Distant Metastases

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Quantitative Assessment of Prognosticators for Rectal Cancer’s Local Recurrence and Distant Metastases

Quantitative Assessment of Prognosticators for Rectal Cancer’s Local Recurrence and Distant Metastases

Abstract: Rectal cancer treatment outcome has improved considerably in the TME era often with the use neoadjuvant chemoradiotherapy. However, the risk of local recurrence/distant metastases could be as high as 10%. We have designed a retrospective cohort study to assess risk factors associated with local recurrence/distant metastasis after primary curative rectal resection. Our analysis of the colorectal database in a district general hospital involved review of 131 patients who had a curative resection between 2007 and 2013. 22 patients of the 131 had local recurrence/distant metastases. We reviewed the risk factors as gender, neoadjuvant chemoradiotherapy, type of operation, anastomotic leak, tumour differentiation, EMVI, CRM and Dukes C and performed a quantitative assessment. Looking at risk factors, the presence of EMVI was found to have a statistically significant association with recurrence and distant metastases (p=0.0006) followed by poor differentiation (p= 0.038) and Dukes C (p=0.045) while CRM involvement (p=0.054), Neoadjuvant chemoradiotherapy (p=0.657), type of resection (p=0.740), Anastomotic leak (p=0.761) and gender (p=0.901) shown no obvious statistical association with recurrence or distant metastases A larger multi-centre study may help in validating our observation.
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Changes in glycoprotein expression between primary breast tumour and synchronous lymph node metastases or asynchronous distant metastases

Changes in glycoprotein expression between primary breast tumour and synchronous lymph node metastases or asynchronous distant metastases

Metacore analysis showed there were distinct changes occurring in hormone signalling. The program displays a thermometer indicating the change in expression of the protein in the lymph node metastasis or distant me- tastasis relative the paired primary tumour. One path- way that scored high and is of great clinical importance is the development of oestrogen receptor ligand inde- pendent activation. For the analysis, the protein expres- sion was normalised against the whole primary tumour data set. Additional file 1: Figure S1(a) shows the changes in expression of the main actors in ligand inde- pendent activation (EGFR (Epidermal growth factor re- ceptor, HER2), ErbB2 (Receptor tyrosine-protein kinase erbB-2) ErbB3 (Receptor tyrosine-protein kinase erbB- 3), IGFR1 (insulin-like growth factor receptor-1), Shc (Shc transforming protein-1), NCOA2 (nuclear receptor co-activator-2), TFF1 (Trefoil factor 1) and PKA-reg (protein kinase A regulatory subunit)) in a comparison between ER+ and ER- lymph node metastasis, relative to the primary tumour. The protein Trefoil factor 1 is under control of the oestrogen receptor and is up regu- lated in the ER+ lymph node metastasis but clearly down-regulated in the ER- lymph node metastasis. However this is reversed in the distant metastases as seen in Additional file 1: Figure S1(b) probably as a re- sult of the strong up-regulation of TFF1 in the ER- and of the down-regulation of the nuclear receptor co- activator-2. The effect seems to develop during the evo- lution of ER- lymph node metastasis to distant metasta- sis as seen in Additional file 1: Figure S1 (c). In contrast, in Additional file 1: Figure S1(d) no effect is seen in the change from ER+ lymph node metastasis to distant me- tastasis since oestrogen signalling is still intact.
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HER2gene status in primary breast cancers and matched distant metastases

HER2gene status in primary breast cancers and matched distant metastases

HER2 FISH status is highly preserved as breast cancers progress to metastatic disease. However, a discrepancy in HER2 status exists in a small fraction of patients. As well as true conversion of HER2 status, interpretational difficulties due to borderline FISH results, rarity of tumour cells and intra- tumoral heterogeneity were identified as important reasons for the discrepancy. Irrespective of the reason, however, every discordance in HER2 status is a diagnostic reality and can lead to inaccurate treatment decisions with medical and eco- nomical effects. To guarantee optimal care of individual patients, we advocate HER2 analysis of distant metastases in all patients irrespective of the result in the primary tumour. The feasibility of this approach will ultimately be determined by economic factors. Future patients with distant metastases after adjuvant treatment for HER2-positive breast cancer will pose additional diagnostic and therapeutic challenges. It is possible that treatment with trastuzumab leads to clonal selec- tion of HER2-negative tumour cells, as observed in individual patients [35]. Thus, HER2 testing of metastasis may become a necessity in every patient.
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Sites of synchronous distant metastases and prognosis in prostate cancer patients with bone metastases at initial diagnosis: a population-based study of 16,643 patients

