients with pdESCC were retrospectively investigated. The rates of intro-thoracic and extra-thoracic LNM in pdESCC were investigated and compared to previous research on ESCC en bloc. The comparison of the rates between pdESCC and ESCC were performed using the Cochran-Mantel-Haenszel test. The clinicopathological factors associated with LNM in pdESCC were analyzed by Chi-squared tests, and Fisher's exact test was used to assess the rate difference of extra-thoracic LNM. Logistic-regression analysis was used to explore risk factors associated with lymph node (LN) station. Results demonstrated that the distribution pattern of LNM in pdESCC was significantly different compared with that of ESCC (P<0.05). Univariate and multivariate analysis indicated that risk factors associated with LNM were depth and length (P<0.001 and P<0.001) and multivariate analysis also indicated that the location of the tumor (P=0.042) was a risk factor associated with LNM in pdESCC. Metastasis in the abdominal cavity was significantly higher than in the neck in the middle and lower thoracic pdESCC (both P<0.01). LN station 102 and 7 for upper thoracic ESCC, 101 and 105 for middle thoracic ESCC, and 100 for lower thoracic ESCC were identified as high-risk stations for metastases in pdESCC compared to ESCC. Several parameters, including location and neck metastasis, were identified as risk factors of metastasis for the above sites, respectively. In conclusion, postoperative therapy should include more LN stations in pdESCC depending on risk factors of tumor metastasis individually.

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AIM: To analyze the metastasis patterns and prognosis differences for extensive-stage small-cell lung cancer patients. METHODS: Log-rank tests were used to calculate and compare survival estimates. Cox regression analyses were used to evaluate the prognosis factors. RESULTS: The liver was the most common metastatic site, and lung was the least common. In two metastatic sites, liver and bone metastases were the most common combination of sites. An isolated liver metastasis had the worst overall survival (OS) and cancer-specific survival (CSS) among metastatic sites (both p < 0.001). Liver and lung metastases were associated with worse CSS (p < 0.039) and OS (p < 0.015). However, for patients with three metastatic sites showed no statistical differences in their CSS and OS (all, p > 0.05). CONCLUSION: Extensive-stage small-cell lung cancer patients with metastasis to the liver alone or in combination with other organs appear to have worse outcomes.

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Studies on prognosis of different metastasis patterns in patients with different breast cancer subtypes (BCS) are limited. Therefore, we identified 7862 breast cancer patients with distant metastasis from 2010 to 2013 using Surveillance, Epidemiology, wand End Results (SEER) population-based data. The results showed that bone was the most common metastatic site and brain was the least common metastatic site, and the patients with HR+/HER2- occupied the highest metastasis proportion, the lowest metastasis proportion were found in HR-/HER2+ patients. Univariate and multivariate logistic regression analysis were used to analyze the association, and it was found that there were significant differences of distant metastasis patterns in patients with different BCS(different P value). Importantly, univariate and multivariate Cox regression analysis were used to analyze the prognosis. It was proven that only bone metastasis was not a prognostic factor in the HR+/HER2-, HR+/HER2+ and HR-/HER2+ subgroup (all, P > 0.05), and patients with brain metastasis had the worst cancer specific survival (CSS) in all the subgroups of BCS (all, P<0.01). Interestingly, for patients with two metastatic sites, those with bone and lung metastasis had best CSS in the HR+/HER2- (P<0.001) and HR+/HER2+ subgroups (P=0.009) However, for patients with three and four metastatic sites, there was no statistical difference in their CSS (all, P>0.05).

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Background and purpose:Breast cancer can be divided into several molecular subtypes according to its biomarkers. The pattern of distant metastasis has a great clinic significance but was rarely investigated. This study investigated the impact of molecular subtype of breast cancer on initial sites of metastasis..Methods:All the patients with operable invasive breast cancer diagnosed in Zhongshan People’s Hospital between 1998 and 2004 were recruited. Subtypes were defined as Luminal A, Luminal B, human epidermal growth factor receptor 2 (HER-2) enriched, and triple negative (TN) according to the expression of estrogen receptor (ER), progestogen receptor (PR) and HER-2 status. The first distant metastatic sites and the time of their appearances were recorded. Survival curves were constructed using the Ka-plan-Meier technique.Results:Among 390 eligible patients, there were 215(55.1%) with Luminal A, 43 (11.0%) with Lu-minal B, 52 (13.3%) with HER-2 enriched, and 80 (20.5%) with TN. The median follow-up time was 118 months (11-163 months). Seventy-two (18.5%) distant metastases occurred during follow-up: 37 metastases in Luminal A, 8 in Luminal B, 10 in HER-2, 17 in TN. Bone was the most common site of the first distant metastasis (39/72, 54.2%) followed by lung (25/72, 34.7%), liver (22/72, 30.6%), and brain (7/72, 9.7%). Among all the metastases, tumors of Luminal type (Luminal A 70.2%, Luminal B 50.0%) had a higher chance of bone involvement than that of HER-2 enriched (30.0%) and TN (35.3%,P=0.03). Both Luminal B (37.5%) and TN (17.6%) subtypes had a higher percentage of brain involvement than Luminal A and HER-2 enriched (P=0.01). The survival analysis showed no significant difference among the four subtypes in 9-year distant metastasis-free survival. However, distant metastasis appeared earlier in HER-2 enriched and TN breast cancer than in Luminal type.Conclusion:Organ-specific metastasis may depend on the molecular subtype of breast cancer. Bone metastasis occurs more in luminal type than in other types. Luminal B and TN types of tumors had more chance of brain metastasis than Luminal A and HER-2 enriched type of tumors.

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BACKGROUND/AIM: Treatment of metastatic neuroblastoma remains a challenge in pediatric oncology. Relevant preclinical models may improve exploration of oncogenesis and new therapies. We developed new orthotopic and metastatic models derived from stage 4 neuroblastoma. MATERIAL AND METHODS: Orthotopic and systemic models were established in BalbC Rag2(-/-)gammaC(-/-) mice following adrenal and intravenous injection of luciferase-transfected IMR-32 and IGR-N91 cells, respectively. RESULTS: All four models exhibited 100% tumor take rate. Metastatic spread of orthotopic IMR-32-Luc cells was observed mainly to the lung, liver and bone; that of IGR-N91-Luc cells to liver, spleen and adrenals. Interestingly, systemic IMR-32-Luc cells metastasized rather to the lung, liver and bone, and IGR-N91-Luc to liver, lung, spleen and adrenals. Feasibility of non-invasive, real-time antitumor response evaluation was validated in the systemic models. CONCLUSION: These neuroblastoma models with distinct patterns of metastatic spread represent relevant tools for exploring local and metastatic tumor cell tropism, mechanisms of spread and evaluating new cancer therapeutics.

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