Clinical analysis of 318 cases of oropharyngeal squamous cell carcinoma / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological features, treatment outcomes and prognosis of patients with oropharyngeal squamous cell carcinoma (OSCC).</p><p><b>METHODS</b>Retrospective review of 318 consecutive cases with OSCC treated from January 1999 to December 2011. Survival rates and prognostic factors were calculated using the Kaplan-Meier method and multivariate Cox model survival analysis respectively. There were 281 males and 37 females, with a median age of 56 years. Of the 318 cases, 163 carcinomas were from tonsil, 108 from tongue base and 47 from soft palate-uvula. The presenting symptoms were pharyngalgia (128 cases, 40.3%), neck masses (71 cases, 22.3%), foreign body sensation in the pharynx (63 cases, 19.8%) and dental ulcer (44 cases, 13.8%). The median time from onset of the first symptoms until diagnosis of OSCC was 3 months. Of the 318 OSCC, 75 were with high grade, 110 with intermediate grade and 133 with low grade, including 10 patients at stageI, 39 at stage II, 68 at stage III and 201 at stage IV.</p><p><b>RESULTS</b>The rates of lymph node metastasis, distant metastasis and second primary carcinoma were 72.3%, 13.2% and 7.9%, respectively. Of 318 patients, 117 received radiotherapy alone, 66 underwent surgery plus postoperative radiotherapy, 59 underwent preoperative radiotherapy plus surgery, 33 received concomitant chemotherapy and radiotherapy, 20 received concomitant molecular targeted therapy and radiotherapy, 16 underwent surgery alone and 7 received induction chemotherapy plus radiotherapy. The 3-, 5-year overall survival (OS) rates were 58.4%, 50.7%, respectively, and the median overall survival time was 60.1 months. Ages (P = 0.034), gender(P = 0.024), smoking and alcohol consumptions(P = 0.008), doses of radiotherapy(P = 0.046) and clinic stages(P = 0.001) were independent factors for OS.</p><p><b>CONCLUSIONS</b>OSCC is poor in prognosis, with a high incidence of cervical lymph node metastasis. Radiotherapy and salvage surgery are the main treatments for OSCC.</p>

Primary squamous cell carcinoma of the thyroid: retrospective analysis of 28 cases / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological features, treatment outcomes and prognosis of patients with squamous cell carcinoma of the thyroid (SCCT).</p><p><b>METHODS</b>Retrospective review of SCCT cases in our hospital from January 1999 to May 2012. Demographic data and clinical charts, including presenting symptoms, histologic grade of tumor, treatment, and outcome of 28 consecutive patients were obtained. Survival rates and prognostic factors were calculated with SPSS 13.0 software using the Kaplan-Meier method and multivariate Cox model survival analysis.</p><p><b>RESULTS</b>SCCT accounted for only 0.36% of all types of thyroid malignancy. There were 15 males and 13 females, and the median age was 63 years. The presenting symptoms were neck masses (26/28) and hoarse voice (18/28). The 28 SCCTs included 15 high grade tumors, eight intermediate grade tumors and five low grade tumors. According to the UICC 2002 staging criteria, 16 patients were stage IVa, and 12 were stage IVb. Of the 28 patients, 19 underwent surgery plus postoperative radiotherapy, seven underwent surgery alone, and two received radiotherapy alone. The rates of lymph node metastasis and distant metastasis were 60.7% and 25.0%, respectively. The 1-year, 2-year and 5-year overall survival (OS) rate were 50.4%, 25.8% and 19.3%, respectively, and the median overall survival time was 12.2 months. Kaplan-Meier univariate survival analyses indicated that the sizes of the tumors, esophageal invasions and treatment policies are prognostic factors, and multivariate Cox model survival analyses confirmed that the sizes of the tumors and treatment policies were independent factors for OS. Multivariate survival analyses confirmed that the sizes of the tumors and treatment policies were independent factors for OS.</p><p><b>CONCLUSIONS</b>SCCT is a rare malignant tumor with strong invasive ability, high malignancy and poor prognosis. Combined modality therapy was strongly recommended, and surgical resection plus postoperative radiotherapy may be the main treatment protocol for patients with SCCT.</p>