Sites of synchronous distant metastases and prognosis in prostate cancer patients with bone metastases at initial diagnosis: a population-based study of 16,643 patients

Our study shows that in PCa patients with bone metas- tases, approximately 10% of patients have synchronous distant metastases at other sites. Among these sites, the lung was the most frequently involved extra-skeletal organ, followed by the liver, whereas brain metastasis was relatively uncommon. These results are in line with those of former studies [18, 28]. A previous autopsy study of 1589 PCa patients also demonstrated that lung was the second most frequent site of involvement, following bone [29]. However, there is very few published researches on the mechanisms of lung metastasis in prostate cancer. Several biological processes, such as hemodynamics, bone-specific signaling interactions, and the “seed and soil” hypothesis, were attributable to the bone metasta- sis of PCa [30]. Lung metastasis of breast cancer, another primary of high incidence and metastatic rate, is often explained by the “seed and soil” hypothesis [31]. To eluci- date the mechanism of lung metastasis from PCa remains a challenge, which need further study to understand its pathogenesis and prognosis.
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Molecular predictors of locoregional and distant metastases in oropharyngeal squamous cell carcinoma

Molecular predictors of locoregional and distant metastases in oropharyngeal squamous cell carcinoma

Molecular biomarkers are known to be useful in pre- dicting survival outcomes for OPSCC patients. Onco- genic HPV infection is associated with upregulation of p16, a protein now widely utilized as a surrogate marker of HPV-positive disease [1,2]. Many authors have shown that HPV-positive oropharyngeal cancers are associated with significantly improved survival. Other molecular biomarkers including epidermal growth factor receptor (EGFR), B-cell lymphoma extra large (Bcl-xL), p53, and Ki67, have been shown to have prognostic significance i [3]. High EGFR expression has been correlated with poorer survival, while low levels of the anti-apoptotic protein, Bcl-xL, have been shown to be associated with improved response to radiation [4]. A recent study has suggested that elevated Ki67 levels may be associated with improved response to radiotherapy [5]. Despite the available data, there has been limited investigation regarding the role of different biomarker profiles in locoregional and distant metastasis of OPSCC. Identify- ing a subset of patients that are more likely to have recurrence and distant metastases is valuable when counselling patients about treatment options and prog- nosis, and making treatment decisions.
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E cadherin expression in primary carcinomas of the breast and its distant metastases

E cadherin expression in primary carcinomas of the breast and its distant metastases

The median age at diagnosis of the primary invasive breast carcinoma was 53.9 years (range, 39–80 years). All primary tumors were treated by surgical excision. Of the primary tumors, 22 were invasive ductal carcinomas and eight were invasive lobular carcinomas. Metastatic sites included the liver (six cases), the bone marrow (five cases), the skin (four cases), the lung (three cases), the femoral head (three cases), the pelvic girdle (two cases), the vertebrae (two cases), the brain (two cases), the colon (one case), the ovary (one case), the pericardium (one case), the abdominal wall (one case), and the contralateral breast (one case). E-cadherin expression in primary and distant metastases
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Atypical manifestation of parathyroid carcinoma with late-onset distant metastases

Atypical manifestation of parathyroid carcinoma with late-onset distant metastases

Parathyroid cancer is a rare endocrine disorder constituting less than 1% of parathyroid neoplasms. It is mainly a sporadic disease with a peak incidence in the fourth or fifth decade of life. Parathyroid carcinoma commonly presents with significantly elevated calcium levels due to high parathyroid hormone (PTH) levels and symptoms are related to severity of hypercalcemia. Distant metastases are developed in about 25% of patients, most commonly to lymph nodes, bone, lung and liver. It is usually difficult to diagnose malignant tumors pre-operatively or on histological examination
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The prognostic relevance of interactions between venous invasion, lymph node involvement and distant metastases in renal cell carcinoma after radical nephrectomy

The prognostic relevance of interactions between venous invasion, lymph node involvement and distant metastases in renal cell carcinoma after radical nephrectomy

Only few studies have analysed survival by comparing N1/N2M1 and N0M1 disease; most patients with M1 dis- ease are grouped together regardless of lymph node status. In the multivariate analysis of interactions of SMD, VI and LNI on survival, LNI showed a significant impact on sur- vival only for the patients in whom we found no distant metastases or venous invasion. In this subgroup of patients there was a hazard ratio of 9.0 for later death of RCC. This finding implies that once RCC has spread to the lymphatic system the risk of haematogenous spread to other regions is high, and it is likely that few patients would benefit from an extensive lymph node dissection. In accordance with other reports, the impact of VI on sur- vival was highest for patients free from nodal and distant metastases, and was insignificant in patients with both LNI and SDM [7,28].
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Distant metastases in phyllodes tumours of the breast: an overview

