Percentage Of Lymph Node Metastasis Research Articles

Genome editing approaches with CRISPR/Cas9: the association of NOX4 expression in breast cancer patients and effectiveness evaluation of different strategies of CRISPR/Cas9 to knockout Nox4 in cancer cells

BackgroundThe increasing prevalence of cancer detection necessitated practical strategies to deliver highly accurate, beneficial, and dependable processed information together with experimental results. We deleted the cancer biomarker NOX4 using three novel genetic knockout (KO) methods. Homology-directed repair (HDR), Dual allele HITI (Du-HITI) and CRISPR-excision were utilized in this study.MethodsThe predictive value of the NOX4 expression profile was assessed using a combined hazard ratio (HR) with a 95% confidence interval (CI). With a 95% confidence interval, a pooled odd ratio (OR) was used to calculate the relationship between NOX4 expression patterns and cancer metastasis. There were 1060 tumor patients in all sixteen research that made up this meta-analysis. To stop the NOX4 from being transcribed, we employed three different CRISPR/Cas9-mediated knockdown methods. The expression of RNA was assessed using RT-PCR. We employed the CCK-8 assay, colony formation assays, and the invasion transwell test for our experiments measuring cell proliferation and invasion. Using a sphere-formation test, the stemness was determined. Luciferase reporter tests were carried out to verify molecular adhesion. Utilizing RT-qPCR, MTT, and a colony formation assay, the functional effects of NOX4 genetic mutation in CRISPR-excision, CRISPR-HDR, and CRISPR du-HITI knockdown cell lines of breast cancer were verified.ResultsThere were 1060 malignant tumors in the 16 studies that made up this meta-analysis. In the meta-analysis, higher NOX4 expression was linked to both a shorter overall survival rate (HR = 1.93, 95% CI 1.49–2.49, P < 0.001) and a higher percentage of lymph node metastases (OR = 3.22, 95% CI 2.18–4.29, P < 0.001). In breast carcinoma cells, it was discovered that NOX4 was overexpressed, and this increase was linked to a poor prognosis. The gain and loss-of-function assays showed enhanced NOX4 breast carcinoma cell proliferation, sphere-forming capacity, and tumor development. To activate transcription, the transcriptional factor E2F1 also attaches to the promoter region of the Nanog gene. The treatment group (NOX4 ablation) had substantially more significant levels of proapoptotic gene expression than the control group (P < 0.01). Additionally, compared to control cells, mutant cells expressed fewer antiapoptotic genes (P < 0.001). The du-HITI technique incorporated a reporter and a transcription termination marker into the two target alleles. Both donor vector preparation and cell selection were substantially simpler using this approach than with “CRISPR HDR” or “CRISPR excision.“ Furthermore, single-cell knockouts for both genotypes were created when this method was applied in the initial transfection experiment.ConclusionsThe NOX4 Knockout cell lines generated in this research may be used for additional analytical studies to reveal the entire spectrum of NOX4 activities. The du-HITI method described in this study was easy to employ and could produce homozygous individuals who were knockout for a specific protein of interest.

Impact of resection margin status on survival after operation for pancreatic head cancer with extrapancreatic nerve plexus invasion

Extrapancreatic nerve plexus (PL) invasion of pancreatic ductal adenocarcinoma (PDAC) is an important factor for determining resectability and surgical method. We sought to clarify the characteristics of PDAC with PL invasion and clinical impact of the resection margin status on prognosis for PDAC with PL invasion. A total of 242 patients with pancreatic head cancer who underwent pancreatectomy were evaluated. Clinicopathological data and patient survival were analyzed. Pathological PL invasion was observed in 68 patients (28.1%). Patients with PL invasion had significantly shorter disease-free survival (DFS) and showed trends toward worse overall survival (OS) than those without PL invasion. While multivariate analysis revealed that PL invasion was not an independent prognostic factor, PL invasion was associated with extensive venous invasion and a high percentage of lymph node metastases, both of which were independent factors affecting DFS and OS. Among patients with PL invasion, there was no significant difference in DFS and OS between the R0 and R1 resection groups. PL invasion is a common pathological feature of aggressive PDAC with high propensity for invasiveness and metastatic potential. The microscopic resection margin status may not affect the survival of pancreatic head cancer patients with PL invasion.

Risk factors for lymph node metastasis in patients with pancreatic neuroendocrine neoplasms.

