Local Regional Lymph Node Metastases Research Articles

Immunohistochemical evaluation of D2-40, Galectin-3, Maspin and MCM7 expression in palate squamous cell carcinomas.

Squamous cell carcinoma (SCC) is the most frequent cancer in oral cavity and its prognosis has exhibited little improvement in the last decades. Although much less common palate SCCs manifests a higher local aggression invading very quickly the adjacent muscles and jawbones, thus being able frequently to lead to dysfunctions in chewing, swallowing, and speech. To elucidate what underlies such local aggression, we investigated the immunohistochemical expression in palate SCCs of Podoplanin (D2-40), Galectin-3 (Gal-3), mammary serine protease inhibitor (Maspin) and minichromosome maintenance complex component 7 (MCM7), markers that are known to be involved in tumor invasiveness. We found a progressive increase in reactivity for D2-40 and MCM7 from the normal epithelium toward dysplastic epithelium and respectively to SCC, which suggests the intervention of these markers in the early stages of squamous cell carcinogenesis in the palate. The highest D2-40, Gal-3 and MCM7 reactivity was observed in basaloid and in poorly differentiated (G3) palate SCCs, while for Maspin the well-differentiated (G1) palate SCCs were the most reactive. The first three markers mentioned above were most intensely expressed at the invasion front, while the Maspin reactivity was low or absent at this level. Statistically, we found significant stratification on localization, grading, muscle invasion, and survival for all investigated markers, but with very high direct correlations between D2-40, Gal-3, and MCM7 immunoreactive score (IRS) values, while between the Maspin and each of the previous markers there were very high inverse correlations. Overall, all these investigate markers proved to be responsible for the local invasiveness and regional lymph node metastasis, thus allowing a prognostic and therapeutic stratification of patients with palate SCCs.

Risk factors for nodal involvement in early-stage rectal cancer: a new scoring system based on the analysis of 326 cases.

the purpose of this study was to identify which clinicopathological features of early-stage rectal cancer (ESRC) are significantly correlated with the risk of local-regional lymph node metastases (LNM) and to quantify the strength of this association through a novel scoring system. According to several case studies, about 20% of operated ESRC are found with occult lymph nodal metastases at the histological examination. The low frequency of local recurrence in these tumors treated with total mesorectal excision (TME) compared to transanal approaches highlights the role of mesorectal lymph nodes as a site of metastatic location. Overall, 386 consecutive patients with ESRC treated with radical resection and TME were examined in a retrospective, observational multi-centric study, operated between 2007 and 2019 in seven centers. Demographic and tumor related clinicopathological characteristics were identified, collected and analyzed. Each variable was specifically weighted based on the strength of its association with the presence of nodal metastases. A scoring system using these weighted variables was developed. Six variables were found to be significantly associated with local regional LNM: lymphatic invasion combined with vascular invasion, poor differentiation (G3), stage T2, age ≥60 years, male sex, perineural invasion. A novel scoring system weighted on the presence of each of these variables able to quantify the risk of LNM in ESRC was developed. The proposed scoring system is a good predictor of the risk of LNM and should be of help in the decision-making process for ESRC cases diagnosed either by local excision or endoscopic biopsy.

Salvage Re-Irradiation Versus-Concurrent Chemoradiotherapy For Esophageal Squamous Cell Carcinoma Patients With Locally Relapse After Definitive Chemoradiotherapy