Distant metastases in phyllodes tumours of the breast: an overview

distant metastasis are the lungs and skeleton; however nearly all other organs have been shown to be affected as well. Patient prognosis is extremely poor after meta- static spread, with death oftentimes ensuing. Several fac- tors, such as stromal overgrowth, have been shown to be significantly associated with the occurrence of distant metastasis, although there are still no established robust pathological characteristics to predict which cases of PTs are at risk of developing distant metastasis. Future work investigating the predictive factors of distant metastases in PTs will be another step closer in identifying patients who are at higher risk of developing distant metastasis, in order to optimize their management.
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A compact VEGF signature associated with distant metastases and poor outcomes

A compact VEGF signature associated with distant metastases and poor outcomes

Results: When compared with each other, primary tumors and regional metastases showed statistically indistinguishable gene expression patterns. Supervised analyses comparing patients with distant metastases versus primary tumors or regional metastases showed that the distant metastases were distinct and distinguished by the lack of expression of fibroblast/mesenchymal genes, and by the high expression of a 13-gene profile (that is, the 'vascular endothelial growth factor (VEGF) profile') that included VEGF, ANGPTL4, ADM and the monocarboxylic acid transporter SLC16A3. At least 8 out of 13 of these genes contained HIF1α binding sites, many are known to be HIF1α-regulated, and expression of the VEGF profile correlated with HIF1α IHC positivity. The VEGF profile also showed prognostic significance on tests of sets of patients with breast and lung cancer and glioblastomas, and was an independent predictor of outcomes in primary breast cancers when tested in models that contained other prognostic gene expression profiles and clinical variables. Conclusion: These data identify a compact in vivo hypoxia signature that tends to be present in distant metastasis samples, and which portends a poor outcome in multiple tumor types.
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Prognostic value of primary tumor surgery in minor salivary-gland carcinoma patients with distant metastases at diagnosis: first evidence from a SEER-based study

Prognostic value of primary tumor surgery in minor salivary-gland carcinoma patients with distant metastases at diagnosis: first evidence from a SEER-based study

undergone PTS. The median follow-up time was 12 months and median age at diagnosis was 62.5 (range 26–91) years. More than half (n = 90, 59.2%) of the patients were male. The vast majority of tumors (n = 128, 84.2%) were high-risk pathologies, and ~ 60% (n = 92, 60.5%) of tumors originated from the oral cavity and oropharynx. One hundred and forty- four (93.4%) of the tumors were categorized as intermediate- or high-risk pathology, and adenoid cystic carcinoma (n = 62, 40.8%) and adenocarcinoma NOS (n = 31, 20.4%) were the two most common histotypes. Eighty-three (25.0%) patients had stage T1–T2 tumors and 48.0% (n = 73) had N + disease. In addition, 55.3% (n = 84) and 48.7% (n = 74) of the entire cohort had undergone radiation and chemotherapy, respec- tively. Patient characteristics of the no-PTS and PTS groups are outlined in Table 1. In the overall cohort, metastases of 43 patients (28.3%) were pathologically confirmed, whereas the rest (71.7%) were confirmed by imaging, such as positron- emission tomography/computed tomography.
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Pattern of distant metastases in colorectal cancer: a SEER based study

Pattern of distant metastases in colorectal cancer: a SEER based study

Review of autopsy data from patients who died from colorectal cancer shows that liver is the only site of metastatic disease in one third of patients. Studies of selected CRC patients undergoing surgery to remove liver metastases have shown that cure is certainly attainable in this population [9]. Therefore patients diagnosed with potentially resectable metastatic CRC should ideally undergo an upfront evaluation by a multidisciplinary team to maximize the curative potential [10-12]. Thus it is crucial to exclude extrahepatic (or extra-pulmonary) metastasis before local treatment. A clear understanding of the metastatic pattern and distribution becomes especially important.
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Evolutionary history of metastatic breast cancer reveals minimal seeding from axillary lymph nodes

Evolutionary history of metastatic breast cancer reveals minimal seeding from axillary lymph nodes