BACKGROUNDAlthough PNENs generally have a better prognosis than pancreatic cancers, some PNENs display malignant behavior including lymph node (LN) metastasis. Complete tumor resection can be the only potentially curative treatment for patients with resectable PNENs. However, the indications for LN dissection are still controversial. Over the last decade, minimally invasive surgery such as laparoscopic pancreatic surgery (LPS) has been increasingly performed for pancreatic tumors including PNENs.AIMTo investigate the risk factors for LN metastasis in PNENs and to select appropriate patients for limited surgery by LPS.METHODSFrom April 2001 to December 2019, 92 patients underwent pancreatic resection for PNENs at Kumamoto University Hospital. Finally, 82 patients were enrolled in this study. Using perioperative factors, we examined the predictive factors for LN metastasis in PNENs.RESULTSAmong the 82 patients, the percentage of LN metastasis according to the pathological findings was 12% (10/82 cases). The median tumor size was 12 mm (range: 5-90 mm). The median tumor size in the LN-positive group (37 mm) was significantly larger than that in the LN-negative group (12 mm) (P = 0.0001). Multivariate analyses revealed that larger tumor size (≥ 20 mm) was an independent risk factor for LN metastasis (odds ratio 16.8, P = 0.0062). In patients with small tumors (≤ 10 mm), LN metastasis was not found.CONCLUSIONLarger tumor size (≥ 20 mm) is an independent risk factor for LN metastasis in PNENs. In smaller PNENs (≤ 10 mm), we may be able to choose limited surgery without LN dissection.

The role of programmed death-ligand 1 and non-epithelial circulating tumor cells in locally advanced prostate cancer.

e17557 Background: Circulating tumor cells (CTCs) is considered as an effective prognostic biomarker in malignancies. It is recently recognized that detections of programmed death-ligand 1 (PD-L1) and mesenchymal markers in CTCs may improve the predictive value. Therefore, we aimed to determine the cut-off values of these CTCs biomarkers in prostate cancer (PCa), assess the rates of PD-L1 positive and non-epithelial (NE) subgroup in CTCs among patients with high-risk (HRPC) and locally advanced PCa (LAPC) before surgery, and evaluate the clinical values of these markers. Methods: Four PCa cell lines selected from Cancer Cell Line Encyclopedia were applied in spiking experiments to establish the cut-offs of PD-L1 positive and NE CTCs. 182 HRPC and 89 LAPC patients were enrolled from June 2016 to December 2018. All patients underwent radical prostatectomy after blood sample collection. CTCs enumeration and biomarkers identification were conducted by Canpatrol CTC enrichment system and the RNA in situ hybridization technique. Lastly, using the cut-offs,we evaluated the association between CTCs markers and other variables in terms of clinical data, disease outcome, tumor tissues immunochemistry (IHC) staining, and the response of immunotherapy. Results: The cut-offs were determined as the lowest rates of NE and PD-L1+ CTCs among the cell lines, 45% and 25%, respectively. In HRPC patients, a higher PSA level and more advanced T stage were observed in the NE CTCs positive group (≥45%), compared with the negative group ( P= 0.041 and P= 0.004). Multivariate analysis showed that the NE CTCs rate, instead of total CTCs number, was an independent risk predictor for progression-free survival (PFS) (HR = 3.85, P= 0.013). In LAPC patients, the PD-L1+ CTCs positive group (≥25%) presented a higher PSA level and higher percentage of lymph node metastasis than negative group ( P= 0.027 and P= 0.028). The median PFSs between the two groups were 16.6 mouths vs. 21.8 mouths, respectively. (HR = 2.87, P= 0.002 ). No significant correlation was found between PD-L1 expression in CTCs and in tumor tissue IHC staining. However, we observed a significant correlation between PD-L1+ CTCs rate and ERG or PTEN expression in tissues ( P= 0.010 and P= 0.009). In addition, patients in PD-L1+ CTCs positive group presented a better PSA response to Durvalumab treatment than those in negative group. Conclusions: PD-L1+ and NE CTCs were an effective prognosis predictors for HRPC and LAPC patients with radical prostatectomy. LAPC patients with PD-L1+ CTCs might benefit from adjuvant immunotherapy

Comparison of clinicopathological characteristics of endogenous and exogenous cervical cancer with its clinical significance

