Locoregional Node Metastases Research Articles

Influence of histopathologic factors on pattern of metastasis in squamous cell carcinoma of the head and neck

Knowledge of histopathological factors, such as perineural invasion (PNI), extracapsular spread (ECS), angiolymphatic vessel invasion, and conglomerate lymph nodes, in patients with head and neck squamous cell carcinoma is important for appropriate treatment decisions. Given the availability of aggressive therapeutic options with known side effects and burdens for the patient, choosing the correct treatment option is vital. Retrospective patient database. Using a retrospective database of patients treated over a 10-year period, independent prognostic factors for disease-free survival and overall survival were assessed. Univariate analysis was used to identify significant variables, and multivariate Cox regression analysis was used to determine independent prognostic factors. Between January 1, 1999 and December 31, 2009, 291 patients with head and neck squamous cell carcinoma were analyzed to identify influence of histopathological factors on pattern of metastasis. PNI tends to set metastasis locoregional, both in ipsilateral and contralateral lymph nodes. Lymphangiosis eases the way toward ipsilateral lymph node metastasis. ECS spread and hemangiosis demonstrated a significantly higher risk of distant metastasis. With the occurrence of conglomerate lymph nodes, patient data demonstrated a highly significant accumulation of distant metastasis. Patients with PNI and lymph vessel invasion tend toward locoregional lymph node metastasis on the ipsilateral side of the neck. In cases of PNI, the patient is at risk for a contralateral neck recurrence of the tumor. In patients with ECS, blood vessel invasion, or conglomerate disease, disseminated spread of the disease to distant locations is more likely and has a high negative impact on survival of the patient.

Superficial EWSR1-negative undifferentiated small round cell sarcoma with CIC/DUX4 gene fusion: a new variant of Ewing-like tumors with locoregional lymph node metastasis

The present study describes a new case of EWSR1-negative undifferentiated sarcoma with CIC/DUX4 gene fusion. This case is similar to tumors described as primitive undifferentiated round cell sarcomas that occur mainly in the trunk and display an aggressive behavior. To our knowledge, this is the first report of such a tumor presenting locoregional lymph node metastasis. In view of previous studies that prove the existence of a particular variant of undifferentiated sarcoma with Ewing-like morphology and CIC/DUX-4 gene fusion, a search for this gene fusion in all undifferentiated round cell sarcomas should be considered if a conclusive diagnosis cannot be reached following other conventional studies. Although additional cases with more extensive follow-up studies are needed, we believe that EWSR1-negative undifferentiated small round cell sarcoma with CIC/DUX4 gene fusion should be added to the list of new sarcoma variants with the possibility of lymph node metastasis.

Intraperitoneal chemotherapy in advanced gastric cancer. Meta-analysis of randomized trials

An important component of treatment failure in gastric cancer (GC) is cancer dissemination within the peritoneal cavity and nodal metastasis. Intraperitoneal chemotherapy (IPC) is considered to give a fundamental contribute in treating advanced GC. The purpose of the study is to investigate the effects of IPC in patients with advanced GC. A systematic review with meta-analysis of randomized controlled trials (RCTs) of IPC + surgery vs. control in patients with advanced GC was performed. Twenty prospective RCTs have been included (2145 patients: 1152 into surgery + IPC arm and 993 into control arm). Surgery + IPC improves: 1, 2 and 3-year mortality (OR = 0.31, 0.27, 0.29 respectively), 2 and 3-year mortality in patients with loco-regional nodal metastasis (OR = 0.28, 0.16 respectively), 1 and 2-year mortality rate in patients with serosal infiltration (OR = 0.33, 0.27 respectively). Morbidity rate was increased by surgery + IPC (OR = 1.82). The overall recurrence and the peritoneal recurrence rates were improved by surgery + IPC (OR = 0.46 and 0.47 respectively). There was no statistically significant difference in lymph-nodal recurrence rate. The rate of haematogenous metastasis was improved by surgery + IPC (OR = 0.63). 1, 2 and 3-year overall survival is incremented by the IPC. No differences have been found at 5-year in overall survival rate. 2 and 3-year mortality rates in patients with nodal invasion and 1 and 2-year mortality rates in patients with serosal infiltration are improved by the use of IPC. IPC has positive effect on peritoneal recurrence and distant metastasis. Morbidity rate is incremented by IPC. Loco-regional lymph-nodes invasion in patients affected by advanced gastric cancer is not a contraindication to IPC.

