Expression of prion protein is closely associated with pathological and clinical progression and abnormalities of p53 in head and neck squamous cell carcinomas.

Prion protein (PrP) is a glycosyl-phosphatidylinositol (GPI)-anchored membrane protein that functions as a unique pathogenic agent in transmissible spongiform encephalopathy (TSE). In the past decade, overexpression of PrP was observed in a number of human malignant tumors, such as gastric, breast and pancreatic cancer. However, the role of PrP expression in squamous cell carcinoma is rarely documented. To screen PrP expression in head and neck squamous cell carcinoma (HNSCCs), the paraffin-embedded specimens of 92 pathologically diagnosed HNSCCs were assessed by PrP-specific immunohistochemistry (IHC). A total of 55.43% (51/92) of the tested carcinoma tissues were PrP-positive. The rate of positivity and the staining intensity of PrP were closely related with the pathological degree of the HNSCCs; a higher rate of PrP expression was noted in the group of poorly differentiated cancers. PrP-positivity rates increased along with the progression of the clinical grade of the carcinomas. Further evaluation of the associations between PrP expression and the data concerning p53 abnormalities and human papillomavirus (HPV) infection in these samples as previously described, revealed that PrP-positive staining was more frequently detected in the tissues with p53-positive accumulation and the wild-type TP53 gene. The patients with a proline (Pro) polymorphism in SNP72 of TP53 showed significantly higher PrP-positive rates than those with arginine (Arg). No notable difference in PrP expression was identified between the HPV-positive and HPV-negative group. These data indicate a close association of PrP expression with clinical and histological differentiation of HNSCCs, as well as abnormalities of p53.

Protection and Dissection of Recurrent Laryngeal Nerve in Salvage Thyroid Cancer Surgery to Patients with Insufficient Primary Operation Extent and Suspicious Residual Tumor.

Some thyroid cancer patients undergone insufficient tumor removal in the primary surgery in China . our aim is to evaluate the impact of dissection of the recurrent laryngeal nerve during a salvage thyroid cancer operation in these patients to prevent nerve injury. Clinical data of 49 enrolled patients who received a salvage thyroid operation were retrospectively reviewed. Primary pathology was thyroid papillary cancer. The initial procedure performed included nodulectomy (20 patients), partial thyroidectomy (19 patients) and subtotal thyroidectomy (10 patients). The effect of dissection and protection of the recurrent laryngeal nerve and the mechanism of nerve injury were studied. The cervical courses of the recurrent laryngeal nerves were successfully dissected in all cases. Nerves were adherent to or involved by scars in 22 cases. Three were ligated near the place where the nerve entered the larynx, while another three were cut near the intersection of inferior thyroid artery with the recurrent laryngeal nerve. Light hoarseness occurred to four patients without a preoperative voice change. In conclusion, accurate primary diagnosis allows for a sufficient primary operation to be performed, avoiding insufficient tumor removal that requires a secondary surgery. The most important cause of nerve damage resulted from not identifying the recurrent laryngeal nerve during first surgery , and meticulous dissection during salvage surgery was the most efficient method to avoid nerve damage.

Associations of TP53 mutations, codon 72 polymorphism and human papillomavirus in head and neck squamous cell carcinoma patients.

To investigate the possible associations between mutations in TP53 and phenotypes of single-nucleotide polymorphisms (SNPs) in codon 72 (SNP72) with the expression profiles of p53 and human papillomavirus (HPV) infection, 93 pathologically diagnosed head and neck squamous cell carcinomas (HNSCCs) were included for study. Using PCR and direct sequencing, 45 TP53 mutations in 35 cases (37.6%) were confirmed out of the 93 HNSCCs. P53 immunohistochemistry (IHC) confirmed 34 (36.6%) cases with positive staining, including 22 cases with strong and 12 with weak positivity. IARC database and software analysis showed similar results that most of the mutated p53 proteins lost their normal function. Further statistical analysis found a negative correlation between p53 IHC and HPV IHC in the tissues from the group of other HNSCCs (of various sites other than the larynx) but not in the tissues from the laryngeal carcinomas. Analyses of SNP72 showed that the patients with the Arg phenotype had a significantly older age at disease onset when compared to patients with the Pro phenotype, particularly in the group of other HNSCCs. In addition, all cases with strong staining for p53 in the laryngeal carcinoma group had the Pro phenotype and all tumors with poor pathological differentiation in the group of other HNSCCs had the Pro phenotype. These data indicate that the profiles of TP53 mutations, SNP72 polymorphism, p53 IHC and HPV E6 IHC are distinct between the groups of laryngeal carcinoma and other HNSCCs.

