经胸锁乳突肌肌间入路甲状腺癌根治手术的临床观察

目的:探讨颈侧切口经胸锁乳突肌肌间入路（腔镜辅助）实施甲状腺癌根治手术的可行性和安全性。方法:选择2018年1月-2019 年9月我院普外科收治的甲状腺恶性结节患者共60例。按照随机数字表法分为两组,每组各30 例。观察组采用颈侧切口经胸锁乳突肌肌间入路（腔镜辅助）实施甲状腺癌根治手术。对照组采用颈前切口颈白线入路实施甲状腺癌根治手术。比较两组手术时间、术中出血量、术后切口疼痛评分、美容满意度、术后住院时间、并发症等指标。结果:观察组在美容满意度、术后疼痛评分、并发症方面要明显优于对照组,其差异有统计学意义。两组在手术时间、术中出血量、术后住院时间方面的比较无明显统计学意义。结论:颈侧切口经胸锁乳突肌肌间入路（腔镜辅助）实施甲状腺癌根治手术要明显优于传统的颈前切口颈白线入路,更值得在临床上推广及实施。     

Amplification of the int-2 gene in human head and neck squamous cell carcinomas

Head and neck squamous cell carcinomas (SCC) from 21 patients were analyzed for structurally rearranged or amplified proto-oncogenes by Southern blot hybridization. The int-2 proto-oncogene was amplified 3-5 fold in 5 (50%) of 10 laryngeal SCC and 2-3 fold in 5 (45%) of 11 nonlaryngeal SCC of the head and neck. Adjacent histologically normal tissue from the same patients had single int-2 gene copy number. Coamplification of int-2 and the epidermal growth factor receptor (c-erbB-1) gene was found in one laryngeal SCC and one SCC metastatic to the neck. No amplification or structural alterations of proto-oncogenes c-erbB-2/HER2, c-myc, H-ras-1, or K-ras-2 was detected in any of the head and neck tumors. In a survey of head and neck tumor-derived cell lines, int-2 was amplified 9 fold in a hypopharyngeal tumor cell line (FaDu), but not amplified in 3 laryngeal tumor cell lines. int-2 has been localized to the q13 band of chromosome 11. We used chromosome 11 specific probes to demonstrate that int-2 amplification was not due to complete or partial chromosome 11 duplication. int-2 amplification was localized to 11q13, but did not extend to the ets-1 locus 11q23. The results indicate that int-2 is frequently amplified in SCC of the head and neck and suggest that int-2 amplification may correlate with clinical disease progression.     

The pectoralis major myocutaneous flap in head and neck reconstruction

The pectoralis major myocutaneous flap (PMMC flap) represents a landmark in the development of head and neck reconstructive surgery. After Stephan Ariyan first described its use for head and neck reconstruction in 1979, it has become tremendously popular and has revolutionised head and neck cancer surgery. Here, we present our initial experience with fourteen PMMC flaps in head and neck reconstruction. In most of the instances it was used for oral or oropharyngeal reconstruction. It was used for five other reconstructive tasks as well. Wound infection was the most common complication. There was no case of total flap loss. It has proven to be a reliable method of reconstuction in the head and neck.     

Early side effects of radiation treatment for head and neck cancer

Purpose of this review of medical literature is to present the immediate side effects of radiation therapy for head and neck cancer and their treatment. The likelihood and severity of these immediate side effects depends on a number of factors, including the total dose of radiation delivered, over what time it was delivered and what parts of the head and neck received radiation. Early side effects include: inflammation of the oropharyngeal mucosa (mucositis), painful swallowing (odynophagia), difficulty swallowing (dysphagia), hoarseness, lack of saliva (xerostomia), orofacial pain, laryngeal radionecrosis, dermatitis, hair loss, nausea, vomiting, inadequate nutrition and hydration, and weight loss. These complications can interfere with, and delay treatment. Most of these side effects generally dissipate over time. In conclusion, radiation treatment for the head and neck cancer causes significant early side effects. Many of these side effects present difficult challenges to the patients. Their recognition and treatment can significantly improve the patients’ health, long-term survival and quality of life. The review provides information that can assist head and cancer survivors deal with radiation side effects.     