Distant metastases are seeded without involvement of the syn- chronous ALN metastasis. In order to investigate whether meta- static lymph nodes can secondarily seed distant metastases, we used the separating property in the phylogenetic trees to analyze 8 patients (patients 2, 3, 8, 10, 14, 15, 17, and 18) with primary cancer, ipsilateral ALN metastases, and distant metastasis. Patient 12 was excluded from this analysis because of unavailable distant metas- tasis sequencing data. Our analysis revealed very low support for ipsilateral ALN–based seeding to distant organ metastases (Fig- ure 5). The highest bootstrap support value for an MRCA of the ALN and a distant metastasis across 8 phylogenetic trees was 23% (patient 8), while the other values were zero or almost zero (Table 4). In 3 patients (patients 2, 10, and 15), we sequenced the only pos- itive ALN (2 blocks sequenced in the case of patient 10), excluding the possibility of a distant metastasis seeded by an unsequenced metastatic lymph node. Subclonal analysis revealed that, except for patient 3, no subclones were shared exclusively among ALN metastases and any distant metastases, thus supporting the phylo- genetic results. Even in patient 3, a distant bone metastasis shared a subclone with the primary tumor, making it equally likely that either the primary cancer or the ALN was responsible for the dis- tant organ metastasis. It is important to note that we cannot rule out the possibility of metastatic seeding from a dormant subclone in the ALN metastasis to a distant metastasis, when, after seed- ing, such a subclone becomes active only in the distant metastasis. Moreover, there is also a possibility that we missed a mutation or a subclone because it was either in an unsequenced part of the ALN or was too rare to be detected by the sequencing coverage of the study. Ideally, one would sequence the entire axillary region, but clinically, it is unethical to conduct such a study. The phylogenetic trees, along with the subclonal composition for patients 2 and 10 (patients with all positive lymph nodes sequenced) and patient 14 (1 of 14 positive lymph nodes sequenced), are shown in Figure 5, A–C, respectively, while similar plots for the other 5 patients are shown in Supplemental Figure 6, C, G, M, O, and P.
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Case Report Adenoid cystic carcinoma of maxillary sinus metastatic to the kidney: a case report and review of the literature

Case Report Adenoid cystic carcinoma of maxillary sinus metastatic to the kidney: a case report and review of the literature

ACC of the head and neck is a salivary gland malignancy. The sinonasal tract is a common site for this malignancy, accounting for 10%- 25% of all head and neck ACCs [3]. The maxil- lary sinus is the most commonly affected pri- mary site, followed by the nasal fossa, ethmoid sinus, and sphenoid sinus [4]. It has distinct characteristics of an indolent but persistent growth and a high rate of perineural spread, local recurrences, and distant metastases [5, 6]. In long-standing cases, distant metastases

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Clinical characteristics of XP11.2 translocation/TFE3 gene fusion renal cell carcinoma: a systematic review and meta-analysis of observational studies

Clinical characteristics of XP11.2 translocation/TFE3 gene fusion renal cell carcinoma: a systematic review and meta-analysis of observational studies

Data extraction fields for each study included the fol- lowing: (1) demographic data concerning patient gen- der, age, treatment and condition during follow-up period; (2) tumor data for different gender and age in- cluding stage, lymphatic and distant metastases. For age, patients was divided into children (≤ 14 years) and adults (> 14 years). When gender-related incidences in children and adults were studied, reference would be excluded if only 1 patient was presented in the study. The cases of Xp11.2 RCC would be excluded if the lymphatic and distant metastases of tumor cannot be determined when we studied tumor metastases and stage. If journal articles contained insufficient informa- tion, we attempted to contact authors to obtain missing details. If failed, we could just present out the existing results.
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Receptor conversion in distant breast cancer metastases

Receptor conversion in distant breast cancer metastases

departments of pathology of the University Medical Center Utrecht, the Academic Medical Center Amster- dam, the Radboud University Nijmegen Medical Centre, the Canisius Wilhelmina Hospital Nijmegen, the Nether- lands Cancer Institute Amsterdam, the Medical Center Alkmaar, the Medical Center Zaandam, the University Medical Center Groningen, the St. Antonius Hospital Nieuwegein, the Diakonessenhuis Utrecht, the Free Uni- versity Medical Center Amsterdam, and the Laboratory for Pathology Dordrecht, all in The Netherlands. Original diagnoses were made between January 1985 and March 2009, and these cases comprised all the paired cases that could be retrieved from the participating labs during this period, minimizing selection bias. All histological speci- mens had been fixed for 12 to 24 hours in neutral buffered formaldehyde. The vast majority of primary specimens were paraffin blocks of breast or lumpectomies, except for 17 cases core biopsies from the primary tumors were used (no cytology). For 11 cases this information was not avail- able. The sites of the distant metastases are shown in Table 1. Use of anonymous or coded left over material for scientific purposes is part of the standard treatment con- tract with patients in hospitals in The Netherlands [29]. Ethical approval was not required.
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Retrospective Review of Chemotherapy Treatment for Locally Advanced and Metastatic Penile Cancer in the North West of England

