The pathogenic mutations of APOA5 in Chinese patients with hyperlipidemic acute pancreatitis.

BACKGROUND AND AIMS: To study the role of gene mutations in the development of severe hypertriglyceridemia (HTG) in patients with hyperlipidemic acute pancreatitis (HLAP), especially different apolipoprotein A5 (APOA5) mutations. METHODS: Whole-exome sequencing was performed on 163 patients with HLAP and 30 patients with biliary acute pancreatitis (BAP). The pathogenicity of mutations was then assessed by combining clinical information, predictions of bioinformatics programs, information from multiple gene databases, and residue location and conservation. The pathogenic mutations of APOA5 were visualized using the software. RESULTS: 1. Compared with BAP patients, pathogenic mutations of APOA5 were frequent in HLAP patients; among them, the heterozygous mutation of p.G185C was the most common. 2. All six pathogenic mutations of APOA5 identified in this study (p.S35N, p.D167V, p.G185C, p.K188I, p.R223C, and p.H182fs) were positively correlated with severe HTG; they were all in the important domains of apolipoprotein A-V (apoA-V). Residue 223 is strictly conserved in multiple mammals and is located in the lipoprotein lipase (LPL)-binding domain (Pro215-Phe261). When Arg 223 is mutated to Cys 223, the positive charge of this residue is reduced, which is potentially destructive to the binding function of apoA-V to LPL. 3. Four new APOA5 mutations were identified, namely c.563A > T, c.667C > T, c.788G > A, and c.544_545 insGGTGC. CONCLUSIONS: The pathogenic mutations of APOA5 were specific to the patients with HLAP and severe HTG in China, and identifying such mutations had clinical significance in elucidating the etiology and subsequent treatment.

Peripheral arterial rather than venous blood is a better source of circulating tumor cells in early lung cancer.

BACKGROUND: Circulating tumor cells (CTCs) play a crucial role in the early diagnosis and prognosis of lung cancer. Identification of a more suitable sample source could be a breakthrough towards enhancing CTC detectability in early-stage lung cancer. We investigated the differences in detectable CTCs between peripheral arterial and venous blood in early- and mid-stage lung cancer patients undergoing surgery and analyzed the association between clinicopathological factors and detectable CTCs in peripheral arterial and venous blood. METHODS: Peripheral arterial and venous blood was collected in 5-mL samples from 56 patients with surgically resected and pathologically clear at early- or mid-stage lung cancer. Blood specimens were enriched for CTCs based on isolation by size of epithelial tumor cells. The CTCs were identified using Swiss Giemsa staining and immunohistochemistry for CD45/CD31. RESULTS: In stage I lung cancer, CTC-positive rate was significantly higher in peripheral arterial than in venous blood (45.45% vs. 17.39%). There was no significant difference in the number of detectable CTCs between peripheral arterial and venous blood. A low degree of differentiation was associated with a high positive rate of CTCs in peripheral venous blood. The number of circulating tumor microemboli was significantly higher in patients with tumor size >3 cm compared with ≤3 cm. CONCLUSION: CTC levels in peripheral arterial and venous blood differed little in lung cancer patients.Compared to peripheral venous blood, peripheral arterial blood had a higher CTC positivity rate in early-stage lung cancer.This study was favorable for early detection and monitoring of lung cancer.

Clinical-Molecular characteristics and Post-Translational modifications of colorectal cancer in north China: Implications for future targeted therapies.