Plasma retinoid levels in head and neck cancer patients: a comparison with healthy controls and the effect of retinyl palmitate treatment

Vitamin A and related compounds, also known as retinoids are thought to play a role in the development of head and neck cancer. We measured levels of the major retinoids, retinol, all-trans retinoic acid, 13-cis retinoic acid and 13-cis-4-oxo retinoic acid in plasma of head and neck cancer patients in comparison with controls without cancer. No differences were found between plasma levels of these retinoids between 25 head and neck cancer patients and 21 controls. Mean baseline levels for the patients were 2458. 6.0, 6.4 and 8.6 nM for retinol, all-trans retinoic acid, 13-cis retinoic acid and 13-cis-4-oxo retinoic acid, respectively. In addition, we selected 10 patients from the chemoprevention trial Euroscan and measured the effect on retinoid levels of 300,000 I.U. daily retinyl palmitate intake during 1 month. Medication caused significant elevations in retinol levels (1.2 fold), all-trans retinoic acid (2.2 fold) and its metabolites 13-cis retinoic acid (5.8 fold) and 13-cis-4-oxo retinoic acid (8.9 fold). Because of its high increase in levels, 13-cis-4-oxo retinoic acid seems a good candidate to serve as a suitable marker to monitor patient compliance in future chemo-prevention trials involving retinoids. No relations were found between the occurrence of side-effects of retinyl palmitate and retinoid levels during treatment. However, the two patients who developed side-effects had the highest pre-treatment levels of 13-cis retinoic acid and 13-cis-4-oxo retinoic acid, suggesting that retinoid toxicity is associated with relatively high basal retinoid metabolism.     

Long-term effects of radiotherapy on taste and salivary function in man

The long-term effects of radiotherapy on taste and salivary function were studied in 13 patients treated by radiation 1–7 years previously for tumors of the head and neck. Taste function was quantitatively evaluated using a standard forced choice, three-stimulus-drop technique for the determination of detection and recognition thresholds and a forced-scaling technique for the determination of taste intensity responsiveness. Parotid salivary function was quantitatively evaluated by determination of flow rate and protein secretion rate. Nine of the 13 patients studied (69%) had measurable taste loss; every patient who had radiotherapy including the parotid glands had measurable salivary dysfunction. Our results demonstrate that curative courses of radiotherapy for tumours of the head and neck may result in long-term changes in taste and salivary function. From the present study, the maximum tolerance doses resulting in a 50% complication rate 5 years after treatment (TD 50/5) are estimated to be 40–65 Gy for xerostomia and 50–65 Gy for taste loss. Therefore, in a standard treatment regimen for tumors of the head and neck, with curative intent, gustatory and salivary gland tissues frequently sustain maximum tolerance injury.     

带蒂胸大肌肌皮瓣移植在头颈癌放疗后手术中的运用

目的:探讨头颈癌放疗后因肿瘤复发进行挽救性手术,带蒂胸大肌肌皮瓣修复手术切除后软组织缺损的可行性和价值。方法:7例头颈部恶性肿瘤进行了根治性放疗后局部复发或颈淋巴结转移,通过手术切除病灶,颈淋巴结清扫,同侧带蒂胸大肌肌皮瓣移植修复软组织缺损创面。结果:7例移植的带蒂胸大肌肌皮瓣全部成活,有2例出现切口裂开,愈合困难。结论:在头颈癌放疗后手术中,带蒂胸大肌肌皮瓣移植是修复手术切除后软组织缺损的有效方法。     

Circulating tumor-derived DNA may permit the early diagnosis of head and neck squamous cell carcinomas

A series of eight microsatellite loci were assayed for both loss of heterozygosity and new mutated alleles in 91 head and neck squamous cell carcinomas. In 58 cases, alterations were detected and used as markers for assaying the presence of circulating tumor-derived DNA in the patients' plasma. This was unambiguously detected in 17 cases. The probability of detecting circulating DNA was independent of tumor stage and was found to be present even in some individuals with stage I tumors. The presence of such DNA, however, could not be correlated with disease outcome or other significant clinical parameters, suggesting that it has no prognostic significance. The results indicate that circulating tumor-derived DNA could be used as a means of early diagnosis of head and neck tumors.     

Loss of E-cadherin and p27 expression is associated with head and neck squamous tumorigenesis

BACKGROUND: In neoplastic head and neck lesions, it has been found that the loss or reduction in E-cadherin expression is a late event and is associated with invasion. Low p27 levels have been associated with a poor prognosis in many different tumors, including laryngeal carcinoma. The authors investigated p27 and E-cadherin protein expression in the early stages of head and neck tumorigenesis and evaluated their predictive roles individually and in association with carcinogenesis. METHODS: Tissue biopsies from 46 patients who were participants in 3 chemoprevention trials were analyzed for E-cadherin expression, and 40 samples were analyzed for p27 expression using immunohistochemistry. RESULTS: The data suggested that loss of both E-cadherin expression and p27 expression occurred early during the preneoplastic steps of head and neck carcinogenesis, and loss of p27 protein expression alone (P=0.02) and in combination with loss of E-cadherin expression (P=0.04) was a significant predictor of the risk for head and neck carcinoma. CONCLUSIONS: The loss of p27 expression may be useful in the construction of a risk model for head and neck carcinogenesis and may represent a potential target for chemopreventive interventions. Longer follow-up of the high percentage of low-risk preneoplastic lesions in the current study and validation in a larger sample size may be required to establish the predictive role of these abnormalities.     