Discussion on the strategies of common hepatic artery lymph node dissection for thoracic esophageal squamous cell carcinoma

Objective To analyze the metastatic rule of common hepatic artery lymph node of thoracic esophageal squamous cell carcinoma,and to investigate the strategies of common hepatic artery lymph node dissection.Methods The clinical data of 682 patients with esophageal squamous cell carcinoma who were admitted to the Cancer Hospital of Fudan University from May 2005 to December 2010 were retrospectively analyzed.The locoregional lymph node metastasis of thoracic esophageal squamous cell carcinoma,relationship between metastatic rates of common hepatic artery lymph node and clinicopathological factors and the postoperative complications were analyzed.The enumeration data were analyzed using the chi-square test.Results A total of 18 277 lymph nodes were dissected (27 lymph nodes per patient).The lymph node metastatic rate was 55.87％ (381/682),and the metastatic lymph node ratio was 7.87％ (1438/18 277).Lymph nodes adjacent to the cardia of stomach,laryngeal nerve,lesser curvature of stomach,cervical esophagus,left gastric artery had a higher metastatic rate,while common hepatic artery lymph node had a lower metastatic rate.All the common hepatic artery lymph node metastasis was accompanied with locoregional metastasis.A total of 1480 common hepatic artery lymph nodes were dissected (2 common hepatic artery lymph nodes per patient).Twenty-four patients had common hepatic artery lymph node metastasis,with the metastatic rate of 3.52％ (24/682) and the lymph node ratio of 2.16％ (32/1480).The common hepatic artery lymph node metastatic rates of upper,middle and lower esophageal squamous cell carcinoma were 2.33％ (1/43),3.76％ (16/425) and 3.27％ (7/217),with no significant difference (x2 =0.295,P ＞ 0.05).The common hepatic artery lymph node metastatic rates of patients in T1,T2 and T3 stages were 2.35％ (2/85),5.46％ (10/183) and 2.90％ (12/414),with no significant difference (x2 =2.850,P ＞ 0.05).The common hepatic artery lymph node metastatic rates of patients with high,moderate and poor differentiated esophageal squamous cell carcinoma were 0(0/63),3.50％ (16/457) and 4.94％ (8/162),with no significant difference (x2=3.259,P ＞ 0.05).The common hepatic artery lymph node metastatic rates of patients with diameter of tumor under 3 cm,3-5 cm and above 5 cm were 2.59％ (6/232),3.02％ (11/364) and 8.14％ (7/86),with significant difference (x2 =6.267,P ＜ 0.05).The common hepatic artery lymph node metastatic rates of patients in N0,N1,N2,N3 stages were 0(0/301),2.53％ (5/198),5.65％ (7/124) and 20.34％ (12/56),with significant difference (x2 =62.368,P ＜ 0.05).The common hepatic artery lymph node metastatic rates of patients in stage Ⅰ,Ⅱ,Ⅲ and Ⅳ were 0(0/62),1.78％ (6/337),5.06％ (13/257) and 19.23％ (5/26),with significant difference (x2=25.959,P ＜0.05).Two hundred and twenty-eight patients had postoperative complications with the complication rate of 33.43％ (228/682).The incidence of anastomotic fistula was the highest,which was 11.58％(79/682).Conclusions The metastatic rates of common hepatic artery lymph node in thoracic esophageal squamous cell carcinoma is the lowest.For patients suffered from esophageal cancer in stage I or the tumor diameter under 5 cm,the dissection of common hepatic lymph node can be ommitted in surgery. Key words: Esophageal neoplasms; Common hepatic artery lymph node; Lymph node dissection

CT-guided 125I seed implantation for locoregional lymph node metastases in patients with recurrent gastric cancer