This study delineated the elucidate molecular changes and their post-translational modifications (PTMs) in heterogenetic colorectal cancer (CRC) for a deeper understanding of the CRC pathophysiology and identifying potential therapeutic targets. In this retrospective study, the profiles of 13 hot spot gene mutations were analyzed and the microsatellite instability (MSI) status was determined.Employing the Circulating Single-Molecule Amplification and Resequencing Technology (cSMART) assay, the clinical-pathological features of CRC were characterized in 249 Chinese patients. PTMs were quantified online.Among the patients with CRC, the mutation frequencies of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC genes were 47.8%, 3.6%, 4.8%, 13.7%, 55.8%, and 36.9%, respectively. The proportion of MSI-high (MSI-H) was 7.8%.Subsequent multiple logistic regression analysis showed significant associations including a link between lung metastasis and KRAS mutation, between liver metastasis and lymph node metastasis, between MSI-H and early-onset CRC (EOCRC) and KRAS mutation, between right-sided colon cancer and peritoneal metastasis, and between PIK3CA mutation and PTEN mutation. Patients with KRAS mutation presented with MSI-H, lung metastasis, and PIK3CA mutation. MSI-H, BRAF mutation, and PTEN mutation were more frequent in EOCRC. Phosphorylation and ubiquitylation were found in KRAS, BRAF, PTEN, and SMAD4; SUMOylation and ubiquitylation were observed in HRAS and NRAS; while phosphorylation was obvious in APC, P53, and MLH1. Notably, Phosphorylation and ubiquitylation were the two most common PTMs. The biological characteristics of CRC in Chinese patients have some unique clinical features, which can be explained by the genetic mutation profile, correlations among gene mutations and clinical characteristics. These distinctions set the Chinese patient population apart from their Western counterparts.

Integrating Preoperative Computed Tomography and Clinical Factors for Lymph Node Metastasis Prediction in Esophageal Squamous Cell Carcinoma by Feature-Wise Attentional Graph Neural Network.

PURPOSE: This study aimed to propose a regional lymph node (LN) metastasis prediction model for patients with esophageal squamous cell carcinoma (ESCC) that can learn and adaptively integrate preoperative computed tomography (CT) image features and nonimaging clinical parameters. METHODS AND MATERIALS: Contrast-enhanced CT scans taken 2 weeks before surgery and 20 clinical factors, including general, pathologic, hematological, and diagnostic information, were collected from 357 patients with ESCC between October 2013 and November 2018. There were 999 regional LNs (857 negative, 142 positive) with pathologically confirmed status after surgery. All LNs were randomly divided into a training set (n = 738) and a validation set (n = 261) for testing. The feature-wise attentional graph neural network (FAGNN) was composed of (1) deep image feature extraction by the encoder of 3-dimensional UNet and high-level nonimaging factor representation by the clinical parameter encoder; (2) a feature-wise attention module for feature embedding with learnable adaptive weights; and (3) a graph attention layer to integrate the embedded features for final LN level metastasis prediction. RESULTS: Among the 4 models we constructed, FAGNN using both CT and clinical parameters as input is the model with the best performance, and the area under the curve (AUC) reaches 0.872, which is better than manual CT diagnosis method, multivariable model using CT only (AUC = 0.797), multivariable model with combined CT and clinical parameters (AUC = 0.846), and our FAGNN using CT only (AUC = 0.853). CONCLUSIONS: Our adaptive integration model improved the metastatic LN prediction performance based on CT and clinical parameters. Our model has the potential to foster effective fusion of multisourced parameters and to support early prognosis and personalized surgery or radiation therapy planning in patients with ESCC.

The Correlations among Circulating Tumor Cells, Epstein-Barr Virus Status, and Epidemiology in Patients with Nasopharyngeal Carcinoma.