This retrospectively study aimed to investigate the effects of re-irradiation therapy (re-RT) and re-concurrent chemoradiotherapy (re-CCRT) with the precise radiation techniques for the patients with locally recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy. From January 2008 to December 2016, 109 patients with locally recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy were involved in the study. Of all, patients with time to recurrence (TTR) over 24 months and ≤24 months were 36 (33.0%) and 73(77.0%) cases. Seventy-five (68.8%) patients had a recurrence of the esophagus and 34 (31.2%) patients suffered from local relapse and regional lymph node metastasis. Re-irradiation dose ranged from 45Gy to 61.2Gy. There were 79 (72.5%) patients treated with re-RT and 30 (27.5%) patients underwent re-CCRT. The objective response rates (ORRs) of the re-RT group and re-CCRT group were 62.0% and 70.0% (χ2 = 0.602, p = 0.438), and improvement rates of dysphagia (DIR) of the two groups were 65.7% and 56.0% (χ2 = 0.731, P = 0.393), respectively. The median survival time (MST) and 1-, 2-, 3-, 5-years survival rates in all patients were 8.0 months and 32.1%,16.5%, 8.3%, 3.7%, respectively. MST and 1-, 2-, 3-years survival rates were 8.0 months and 30.4%, 13.9%, 5.7% for re-RT versus 7.0 months and 33.3%, 23.3%, 16.6% for re-CCRT (χ2 = 2.085, p = 0.149). The MST in re-irradiation dose of ≤50Gy, >50to≤54Gy, and >54Gy groups were 6.0, 10.0 and 8.0 months, respectively (χ2 = 6.385, P = 0.041). The 1-, 2- and 3-years survival rates were 41.7%, 22.2% and 11.1% for patients with TTR over 24 months, which is significantly longer than those of 26.0%, 13.7% and 7.8% for patients with TTR ≤24 months (χ2 = 6.172, P = 0.013). Multivariate analysis showed that TTR was the independent factor for overall survival (hazard ratio, 0.573; 95% confidence interval, 0.365-0.900; P = 0.016).There was no significant difference between re-RT and re-CCRT groups in pneumonitis of grade ≥2, radiation esophagitis of grade 2-3 and the esophageal fistula (χ2 = 0.248, p = 0.619; χ2 = 0.509, P = 0.808; and χ2 = 0.030, P = 0.862). The morbidity of grade ≥2 myelosuppression was much lower in re-RT group than in re-CCRT group (3.7% vs 36.7%; χ2 = 18.151, p<0.001). Salvage re-irradiation therapy could be a treatment choice for patients with local relapse of esophagus after definitive chemoradiotherapy owing to ORR and improving dysphagia. However, overall survival still remains poor. Re-CCRT shows a higher toxicity of myelosuppression than re-RT. Re-radiation dose of >50 to ≤54Gy may be suitable for locally relapse patients as salvage. Patient with TTP over 24 months is a favorable factor for dim survival.

Relationship of Galectin-3 Expression in Canine Cutaneous Squamous Cell Carcinomas with Histopathological Grading and Proliferation Indices

Squamous cell carcinoma (SCC) is a frequent malignant neoplasm of the skin that usually arises from areas of solar dermatosis. It is characterized by local invasiveness and regional lymph node metastasis, mainly in poorly differentiated tumours. Galectin-3 (Gal-3) is a lectin that is expressed in the nucleus or cytoplasm and has been identified as a prognostic tool for human neoplasms. The purpose of this study was to characterize Gal-3 expression in canine cutaneous SCCs and to investigate its relationship with tumour differentiation and cell proliferation indices. Immunohistochemical analysis of 50 SCCs for Gal-3 revealed no correlation between the localization or intensity of immunolabelling, or number of immunopositive cells, with histological grade of tumour or proliferative activity. The results suggest that Gal-3 expression is not a reliable prognostic marker for cutaneous SCC in dogs.

Fucoidan affects oral squamous cell carcinoma cell functions in vitro by regulating FLNA-derived circular RNA.

Oral squamous cell carcinoma (OSCC) is one of the most common cancer types, with a high annual incidence. Although chemotherapy contributes to suppressing OSCC tumorigenesis, the available treatments result in poor prognosis because of local recurrence and regional lymph node metastasis. Thus, it is necessary to discover novel and safe drugs with greater effectiveness and fewer side effects. Fucoidan is a component of the cell wall of brown seaweed that has been shown to produce a wide range of biological activities. The present study aimed to investigate the effectiveness of fucoidan in treating OSCC. In in vitro studies, we found that fucoidan inhibited OSCC growth and suppressed migration and invasion of OSCC cells. In addition, the potential interaction between fucoidan and filamin A (FLNA)-derived circular RNA (circFLNA) was predicted using bioinformatics databases and then confirmed in OSCC samples and cell lines. Indeed, fucoidan increased the expression of circFLNA in OSCC cell lines. Furthermore, both fucoidan and circFLNA could mediate the expression of key proteins related to cell growth, apoptosis, migration, and invasion. In conclusion, our research demonstrated that fucoidan might be considered as a potential natural drug in the treatment of OSCC patients by targeting circFLNA.

Eyelid sebaceous carcinoma: Validation of the 8th edition of the American Joint Committee on cancer T staging system and the prognostic factors for local recurrence, nodal metastasis, and survival.