Objective To evaluate the safety and short term effect of 125I seed implantation for locoregional lymph node metastases in patients with recurrent gastric cancer.Methods The data of 23 gastric cancer patients with locoregional lymph node metastases treated by CT-guided 125I seed implantation were retrospectively studied.Patient characteristics and survival data were collected and analyzed.The procedure for seed implantation was performed under CT guidance according to preoperative treatment planning.Evaluation of short-term effect was carried out two months after the 125I seed implantation using response evaluation criteria in solid tumors (RECIST).The 1-,2-and 3-year survival rates were plotted using the life table method.The potential predictors of survival were tested using univariate Cox models.Log-rank method was used to test the difference of survival in subgroups with tumor size ＞3 cm and ＜3 cm.Twenty patients underwent fluoropyrimidine-based chemotherapy after 125I seed implantation.Results None of the 23 patients had serious complications.Two months after 125I seed implantation,the CR,PR and PD rates were 60.9％ (14/23),21.7％ (5/23) and 17.4％ (4/23),respectively.The median survival time was (22.1±5.1) months,and the 1-,2-,3-year survival rates were (87±7) ％,(47± 11) ％ and (13 ±9) ％,respectively.The tumor size (longest diameter) was the most significant factor for prognosis (x2=9.752,P=0.002).Patients with tumor ＜3 cm in diameter had longer survival time than those with tumor ＞3 cm ((30.0±5.1) vs (17.0±5.0) months;x2 =5.828,P=0.016).Conclusion CT-guided brachytherapy using 125I seed implantation is a safe and effective method for palliative treatment of locoregional lymph node metastases for recurrent gastric cancer. Key words: Stomach neoplasms ; Lymphatic metastasis ; Brachytherapy ; Iodine radioisotopes ; Tomography, X-ray computed

Acetylated Tubulin (AT) as a Prognostic Marker in Squamous Cell Carcinoma of the Head and Neck

Acetylated tubulin (AT) expression has been proposed as a marker for sensitivity to taxane chemotherapy. We wanted to explore AT as a prognostic marker in squamous cell carcinoma of the head and neck (SCCHN). We assessed AT expression in archival tissue from our institutional tissue bank of primary SCCHN specimens. We also examined AT expression on pre-therapy tissues of patients with SCCHN receiving induction chemotherapy with docetaxel, cisplatin and 5FU (TPF IC). AT expression was assessed on archival cases of SCCHN with (N = 63) and without (N = 82) locoregional lymph node metastases (LNM). The predominant tumor site was oral cavity (52 %). Immunohistochemistry staining was based on staining intensity and percentage of tumor cells stained to create a weighted index (WI). A total of nine patients who received TPF IC were evaluable for response by RECIST and also had pre-therapy tissues available. A significant independent correlation between AT and tumor grade (p = 0.001) and primary location (p = 0.008) was noted. There was a trend of higher AT in patients with presence of LNM (p = 0.052) and a trend in improved OS for patients with an AT WI below the median compared to those above the median for patients with no LNM (p = 0.054). For patients treated with induction TPF, we observed an inverse correlation between AT expression and response to TPF IC (p = 0.0071). AT expression is correlated with tumor grade and primary site. There was an observed trend correlating AT with presence nodal metastases. The observed inverse correlation with response to taxane based chemotherapy needs validation in a larger sample size.

Aggressive local therapy combined with systemic chemotherapy provides long‐term control in gradeIIstage 2 canine mast cell tumour: 21 cases (1999–2012)

This retrospective case series evaluates the outcome of 21 dogs with grade II stage 2 mast cell tumour (MCT) treated with adequate local therapy and adjuvant systemic chemotherapy (prednisone, vinblastine and CCNU). The median survival for all dogs was 1359 days (range, 188-2340). Median disease-free interval was 2120 days (149-2325 days). Dogs treated with surgery and chemotherapy had shorter survival (median, 1103 days; 188-2010 days) than those that underwent surgery, radiation therapy and chemotherapy as part of their treatment (median, 2056 days; 300-2340 days). Two patients had local recurrence in the radiation field and four patients had de novo MCT. Distant metastasis was not observed in any dogs. The results of this study suggest that, in the presence of loco-regional lymph node metastasis in grade II MCT, the use of prednisone, vinblastine and CCNU after adequate local-regional therapy can provide a median survival in excess of 40 months.