BACKGROUND: Studies have shown that circulating tumor cells (CTCs) can be detected in nasopharyngeal carcinoma (NPC). However, the relationship between CTCs and tumor stage is still controversial. This study aims to investigate the correlations among CTCs, Epstein-Barr virus (EBV) status, clinicopathologic features, and epidemiological risk factors in patients with NPC. METHODS: Three hundred and thirty primary NPC patients with complete clinical data and epidemiology information were collected. Analysis of CTCs was performed using the CTCBIOPSY system. The plasma EBV DNA load was detected by quantitative real-time PCR. Detection of VCA-IgA and EA-IgA antibodies titers was conducted by immunoenzymatic assay. EBNA1-IgA and Zta-IgA were measured using an enzyme-linked immunosorbent assay. RESULTS: The presence of CTCs was associated with high EBV DNA load (p < 0.05). The positive rate of CTCs was correlated with T and M classifications of NPC (T: 13.2% vs. 22.9%; M: 17.9% vs. 34.8%, p < 0.05). Compared with never and former smokers, current smokers exhibited a higher positive rate of EBNA1-IgA (83.3% and 81.0% vs. 92.5%, p < 0.05); the patients with pack-years of smoking ≥ 15 displayed a significantly higher positive rate of EBNA1-IgA than those with pack-years of smoking < 15 (98.0% and 92.5% vs. 81.0%, p < 0.05). CONCLUSIONS: CTCs positivity was closely associated with tumor burden and distant metastasis of NPC. Smoking status and smoking cumulative dose of NPC patients might be correlated with EBV activation.

Lymph node metastases outside tumor-bearing lobes and/or segments in non-small cell lung cancer.

Objective: Hilar and lung lymph node metastases (N1) are defined as ipsilateral bronchial and intrapulmonary lymph nodes. However, the cleaning standards for ipsilateral bronchial lymph nodes in different lobes and segments within the same lobe in segmentectomy are not clearly defined. Materials and methods: Sixty-six patients undergoing pulmonary resection for the treatment of lung cancer were evaluated. Intraoperatively visible non-tumor-bearing lobe (NTBL) and post-operatively non-tumor-bearing segment (NTBS) lymph nodes were removed and analyzed. The associations between the NTBL LNs and clinicopathological characteristics were analyzed. Results: Non-tumor-bearing lobe LNs metastases were found in 8 (12.1%) of the 66 patients, NTBS LNs metastasis were not found (0/13). The presence of NTBL metastases was significantly associated with age (<60 years vs. ≥60 years, P = 0.037), differentiation (Grade 1 well differentiated vs. Grade 2 moderately differentiated vs. Grade 3 poorly differentiated, P = 0.012), CAT-scan-findings of Mediastinal and hilar lymph nodes metastasis (node-positive vs. node-negative, P = 0.022), pN stage (N0 vs. N1 vs. N2, P = 0.003) and p stage (I vs. II vs. III, P = 0.009). Multivariate logistic analysis showed that tumor differentiation (P = 0.048, HR 6.229; 95% CI 1.016-38.181) and pN (P = 0.024, HR 5.099; 95% CI 1.245-20.878) were statistically significant predictors. Conclusions: Lobar lymph node metastasis of NTBL occurs frequently in patients with NSCLC, but lymph node metastases in NTBS LNs are rare. Advanced age, poorly differentiated and N1 and N2 status of CAT-scan-findings were independent risk factors for the involvement of the NTBL lobar lymph nodes. Although lymph node metastases in NTBS are rare, further investigation of the need to dissect is required.

Intertumoural Heterogeneity and Branch Evolution of Synchronous Multiple Primary Lung Adenocarcinomas by Next-Generation Sequencing Analysis.

OBJECTIVES: Multiple primary lung cancers (MPLCs) are an increasingly well-known clinical phenomenon, but there is a lack of high-level evidence for their optimal clinical diagnosis and therapeutic approaches. Thus, we analysed genetic variation to determine the intertumoural heterogeneity and branch evolution of synchronous multiple primary lung adenocarcinomas. METHODS: We performed multiplex mutational sequencing on 93 synchronous multiple primary lung adenocarcinoma lesions from 42 patients who underwent surgical resection. RESULTS: The high discordance rate of mutation was 92.9% (n=39) between tumours in individual patients. EGFR, TP53 and KRAS mutations were detected in 57 (61.3%), 19 (20.4%) and 11 (11.8%) of the 93 tumours, respectively. 16 cases of multiple primary lung adenocarcinomas simultaneously harboured EGFR mutations and TP53 mutations. Matching mutations between paired tumours were observed in 1 (2.4%) patient for P20. The genotypes were all EGFR L858R mutations, but the pathological type of P20T1 was lepidic predominant, and P20T2 was adenocarcinoma in situ. In the phylogenetic tree, genetic variations were divided into trunk, shared and branch subtypes. Branch mutations accounted for 91.09% of variations in sMPLA, while the ratio of trunk (4.95%) and shared (3.96%) variations was significantly lower. CONCLUSIONS: Remarkable intertumoural heterogeneity and frequent branch mutations were found in synchronous multiple primary lung adenocarcinomas.