Cleavage of caspases-1, -3, -6, -8 and -9 substrates by proteases in skeletal muscles from mice undergoing cancer cachexia

A prominent feature of several type of cancer is cachexia. This syndrome causes a marked loss of lean body mass and muscle wasting, and appears to be mediated by cytokines and tumour products. There are several proteases and proteolytic pathways that could be responsible for the protein breakdown. In the present study, we investigated whether caspases are involved in the proteolytic process of skeletal muscle catabolism observed in a murine model of cancer cachexia (MAC16), in comparison with a related tumour (MAC13), which does not induce cachexia. Using specific peptide substrates, there was an increase of 54% in the proteolytic activity of caspase-1, 84% of caspase-8, 98% of caspase-3 151% to caspase-6 and 177% of caspase-9, in the gastrocnemius muscle of animals bearing the MAC16 tumour (up to 25% weight loss), in relation to muscle from animals bearing the MAC13 tumour (1-5% weight loss). The dual pattern of 89 kDa and 25 kDa fragmentation of poly (ADP-ribose) polymerase (PARP) occurred in the muscle samples from animals bearing the MAC16 tumour and with a high amount of caspase-like activity. Cytochrome c was present in the cytosolic fractions of gastrocnemius muscles from both groups of animals, suggesting that cytochrome c release from mitochondria may be involved in caspase activation. There was no evidence for DNA fragmentation into a nucleosomal ladder typical of apoptosis in the muscles of either group of mice. This data supports a role for caspases in the catabolic events in muscle involved in the cancer cachexia syndrome.     

192Ir pharyngoepiglottic fold interstitial implants. The key to successful treatment of base tongue carcinoma by radiation therapy

Twenty-eight patients with squamous carcinomas of the base tongue were seen and evaluated in a conjoint Head and Neck Tumor Board at Stanford between 1976 and 1982. Fourteen patients were treated by combined external beam and interstitial irradiation, 11 of whom had Stage III and IV carcinomas (American Joint Committee). An initial dose of 5000 to 5500 rad was first delivered by external beam irradiation in 5 to 5.5 weeks, followed approximately 3 weeks later by an iridium 192 (192Ir) interstitial implant boost by the trocar and loop technique. The key to successful treatment of these neoplasms was found to be the use of a lateral percutaneous cervical technique, which placed horizontal loops through the oropharyngeal wall above and below the hyoid bone; the superior loop included the pharyngoepiglottic fold and the tonsilloglossal groove. Standard multiple loop implants (submentally inserted) of the base tongue from the vallecula anteriorly to the circumvallate papillae were also used routinely. This approach has been successful, since 10 of the 14 patients (71%) remain without evidence of disease (mean follow-up, 32 months). There have been only two local recurrences, both on the pharyngoepiglottic fold in patients who did not receive the now standard pharyngoepiglottic fold/lateral pharyngeal wall implants. No patients have relapsed after 18 months. The other 14 patients were treated prospectively during the same period by combining initial resection, radical neck dissection, and postoperative irradiation. In this group, there were more locoregional failures compared to the group treated with radiation therapy alone (5 tongue recurrences and 7 neck relapses); in addition, more severe complications were noted in these 14 patients who received surgery and postoperative irradiation. The authors believe that combined external beam and interstitial irradiation is effective treatment for base tongue carcinomas, especially when the high-dose distribution includes the adjacent tonsilloglossal groove, pharyngoepiglottic fold, and oropharyngeal wall to and below the level of the hyoid bone, in addition to treating an adequate base tongue volume.     

Giant supraglottic schwannoma

Schwannomas arising from the supraglottis are uncommon, if not rare. They are known to arise from the head and neck region but oropharyngeal presentation is not often seen. Few cases of pedunculated schwannoma arising from the aryepiglottic fold presenting as giant tumours in the oropharynx have been reported so far. The tumour in this case has been excised via intraoral approach, with nil residual morbidity. A follow up period of one year was uneventful without any recurrence.     