Gene construction and screening of humanized single chain antibody library against VSTM1-v2 cytokine / 药学学报

To rapidly select potent anti-VSTM1-v2 scFv (single-chain antibody fragment) by construction and screening of a humanized scFv library in which a murine VH-CDR3 library was grafted onto a human scFv framework. A murine VH-CDR3 library was amplified from anti-VSTM1-v2 murine cDNA and grafted on human scFv (VH3-VK1) framework. Anti-VSTM1-v2 scFv templates were selected and enriched through ribosome display, TA-cloned into expression vector, and transformed into BL21 (DE3) for soluble expression of target scFv. A total of 1000 clones were randomly picked. Positive ones were first identified using colony PCR, indirect ELISA, Western blotting and then verified with sequencing and dose response ELISA. At last an anti-VSTM1-v2 humanized scFv with good binding affinity (EC50 = 21.35 nmol x L(-1)) was selected from the humanized library of 10(12) members generated in this study. This scFv antibody might have potential applications. This study provides a new approach for rapid screening of humanized antibodies.

Human papillomavirus infection in oropharyngeal squamous cell carcinoma and prognosis: a preliminary analysis of 66 cases / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To analyze the relationship between the prognosis of patients with oropharyngeal squamous cell carcinoma (OSCC) and human papillomavirus (HPV) infection in OSCC.</p><p><b>METHODS</b>Sixty-six patients with oropharyngeal carcinoma who met the enrollment criteria during the period from January 1999 to December 2009 were retrospectively reviewed. The presence or absence of HPV oncogenic types in OSCC specimen was determined by multiplex polymerase chain reaction (PCR). Overall survival (OS) and disease specific survival (DSS) for HPV-positive and HPV-negative patients were estimated by Kaplan-Meier analysis. Cox regression model was used for multivariate analysis.</p><p><b>RESULTS</b>HPV-DNA was detected in 11(16.7%) of all specimens. Among them, 7 were positive for HPV-16, 1 for HPV-16/11, 1 for HPV-35, 1 for HPV-58/52, and 1 for HPV-33/52/54. With the follow-up of 3-78 months (a median of 24.5 months), patients with HPV-positive tumors had significantly better overall survival (χ2=5.792, P=0.016) and disease specific survival (χ2=4.721, P=0.030), the 3-year OS and DSS were 90.0% vs 52.4% and 90.0% vs 56.4%, respectively. Multivariate analysis by Cox regression model showed that HPV infection and nodal status were both independent prognostic factors for patients with OSCC (P<0.05).</p><p><b>CONCLUSIONS</b>Patients with HPV-positive OSCC have significantly better prognosis than patients with HPV-negative tumors. HPV infection is an independent prognostic factor.</p>

Detection of human papillomavirus in oropharyngeal squamous cell carcinoma / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the infection rate and subtypes of human papilloma virus(HPV) in patients with oropharyngeal squamous cell carcinoma (OSCC) and analyze the clinicopathologic features of patients with or without HPV infection.</p><p><b>METHODS</b>A total of 66 biopsy or surgical specimens of OSCC archived in the Pathology Department of Chinese Academy of Medical Sciences were analyzed by polymerase chain reaction (PCR), and the generic amplification products were detected by DNA enzyme immunoassay (DEIA) and typed by reverse hybridization line probe assay.</p><p><b>RESULTS</b>HPV-DNA was detected in 11 (16.7%) of all specimens. Among them, 7 were infected with HPV-16,and the remaining 4 patients were infected with HPV-16/11, HPV-35, HPV-58/52, and HPV-33/52/54, respectively. HPV-16 was detected in 72.7% of all positive specimens. There were more females in HPV-positive group than HPV-negative group (36.4% vs. 1.8%,P=0.002). Patients with HPV-positive tumors were more likely to be non-smokers (36.4% vs. 0,p=0.001) and non-drinkers (45.5% vs. 1.8%,p=0.001) than those with HPV-negative tumors. The proportion of moderately or poorly differentiated tumors was higher in HPV-positive patients than HPV-negative patients (81.8% vs. 63.7%), although without statistical significance (p=0.409). No difference was observed in T classification, N classification, and overall tumor stage.</p><p><b>CONCLUSIONS</b>HPV infection rate was 16.7% in this cohort. HPV-positive OSCC has its unique etiologic and clinicopathological characteristics.</p>