&lt;p class="abstract"&gt;&lt;strong&gt;&lt;span lang="EN-US"&gt;Background: &lt;/span&gt;&lt;/strong&gt;Cervical cancer is the third leading cause of cancer death in women of less developed countries due to poor screening and decreased diagnostic approaches. We aimed to investigate and differentiate the distinct clinicopathological characteristics and prevalence of endogenous and exogenous cervical in hospitalized patients&lt;span lang="EN-US"&gt;.&lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;&lt;span lang="EN-US"&gt;Methods: &lt;/span&gt;&lt;/strong&gt;A study was performed contained 663 patients that were enrolled and underwent for screening of endogenous and exogenous cervical cancer in Qilu Hospital of Shandong University, from January 2010 to March 2015. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;&lt;span lang="EN-US"&gt;Results: &lt;/span&gt;&lt;/strong&gt;Our results indicated that combined examination of thin-prep liquid-based cytology test and human papillomavirus (HPV)-DNA are effective for diagnosis of endogenous and exogenous cervical cancer. The clinicopathological characteristics based on tumor growth pattern, and high risk HPV-DNA incidence had no significant difference (p&amp;gt;0.05) in endogenous and exogenous cervical cancer patients. The higher ratio of lymph node metastasis in endogenous cervical cancer and exogenous cervical cancer during IB1-stage (24.3% vs 12.9%), and in IIA2-stage (36.4% vs 25%) was observed respectively. In addition, our data provide compelling evidence that the level of deep interstitial infiltration, and lymphatic vascular infiltration in endogenous cervical cancer was collectively higher (82.7% and 33%) compared to exogenous cervical cancer (62.4% and 18.3%) respectively during all stages&lt;span lang="EN-US"&gt;.&lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;&lt;span lang="EN-US"&gt;Conclusions: &lt;/span&gt;&lt;/strong&gt;The higher percentage of lymph node metastasis,&lt;strong&gt; &lt;/strong&gt;deep interstitial infiltration, and lymphatic vascular infiltration was observed in endogenous cervical cancer which might be the biomarker and differential key points for the diagnosis of endogenous cervical cancer. Taken together, our study provides clinicopathological features to diagnose, and differentiate the endogenous and exogenous type cervical cancer with its prevalence.&lt;/p&gt;

Serum mucin 3A as a potential biomarker for extrahepatic cholangiocarcinoma.

Background/Aims:The aim of this study is to evaluate serum mucin 3A (MUC3A) as a candidate biomarker for extrahepatic cholangiocarcinoma (EHCC).Patients and Methods:35 Patients with EHCC, 30 patients with pancreatic cancer, 35 patients with gallbladder carcinoma and 78 patients with benign biliary disease were enrolled during January 2015 to January 2016. Serum MUC3A, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) were measured in these patients. Pathology reports of patients with EHCC were collected.Results:(1) The serum levels of MUC3A (87.3 ± 10.8 ng/ml) in patients with EHCC were higher than in patients with pancreatic cancer (63.2 ± 7.7 ng/ml, P < 0.001), patients with gallbladder carcinoma (59.0 ± 10.3 ng/ml, P < 0.001) and patients with benign biliary disease (56.6 ± 13.1 ng/ml, P < 0.001). (2) ROC analysis showed that using MUC3A could clearly distinguish patients with EHCC from those without EHCC with a threshold of 73.2 ng/ml. (3) According to ROC analysis, the sensitivity, specificity, and accuracy of serum MUC3A for diagnosis of EHCC were 94.3%, 89.5% and 90.4%, respectively, which were all significantly higher than CA19-9 and CEA. (4) The serum levels of MUC3A at 1 month post-operatively in 35 patients with EHCC were decreased compared to pre-operative levels (51.8 ± 5.6 vs. 87.3 ± 10.8 ng/ml, P < 0.01). (5) Compared with 20 patients with low MUC3A levels (≤88.8 ng/ml), 15 patients with high MUC3A levels (>88.8 ng/ml) had higher percentage of lymph node metastasis (66.7% vs. 25%, P = 0.014), surrounding tissue infiltration (80% vs. 30%, P = 0.003), and UICC staging IIa-III (86.7% vs. 35%, P = 0.002).Conclusion:The diagnostic efficiency for EHCC of MUC3A is obviously superior to CA19-9 and CEA, and a high level of serum MUC3A indicates a poor prognosis, therefore, MUC3A can be used as a potential diagnostic and prognostic biomarker for EHCC.

The evaluation of sequential type or de novo type in 100 cases of oral squamous cell carcinoma