To investigate the clinicopathological features and prognostic factors for eyelid sebaceous gland carcinoma (SGC) in an ethnic Chinese population and to validate the performance of the T category of the 8th edition AJCC staging systems, with the aim of providing information for refinements. Sixty-three patients with pathological diagnosis of SGC were enroled retrospectively. The clinicopathological features, treatments, and outcomes were collected. Prognostic factors associated with the outcome of local recurrence, regional lymph node metastasis, and tumour-related death were analysed. The performance analysis was performed by comparing the predictive value for survival and the monotonicity of gradients between the 7th and 8th staging systems. The distribution of T1:T2:T3:T4 tumours according to the 7th and 8th edition was 6:40:16:1 and 23:26:5:9, respectively. Positive surgical margin was a poor prognostic factor. Local recurrence was associated with more aggressive histopathological features and surrounding structure invasions. Regional lymph node metastasis was associated with larger tumours. The T category of 8th edition showed better predictability for local recurrence and regional lymph node metastasis, while the T category of 7th edition had better monotonicity of gradients. Tumours classified as T2c or worse had higher risk of regional lymph node metastasis, while tumours T3b or worse in the 8th edition had more tumour-related death. Patients with higher T category are at risk of regional lymph node metastasis and tumour-related death. Further refinement of the T category of AJCC staging system can focus on the predictability for local recurrence and the monotonicity of gradients.

Expression of HER2/c-erbB-2, EGFR Protein in Gastric Carcinoma and its Clinical Significance.

ObjectiveTo investigate the HER2/c-erbB-2, epidermal growth factor receptor (EGFR) protein expression in gastric cancer and association with patients’ clinical pathology characteristics and prognosis.MethodsHER2/c-erbB-2 and EGFR protein expression was examined by immunohistochemical assay in gastric cancer tissue and corresponding paired normal gastric tissue of 67 patients of gastric carcinoma. The HER2/c-erbB-2, EGFR protein positive expression rate in cancer tissue and normal gastric tissue were compared. The correlation between HER2/c-erbB-2, EGFR protein positive expression and patients’ clinical pathology characteristics and survival was evaluated.ResultsThe positive expression rate of HER2/c-erbB-2 in the cancer and paired normal gastric tissues were 32.8% (22/67) and 4.5% (3/67), respectively with statistical difference (p<0.05). And the positive expression rate of EGFR in cancer and paired normal gastric tissues were 41.8% (28/67) and 5.9 (4/67), respectively, with statistical difference (p<0.05). HER2/c-erbB-2 positive expression in cancer tissue was significant correlated with the pathology grading (p<0.05), tumor invasion depth (p<0.05) and local regional lymph node metastasis (p<0.05); EGFR positive expression in cancer tissue was significant correlated with the tumor invasion depth (p<0.05) and local regional lymph node metastasis (p<0.05). The median survival time was 13.14 and 23.6 months respectively for HER2/c-erbB-2 positive and negative expression groups respectively with statistical difference ( HR=2.26, 9%CI:1.06-4.80, p<0.05). However, the median survival time was 15.47 and 22.87 months for EGFR positive and negative expression groups respectively, without statistical difference (HR=1.78, 9%CI:0.96-3.29, p>0.05).ConclusionPositive expression of HER2/c-erbB-2 and EGFR proteins in cancer tissue was significant higher than normal gastric tissue and have significant correlation with prognosis.

Two cases of pediatric epithelioid sarcoma of the hand and coverage with Integra

Epithelioid sarcoma is an uncommon soft tissue tumor of the hand characterized by high frequency misdiagnosis and high potential for local recurrence and regional lymph node metastasis. The recommended treatment is wide excision, which leaves complex tissue defects with tendon or neurovascular structure exposure requiring coverage. We present two patients who had tumor excision followed by wound coverage with dermal regeneration template and split-thickness skin graft. Integra® template represents a different approach, which provides a safe, reliable and effective means of soft tissue coverage of the hand.

Cushing\u2019s syndrome caused by ACTH-producing thymic typical carcinoid with local invasion and regional lymph node metastasis: a case report

BackgroundEctopic ACTH-producing thymic carcinoid tumors are rare, but often behave aggressively with local invasion and distant metastasis. We herein report a case of ACTH-producing thymic typical carcinoid tumor with lymph node metastasis treated by surgery and postoperative radiation therapy.Case presentationA 61-year-old woman was admitted to be evaluated for hypoglycemia and hypokalemia. Laboratory data revealed elevation of serum cortisol and ACTH levels. Overnight administration of 8 mg dexamethasone did not suppress plasma ACTH. Chest CT demonstrated a tumor of 30 mm in diameter and enlargement of the lymph node at the anterior mediastinum. Ectopic ACTH syndrome was suspected and total thymectomy and lymph node dissection were performed. The histopathological examination indicated typical carcinoid tumor and mediastinal lymph node metastasis, and immunohistochemical staining was positive for ACTH. The plasma ACTH level decreased immediately after surgery. She received postoperative radiation therapy of 60 Gy.ConclusionEctopic ACTH-producing thymic typical carcinoid tumors are rare, and it is important to consider this disease and perform appropriate treatment.