Comparison of CellSearch and Circulating Tumor Cells (CTC)-Biopsy Systems in Detecting Peripheral Blood Circulating Tumor Cells in Patients with Gastric Cancer.

BACKGROUND The purpose of this study was to compare circulating tumor cells (CTCs)/circulating tumor microemboli (CTM) detection rates of the CellSearch and CTC-Biopsy systems in patients with gastric cancer (GC). We also investigated potential correlations between clinicopathological characteristics and prognosis in patients with GC. MATERIAL AND METHODS This prospective study was conducted at the Shandong Institute of Cancer Prevention and Control in China. Fifty-nine patients with GC and 22 healthy volunteers were recruited and their peripheral blood samples were examined by the CTC-Biopsy system and CellSearch system for CTC. RESULTS The rate of detection of CTCs/CTM was significantly higher with the CTC-Biopsy system than with the CellSearch system (59.32% vs. 27.12%, P<0.001). The Kappa value was 0.179, indicating poor consistency. CTCs detected with the CellSearch system in patients with stage III/IV GC was significantly correlated with neutrophil count (P=0.020), neutrophil/lymphocyte ratio (N/L ratio) (P=0.009), CA19-9 (P=0.049), tumor size (P=0.026), and the extent of vascular invasion (P=0.007). CTCs detected with the CTC-Biopsy system correlated with tumor differentiation (P=0.010). CTM in patients with stage I/II GC and stage II/IV GC correlated with CEA (P=0.004) and tumor differentiation (P=0.030), respectively. A CTC count >3 detected with the CellSearch system, and not the CTC-Biopsy system, correlated with reduced progression-free survival and overall survival. CONCLUSIONS The CTC-Biopsy system was superior to the CellSearch system for detecting CTCs in GC patients. CTM were detected with the CTC-Biopsy system but not with the CellSearch system. CTCs detected with the CellSearch system correlated with various clinicopathological factors and long-term survival outcomes.

Erratum: Isolation of circulating tumor cells in patients undergoing surgery for esophageal cancer and a specific confirmation method.

[This corrects the article DOI: 10.3892/ol.2019.10017.].

Isolation of circulating tumor cells in patients undergoing surgery for esophageal cancer and a specific confirmation method.

The clinical significance of circulating tumor cells (CTCs) in patients with esophageal squamous cell carcinoma (ESCC) who have undergone radical surgery was investigated. A novel confirmation method for identifying CTCs or circulating tumor microemboli (CTM) in ESCC was also investigated. Blood samples from 55 patients with ESCC were collected 1-3 days prior to surgery and 7 days post-surgery. All patients underwent curative thoracic esophagectomy and lymphadenectomy. Blood samples from 20 healthy volunteers were obtained as controls. Isolation by size of epithelial tumor cells (ISET) was performed also. The overall CTC detection rate was 52.7% preoperatively and 49.1% postoperatively. The presence of CTCs correlated with the Tumor-Node-Metastasis stage and the Log odds of positive lymph nodes. No significant difference in perioperative CTC transformation was discovered between the thoracoscopic and laparoscopic approach, and the open approach. The P40+/cluster of differentiation (CD)45- phenotype was confirmed in the CTCs and CTM. ISET appeared to have high sensitivity for detecting CTCs within ESCC patients. Immunofluorescence staining for CD45 and P40 was a specific, accurate and convenient method for confirming the presence of CTCs or CTM in patients with ESCC, and is strongly recommended as a supplement to morphological analysis.