Objectives Oral potentially malignant disorders (OPMDs) have been suggested as oral precancers, including both oral precancerous regions and oral precancerous conditions. Oral squamous cell carcinoma (OSCC) is divided into 2 types according to the appearances of the cancerous regions. One type is carcinomas with precancerous white lesions—the sequential type. The other type is accompanied SCC without precancerous white lesions—the de novo type. The aim of this study was to evaluate the clinicopathologic characteristics in the sequential type and the de novo type of OSCC. Study Design We analyzed 100 cases of OSCC of the tongue diagnosed at Jichi Medical University. We divided these OSCC cases into 2 types, using intraoral photographs taken by an oral surgeon. Statistical analysis was done by using the χ2 test (P Results Of the 100 cases, there were 51 cases of the sequential type (51%) and 49 cases of the de novo type (49%). The percentage of the T1+T2 group (92.2%) in the sequential type was considerably higher than that of T3+T4 group (7.8%). In the de novo type, the T1+T2 group showed 77.6% and the T3+T4 group showed 22.4%. The percentage of lymph node metastasis in the negative group (84.3%) in the sequential type was higher than that of the positive group (15.7%). In the de novo type, the lymph node metastasis–negative group showed 65.3% and the positive group showed 34.7%. These were significant differences. With regard to postoperative lymph node metastasis and the Yamamoto-Kohama classification of modes of invasion, there were no significant differences in the sequential type and the de novo type. With regard to pathologic findings, the margins of the cancerous lesions in the sequential type tended to be connected to dysplasia or oral intraepithelial neoplasia. It also showed the unclear margin. However, it showed clear margins in the de novo type. Conclusions In this study, we found that patients with sequential type tended to seek treatment in T1+T2 (early stages) and to have no lymph node metastasis, compared with the cases of the de novo type. Our results suggested that there was a relationship between the sequential type and OPMDs.

Parallel Analyses of Somatic Mutations in Plasma Circulating Tumor DNA (ctDNA) and Matched Tumor Tissues in Early-Stage Breast Cancer.

Early detection and intervention can decrease the mortality of breast cancer significantly. Assessments of genetic/genomic variants in circulating tumor DNA (ctDNA) have generated great enthusiasm for their potential application as clinically actionable biomarkers in the management of early-stage breast cancer.Experimental Design: In this study, 861 serial plasma and matched tissue specimens from 102 patients with early-stage breast cancer who need chemotherapy and 50 individuals with benign breast tumors were deeply sequenced via next-generation sequencing (NGS) techniques using large gene panels. Cancer tissues in this cohort of patients showed profound intratumor heterogeneities (ITHGs) that were properly reflected by ctDNA testing. Integrating the ctDNA detection rate of 74.2% in this cohort with the corresponding predictive results based on Breast Imaging Reporting and Data System classification (BI-RADS) could increase the positive predictive value up to 92% and potentially dramatically reduce surgical overtreatment. Patients with positive ctDNA after surgery showed a higher percentage of lymph node metastasis, indicating potential recurrence and remote metastasis. The ctDNA-positive rates were significantly decreased after chemotherapy in basal-like and Her2+ tumor subtypes, but were persistent despite chemotherapy in luminal type. The tumor mutation burden in blood (bTMB) assessed on the basis of ctDNA testing was positively correlated with the TMB in tumor tissues (tTMB), providing a candidate biomarker warranting further study of its potentials used for precise immunotherapy in cancer. These data showed that ctDNA evaluation is a feasible, sensitive, and specific biomarker for diagnosis and differential diagnosis of patients with early-stage breast cancer who need chemotherapy.

Sentinel Node Navigation in Gastric Cancer: Where Do We Stand?

Early gastric cancer (EGC) is more common nowadays and is related a to low percentage of lymph node metastasis. For this reason, there is enormous interest to implicate minimally invasive approaches. Recently, special efforts have been made towards a potential intraoperative (real-time) lymph node metastasis (LNM) assessment, as nodal disease status could not be identified with precision before or during surgery. In this direction, accurate prediction of the LNM status through sentinel LN mapping has been attempted, as an approach to the intraoperative detection of sentinel lymph nodes (SLNs). A careful literature search was conducted in order to clarify the potential clinical application of SN biopsy in the gastric cancer field. The real clinical application of SN biopsy in gastric cancer treatment has been more than challenging due to the "complicated" nature of gastric lymphatic drainage and the high possibility of "skip" metastasis phenomenon. Notably, sophisticated technical aspects, such as the preferred tracer used and the potential "ideal" method to verify the presence of metastases in the resected SLNs, made SN biopsy application in gastric cancer field extremely demanding. Assessing the potential role of SN navigation for gastric cancer treatment in the era of advanced technology, where the minimally invasive surgical approaches are in the top of the scientific interest, it has to be highlighted that SN navigation for gastric cancer is a topic that remains highly controversial, and the need for future clinical trials on this topic is obvious.