A phase II trial of concurrent chemoradiotherapy with weekly paclitaxel and carboplatin in advanced oesophageal carcinoma

BackgroundThis study was performed to assess the efficacy and feasibility of definitive chemoradiotherapy consisting of weekly doses of combined paclitaxel and carboplatin concurrent with radiation therapy, followed by 2 cycles of consolidation chemotherapy for advanced esophageal carcinoma.MethodsEligibility criteria included local, advanced, newly diagnosed and postoperative local regional lymph node metastasis; Eastern Cooperative Oncology Group (ECOG) score ≤ 2; and adequate organ function. Patients received concurrent chemoradiation therapy consisting of radiotherapy (50.4 Gy/28 Fx or 61.2 Gy/34 Fx) and concurrent paclitaxel (50 mg/m2) and carboplatin (area under the curve, AUC = 2) on days 1, 8, 15, 22 and 29. The two-cycle consolidation chemotherapy protocol was paclitaxel (175 mg/m2) plus carboplatin (AUC = 5) administered on days 57 and 85, after concurrent chemoradiotherapy.ResultsBetween August 2013 and February 2015, 65 patients with oesophageal carcinoma were enrolled in the study; 34 (52.3%) were newly diagnosed and 31 (47.6%) had postoperative local regional lymph node metastasis. The median overall survival time was 21.7 months (95% confidence interval [CI] 16.7–26.6), and the median progression-free survival time was 12.1 months (95% CI 9.0–15.3). A total of 96.9% (63/65) and 67.6% (44/65) patients completed ≥5 cycles and all 7 cycles of chemotherapy, respectively. A total of 93.8% (61/65) patients completed radiation therapy. The 1- and 2-year overall survival rates were 73.7 and 42.0%, respectively. The 1- and 2-year progression-free survival rates were 50.6 and 31.1%, respectively. Grade 3–4 toxicity during chemoradiotherapy included neutropenia (24.5%), thrombocytopenia (4.6%), fatigue (1.5%), anaemia (1.5%), radiation dermatitis (1.5%), pneumonitis (1.5%), oesophagitis (4.6%) and vomiting (1.5%).ConclusionsIn patients with locally advanced oesophageal cancer, the combination of weekly doses of paclitaxel and carboplatin was well tolerated and produced comparable results. A three-arm randomised phase III trial (NCT02459457) comparing paclitaxel in combination with cisplatin, carboplatin or 5-fluorouracil with concurrent radiotherapy is on-going at our hospital.

Nimotuzumab plus paclitaxel and cisplatin as 1st line treatment for unresectable esophageal squamous cell carcinoma: Long term follow-up of survival in a phase II study.

e15573 Background: The role of anti-epidermal growth factor receptor (EGFR) targeting treatment in esophageal squamous cell carcinoma (ESCC) is still uncertain. We conducted a prospective phase 2 study of paclitaxel, cisplatin, and nimotuzumab (TPN) as first-line treatment in unresectable or metastatic ESCC (NCT01336049). The objective response rate was 51.8%. Here we reported long-term follow-up results of that initial trial. Methods: 59 patients were enrolled from Mar 2011 to Apr 2013 and treated with the TPN regimen (nimotuzumab 200mg weekly, paclitaxel 175mg/m2 on day1, and cisplatin 30mg/m2 on day1 and 2, repeat every 3 weeks for total six cycles). Patients were allowed to receive sequential radiotherapy in case of local-regional disease or controlling symptom. Results: 56 of 59 patients were eligible for evaluation. After a median follow-up of 32.2months, the median progression-free survival (PFS) and overall survival (OS) were 18.1±4.2 months (95% Confidence: 9.8-26.4) and 26.2±10.0 months (95% Confidence: 6.6-45.8) in 29 patients with unresectable local-regional disease, while those were 6.6±0.4 months (95% Confidence: 5.8-7.5) and 11.5±3.7 months (95% Confidence: 4.2-18.8) respectively in 27 patients with metastatic disease. Patients of male, with multiple lymph node station metastasis, visceral metastasis, no response to TPN treatment, and without radiotherapy had worse OS. Even in some patients with multiple stations lymph node metastasis or recurrent disease of local-regional lymph node metastasis, TPN with sequential radiation seemed could bring longer survival time. But multivariate cox-regression analysis only confirmed that the TPN treatment was associations with OS. Compared with those of complete and partial response, patients of stable disease and progression had poor OS (HR = 2.32, 95% CI: 1.03-5.05, p = 0.03). Conclusions: the combination of nimotuzumab, paclitaxel, and cisplatin is effective as first-line treatment for patients with unresectable and metastatic ESCC, especially those with sequential radiotherapy. Clinical trial information: NCT01336049.