Comparison of two detection systems for circulating tumor cells among patients with renal cell carcinoma.

BACKGROUND/AIMS: Detection of circulating tumor cells (CTCs) in cancer patients has diagnostic and prognostic importance. However, the clinical implications of CTC detection in patients with renal cell carcinoma (RCC) are still unclear. In this study, we investigated the clinical significance of CTCs using two detection systems, the CellSearch system (CSS) and isolation by size of epithelial tumor cells (ISET), among RCC patients. METHODS: We recruited 36 RCC patients and 22 healthy volunteers as controls. Blood was drawn before treatment. Samples were analyzed using the CSS and ISET. We prospectively followed the RCC patients to determine overall and progression-free survival. RESULTS: We did not detect CTCs in the control group using either the CSS or ISET. CTCs were detected in 7/36 patients (19.4%) using the CSS and in 13/36 patients (36.1%) using ISET, while circulating microemboli (CTMs) were detected in three patients (8.3%). The presence of ISET-detected CTCs correlated with clinical tumor node metastasis (TNM) stages, while the CSS-detected CTCs did not. After 36 months (median), CTCs detected by both methods failed to correlate with overall and progression-free survival among RCC patients. CONCLUSION: We discovered that ISET is more suitable than the CSS for detecting CTCs in RCC patients. The presence of CTCs/CTMs in RCC patients correlated with higher TNM stages, suggesting that the presence of CTCs could be a prognostic marker in RCC patients.

NEOADJUVANT TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION FOR BILIARY TUMOR THROMBOSIS: A RETROSPECTIVE STUDY.

OBJECTIVES: Curative hepatectomy and tumor thrombectomy for hepatocellular carcinoma with complicating biliary tumor thrombosis (HCC/BTT) is associated with high surgical morbidity and mortality. This retrospective study evaluated the effectiveness and safety of neoadjuvant transcatheter arterial chemoembolization (TACE) in HCC/BTT patients scheduled for curative resection. METHODS: Thirty consecutive patients with diagnosed HCC/BTT were hospitalized for neoadjuvant TACE and elective curative liver resection (group A; n=20) or curative liver resection alone (group B; n=10). The primary outcome measure was median survival. RESULTS: Group A had a significantly shorter overall operative time (160±25 versus 190±35 min; p < .01) and duration of inflow control (14.3±3.6 versus 25.1±5.1 min; p < .01) and significantly less intraoperative blood loss (150±35 versus 520±75 ml; p < .01) and transfusion (100±40 versus 375±55 ml; p < .01) as compared to group B. Among patients undergoing both thrombectomy and curative resection, the median survival of group A was significantly longer than that of group B (28.5 [9-54] versus 21.5 [6-39] months; p < .01); among those who received thrombectomy alone, the median survival of group A was also significantly longer than that of group B (12.8 [6-25] versus 4.5 [2-7] months; p < .01). CONCLUSIONS: Neoadjuvant TACE significantly reduced the surgical risk of curative liver resection and significantly prolonged median survival in HCC patients with complicating BTT.

Fluorouracil implants caused a diaphragmatic tumor to be misdiagnosed as liver metastasis: a case report.

BACKGROUND: Fluorouracil implants are widely used in peritoneal interstitial chemotherapy. Curative effects have been obtained, but implants have also caused some complications. CASE PRESENTATION: We performed an analysis of a 66-year-old male patient's case history, as well as conventional pathological analysis and Raman spectroscopic detection of the diaphragmatic tumor. We also analyzed the underlying causes of this condition to prevent complications and reduce misdiagnoses in future cases. The patient had a history of peritoneal fluorouracil implantation. Pathological analysis of the diaphragmatic mass revealed foreign particles, and Raman detection showed that the mass contained fluorouracil. CONCLUSION: Fluorouracil implants may persist due to the high concentrations of this drug used in peritoneal chemotherapy. This finding should provide guidance and improve the application of peritoneal implants. In clinical trials, and the diagnosis of liver metastasis should be based on pathological results.