Mo1346 THERAPEUTIC EFFECTS OF ENDOSCOPIC ULTRASOUND-GUIDED CELIAC NEUROLYSIS (EUS-CPN) IN PATIENTS WITH UPPER ABDOMINAL-ASSOCIATED PAIN (UAP)

EUS-CPN has been shown to have a therapeutic effect on pancreatic cancer (PC) pain. However, little information is available about the use of EUS-CPN for UAP arising from non-pancreatic forms of cancer (nPC). The objective of the study was to compare the efficacy and safety of EUS-CPN in patients with PC and those with nPC. Clinical information was obtained retrospectively from the medical records and endoscopy reporting system. The follow-up period was until the patient died or was lost to follow-up. Patients were excluded from the study if they died or were lost to follow-up within 2 weeks of undergoing EUS-CPN. Patients who underwent biliary drainage within 1week before or after EUS-CPN were also excluded. Between November 2014 and October 2017, 80 patients were enrolled (PC: 68, nPC: 12). The nPC classifications were 6 bile duct cancer (CA) patients, 1 gastric CA patient, 2 colon CA patients, 1 germ cell tumors patient, 1 gallbladder CA patient, and 1 esophageal CA patient. We used the same EUS-CPN method in both groups: 5 mL of bupivacaine mixed with 15 mL of pure ethanol was injected into the celiac plexus and superior mesenteric plexus with or without ganglion ablation using a 22G endoscopic ultrasound-guided fine needle aspiration needle. The amount of narcotic analgesics consumption was converted into morphine dosage level. Treatment response was defined by the patients rational symptoms and the amount of morphine consumption. Treatment response using morphine was defined as a decreased or stable amount of morphine consumption after EUS-CPN. If morphine consumption was temporarily elevated within 2 weeks after the procedure because of the delayed response of EUS-CPN but achieved a stable dosage level for 4 weeks after elevation, it was defined treatment response. The overall response rate (RR) was 72.5% (58/80) in all patients. The median duration of pain relief was 4.6 months. Temporary diarrhea (16/80, 20.0%), low blood pressure (14/80, 17.5%) and tachycardia (4/80, 5.0%) were seen after the procedure but self-limited. The RR did not differ between the PC and nPC groups (73.5% vs. 66.7%, p=0.63). The median duration of response was 4.6 months for both. Diarrhea was significantly more frequent in nPC (41.6% vs. 16.1%, p=0.04). As for the patient characteristics, nPC had a larger percentage of lymph node metastasis around the celiac plexus (100% vs. 57.4%, p<0.01). EUS-CPN had a similar therapeutic effect on intractable UAP on PC and nPC patients in our study. There is a possibility that EUS-CPN can become a useful approach for pain relief in nPC patients with UAP. Although more cases are needed to assess the potential long-term benefits of EUS-CPN in this patient population.

A favorable tumor size to define papillary thyroid microcarcinoma: an analysis of 1176 consecutive cases.

BackgroundThe optimal treatment strategy for papillary thyroid microcarcinoma (PTMC) has remained controversial. The purpose of this study was to provide a new reference value for PTMC to aid the selection of optimal management for minute lesions.Patients and methodsA pool of 1176 consecutive patients who met the inclusion criteria were ultimately enrolled in this study. The correlation of papillary thyroid carcinoma (PTC) tumor size and lymph node metastasis was analyzed. Receiver operating characteristic curve studies were conducted to identify the reference value by determining the optimal cut-off point of size related to lymph node metastasis. To validate our results, all selected patients were divided into two groups according to the cut-off point and some of the prognostic factors were compared.ResultsA moderate significant correlation was found between the tumor size and the average number of lymph node metastases (r=0.502, P<0.01) and the percentage of lymph node metastasis (r=0.625, P<0.01). The optimal cut-off reference value was 8.5 mm according to the receiver operating characteristic curves. Significant differences were observed for PTC prognostic factors, for example, extrathyroidal extension, multifocality, pathologic (p) N+ stage, occult metastasis in clinical (c) N− stage, radioactive iodine ablation, and recurrence between the two groups.ConclusionDue to more aggressive behavior and poorer prognosis in larger tumor size (>8.5 mm), a tumor size ≤8.5 mm in diameter may be favorable to discriminate PTMC from PTC and aid the selection of optimal management.

Therapeutic Outcomes of Patients with Multifocal Papillary Thyroid Microcarcinomas and Larger Tumors.

A retrospective review of 626 patients with multifocal papillary thyroid carcinoma (PTC) including 147 patients (23.5%) with multifocal papillary thyroid microcarcinoma (PTMC) from a total of 2,536 patients with PTC who visited the Chang Gung Medical Center in Linkou, Taiwan, was performed. A comparison of the clinical features between 626 multifocal and 1,910 solitary PTC cases showed that patients in the multifocal PTC group were older and had a smaller mean tumor size, a more advanced tumor-node-metastasis (TNM) stage, and a higher percentage of nonremission status compared to patients in the solitary PTC group. Of the 626 patients with multifocal PTC, the group with larger tumors showed a more advanced TNM stage, a higher percentage of lymph node metastasis and soft tissue invasion, and a higher nonremission rate compared to the multifocal PTMC group. Of the 626 patients with multifocal PTC, 25 patients (4%) died during a mean follow-up period of 7.1 ± 5.3 years. Kaplan-Meier survival curves showed a significantly lower survival rate associated with multifocal PTMC compared to that with solitary PTMC.