Current status on the diagnosis and evaluation of pancreatic tumor in Asia with particular emphasis on the role of endoscopic ultrasound

In Asia, the incidence of pancreatic cancer in some countries has been increasing. Owing to most cases being diagnosed late, prognosis for pancreatic cancer remains dismal. It is clear that the future for pancreatic cancer lies in early detection. While the possible presence of pancreatic masses is often first raised by non-invasive abdominal imaging, such as computerized tomography and magnetic resonance imaging, smaller lesions and locoregional lymph node metastases are often not detectable by these means. Endoscopic ultrasonography (EUS) offers a higher sensitivity (93-100%) for detection of small potentially curable pancreatic masses than other existing imaging modalities. It is also recommended for the evaluation of portal vein confluence, portal vein, celiac axis, and superior mesentric artery origin, and exclusion of resectability. Due to the closer proximity of EUS to the target structure, and lower rate of needle tract seeding, EUS-guided fine-needle aspiration of pancreatic mass is considered the most suitable tissue acquisition technique. Lastly, EUS also enables the performance of endoscopic interventions. Its performance can be further enhanced with newer techniques, including contrast-enhanced ultrasound and elastrography. It is anticipated that in the near future, molecular technologies may make it possible to detect microscopic amounts of cancer in tissue or blood, predict relapse and survival after therapy, as well as determine optimal therapy.

Routine preoperative 111In-octreotide scintigraphy in patients with medullary thyroid cancer

Surgery is the only potential cure for patients with medullary thyroid carcinoma (MTC). Preoperative ultrasound, computed tomography and magnetic resonance imaging are not sensitive enough for detection of microscopic disease. The aim of this study was to investigate if routine preoperative (111)In-labelled (DTPA-D-Phe(1))-octreotide scintigraphy (SRS) could be used as a staging procedure in planning primary surgery in patients with MTC. This study included patients with primary sporadic clinically overt MTC diagnosed between 1996 and 2009. All patients underwent conventional imaging of neck and thorax and SRS prior to standardised surgery. The findings on SRS were correlated to the findings on conventional imaging, histopathology and to postoperative biochemical results and survival. A total of 19 patients with sporadic MTC were enrolled. Median follow-up was 77(9-184) months. SRS visualised the primary tumour in 16 (84%) patients. Fifteen (79%) patients had locoregional lymph node metastases, but SRS detected metastatic lesions in only 8 (53%) patients. In three patients with distant spread, SRS failed to detect metastatic lesions in two. At latest follow-up, six (32%) patients had died, nine (47%) patients were alive with elevated tumour markers, and four (21%) patients were considered in complete biochemical remission. This study provided further evidence that SRS, compared to conventional imaging, is fairly sensitive for detection of primary MTC but not metastatic disease. Although preoperative SRS may be of prognostic value, there is no indication for its routine use as a staging procedure in planning primary surgery.

Multimodality imaging evaluation of esophageal cancer: staging, therapy assessment, and complications

Esophageal cancer is among the leading causes of cancer-related deaths worldwide. The management of patients with esophageal cancer is determined to a large extent by patient performance status, location of the primary cancer, and stage of disease at presentation. Multimodality regimens combining neoadjuvant chemotherapy and/or radiotherapy followed by surgery have been increasingly used in suitable candidates with locally advanced cancer. There is substantial morbidity and mortality associated with this treatment strategy, which makes appropriate patient selection important. Endoscopic esophageal ultrasound is the optimal modality to evaluate the local extent of the primary tumor and diagnose locoregional nodal metastasis. Computed tomography is more useful in detecting distant nodal and systemic metastasis. Positron emission tomography/CT is increasingly being used in patient management and improves the accuracy of staging, particularly in the detection of distant nodal and systemic metastatic disease. In this article, we review the role of imaging in the staging, assessment of therapeutic response, and detection of recurrent disease, as well as the evaluation of therapeutic complications in patients with esophageal cancer.

A novel simplified approach to incorporating lymph node ratio into gastric cancer staging.