Prognostic value of circulating tumor cells in patients with squamous cell carcinoma of the head and neck: a systematic review and meta-analysis.

The prognostic value of circulating tumor cells (CTCs) in patients with squamous cell carcinoma of the head and neck (SCCHN) is controversial. The objective of this study was to evaluate the prognostic value of CTCs in patients with SCCHN by conducting a meta-analysis. We systematically searched scientific literature published before June 10, 2014, using the PubMed, ScienceDirect, Cochrane Library, and EMBASE databases. Studies evaluating the correlation of CTC status with tumor-node-metastasis (TNM) disease stage, nodal involvement, and disease progression (recurrence or metastasis) in patients with SCCHN were selected for the analysis. Pooled odds ratio (OR) and 95 % confidence interval (CI) were calculated using the fixed-effects model or the random-effects model in the presence of heterogeneity. Our analysis consisted of eight studies, enrolling a total of 433 patients. The disease progression (recurrence/metastasis) rate in the CTC-positive patients was significantly higher (OR 3.44; 95 % CI 1.87-6.33; p < 0.01) compared with the patients without disease progression. However, there was no significant difference between TNM disease stage III-IV and stage I-II in the presence of CTCs (OR 1.54; 95 % CI 0.87-2.72; p > 0.05). CTC status did not correlate with nodal involvement (OR 1.20; 95 % CI 0.67-1.90; p > 0.05). This meta-analysis indicates that detection of CTCs has a predictive value in patients with SCCHN, particularly those with tumor progression. The presence of CTCs in patients with SCCHN has a poor prognosis compared with the patients without CTCs. Detection of CTCs might be served as a prognosticator in patients with SCCHN. Further studies based on homogeneous populations are warranted to confirm these findings.

Screening analysis of candidate gene mutations in a kindred with polycystic liver disease.

AIM: To find potential mutable sites by detecting mutations of the candidate gene in a kindred with polycystic liver disease (PCLD). METHODS: First, we chose a kindred with PCLD and obtained five venous blood samples of this kindred after the family members signed the informed consent form. In the kindred two cases were diagnosed with PCLD, and the left three cases were normal individuals. All the blood samples were preserved at -85 °C. Second, we extracted the genomic DNA from the venous blood samples of the kindred using a QIAamp DNA Mini Kit and then performed long-range polymerase chain reaction (PCR) with different primers. The exons of PKD1 were all sequenced with the forward and reverse primers to ensure the accuracy of the results. Next, we purified the PCR products and directly sequenced them using Big Dye Terminator Chemistry version 3.1. The sequencing reaction was conducted with BiomekFX (Beckman). Finally, we analyzed the results. RESULTS: A total of 42 normal exons were identified in detecting mutations of the PKD1 gene. A synonymous mutation occurred in exon 5. The mutation was a homozygous T in the proband and was C in the reference sequence. This mutation was located in the third codon and did not change the amino acid encoded by the codon. Missense mutations occurred in exons 11 and 35. These mutations were located in the second codon; they changed the amino acid sequence and existed in the dbSNP library. A nonsense mutation occurred in exon 15. The mutation was a heterozygous CT in the proband and was C in the reference sequence. This mutation was located in the first codon and resulted in a termination codon. This mutation had an obvious influence on the encoded protein and changed the length of the protein from 4303 to 2246 amino acids. This was a new mutation that was not present in the dbSNP library. CONCLUSION: The nonsense mutation of exon 15 existed in the proband and in the third individual. Additionally, the proband was heterozygous for this mutation, so the mutable site was a pathogenic mutation.