Nomograms incorporated serum direct bilirubin level for predicting prognosis in stages II and III colorectal cancer after radical resection.

An elevated serum bilirubin has been reported to be associated with a reduced risk of some cancer; however, the prognostic significance of serum bilirubin in colorectal cancer wasn’t fully understood. The purpose of this study was to evaluate whether serum bilirubin could predict the prognosis of patients in stages II and III colorectal cancer. A retrospective cohort of 986 patients with colorectal cancer who received surgical resection between January 2005 and December 2010 was included in the study. Levels for serum bilirubin were obtained from medical records. Survival analysis was used to evaluate the predictive value of bilirubin. Serum direct bilirubin (DBIL) was validated as a significant prognostic factor by univariate cox regression test for both overall survival (OS) and disease free survival (DFS) (P < 0.05). X-tile program identified 3.6 as optimal cutoff values for DBIL in terms of OS and DFS. Patients were then divided into DBIL high (DBIL ≥ 3.60 μmol/l) and low group (DBIL < 3.60 μmol/l) according to the optimal cutoff. High DBIL had higher percentage of lymph node metastasis and lymphovascular invasion as compared with low DBIL levels (P < 0.05). Multivariate cox regression analyses confirmed that high DBIL level was an independently prognostic factor for both OS (HR: 1.337, 95% CI: 1.022–1.748, P = 0.034) and DFS (HR: 1.312, 95% CI: 1.049–1.643, P = 0.018). In addition, nomograms on OS and DFS were established according to all significant factors, and c-indexes were 0.715 (95% CI: 0.683–0.748) and 0.704 (95% CI: 0.678–0.730), respectively. Nomograms based on OS and DFS can be recommended as practical models to evaluate prognosis for CRC patients.

Clinical Relationship Between IgG4-Positive Hashimoto's Thyroiditis and Papillary Thyroid Carcinoma.

Hashimoto's thyroiditis (HT) can be divided into IgG4-positive and IgG4-negative HT. The potential association between IgG4-positive HT and papillary thyroid carcinoma (PTC) remains poorly understood. The aim was to investigate the relationship between IgG4-positive HT and PTC and to compare the prognostic parameters of PTC patients with and without IgG4-positive HT. This was a retrospective study. A total of 66 HT patients (18 HT-alone, 48 HT with PTC) with serum samples stored before the operation were collected. Another 18 PTC-alone patients were collected as controls. Expression of IgG4, IgG, and TGF-β1 in thyroid tissues and serum levels of IgG4, TgAb IgG, TgAb IgG4, TPOAb IgG, and TPOAb IgG4 were measured. Seventeen HT patients with PTC (35.4%) were IgG4-positive HT, whereas only one patient (5.6%) was found to be IgG4-positive in the HT-alone group. In contrast, there were only a few IgG4-positive plasma cells in the PTC-alone group. The association of IgG4-positive HT and PTC was statistically significant (P < .05). Moreover, serum levels of TgAb IgG4 and the ratios of TgAb IgG4 to TgAb IgG were significantly higher in the HT with PTC and the PTC-alone groups than in the HT-alone group (P < .05). Furthermore, in the HT with PTC group, the average tumor diameter of 17 IgG4-positive HT with PTC patients was 1.7 ± 0.8 cm, whereas of 31 IgG4-negative HT patients with PTC, the diameter was 1.2 ± 0.6 cm (P = .01). A considerably higher percentage of lymph node metastasis (41.2% vs 12.9%; P = .026) was found in PTC patients with IgG4-positive HT as compared with those with IgG4-negative HT. PTC may be facilitated by preexisting autoimmune inflammation of IgG4-positive HT. IgG4-positive HT with PTC cases may have worse clinical outcomes. The high levels of TgAb IgG4 might present a risk factor for PTC.

Clinical analysis of a patient with a benign lesion of the pharynx misdiagnosed as functional thyroid cancer metastasis.