Association of RAD 51 135 G/C, 172 G/T and XRCC3 Thr241Met Gene Polymorphisms with Increased Risk of Head and Neck Cancer

Homologous recombination repair (HRR) plays an important role in protection against carcinogenic factors.Genes regulating the HRR mechanisms may impair their functions and consequently result in increased cancersusceptibility. RAD 51 and XRCC3 are key regulators of the HRR pathway and genetic variability in these maycontribute to the appearance and progression of various cancers including head and neck cancer (HNC). Theaim of the present study was to compare the distribution of genotypes of RAD51 (135G/C, 172 G/T) and XRCC3(Thr241Met) polymorphisms between HNC patients and controls. Each polymorphism was genotyped using thepolymerase chain reaction-restriction fragment length polymerase (PCR-RFLP) technique in 200 pathologicallyconfirmed HNC patients along with 150 blood samples from normal, disease free healthy individuals. We observedthat homozygous variant CC genotype of RAD51 135G/C was associated with a 2.5 fold increased HNC risk(OR=2.5; 95%CI=0.69-9.53; p<0.02), while second polymorphism of RAD 51 172 G/T, heterozygous variantGT genotype was associated with a 1.68 fold (OR=1.68; 95%CI=1.08-2.61; p<0.02) elevation when comparedwith controls. In the case of the Thr241Met polymorphism of XRCC3, we observed a 16 fold (OR=16; 95% CI=3.78-69.67; p<0.0002) increased HNC risk in patients compared to controls. These results further suggested thatRAD51 (135G/C, 172 G/T) and XRCC3 (Thr241Met) polymorphisms may be effective biomarkers for geneticsusceptibility to HNC. Larger studies are needed to confirm our findings and identify the underlying mechanisms.     

胸锁乳突肌肌瓣修复腮腺术后缺损畸形的应用

目的：探讨腮腺肿瘤术后同期应用胸锁乳突肌肌瓣填充修复对面部凹陷畸形的预防作用。方法：对40例腮腺肿瘤病人行肿瘤及腮腺浅叶或浅叶部分切除同期行胸锁乳突肌肌瓣填充修复,观察治疗效果。结果：患者术后创面愈合良好,手术腮腺区及颈部外形良好,颈部功能正常。结论：胸锁乳突肌肌瓣修复腮腺切除术后缺损能改善术后凹陷畸形发生。     

Umami taste dysfunction in patients receiving radiotherapy for head and neck cancer

Taste loss is a major cause of morbidity in patients undergoing head and neck irradiation. Previous studies have reported the alteration of the four basic tastes in patients with head and neck cancer during radiotherapy. However, only a few studies have been conducted on the effects of irradiation on the function of umami taste, a novel and basic taste recently recognized. In a prospective study, 52 patients undergoing radical head and neck irradiation were assessed for taste loss. Taste ability was measured by the taste threshold for umami quality using the whole-mouth taste method in patients before, during, and immediately after radiotherapy. Umami taste declined of the 3rd week after the start of radiotherapy and improved of the 8th week.     

放疗剂量与鼻咽癌患者胸锁乳突肌体积变化及晚反应关系

目的 探讨放疗剂量与鼻咽癌患者胸锁乳突肌体积及晚反应关系。方法 对2010-2014年间收治的38例鼻咽癌患者的胸锁乳突肌以环状软骨下缘分为上下颈部,根据CTV₂处方剂量0、54、60 Gy分为1、2、3组。放疗剂量学参数包括整条肌肉和上下颈部的D_mean、V₆₆、V₆₀。在TPS的CT图像中分别勾画疗前和疗后6、12、18个月胸锁乳突肌轮廓并计算体积,在C₃-C₄、C₄-C₅、C₅-C₆、C₆-C₇椎间盘水平分别测量并记录胸锁乳突肌前后径及左右径。颈部皮肤、胸锁乳突肌晚反应采用CTCAE4.0标准记录。两两比较采用配对t检验或非参数Kruskal-Wallis法;单因素方差分析进行组间样本率比较;采用Spearman法行相关分析。结果 疗后6、12、18个月SM体积变化之间差异有统计学意义(P=0.000)。疗后12、18个月胸锁乳突肌体积较疗前明显减小(P=0.000、0.000),且体积萎缩百分比与≥V₆₆有明显相关性(P=0.015、0.020)。疗后18个月胸锁乳突肌纤维化与上颈部V₆₀呈明显相关性(P=0.030);颈部皮肤纤维化与上颈部D_mean、V₆₀呈明显相关性(P=0.029、0.005)。结论 放疗计划优化中应尽量提高剂量均匀度,以避免颈部皮肤及胸锁乳突肌纤维化发生。     