Transplantation of human umbilical cord-derived mesenchymal stems cells for the treatment of Becker muscular dystrophy in affected pedigree members.

The regeneration of muscle tissue has been achieved using multipotent mesenchymal stem cells in mouse models of injured skeletal muscle. In the present study, the utility of multipotent human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in the treatment of Becker muscular dystrophy (BMD), a genetic disease where muscle tissue fails to regenerate, was examined in members from a pedigree affected by BMD. The disease status was evaluated in 4 affected pedigree members (II1, II2, II3 and III2; aged 50, 46, 42 and 6 years, respectively). The transplantation of the hUC­MSCs (performed on 3 patients, I2, II3 and III2) was performed by infusion with an intravenous drip over a 30­min period, and the patients were evaluated at 1, 3, 4 and 12 weeks following the procedure. The evaluation was based on physical characteristics, as well as on molecular testing for serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels and a histological examination of muscle biopsies. The patients suffered no adverse reactions in response to the transplantation of the hUC­MSCs. At 1 week following transplantation all 3 patients showed improvement in the muscle force of the limbs, muscle size and daily activity. The walking gait of patient III2 had improved by 1 week post-transplantation and reached a normal status by 12 weeks. Serum CK and LDH levels were decreased relative to the baseline levels. A histological examination of muscle biopsies displayed no obvious tissue regeneration. In conclusion, the treatment of patients with BMD using hUC-MSCs was safe and of therapeutic benefit that lasted for up to 12 weeks. hUC-MSCs are, therefore, a potential cell therapy-based treatment option for patients with muscular dystrophies.

Hemangioendothelioma arising from the spleen: A case report and literature review.

Primary hemangioendotheliomas (HEs) of the spleen are rare, low-grade borderline-malignant vascular tumors. To date, only a few splenic HE cases have been reported in adults. In infants, one 9-year-old male patient has previously been reported, and the patient succumbed to the disease shortly following surgery. Currently, the clinical treatment and prognosis of the disease remains challenging to define, due to the extremely low number of cases reported. The current report presents the case of a 9-year-old pediatric patient with splenic HE, who survived with no recurrence or complications following a partial splenectomy. Additionally, a literature review was conducted to analyze the treatment and prognosis of the disease.

Neoadjuvant therapy combined with a BMP regimen for treating penile cancer patients with lymph node metastasis: a retrospective study in China.

BACKGROUND AND AIM: Combination chemotherapy is emerging in the management of advanced penile cancer. However, evidence-based chemotherapeutic regimens in the current guidelines are lacking. The aim of this study was to evaluate the efficacy of preoperative neoadjuvant chemotherapy combined with a BMP regimen including bleomycin (BLM), methopterin (MTX) and cisplatin (DDP) for treating advanced penile cancer patients. METHODS: We retrospectively audited the clinical and follow-up data of 24 penile cancer patients with fixed inguinal lymph node metastasis that were admitted in our hospital from 2001 to 2010 and received preoperative neoadjuvant chemotherapy. RESULTS: A total of 24 patients with advanced penile cancer (pN3) were recruited in this study. All patients received preoperative neoadjuvant chemotherapy combined with a BMP regimen. The average cycle of chemotherapy was two cycles (range 1-4 cycles). Among 24 adjuvant cases, 15 patients that responded to neoadjuvant chemotherapy underwent penectomy and inguinal lymphadenectomy. In contrast, nine cases did not respond to chemotherapy and received palliative local radiotherapy. Overall, the 1-, 2- and 5-year survival rates were 70.8, 50.0 and 45.8 %, respectively. The 5-year survival rate between the responder and non-responder groups was statistically significant (73.3 vs. 0 %, P < 0.001). CONCLUSION: Neoadjuvant chemotherapy combined with a BMP regimen followed by surgery is beneficial to patients with advanced penile cancer.