Papillary thyroid carcinoma (PTC) usually has a lower malignancy rate and better prognosis than other types of thyroid cancer. It tends to spread through the lymphatic system, and the percentage of lymph node metastasis to the neck is 50-70% in patients at the time of diagnosis. Iodine-131 (131I) whole-body scanning is very valuable in the diagnosis and positioning of functional metastatic lesions. However, a variety of comprehensive test results are frequently required to make an appropriate judgment. The present case report describes the case of a patient with PTC where a benign lesion of the pharynx was misdiagnosed as functional metastasis. Some remnant thyroid tissue and an abnormal accumulation of 131I in the oropharynx and at the right side of the neck were observed by 131I whole-body scanning one week after the first therapeutic dose. Following the second therapeutic dose, quasi-circular trapping of 131I by the pharynx persisted. Magnetic resonance imaging enhanced scanning of the oropharynx showed markedly uneven enhancement inside the lesion, and it was considered as a metastatic lesion. However, the serological test results of the patient revealed that there was no increase in the thyroglobulin level and did not support the diagnosis of progressive disease. Therefore, a biopsy on the lesion was conducted under local anesthesia. The histopathological examination exhibited salivary gland tissue and chronic inflammation. Thus, it was necessary to analyze the imaging results, as well as serologic testing outcomes and pathological findings comprehensively, in order to make the correct diagnosis.

Preoperative subclinical hypothyroidism in patients with papillary thyroid carcinoma

ObjectiveTo assess the effect of preoperative subclinical hypothyroidism on prognosis and on the tumour's clinicopathological features at initial diagnosis of papillary thyroid carcinoma (PTC). Materials and methods328 patients who underwent surgery for PTC between January 2001 and December 2006 were enrolled in this study. Of these, we compared 35 patients with preoperative subclinical hypothyroidism with 257 patients who were euthyroid before the operation, with respect to clinicopathological characteristics and prognosis. ResultsNo significant differences were observed in tumour size, extrathyroidal extension, and multifocality between subclinical hypothyroidism and euthyroid patients. Patients with subclinical hypothyroidism had a considerably lower percentage of lymph node metastasis than did euthyroid patients (8.6% vs. 21.8%, p=0.068). Although preoperative subclinical hypothyroidism decreased the risk of lymph node metastasis at 0.313 of odds ratio in the multivariate analysis, its significance was not verified (95% confidence internal, 0.089–1.092; p=0.068). Patients with preoperative subclinical hypothyroidism tended to have a better prognosis than did preoperative euthyroid patients, for both recurrence (2.9% vs. 14.0%, p=0.099) and 7-year disease-free survival (97.1% vs. 87.8%, p=0.079), during the 82-month mean follow-up period. However, even as thyroid-stimulating hormone (TSH) concentration increased, there were no consistent relationships observed between the TSH levels and the prognostic parameters. ConclusionWe could find neither a consistent positive nor a negative linear relationship between TSH levels and several prognostic parameters, indicating that subclinical hypothyroidism with elevated TSH is not an independent predictor of tumour aggressiveness and poor prognosis in PTC.

Warty carcinoma of the penis: A clinicopathological study from South India

Aims:There are few studies on the pathology of warty carcinoma (WC) of the penis and these have been from South America. Penile cancers are not uncommon in India. We reviewed the frequency of subtypes of penile squamous carcinoma (SC) and the pathological features and outcome of WC when compared to squamous carcinoma-not otherwise specified (SC-NOS). We also compared the clinicopathological features of WC in our series with those published earlier.Materials and Methods:We studied 103 cases of penile cancers over 6 years. Cases were classified into different subtypes according to established histologic criteria. Clinicopathologic features were studied in detail and compared among the different subtypes, especially between WC and SC-NOS. The patients were followed-up and disease free survival in months was noted.Results:SC-NOS constituted 75.7% of all penile cancer cases in our series. The frequency of other subtypes was WC: 9.7%, verrucous: 3.9%, basaloid type and papillary type: 0.97% each, and mixed types 8.7%. The average tumor size and depth of invasion did not differ significantly between the two subtypes. Frequency of lymphovascular emboli and percentage of lymph node metastasis in WC (30 and 10%) were lesser than in SC-NOS (49.37 and 26.58%), respectively. There were no recurrences after partial penectomy in the WC subtype. In the SC-NOS type, three cases had recurrence after partial/total penectomy.Conclusion:Warty carcinoma constitutes nearly 10% of all penile squamous cell cancers. These patients seem to have a less aggressive behavior than SC-NOS.