[Analysis of the human papillomavirus in laryngeal squamous cell carcinoma patients].

OBJECTIVE: To analyze the infection of human papillomavirus in laryngeal squamous cell carcinoma patients. METHODS: The pathological samples of 64 clinical diagnosed laryngeal squamous cell carcinoma patients were collected. Lunimex and PCR techniques were used to detect the HPV gene infection and immunohistochemistry method was used to analyze the HPV protein expression in the samples. RESULTS: In the 64 cases, 7 were positive for HPV infection by Luminex and PCR tests. 18 were positive for HPV16/18 E6 protein expression. The total positive rate was about 39. 1%. CONCLUSION: The high HPV infection rate in laryngeal squamous cell carcinoma patients in the study indicated indirectly that the importance of the HPV infection in pathogenesis of the laryngeal squamous cell carcinoma.

Completion lobectomy and central compartment dissection in low-risk patients who had undergone less extensive surgery than hemithyroidectomy.

Many low-risk patients with solitary papillary thyroid cancer located in one lobe had undergone surgery that was less extensive than hemithyroidectomy in China. An acceptable completion surgery regimen was suggested for these patients based on our experience. A total of 117 enrolled patients underwent completion surgery. Thirty-two patients had prior tumor resection, 46 patients had prior partial thyroidectomy and 39 patients had prior subtotal thyroidectomy. No neck dissection was performed. Reoperation was scheduled a median of 1.2 months (range, 3 days-6.5 months) after primary surgery for papillary thyroid cancer (PTC). Among the 117 patients, residual tumor was pathologically confirmed in 60 patients, with a residual rate of 51.28%. Among these 60 patients, residual tumor was identified in the thyroid bed alone in 18 patients and in compartment VI alone in 28 patients, while 14 patients exhibited residual tumor in both of these regions. Lymph node metastasis was observed in compartment VI in 42 patients (35.90%), and an average of 6.5 nodes were removed (range, 2-14 nodes for each patient). Additionally, 3.14 positive lymph nodes were removed on average from each of the 42 patients. We conclude that the completion regimen, including the ipsilateral residual lobe, the isthmus and ipsilateral compartment VI (prelaryngeal, pretracheal and paratracheal lymph nodes), is reasonable and acceptable for low-risk patients undergoing surgery that is less extensive than hemithyroidectomy.

[Evaluation of the function of autotransplanted parathyroid tissues].

OBJECTIVE: To evaluate the function autotransplanted parathyroid tissues in thyroid surgery. METHODS: The control group comprised 120 volunteers with normal parathyroid glands in whom serum parathyroid hormone (PTH) levels in blood samples taken from the bilateral elbow head veins. The experimental group comprised 34 patients in whom the parathyroid glands, which were mistakenly cut or could not be preserved during thyroid surgery because of ischemia, were fragmented and autografted into the brachioradialis muscle of the nondominant forearm. On the day of surgery and at 3 days, 7 days, and 2 months postoperatively, contrast imaging and detection of serum PTH levels were performed to evaluate the function of the transplanted parathyroid tissues. RESULTS: In the control group, the mean value of the difference between the bilateral brachiocephalic vein PTH levels was (1.19 ± 0.98) ng/L (maximum 4.52 ng/L). In this study, twice the maximum value (9.04 ng/L) was taken as the effective standard. Based on the 9.04 ng/L effective value, the effective number was 26 patients and the effective rate was 76.5% at 2 months postoperatively in the 34 patients of the experimental group. CONCLUSIONS: The autotransplanted parathyroid tissues showed their functions in most patients, therefore, parathyroid gland autotransplantation is an effective method of preserving function of parathyroid glands that are free or severely ischemic in thyroid surgery.

Is level V dissection necessary for low-risk patients with papillary thyroid cancer metastasis in lateral neck levels II, III, and IV.

Whether it is beneficial to dissect level V in papillary thyroid cancer (PTC) patients with positive lateral neck lymph nodes at levels II-IV is still controversial, especially for low risk cases. In this study, we reviewed the medical records of 47 patients who underwent 47 ipsilateral selective lateral neck dissections (levels II-IV) for previously untreated papillary thyroid carcinomas between October 2006 and October 2008 to assist in establishing the optimal strategy for lateral neck dissection in low risk PTC patients with clinically negative level V nodes. All 47 patients were confirmed to have positive lymph nodes pathologically. Seventeen (36.12%), 36 (76.6%), and 34 (72.34%) patients had positive lymph nodes in levels II, III, and IV, respectively. The mean number of pathologically positive lymph nodes was 1.7 in level II, 2.9 in level III, 2.8 in level IV. No death and distant metastasis were recorded during follow up period. Just 2 patients exhibited recurrence to lymph nodes, and only one showed nodal recurrence in ipsilateral level V, who had positive lymph nodes in all of levels II, III, and IV at initial neck surgery. In conclusion, for PTC low risk patients with clinically negative lymph nodes in level V, non-performance of level V dissection would still achieve good survival results as traditional modified radical neck dissection, with a "wait and see" strategy to be recommended.