Ezrin Ser66 phosphorylation regulates invasion and metastasis of esophageal squamous cell carcinoma cells by mediating filopodia formation

Ezrin, links the plasma membrane to the actin cytoskeleton, and plays an important role in the development and progression of human esophageal squamous cell carcinoma (ESCC). However, the roles of ezrin S66 phosphorylation in tumorigenesis of ESCC remain unclear. Distribution of ezrin in membrane and cytosol fractions was examined by analysis of detergent-soluble/-insoluble fractions and cytosol/membrane fractionation. Both immunofluorescence and live imaging were used to explore the role of ezrin S66 phosphorylation in the behavior of ezrin and actin in cell filopodia. Cell proliferation, migration and invasion of ESCC cells were investigated by proliferation and migration assays, respectively. Tumorigenesis, local invasion and metastasis were assessed in a nude mouse model of regional lymph node metastasis. Ezrin S66 phosphorylation enhanced the recruitment of ezrin to the membrane in ESCC cells. Additionally, non-phosphorylatable ezrin (S66A) significantly prevented filopodia formation, as well as caused a reduction in the number, length and lifetime of filopodia. Moreover, functional experiments revealed that expression of non-phosphorylatable ezrin (S66A) markedly suppressed migration and invasion but not proliferation of ESCC cells in vitro, and attenuated local invasion and regional lymph node metastasis, but not primary tumor growth of ESCC cells in vivo. Ezrin S66 phosphorylation enhances filopodia formation, contributing to the regulation of invasion and metastasis of esophageal squamous cell carcinoma cells.

A phase II study of concurrent chemoradiotherapy combined with a weekly paclitaxel and 5-fluorouracil regimen to treat patients with advanced oesophageal carcinoma

BackgroundA phase II study was performed to investigate the safety and efficacy of weekly doses of combined paclitaxel and 5-fluorouracil (5-FU) with concurrent radiation therapy, followed by 2 cycles of consolidation chemotherapy to treat patients with advanced oesophageal carcinoma.MethodsThe eligibility criteria included local, advanced, newly diagnosed and postoperative local regional lymph node metastasis; an Eastern Cooperative Oncology Group (ECOG) score of ≤ 2; and adequate organ function. Patients received chemoradiotherapy consisting of radiotherapy (50.4 Gy/28 Fx or 61.2 Gy/34 Fx) and concurrent paclitaxel (50 mg/m2) and 5-FU (300 mg/m2) for 96 h on days 1, 8, 15, 22, and 29. The two-cycle consolidation chemotherapy protocol included paclitaxel (175 mg/m2) plus continuously infused 5-FU (1800 mg/m2) for 72 h administered on days 57 and 85, after concurrent chemoradiotherapy.ResultsBetween February 2012 and August 2013, 53 patients with oesophageal carcinoma were enrolled in the study. Among these patients, 33 (62.2%) were newly diagnosed and 20 (37.7%) had postoperative local regional lymph node metastasis. The median overall survival (OS) time was 17.9 months (95% CIs = 11.9-23.9), and the median progression-free survival (PFS) time was 12.4 months (95% CIs = 8.6-16.1). Approximately 84.9% (45/53) and 50.9% (27/53) of the patients completed ≥ 5 cycles and all 7 cycles of chemotherapy, respectively. Approximately 86.7% (46/53) of patients completed radiation therapy. The 1-, 2-, and 3-year OS rates were 66.0%, 37.7%, and 35.8%, respectively. The 1-, 2-, and 3-year local control rates were 76.9%, 66.4%, and 66.4%, respectively. Seventeen patients (32%) experienced grade 3 or higher toxicity. Grade 3 to 5 toxicity during chemoradiotherapy included neutropaenia (7.5%), thrombocytopaenia (1.8%), fatigue (7.5%), anaemia (1.8%), dermatitis radiation (1.8%), pneumonitis (5.6%), oesophagitis (9.4%) and vomiting (3.7%).ConclusionsThe combination of weekly doses of paclitaxel and 5-FU was well tolerated and produced comparable results among patients with locally advanced oesophageal cancer. A randomised phase III trial (NCT01591135) comparing paclitaxel plus 5-FU with cisplatin plus 5-FU is on-going at our hospital.