Systematic Pelvic and Aortic Lymphadenectomy in Advanced Ovarian Cancer Patients at the Time of Interval Debulking Surgery: A Double-Institution Case–Control Study

The prognostic role of systematic lymphadenectomy remains unclear in advanced ovarian cancer (AOC). Only few retrospective case series have investigated the percentage of lymph node metastases after neoadjuvant chemotherapy. This multi-institutional case-control study analyzed the prognostic role of systematic lymphadenectomy in AOC patients at the time of interval debulking surgery (IDS). From January 2005 to December 2010, the records of patients with AOC admitted to IDS at the Catholic University of Rome (n = 101, controls) and at the University of Bologna (n = 50, cases) were retrospectively analyzed. The cases, routinely submitted to systematic pelvic and aortic lymphadenectomy, were matched 1:2 with the controls, who did not routinely undergo lymphadenectomy. To correctly assess the prognostic role of lymphadenectomy, only patients with optimally debulked disease were included. Progression-free survival and overall survival were analyzed by a log-rank test. After an overall mean follow-up of 36 months (95% confidence interval 33-39), 35 and 63 recurrences (70.0 vs. 62.4%; p = NS) and 15 and 24 deaths due to disease (30 vs. 23.7%; p = NS) were observed in the case and controls, respectively. The 2-year progression-free survival rate was 36 versus 25% (p = 0.834), and the 2-year overall survival rate was 69 versus 88% (p = 0.777), in the case and controls, respectively. The median operating time was longer, and the percentage of patients requiring blood transfusions was higher in the cases than in the controls (225 vs. 210 min, p = 0.023, and 54 vs. 22.8%, p = 0.0001, respectively). Lymphadenectomy at the time of IDS could be omitted, at least in high-risk patients.

Outcomes of T1b esophageal adenocarcinoma patients

Esophagectomy is usually recommended for patients with submucosal esophageal adenocarcinoma (T1b EAC) because of the potential for lymph node metastasis (LNM). Endoscopic management often differs based on the risk of metastasis. There is limited information on the difference in outcomes for T1b-EAC with and without esophagectomy. To investigate (1) the outcomes of T1b EAC treatments with and without esophagectomy and (2) the percentage of LNM at esophagectomy for T1b-EAC. Retrospective cohort. A tertiary Barrett's esophagus unit. Sixty-eight T1b EAC patients based on EMR histology. Esophagectomy and endoscopic therapies. Survival duration and mortality rate. A total of 68 patients had T1b EAC; cumulative mortality rate was 30.9% and median survival duration was 39.5 months. Thirty-nine underwent esophagectomy and 29 did not. Among patients who underwent esophagectomy, 13 (33.3%) had LNM, and the mortality rate was 50.0% and 11.1% for those with and without LNM, respectively (P < .01). For those with and without esophagectomy, the cumulative mortality rates were 25.6% and 37.9%, and median survival duration was 48.9 and 34.8 months, respectively. There was no statistical difference in Charlson comorbidity index, number of EMRs, mortality rate, or survival duration. In Cox proportional hazard model analysis, the hazard ratio for esophagectomy was 0.5 (P = .21). Retrospective, nonrandomized small sample size cohort. Among the patients with T1b EAC found in EMR specimens who underwent esophagectomy, one third had regional LNM. In our small series, patients who underwent esophagectomy did not have a significantly different survival duration from that of those who did not, indicating that these patients may have similar outcomes [corrected].

Risk of lymph node metastasis in submucosal esophageal cancer: a review of surgically resected patients

Objectives: Endoscopic local procedures are increasingly applied in patients with superficial esophageal cancer as an alternative to radical oncologic resection. The objective of this article is to determine the risk of nodal metastases in submucosal (sm) esophageal cancer, comparing the two predominating histologic tumor types, squamous cell cancer (SCC) and adenocarcinoma (ADC). Methods: A query of PubMed, MEDLINE, Embase and Cochrane Library (1980–2009) using predetermined search terms revealed 675 abstracts, of which 485 full-text articles were reviewed. A total of 105 articles met the selection criteria. A review of article references and consultation with experts revealed additional articles for inclusion. Studies that enrolled patients with submucosal esophageal cancer and provided adequate extractable data were included. Results: The pooled outcomes of 7645 patients with esophageal cancer involving the sm level of infiltration were included in the analysis. Overall, the percentage of lymph node metastasis in submucosal cancer was 37%. Lymph node (N), lymphatic (L) and vascular (V) invasion in sm1 esophageal cancers was 27, 46 and 22%, respectively. Within sm2 lesions, N, L and V invasion were involved in 38, 63 and 38% of patients, respectively. Finally, N, L and V involvement in patients with sm3 lesions was 54, 69 and 47%, respectively. The rates of lymph node metastasis for sm1 and sm2 were higher in SCC compared with ADC, whereas the lymph node metastasis for sm3 was comparable, with >50% involvement in both histologic subtypes. SCC revealed an overall more aggressive behavior compared with ADC (N+: 45 vs 26%; L+: 57 vs 37%; V+: 40 vs 18%). Discussion: While endoscopic therapy may be adequate in selected patients with ‘low-risk’ sm1 ADC, submucosal SCC necessitates esophageal resection and systematic lymphadenectomy because of its aggressive nature and tendency for early metastasis.