The distribution of human papillomavirus in tissues from patients with head and neck squamous cell carcinoma.

Several types of HPVs have been shown to be associated with the development of malignant cancers in various head and neck tumors. More information on the HPV prevalence in patients with head and neck squamous cell carcinomas (SCCs) need to be obtained. In this study, formalin-fixed and paraffin-embedded tissues of 93 pathologically diagnosed head and neck SCC patients were collected from Peking University Cancer Hospital. HPV DNA sequences in tumor tissues were screened by a commercial Luminex technique for HPVs and HPV-specific PCR assays. Presence of HPV16/18 oncoprotein in tumor tissues was assessed by immunohistochemistry (IHC) with HPV16/18 E6-specific antibodies. Of the 93 patients, 16 (17.2%) cases were found to be HPV DNA-positive, including 7 HPV18-positive, 8 HPV16-positive and 1 HPV52-positive. IHC assays demonstrated that 31.2% (29/93) tested sections showed positive signals in the tumor cells. The total positive rate of HPV genome and its encoding products in the tested samples was 44.1% (41/93). Further analyses revealed that HPV infections in head and neck SCCs were significantly related with the tumor anatomic sites, showing decreasing tendency from outside (lip cancer) to inside (laryngeal cancer), but had no correlation with pathological, clinical grades and age of the patients. In all, HPV infections are commonly identified in the tumor tissues of patients with head and neck SCCs, in which HPV16 and 18 are the most prevalent HPV genotypes. Direct detection of high-risk HPV oncoprotein by IHC may be a good tool for classifying a tumor as truly HPV-associated.

[Salvage central neck dissection for papillary thyroid cancer].

OBJECTIVE: To evaluate the salvage central neck dissection (CND) for papillary thyroid cancer in the patients with suspicious residual positive lymph nodes in the central compartment. METHODS: A total of 85 cases undergoing salvage CND between January 2006 to January 2009 was reviewed. RESULTS: Fifty-nine (69.4%) of the 85 patients showed residual positive lymph nodes in the central compartments. The number of dissected lymph nodes for each dissection ranged 2 - 13 nodes, with an average of 5.7 nodes. A total of 159 positive lymph nodes were found in the 59 cases, with an average of 2.7 positive nodes in each case. Four of 6 patients who underwent initial CND in other hospitals were found with residual positive nodes in the central apartments. The incidence of postoperative complications for the salvage CND was 10.6% (9/85), of them 5 cases with hoarseness, 2 cases with transient hypoparathyroidism, 1 case with postoperative bleeding, and 1 case with subplatysmal effusion. The median of follow-up after salvage CND was 44 months (3 - 5 years), showing contralateral central recurrence in 1 case, lateral neck recurrence in 4 cases, lung metastasis in 1 case, and no death case. CONCLUSIONS: Salvage CND should be done for those patients without undergoing initial CND but with positive nodes found after thyroidectomy or the high risks (T3, T4, extra thyroid extension, residual in primary site, and vascular or lymphatic vessel invasion); and also for those patients with initial CND but insufficient extent.

[Selective neck dissection in clinical node positive low risk papillary thyroid cancer patients].

OBJECTIVE: To explore the improvement of modified radical neck dissection in clinical node positive (cN(+)) low risk papillary thyroid cancer patients. METHODS: Seventy-one cases of papillary thyroid cancer with cN(+) underwent selective neck dissection (IIa, III, IV) from 2007 to 2010 were reviewed, including 10 men and 61 women. All patients were at stage I, including 15 T1, 46 T2, 10 T3. Twenty-six patients were found Positive nodes were found by palpation in 26 cases and by ultrasonagraphy in 45 cases. RESULTS: Cervical lymph node metastasis were confirmed pathologically in 63 cases, with metastatic rate of 88.7%; 100% in cN(+) cases by palpation and 82.2% in cN(+) cases by ultrasonagraphy, respectively. Metastatic nodes existed in one level in 13 cases, two levels in 31 cases, and three levels in 19 cases. Recurrence occurred to 4 patients during follow up, with a recurrent rate of 5.6%, and 2 cases of them were found recurrence in the anterior part of Vb, 2 cases in the carotid sheath. CONCLUSION: Selective neck dissection (IIa, III, IV) is acceptable for cN(+) low risk papillary thyroid cancer patients, which can decrease complications in neck and shoulder greatly.