Test de lecture

Following initial “curative” operative procedures for gastric carcinoma, 107 patients had planned single or multiple re-operations at the University of Minnesota. Later evidence of cancer was found in 86 patients at re-operation and/or other follow-up. Initial operative-pathologic extent of disease was correlated with incidence and patterns of failure. Distant metastasis (DM) alone was uncommon, but was found as a new component in 25.6 °k of the failure group. Nearly half of the peritoneal failures (PS) were localized, and when diffuse, were usually accompanied by a moderate sized local-regional failure. Local recurrence and/or regional lymph node metastasis (LF-RF) occurred as the only failure in 53.7% of the failure group if localized peritoneal failures were included, and as any component of failure in 87.8% (67.3% of the total 107 patients). Operation alone yields inadequate results for the majority of patients with gastric carcinoma. The rationale of adjuvant radiation and systemic therapy alone or in combination is discussed.

Differences in Survival between Colon and Rectal Cancer from SEER Data

BackgroundLittle is known about colorectal cancer or colon and rectal cancer. Are they the same disease or different diseases?ObjectivesThe aim of this epidemiology study was to compare the features of colon and rectal cancer by using recent national cancer surveillance data.Design and settingData included colorectal cancer (1995–2008) from the Surveillance, Epidemiology, and End Results Program (SEER) database. Only adenocarcinoma was included for analysis.PatientsA total of 372,130 patients with a median follow-up of 32 months were analyzed.Main outcome measuresMean survival of patients with the same stage of colon and rectal cancer was evaluated.ResultsAround 35% of patients had stage information. Among them, colon cancer patients had better survival than those with rectal cancer, by a margin of 4 months in stage IIB. In stage IIIC and stage IV, rectal cancer patients had better survival than colon cancer patients, by about 3 months. Stage IIB colorectal cancer patients had a poorer prognosis than those with stage IIIA and IIIB colorectal cancer. After adjustment of age, sex and race, colon cancer patients had better survival than rectal cancer of stage IIB, but in stage IIIC and IV, rectal cancer patients had better survival than colon cancer.LimitationsThe study is limited by its retrospective nature.ConclusionThis was a population-based study. The prognosis of rectal cancer was not worse than that of colon cancer. Local advanced colorectal cancer had a poorer prognosis than local regional lymph node metastasis. Stage IIB might require more aggressive chemotherapy, and no less than that for stage III.

SPRR2A expression in cholangiocarcinoma increases local tumor invasiveness but prevents metastasis

Cholangiocarcinoma morbidity and mortality is attributable to local invasiveness and regional lymph node and distant organ metastasis. Cholangiocarcinoma progression follows a series of sequential events that resemble wound healing reactions: local invasion resembles the epithelial migration phase involving epithelial-mesenchymal transition (EMT); colonization at distant sites resembles epithelial restitution seen during the reverse process, mesenchymal-epithelial transition (MET). In this study we compare the in vivo local and metastatic growth potential of cholangiocarcinoma cell lines with respect to expression of a novel pSTAT3-dependent, biliary epithelial cell wound healing protein, small proline-rich protein 2A (SPRR2A). SPRR2A has been associated with local aggressiveness, but decreased metastatic capabilities in other cancers. Stable SPRR2A transfection into two cholangiocarcinoma cell lines (SG231 and HuCCT-1), previously shown by us to induce permanent EMT, resulted in local aggressiveness but an inability to form metastases. In contrast, SPRR2A-negative epithelial control cells showed relatively poor local aggressiveness, but readily formed metastatic tumors. Post-intrasplenic injection cell tracking showed that: (a) mesenchymal (SPRR2A+) cells were not trapped in the liver, but were rapidly cleared through mesenteric lymph nodes and did not form metastases; whereas (b) epithelial (SPRR2A-) controls were primarily entrapped within MUC-1-associated liver "micro-infarcts" that later evolved into metastatic colonies. SPRR2A-associated tumor behavior was mimicked by MUC1 shRNA, which induced EMT and, like SPRR2A+ cells, showed reduced metastatic capabilities. Cholangiocarcinoma local invasion involves EMT processes, whereas MET and MUC1 expression promote metastasis. A better understanding of disease progression should help target treatment for this deadly neoplasm.