24 Background: Previous investigators have reported on the value of lymph node ratio (LNR, defined as the number of positive nodes divided by the total number of nodes assessed) in gastric adenocarcinoma (GAC) staging. Given the complexity of previously proposed staging systems, it has not gained widespread acceptance. The aim of our study was to offer a novel simplified approach to incorporating LNR into gastric cancer staging. Methods: 131 patients who underwent curative intent resection with lymphadenectomy for GAC between 1/00-6/11 were identified. Clinicopathologic factors were assessed. Primary outcome was overall survival (OS). Results: Median age was 64 yrs, 51% were male. Median tumor size was 3.5 cm, 67% were poorly differentiated, 20% had perineural invasion, 31% had lymphovascular invasion, and 6% had a positive margin. Locoregional nodal metastases were present in 59% (n=77, N0: 41%, N1: 18%, N2: 22%, N3a: 14%, N3b: 5%). Median number of lymph nodes (LN) assessed was 15.5. Mean FU was 27.3 mos, median OS was 29.3 mos. Median LNR was 0.4 (.04-1). Patients with LNR ≥0.4 had decreased OS as compared to patients with LNR <0.4 (15.1 vs 41.5 mos, p<0.0001); the survival of patients with LNR <0.4 was similar to that of node negative pts (48 mos, p=0.882). On Cox regression analysis, LNR ≥0.4 was more strongly associated with decreased OS (HR 3.09, 95%CI: 1.81-5.26; p<0.0001) compared to the AJCC 7th edition N stage (HR 1.36, 95%CI: 1.11-1.68; p=0.004). In the subset of patients who were inadequately staged and had <16 nodes examined, a LNR ≥0.4 was associated with reduced survival compared to a LNR <0.4 (17.3 vs 41.5 mos, p=.04). Conclusions: Compared to the current lymph node staging system, a lymph node ratio using 0.4 as the cutoff may more accurately predict survival outcomes. It seems to be particularly useful in patients who have inadequate nodal assessment. This simplified approach to lymph node ratio may be a more valuable staging tool than the current AJCC nodal staging system for gastric cancer and needs to be validated.

Locoregional Lymphadenectomy in the Surgical Management of Anorectal Melanoma

The effect of lymph node metastasis on local tumor control and distant failure in patients with anorectal melanoma has not been fully studied. Understanding the significance of lymphatic dissemination might assist in stratifying patients for either organ preservation or radical surgery. A retrospective review of all patients with anorectal melanoma who underwent surgery at our institution between 1985 and 2010. Abdominoperineal resection (APR) was performed in 25 patients (39 %), and wide local excision (WLE) in 40 (61%). Extent of primary surgery and locoregional lymphadenectomy (mesorectal vs. inguinal vs. none) and pattern of treatment failure were analyzed. Recurrence-free survival (RFS) and disease-specific survival (DSS) were calculated. In patients undergoing APR, DSS was not associated with presence (29 %) or absence (71 %) of metastatic melanoma in mesorectal lymph nodes. There was a trend toward improved DSS in patients with clinically negative inguinal lymph nodes (n = 17) compared with patients with proven inguinal metastasis (n = 6; P = 0.12). Type of surgery (WLE vs. APR) was not associated with subsequent development of distant disease. Twelve patients (18 %) had synchronous local and distant recurrence. Synchronous recurrence was not associated with surgical strategy used to treat primary tumor (P = 0.28). Perineural invasion (PNI) was significantly correlated with RFS (P = 0.002). Outcome following resection of anorectal melanoma is independent of locoregional lymph node metastasis; lymphadenectomy should be reserved for gross symptomatic disease. PNI is a powerful prognostic marker warranting further exploration in clinical trials.