Ribosome display screening of a novel human anti-IgE scFv fragment / 药学学报

Total mRNA was extracted from lymphocytes separated from the peripheral blood of allergic patients, and then variable region of heavy chain (VH) and variable region of light chain (VL) cDNA library were constructed by RT-PCR. Human scFv templates for rabbit reticulocyte lysate ribosome display were assembled by primers and linker peptide (Gly4Ser)3. mRNA bound in antibody-ribosome-mRNA complexes was recovered using in-situ single primer RT-PCR, and three rounds of anti-IgE scFv DNA were enriched. The target DNA fragments were double enzyme digested and ligated into plasmid pET22b (+), followed by transformation in E. coli Rosseta (DE3). Positive clones were screened using clone PCR, Dot blotting and antigen ELISA. The correct lengths of VH (400 bp) and VL (710 bp) PCR products were obtained. The expected 1,000 bp ribosome display templates were also observed in agarose gel electrophoresis. After three rounds of ribosome display target sequences were effectively enriched, leading to a library of 10(13) members. Antibodies with the highest ELISA value for IgE were generated in the strain pET-IgE-6. A human anti-IgE scFv library was successfully constructed as described herein. Ribosome display using single primer in-situ RT-PCR as the recovery procedure effectively enriched target sequences. Anti-IgE scFv with high affinity and specificity were identified. The prepared human anti-IgE scFv fragment might be self-developed to a lead drug for treating asthma. Our study provides an alternative method for rapid discovery of human antibodies of therapeutic importance.

Analysis of arterial spin labeling in 33 patients with hypoxic ischemic encephalopathy / 中华儿科杂志

<p><b>OBJECTIVES</b>To evaluate the diagnostic value of arterial spin labeling (ASL) technology in newborns with hypoxic ischemic encephalopathy (HIE).</p><p><b>METHOD</b>Seven full-term newborn infants without any history of asphyxia and other nervous system diseases were selected as the control and 33 full-term newborn infants were assigned into HIE group. The patients in HIE group were further divided into three subgroups (19 cases of mild, 6 cases of moderate and 8 cases of severe HIE) based on their clinical diagnosis. The control group and HIE group were examined with GE Signa EXCITE HD 3.0T superconducting MRI scanner with a head phase array coil. Both groups were scanned with conventional axial MRI (T1FLAIR, T2WI and T2FLAIR), 1HMRS (PRESS sequence) and ASL (FAIR). Original images of 1HMRS and ASL were processed by Functool software of ADW 4.3 workstation. ASL perfusion images were observed and the signal intensity values of the region of interest (bilateral gray, white matter and basal ganglia) of the two groups were quantitatively measured, and mean value were calculated and compared between groups. Statistical analysis was performed with SPSS 13.0 software, and statistically significant difference was set at P < 0.05.</p><p><b>RESULT</b>The perfusion images of two groups were obtained perfectly. The signal intensity values of bilateral gray, white matter and basal ganglia of control group were 125.34 ± 11.76, 73.42 ± 11.67 and 173.65 ± 15.49, respectively and there was a statistically significant difference between the different areas. The signal intensity values of bilateral gray, white matter and basal ganglia of HIE group were 153.47 ± 11.72, 71.35 ± 10.37 and 217.13 ± 12.51, respectively. There was a statistically significant difference (P < 0.05) in the average signal intensity value of gray matter and basal ganglia, but there were no statistically significant difference (P > 0.05) in white matter between the two groups.</p><p><b>CONCLUSION</b>ASL Perfusion technique can assess HIE comprehensively and accurately. Furthermore, it can evaluate the brain damage of hypoxic ischemia. The results provide a strong basis for clinical treatment.</p>