[The analysis of human papillomavirus infection in lip squamous cell carcinoma patients].

OBJECTIVE: To analyze the infection of human papillomavirus in lip squamous cell carcinoma patients. METHODS: The pathological samples of 9 clinical diagnosed lip cancer patients were collected. Lunimex and PCR techniques were used to detect the HPV gene infection and immunohistochemistry method was used to analyze the HPV protein expression in the samples. RESULTS: In the 9 cases, 1 was positive for HPV16 gene and 7 were positive for HPV16/18 E6 protein expression. The total positive rate was about 8/9. CONCLUSION: The high HPV infection rate in lip cancer patients in the study indicated indirectly that the importance of the direct contact to the infection of HPV what was the basis for pathogenesis of the lip squamous cell carcinoma.

[Re-operation extent of primary lesion of thyroid cancer].

BACKGROUND AND OBJECTIVE: Many thyroid cancer patients need to receive second operation because of tumor residue. This study was to explore the resection extent of primary lesion in re-operation of thyroid carcinoma. METHODS: Clinical data of 55 thyroid carcinoma patients who received re-operation were reviewed. The patients, including seven men and 48 women, were aged of 18-56. All patients received ipsilateral residual lobectomy, isthmectomy, ipsilateral anterior cervical muscle and level VI lymph node dissection. The optimal extent for radical re-resection of primary lesion was explored. RESULTS: Tumor residue was proved by pathology in 29 patients, with a rate of 52.73%. Of the 29 patients, eight had primary lesion residue, seven had level VI lymph node residue, and 14 had both. Tumor cells were connected with muscle in four patients. Forty-five metastatic lymph nodes were found. CONCLUSION: Ipsilateral residual lobectomy, isthmectomy, ipsilateral anterior cervical muscle and level VI lymph node dissection is the basic re-resection extent of primary lesion for thyroid carcinoma patients.

[Use of en bloc principle in re-operation of thyroid carcinoma].

OBJECTIVE: The study is to explore the extent, main-point and use of en bloc principle in re-operation of thyroid carcinoma. METHODS: Clinical data of 75 patients received re-operation from 2002 to 2006 because of nonstandard operation were reviewed, including 10 men, 65 women, age ranging from 21-56. Ipsilateral completing lobectomy, isthmectomy, ipsilateral anterior cervical muscle, and level VI dissection were done in all the patients by en bloc principle. RESULTS: Residual tumor was found in 39 cases. There were, 10 in primary site, 8 in VI level, and 21 in both. Therefore tumor residual rate was 52.0%. The total metastatic lymph nodes in VI level were 63. Among the eight patients with recurrent laryngeal nerves paralyses which were hurt in the first operation, 4 were found been cut completely, 4 were ligated. The ligated locations were all near the place which the nerve enter the larynx. The ligated nerves were released, and the patients voice was improved greatly. CONCLUSIONS: Ipsilateral completing lobectomy, isthmectomy, ipsilateral anterior cervical muscle and VI level dissection is adequate for thyroid carcinoma patients who received nonstandard operation. The principle of en bloc resection can be used in the reoperation of thyroid carcinoma.

[Parotidectomy of deep-lobe tumors].

OBJECTIVE: To evaluate advantages of the superficial lobe preservation in the parotidectomy of deep-lobe tumors, which include much lower incidence in postparotidectomy depression, variable aesthetic deformities, facial nerve injury and Frey's syndrome. METHODS: This retrospective review included 114 patients with benign parotid gland tumors hospitalized from 2001 to 2004, among which 13 patients with deep-lobe parotid tumors and 101 patients in the superficial lobe of parotid gland. Seven in the 13 patients with deep-lobe tumors were operated with the method of the superficial lobe preservation. RESULTS: During median 3 years and 3 months following-up, no any cases with either tumor recurrence, permanent facial nerve injury, postparotidectomy depression, or Frey's syndrome was found in the 7 operated patients. Only 1 case with the facial nerve marginal mandibular branch palsy occurred, but completely recovered over a 3-month period of time. CONCLUSIONS: Preservation of the superficial lobe for deep-lobe tumors parotidectomy could decrease the incidence of parotidectomy complications without any influence in the treatment effect. Additionally, the parotid function preservation and cosmetic appearance after operation also satisfy both the patients and surgeons.