Comparison of 11C-Choline PET/CT and Enhanced CT in the Evaluation of Patients With Pulmonary Abnormalities and Locoregional Lymph Node Involvement in Lung Cancer

BackgroundThis study compares the diagnostic abilities of integrated 11C-choline PET/CT imaging and contrast-enhanced helical CT imaging in pulmonary lesions and locoregional lymph node metastases in patients with lung cancer. Patients and MethodsOne hundred eight patients with proven or suspected lung cancer underwent integrated 11C-choline PET/CT and contrast-enhanced CT, followed by surgical resection and nodal staging. ResultsThe 11C-choline PET/CT and CT diagnoses of pulmonary lesions and locoregional lymph node metastases were compared with pathologic findings, which revealed benign lesions in 26 patients (tuberculoma [8 patients], inflammatory pseudotumor [7 patients], hamartoma [6 patients], sclerosing hemangioma [4 patients], and pulmonary sequestration [1 patient]) and lung cancers in 82 patients (adenocarcinoma [39 patients], squamous cell carcinoma [23 patients], carcinoid [7 patients], small-cell lung cancer [5 patients], adenosquamous carcinoma [5 patients], and large-cell lung cancer [3 patients]). The accuracy, sensitivity, and specificity of 11C-choline PET/CT for diagnosing lung cancer were 82.4%, 85.4%, and 73.1%, respectively, compared with 73.1%, 76.8%, and 61.5%, respectively, for CT. Differences between 11C-choline PET/CT and CT in diagnosing lung cancer were not statistically significant (p = .503, .118, and .375, respectively). We used receiver operating characteristic (ROC) curve for analysis, finding the ROC of standard uptake value (SUVmax) for diagnosing lung cancer. The cutoff value of SUVmax was 3.54. Preoperative nodal staging was compared with postoperative histopathologic staging. 11C-choline PET/CT correctly staged 80.5% of patients, 12.2% were overstaged, and 7.3% were understaged; for CT these values were 58.5%, 24.4%, and 17.1%, respectively. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 11C-choline PET/CT for lymph nodes were 83.8%, 82.4%, 84.1%, 50.3%, and 96.1%, respectively, compared with 69.3%, 63.7%, 71.2%, 30.2%, 91.0%, respectively, for CT. ConclusionDifferences in the accuracy, sensitivity, specificity, PPV, and NPV between 11C-choline PET/CT and CT are thus statistically significant for nodal staging (p = .003, .007, .000, .000, and .004, respectively). Although 11C-choline PET/CT is not significantly better at diagnosing pulmonary lesions than is enhanced CT, 11C-choline PET/CT has improved sensitivity, specificity, accuracy, PPV, and NPV relative to enhanced CT in the evaluation of locoregional lymph nodes.

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

Comparison of the diagnostic value of 3-deoxy-3-18F-fluorothymidine and 18F-fluorodeoxyglucose positron emission tomography/computed tomography in the assessment of regional lymph node in thoracic esophageal squamous cell carcinoma: a pilot study

We used pathological examination as golden standard to determine whether 3-deoxy-3-(18)F-fluorothymidine positron emission tomography/computed tomography (FLT PET/CT) can detect regional lymph node metastasis in untreated thoracic esophageal squamous cell carcinoma and additionally performed (18)F-fluorodeoxyglucose (FDG) PET/CT for direct comparison with that of FLT. Twenty-two patients with thoracic esophageal squamous cell carcinoma underwent dual-tracer PET/CT examinations before surgery. The results of reviewing CT images and side-by-side FDG PET and FLT PET images for the diagnosis of locoregional lymph node metastasis were compared prospectively in relation to pathologic findings. All patients underwent esophagectomy and lymphadenectomy. Pathologic examination confirmed nodes positive for metastasis in 16 patients and 47 of 424 excised nodes. The uptake of FDG (median SUVmax, 5.4; range, 2.4-10.6) in locoregional lymph nodes metastases was significantly higher than that of FLT (median SUVmax, 2.8; range, 1.3-4.6). There were 14 false-positive nodes in FDG PET/CT and only 3 in FLT PET/CT; 8 false-negative nodes in FDG PET/CT, while there were 12 false negative nodes in FLT PET/CT. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of FLT PET/CT were 74.47%, 99.20%, 96.46%, 92.11%, and 96.89%, respectively, whereas those of FDG PET/CT were 82.98%, 96.29%, 94.81%, 82.98%, and 96.29%, respectively. P-values were 0.450, 0.014, 0.313, 0.050, and 0.555, respectively. FLT uptake in regional lymph nodes of esophageal carcinoma is significantly lower compared with FDG uptake. FLT PET/CT has fewer false-positive findings and higher specificity compared with FDG PET/CT.