Fine-needle aspiration cytology of thyroid nodules: a clinical evaluation / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the clinical application of fine needle aspiration (FNA) cytology of thyroid nodules.</p><p><b>METHODS</b>A retrospective review was performed of 474 consecutive cases of FNA cytology of thyroid nodules from October 2005 to January 2011. Two hundred and eighteen patients underwent ultrasound-guided FNA, and 256 patients experienced palpation-guided FNA. Cytologic diagnoses were classified as unsatisfactory, benign, atypical cellular lesion, follicular neoplasm, suspicious for malignancy, and positive for malignancy. The discrepancies between initial cytologic diagnoses and histologic diagnoses were evaluated in 157 surgical specimens.</p><p><b>RESULTS</b>According to the cytological categories, the rates for histologically confirmed malignancy in the 157 patients were as follows: 2/7 of unsatisfactory results, 16.7% (9/54) of benign lesion, 3/9 of atypical cellular lesion, 1/3 of follicular neoplasm, 83.3% (35/42) of suspicious for malignancies, and 97.6% (41/42) of positive for malignancies. The sensitivity, specificity and positive predictive value of thyroid FNA for the diagnosis of malignancy were 85.4%, 86.9% and 90.5%, respectively.</p><p><b>CONCLUSIONS</b>FNA can provide an accurate diagnosis of thyroid malignancy preoperatively. The 6 diagnostic categories were beneficial for either clinical follow-up or surgical management of the patients with thyroid nodules.</p>

Microvascular free flap reconstructive options in patients with different types of maxillectomy defects / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of the distinct free flaps in reconstruction of different types of maxillectomy defects.</p><p><b>METHODS</b>A retrospective reviews was performed of in 66 consecutive cases of reconstructions with free flaps for maxillary tumor ablation defects from October 1997 to June 2010. There were 43 patients who had recurrences after previous operations and 46 patients had accepted radiation therapy before. According to the classification of Brown's maxilla defect:10 cases were in class I, 13 in class II, 23 in class III and 20 in class IV. The reconstructive free flaps included 26 fibula flaps, 10 radial forearm flaps, 7 latissimus dorsi flaps, 7 rectus abdominis flaps, 7 anterolateral thigh perforator flaps, 5 deep inferior epigastric artery perforators, 2 latissimus dorsi/rib flaps and 2 iliac crest flaps. Postoperative features and functions were assessed in 29 patients.</p><p><b>RESULTS</b>The overall free flap success rate was 93.9% (62/66). Three rectus abdominis flaps and one fibula flap failed. There were 29 patients who received postoperative function assessment. Sixty-two percent of the patients restored to taking regular diets, 24 (82.8%) patients had normal language communication ability, and 25 (86.2%) patients were satisfied with their feature.</p><p><b>CONCLUSIONS</b>Radial forearm flap was recommended to reconstruct the class 1 defect, fibula flap to class 2 or class 3 and preformatted flap to class 4.</p>

Free tissue transfer for skull base reconstruction of advanced oncological defects / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To analyze the results and the indications of free flaps in the skull base reconstruction.</p><p><b>METHODS</b>A retrospective review was performed of 25 free flaps reconstructions for skull base tumor ablation defects between March of 1999 and March of 2009. There were 9 latissimus dorsi flaps, 6 rectus abdominis flaps, 4 deep inferior epigastric artery perforator flaps, 3 anterolateral thigh flaps, 2 radial forearm flaps and 1 fibular flap. The defects were classified as cranial bone (100%), dura (40%), brain (12%), sino-nasal cavity (52%), mucosa (56%) and skin (80%).</p><p><b>RESULTS</b>Twenty-three of 25(92%) free flaps survived. One total flap failure and 1 partial flap failure occurred. Five patients (20%) had central nervous system related postoperative complications which including 1 mortality, 2 central nerve system infection and 2 cerebrospinal fluid fistula.</p><p><b>CONCLUSIONS</b>Free flaps transfer is a reliable reconstruction technique for cranial base surgery. This provides a solution to the select advances disease otherwise surgical contraindications. Free flap is the choice for reconstruction of advanced oncological defects, especially when skin and mucosa are violated.</p>