Impact of human papillomavirus on head and neck squamous cell cancers in Gabon

Head and neck squamous cell cancers are among the most aggressive. Their incidence and mortality rates are relatively lower in Middle Africa than worldwide, but in Gabon, these rates tend to be 2–3 fold higher than in neighboring countries. The main risk factors are alcohol and tobacco consumption. However, in the last decades, there was cumulated evidence that human papillomaviruses were a significant risk factor, particularly for oropharyngeal squamous cell cancer. In Gabon, as elsewhere in Africa, assessment of these 3 risk factors need to be improved to determine their respective role in the development of head and neck squamous cell cancers. The potential differences in alcohol/tobacco consumption habits as well as in infectious ecology between developing and developed countries can make it difficult to transpose current data on this issue. Determining the respective role of alcohol/tobacco consumption and human papillomaviruses in the development of head and neck squamous cell cancers is crucial for the management of these cancers that could become a serious public health issue in Gabon. Human papillomaviruses are not only a risk factor but also a biomarker with promising clinical potential for the follow-up of head and neck squamous cell cancers potentially able to select an adequate treatment. Then, assessing the epidemiological impact of human papillomaviruses in Gabon and in all of Africa would prove useful for the clinical follow-up of head and neck squamous cell cancers, and would also provide essential data to plan a global prevention strategy against head and neck squamous cell cancers due to human papillomaviruses.     

Mutagen sensitivity and environmental exposures as contributing causes of chromosome 3p losses in head and neck cancers

The interaction between environmental exposures and host susceptibility may lead to specific mutational events within head and neck squamous cell carcinoma (HNSCC). Furthermore, this interplay may determine not only the probability of cancer development but also the biologic characteristics of the tumor once it occurs. To better understand the relationship of mutagen sensitivity and tobacco and/or alcohol consumption on HNSCC carcinogenesis, we examined loss of heterozygosity on chromosome 3p in 58 HNSCCs using 10 microsatellite markers. Mutagen sensitivity was determined in vitro by quantitating bleomycin-induced chromatid breaks utilizing peripheral blood lympocytes from respective patients. Forty-six of the 58 invasive cancers showed allelic loss at one or more loci. Consistent with previous investigations, three discrete regions of deletions were identified: 3p13-14.2, 3p21.1-21. 2, and 3p25.1-26.1. The frequency and types of deletions were dependent upon tobacco and alcohol exposures. The distal region of 3p but not the remaining two regions was most frequently influenced by tobacco exposure. In contrast, heavy alcohol use when combined with tobacco use was associated with whole-arm loss of 3p rather than identifiable site-specific damage. Furthermore, this combined influence of alcohol and tobacco exposures on whole-arm loss was most apparent in those patients who expressed mutagen-sensitivity; the odds ratio of whole-arm loss increasing from 2.67 (95% CI 0. 21-33.49) in those individuals who were mutagen resistant to 13.5 (95% CI 1.3-136.0; P = 0.02 by Fisher's exact test) in those who were mutagen sensitive. An assessment of clinical parameters in this population demonstrated that patients with whole-arm loss were more likely to present with cervical lymph node metastases and advanced stage disease than patients with partial losses. Results indicate that various environmental exposures as well as the expression of mutagen sensitivity will influence the types of chromosome 3p allelic losses in head and neck cancers as well as the behavior of disease once it develops.     

Evidence for the contribution of insulin resistance to the development of cachexia in tumor‐bearing mice

Cancer cachexia is a syndrome of unintentional weight loss that is characterized by wasting of both skeletal muscle and adipose tissue. Glucose intolerance and insulin resistance have been associated with cancer cachexia. However, it is unknown whether resistance to insulin has a role in the development of cachexia. In the present study, male CD2F1 mice with colon‐26 adenocarcinoma tumors underwent an insulin tolerance test before the onset of weight loss. Compared to mice without tumors, mice with tumors had a profoundly blunted blood glucose response to insulin. Corroborating these findings, mice with tumors had decreased phosphorylation of Akt in quadriceps muscle and epididymal adipose tissue at the end of the study. Expression of Akt‐regulated genes Atrogin‐1, MuRF‐1, and Bnip3 was increased in muscle, suggesting a role for decreased insulin signaling in the induction of both proteasomal proteolysis and autophagy in cachectic muscle. Rosiglitazone treatment increased serum adiponectin, insulin sensitivity, and body weight, and decreased Atrogin‐1 and MuRF‐1 expression in the skeletal muscle of tumor‐bearing mice. In conclusion, insulin resistance is an early event in mice with cachexia induced by colon‐26 tumors. Rosiglitazone improves insulin sensitivity and decreases early markers of cachexia. These data provide evidence that insulin resistance is not only present in cachexia, but also has a role in cachexia pathogenesis. Correction of insulin resistance may be a novel therapeutic target for the treatment of cancer cachexia.