Outcome of Antegrade Radical Prostatectomy with Intended Wide Resection in Prostate Cancer Patients with a Preoperative Serum PSA Level >100 ng/ml

Objective: It was the aim of this study to assess the outcome of prostate cancer patients with preoperative prostate-specific antigen (PSA) levels ≧100 ng/ml who were treated with antegrade radical prostatectomy with intended wide resection (aRP). Patients and Methods: Eighteen patients who underwent aRP had an initial PSA level ≧100 ng/ml. Overall survival, disease-specific survival and biochemical progression-free survival (bPFS) rates were determined, and predictors of treatment outcome were examined. Results: The median serum PSA level was 159.5 ng/ml. All patients but one had received neoadjuvant androgen deprivation therapy (ADT), while only 2 patients received adjuvant ADT. Five patients were classified as stage pT2, 6 as pT3a, 6 as pT3b and 1 as pT4. Four patients had locoregional lymph node metastases. Twelve patients developed PSA failure. Eight of them received salvage ADT. The estimated 10-year bPFS rate was 25.0% and the overall survival and disease-specific survival rates were 92.9 and 100%, respectively, at a median follow-up of 6 years. Multivariate analysis revealed only the clinical stage to be predictive of bPFS based on preoperative variables. On the other hand, surgical margin status, extracapsular extension and organ-confined disease were identified as being significant postoperative predictors. Conclusions: This study showed a comparatively satisfactory outcome for clinically non-metastatic prostate cancer with PSA levels ≧100 ng/ml treated by aRP.

Animal‐type melanoma – tumor cell invasion of dermal lymphatics and molecular identification of lymph node metastasis

Animal-type melanoma (ATM) represents a rare subtype within the wide spectrum of melanocytic tumors. Clinically, ATM lesions appear as sharply demarcated, brown, black and dark blue pigmented nodules, which show grey-white surface elements on dermatoscopy. The tumor is restricted to the dermis and arranged in irregular fascicles, which are composed of spindle-shaped and epithelioid melanocytes. Moderate tumor cell pleomorphism, mitoses and apoptotic cells all suggest a malignant process. Abundant, finely dispersed melanin pigment within tumor cells as well as numerous melanophages are strongly suggestive of ATM. Even though locoregional lymph node metastases are frequently found at diagnosis, the course of ATM is generally benign. Specific molecular changes may be detected in melanocytes from lesions and lymph nodes on fluorescence in situ hybridization (FISH). Such findings strongly indicate the malignant potential of ATM. The peculiar biology of ATM, as a moderately malignant tumor, is reflected in a new histopathological classification within the spectrum of dermal borderline melanocytic tumors (BMT).

Clinical usefulness of dual-time FDG PET–CT in assessment of esophageal squamous cell carcinoma

We conducted this study to investigate the value of the dual-time 2-[(18)F]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography-computed tomography (PET-CT) in assessment of the primary tumor, loco-regional lymph node and distant metastasis in patients with esophageal squamous cell carcinoma. Twenty-six patients with histologically proved esophageal squamous cell carcinoma underwent dual-time FDG PET-CT before radical surgery. The standardized uptake values (SUV(max)) were obtained including early SUV(max) and delayed SUV(max), respectively. The retention index (RI) was also calculated. The results were evaluated retrospectively according to the final pathologic findings. Four diagnostic criteria including (1) early SUV(max)≧ 2.5 alone, (2) RI ≧ 10% alone, (3) a combination of early SUV(max)≧ 2.5 and RI ≧ 10%, and (4) a combination of early SUV(max)≧ 2.5 or RI ≧ 10% were used for differentiating malignancy from a benign lesion, respectively. The sensitivity of FDG PET-CT in detecting the primary tumor with combination of early SUV(max)≧ 2.5 or RI ≧ 10% was 96.2%. It was statistically significantly higher than the results using the other three criteria (p<0.0001). For loco-regional lymph node detection, there was no significant difference among the 4 criteria. For distal metastases, the significantly higher specificity (100%) was found when using combination of early SUV(max)≧ 2.5 and RI ≧ 10% or using early SUV(max)≧ 2.5 alone than using the other two criteria (p=0.0058). With regard to accuracy, no significant correlations were observed among primary tumor, loco-regional lymph nodes and distant metastasis (p>0.05). The preliminary result of this study demonstrated that dual-time point FDG PET-CT had limited value in detection of primary tumor and loco-regional lymph nodes metastasis. For the distant metastasis, the sensitivity and specificity would be improved if RI ≧ 10% is used as a supplemental criterion. Efforts should be made to improve the ability of the dual-time FDG PET-CT technique to assess primary tumor and loco-regional lymph nodes metastasis.