Expression of pAkt affects p53 codon 72 polymorphism-based prediction of response to radiotherapy in nasopharyngeal carcinoma

BackgroundCodon 72 (Arg/Pro), the most frequently studied single nucleotide polymorphism (SNP) of p53 to date, is associated with the ability of the gene to induce cell apoptosis. The PI3K/Akt pathway plays an essential role in the transcriptional activation function of p53, and is an important factor in radiotherapy resistance. The present study was designed to evaluate the prediction of response to radiotherapy based on p53 codon 72 SNP and pAkt expression in biopsy specimens of locoregional nasopharyngeal carcinoma (NPC) before treatment.Materials and methodsIn total, 75 consecutive patients with locoregional NPC were enrolled. The p53 codon 72 SNP was identified from retrospectively collected paraffin-embedded biopsy specimens using Sanger sequencing. Expression patterns of p53, p21, 14-3-3σ, and pAkt proteins were investigated using immunohistochemical analyses. The effects of genetic polymorphisms and protein expression on progression-free survival (PFS) were evaluated using the Cox proportional hazards model, Kaplan–Meier method, and log-rank test.ResultsThe p53 codon 72 Pro/Pro carriers showed lower risk of disease progression (local recurrence and distant metastases) (HR: 0.300; 95% CI: 0.092–0.983; p=0.047). However, this association between the p53 codon 72 polymorphism and PFS was not significant in the pAkt-positive subgroup. No association was observed between protein expression of p53, p21 or 14-3-3σ and p53 codon72 polymorphisms. Notably, positive expression of p53 protein appeared to be correlated with poorer PFS among patients diagnosed as local regional lymph node metastasis (N+) before treatment (p=0.032).ConclusionsThe p53 codon 72 Pro/Pro genotype may be an effective independent prognostic marker for better outcome in patients with locoregional NPC. Based on the current findings, we hypothesize that pAkt weakens the predictive value of p53 codon 72 SNP in NPC. A combination of positive p53 protein expression and local regional lymph node metastasis may additionally be predictive of high risk of disease progression.

Endobronchial metastasis from primary anorectal melanoma

Patient: Male, 64Final Diagnosis: Metastatic anorectal melanoma with endotracheal metastasisSymptoms: Fatigue • weight loss • hematochezia • coughMedication: NoneClinical Procedure: Biopsy of anal mass • rigid bronchoscopySpecialty: Internal medicine • oncology • pulmonologyObjective:Rare diseaseBackground:Anorectal melanoma is a rare cancer with a poor prognosis. The mean survival after diagnosis is 15–25 months. At the time of diagnosis, 61% of patients have local regional lymph node metastases, and 21% have distant metastases. The lungs are a common site for metastasis for all tumors including melanoma. However endobronchial metastasis is a rare phenomenon. Endotracheal metastases are even rarer, occurring in only 5% of patients with extrapulmonary endobronchial metastases. It is most commonly seen in breast, colorectal, and kidney cancers. It is extremely rare for cutaneous melanoma. The mean survival after diagnosis is only 15 months and treatment options are limited.Case Report:We report the case of a 64 year-old gentleman with newly diagnosed metastatic anorectal melanoma. A 3 cm by 3 cm bluish-black, oval-shaped, exophytic mass protruding from his anus was found on physical exam. Endobronchial and endotracheal metastasis to the trachea were discovered on computed tomography and he was subsequently taken to the operating room for argon plasma coagulation laser recanalization of his trachea via rigid bronchoscopy, and resection of his anal mass.Conclusions:We have presented the first known case of anorectal melanoma with endobronchial metastasis. Palliative APC laser recanalization was used to prevent asphyxiation from the endotracheal mass. Endobronchial metastasis is uncommon and can be easily mistaken for primary bronchogenic carcinoma. It should always be considered when evaluating patients with new lung masses.