Retrospective Review of Chemotherapy Treatment for Locally Advanced and Metastatic Penile Cancer in the North West of England

Penile cancer is rare in Western countries, with a UK incidence of approximately 1 in 100,000 [1]. Early stage disease is treated primarily with surgery or radiotherapy. Although only a small proportion of patients will present with distant metastases (around 3%), up to a third will have locally advanced disease [2] and around 30% of patients will have recurrent disease after surgery [3]. This risk is much increased if there are bilateral or multiple inguinal lymph node metastases with five year cancer specific survival falling from approximately 80% for N1 disease to 50% in N2 disease. Fixed inguinal nodes and pelvic lymphadenopathy carry a significantly worse prognosis [4].
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Factors Associated with Clinical Outcomes of Differentiated Thyroid Cancer Following Radioiodine Therapy in Tanzania

Factors Associated with Clinical Outcomes of Differentiated Thyroid Cancer Following Radioiodine Therapy in Tanzania

Abstract: Background: Thyroid cancer is the most common endocrine type of malignancy, accounting for 1-5% of all cancers worldwide. Most of the differentiated thyroid cancers are asymptomatic. Surgery is the mainstay of management to be followed by radioactive iodine (RAI). RAI accessibility is still a challenge in most developing countries including Tanzania. The aim of this study was to determine factors affecting the clinical outcome of patients with differentiated thyroid cancer (DTC) following RAI treatment in a resource limited setting. Methods: This was a prospective cohort study carried out from 2014 to 2018 at the Ocean Road Cancer Institute, in Tanzania. A total of 52 histologically proven differentiated thyroid cancer patients post- near or total thyroidectomy were recruited. All patients received RAI therapy until ablation was achieved, were maintained on thyroxine suppression dose, and were followed for two years. Results: A total of 52 differentiated thyroid cancer patients were recruited after surgery by convenience sampling. The median age of patients was 46 years (range 17-77), and 87% (n=45) were female. Distant metastases were detected in 60% of patients (n=20) at initial presentation. The most common clinical presentation was a neck mass without compression symptoms (85%). Analysis at the end of two years revealed that female gender, clinical-pathological presentation, and the absence of distant metastasis(es) at diagnosis and amount of RAI received, contributed significantly to improved outcome. Conclusion: In a limited resource setting, the outcome of DTC patients post RAI therapy can be improved by early diagnosis hence improving clinical outcome.
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Cervical lymphadenopathy – an unusual presentation of carcinoma of the cervix: a case report

Cervical lymphadenopathy – an unusual presentation of carcinoma of the cervix: a case report

In Henriksen's study [2], incidence of metastasis of carci- noma of the cervix to left supraclavicular nodes was 0.1% in untreated patients but up to 1.5% in treated patients. As further recent studies have shown, modern radiotherapy achieves better control of cancer in the pelvis and allows more patients to survive longer, which, in turn, permits distant metastases to become clinically evident. Hilar, mediastinal [3,4] and supraclavicular lymphadenopathy [5] have been described as the first evidence of tumour recurrence.

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Metastatic nonpalpable invasive lobular breast carcinoma presenting as rectal stenosis: a case report

Metastatic nonpalpable invasive lobular breast carcinoma presenting as rectal stenosis: a case report

Introduction: Invasive lobular carcinomas have an increased propensity for distant metastases, particularly to the peritoneum, ovaries, and uterus. In contrast, distant metastases of nonpalpable lobular carcinomas are extremely rare, and the causes of underlying symptoms of primary carcinomas remain unclear. We report a case of an asymptomatic invasive lobular carcinoma with a primary mammary lesion in a patient with rectal stenosis. Case presentation: A 69-year-old Japanese woman presented to our hospital for treatment of constipation. Although rectal stenosis was confirmed, thorough testing of her lower digestive tract did not identify its cause. Thus, an exploratory laparotomy and tissue biopsy was performed, and the presence of an invasive lobular carcinoma was confirmed. Subsequent breast examinations showed that the invasive lobular carcinoma that led to the rectal stenosis was a metastatic lesion from a primary lesion of the breast duct. As the present breast lobular carcinoma was asymptomatic and nonpalpable, we did not initially consider metastatic breast cancer as a cause of her symptoms, and the final diagnosis was delayed.
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