Upper urinary tract urothelial carcinoma with loco‐regional nodal metastases: insights from the Upper Tract Urothelial Carcinoma Collaboration

• To describe a multicentre experience with preoperative platinum-based chemotherapy before radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC) with loco-regional nodal metastases. • We identified 313 patients from the UTUC Collaboration (over 1200 patients), who underwent RNU with concomitant retroperitoneal lymph node dissection between 1990 and 2007 and met the inclusion criteria for one of three groups. • Group 1 comprised patients who received chemotherapy before RNU because of biopsy-proven loco-regional nodal metastases. • Group 2 consisted of patients who underwent primary RNU and were found to have metastatic nodal disease on final pathological review (node-positive). • Group 3 comprised a comparative cohort of patients treated with primary RNU for invasive or locally advanced (pT2/pT4) node-negative (N0) UTUC. • Groups 1, 2 and 3 included 18, 120 and 175 patients, respectively. The 5-year disease-free survival rates were 49%, 30% and 64%, whereas the 5-year cancer-specific survival rates were 44%, 36% and 69% in groups 1, 2 and 3, respectively. • In group 1, on final pathological evaluation, nine patients were pN0, six patients were pT0 and five patients had pT0N0 disease. Kaplan-Meier survival analyses showed similar recurrence and survival rates in group 1 compared with group 3 (P= 0.14 and P= 0.06, respectively). • Meanwhile, group 2 had significantly lower disease-free and cancer-specific survival rates compared with group 3 (P < 0.001 and P < 0.001, respectively) and compared with group 1 (P= 0.04 and P= 0.06, respectively). • Preoperative chemotherapy followed by aggressive surgical consolidation may yield favourable oncological outcomes in patients with UTUC with loco-regional nodal metastases. • These data support further evaluation of neoadjuvant systemic therapy in patients at risk for locally advanced UTUC.

Retracted: Restoring sensitivity to oxaliplatin by a novel approach in gemcitabine‐resistant pancreatic cancer cells in vitro and in vivo

Oxaliplatin (OxP) has been used in combination therapy with gemcitabine for the treatment of pancreatic cancer (PC), but the beneficial effect was marginal, which is believed to be due to de novo and acquired drug resistance of PC. Here, we report our in vitro and in vivo preclinical evidence in support of chemosensitization of drug-resistant cells by a nontoxic chemopreventive agent (genistein). Genistein pretreatment together with low concentration of OxP showed significant reduction in cell viability and colony formation concomitant with increased apoptosis (p < 0.01), which was highly synergistic. Drug resistance of PC is allegedly linked with both constitutive and OxP-induced activation of NF-κB, and we found that inactivation of (nuclear factor kappa B) NF-κB by genistein before treatment of cells with OxP was required for cell killing, which was consistent with the downregulation of NF-κB and its downstream antiapoptotic genes (Bcl-2, XIAPs and survivin). Most importantly, our in vivo experiments using orthotopic mouse model showed significant reduction in tumor size (p < 0.01) and reduction of locoregional lymph node metastasis by combination treatment. These results were also consistent with inactivation of NF-κB and the downregulation of NF-κB downstream genes, decreased proliferation marker (Ki-67) and increased apoptosis (TUNEL) in tumor remnants, all of which was consistent with in vitro findings. From these results, we conclude that genistein sensitizes drug-resistant PC to OxP, which is mechanistically linked with inactivation of NF-κB signaling, resulting in greater antitumor effects, and thus our data suggest that this approach could be useful in improving the treatment outcome for patients diagnosed with PC.