Value of dual time point F-18 FDG-PET/CT imaging for the evaluation of prognosis and risk factors for recurrence in patients with stage I non-small cell lung cancer treated with stereotactic body radiation therapy

To investigate prognostic and risk factors for recurrence after stereotactic body radiation therapy (SBRT) in patients with stage I non-small cell lung carcinoma (NSCLC), focusing on dual time point [18]F-fluorodeoxyglucose positron emission tomography (FDG PET). We prospectively evaluated 57 patients with stage I NSCLC (45 T1N0M0 and 12 T2N0M0) who had undergone pretreatment FDG-PET/CT and were subsequently treated with SBRT. All patients received a whole-body PET/CT scan at 60 min and a whole-lung at 120 min after the injection. The maximum standardized uptake value (SUV) and retention index (RI) of the lesions were calculated. Local recurrence, regional lymph node metastasis, distant metastasis, and the recurrence pattern were evaluated. Cox proportional hazard regression analyses were performed to evaluate prognostic factors or risk factors of recurrence. During the median follow-up period of 27 months, local recurrence, regional lymph node metastasis, and distant metastasis were seen in 17 (30%), 12 (21%), and 17 (30%) of the 57 patients, respectively. The 3-year overall survival rate was 63.4%. SUVmax did not affect any recurrence, DFS, OS, or CSS. RI significantly predicted higher distant metastasis (HR 47.546, p=0.026). In contrast, RI tended to predict lower local recurrence (HR 0.175, p=0.246) and regional lymph node metastasis (HR 0.109, p=0.115). SUVmax at staging FDG-PET does not predict any recurrence, DFS, OS or CSS. In contrast, higher RI predicts higher distant metastasis and tended to predict lower local or regional lymph node metastasis.

Prognosis comparison of three-dimensional conformal radiotherapy/intensity modulated radiation therapy for esophageal carcinoma with localregional lymph node metastasis

Objective To explore the prognosis and related factor of esophageal carcinoma with locoregional lymph node metastasis ( N1 ) treated with three-dimensional conformal radiotherapy (3DCRT) or intensity modulated radiation therapy (IMRT).Methods From January 2001 to December 2008,60 patients of esophageal carcinoma with localregional lymph node metastasis were treated with 3DCRT and 52 with IMRT.For all patients,dose of tumor was 56 - 70 Gy/28 - 35 fraction/5.6 - 7.0 weeks.Among them,58 cases was treated with chemotherapy including cisplatin and 5-fluorouracil;40 with concurrent chemoradiotherapy and 18 with sequential radiotherapy and chemotherapy.Results After radiotherapy,the total efficiency rate was 98.2％,96.7％ in 3DCRT and 100％ in IMRT ( x2 =1.77,P =0.184 ).The follow-up rate was 99.1％.The number of patients completed follow-up were 68 and 53,respectively at 2-year and 3-year.The 1 and 3-year overall survival rates were 62.5％,23.7％,respectively; the median survival time was 17 months.The 1and 3-year survival rates and median were 52％,19％ and 12.4 months in 3DCRT and 75％,40％ and 17 months in IMRT,respectively (x2 =4.74,P =0.030).The 1 and 3-year free-recurrence survival rates were 64％,45％ in 3DCRT and 72％,59％ in IMRT ( x2 =2.27,P =0.132),respectively.With uninvariate analysis,for female,ages ≤ 65,tumor located in cervical and upper-thoracic,＞5 cm lesion length in barium esophagogram,≤4 cm the largest diameter of lesion in CT scanning image,T4 stage,or semiliquid or liquid diet before radiotherapy,survival rate were higher in IMRT than in 3DCRT group (x2 =4.63,5.56,7.19,5.08,4.43,4.48,8.25;P=0.031,0.018,0.007,0.025,0.035,0.034,0.004,respectively) ; but for male,ages ＞ 65,tumor located in middle and lower-thoracic,≤5 cm lesion length in barium esophagogram,＞4 cm the largest diameter of lesion in CT scanning image,T1 -3 stage,or normal diet before radiotherapy,chemotherapy and dose of radiotherapy ( ＜66 Gy vs ≥66 Gy),no significant difference were found between IMRT and 3DCRT (x2 =1.28,0.27,0.17,0.03,1.98,0.01,0.43,2.45,1.73,1.24,2.64;P=0.258,0.602,0.684,0.859,0.160,0.973,0.511,0.117,0.189,0.234,0.104,respectively).By Cox multivariable regression,only T stage was independent prognostic factor (x2=9.50,P =0.002 ).Conclusions There was some advantage treated with IMRT compared with 3DCRT in patients of esophageal cancer with locoregional lymph node metastasis,but further prospective clinical study is needed to support the conclusion. Key words: Esophageal neoplasms/three-dimensional radiotherapy; Neoplasms metastasis,lymph node; Prognosis