Melanocytic nevi of the oral mucosa - no evidence of increased risk for oral malignant melanoma: an analysis of 119 cases

Pigmented nevi of the oral mucosa are rare benign melanocytic tumours. Epidemiological data are scanty, and the etiology and pathogenesis of these lesions are poorly understood. Reports are mainly based on isolated cases or a relatively small series of cases. Some reviews have drawn attention to the frequent localization of these lesions on the hard palate, the site of preference for oral malignant melanoma (OMM). However, as yet, there is no direct proof that oral melanocytic nevi (OMNs) constitute precursor lesions of OMM. 119 cases of OMNs, registered at the nationwide Registry of Pathology (PALGA) in The Netherlands during the period 1980–2005, have been evaluated. Subepithelial OMNs were the most commonly recorded lesions (96 cases), followed by blue (10 cases), compound (7 cases) and junctional OMNs (5 cases). Only one case of a combined nevus was recorded. None of the patients developed OMM during a mean follow-up period of 8.6 years.

We present an analysis of this series of cases, together with a review of the literature. The findings of the present evaluation do not give support for the hypothesis of OMN being a marker for an increased risk of future development of OMM.     

口腔黏膜恶性黑色素瘤肺转移特征及预后分析

背景与目的：口腔黏膜恶性黑色素瘤（oral mucosal melanoma，OMM）是一类高度恶性的实体肿瘤，其远处转移率约40%，其中肺是最常见的远处转移部位；本研究旨在探讨OMM肺转移特征及预后影响因素，以期找到肺转移OMM最佳的治疗模式。方法：回顾性分析2017年1月—2021年1月于上海交通大学医学院附属第九人民医院确诊的肺转移OMM病例，总结胸部计算机体层成像（computed tomography，CT）的影像学特征，采用Kaplan-Meier方法进行生存分析。结果：88%的OMM患者在术后2年内确诊肺转移，其中第1年22例（52%），第2年15例（36%）；71%的患者胸部CT表现为大小不一、多发、圆形或椭圆形结节，寡转移少见（10%）；不按期随访（P = 0.009）、合并局部复发（P = 0.037）、合并胸腔积液（P = 0.042）以及未行免疫治疗（P = 0.000）会显著缩短患者的生存期。合并复发的患者对程序性死亡[蛋白]-1（programmed death-1，PD-1）免疫治疗的应答显著降低（P = 0.009），PD-1单药治疗的中位生存期只有10个月，联合抗血管靶向药物后中位生存期可延长至19个月（P=0.019）。结论： OMM易发生肺转移，即使小于1 cm的微小结节也可以发生转移灶。OMM转移最常发生在术后1~2年内，定期随访一定程度上能及早发现转移病灶从而延长患者的生存期。既复发又转移的OMM患者接受单纯免疫治疗往往效果欠佳，联合抗血管靶向治疗也许会有更好的治疗结局。     

Evaluation of surgical excision of non-homogeneous oral leukoplakia in a screening intervention trial, Kerala, India

It is well established that most invasive oral cancers arise from precancerous lesions such as leukoplakia, erythroplakia and oral submucous fibrosis. One of the approaches for control of oral cancer is to detect oral precancerous lesions early in their development and prevent their malignant transformation to invasive cancer either by chemoprevention or by surgical excision of the lesions, with concurrent control of tobacco and alcohol use and other specific aetiological factors. However, the value of specific approaches such surgery in long-term control of lesions and prevention of malignant transformation is not known. We describe our experience with cold knife surgical excision of 59 cases of non-homogeneous leukoplakia of the oral cavity diagnosed in the context of a community-based oral cancer cluster randomised oral cancer screening trial in Kerala, India. Two-thirds of these revealed dysplasia on histology. After a minimum follow-up of 12 months (range 12-37 months) after surgical excision, 44 (74.8%) were remaining disease free with no evidence of recurrent/new lesions; during follow-up, three (5%) developed new luekoplakic lesions, and six (10.1%) developed recurrent lesions, while six (10.1%) could not be traced after treatment. There was no event of malignant change during follow-up. The proportion of subjects remaining with no evidence of disease at 3 years by Kaplan-Meier method of analysis was 62.1% (95% CI: 0.36-0.87). Accrual and long-term follow-up of large number of surgically treated cases may provide valuable leads to management policies of oral leukoplakia, since, as of now, the added value of specific treatments over and above primary prevention by tobacco and alcohol control remains to be established.     

Mapping of a novel ocular and cutaneous malignant melanoma susceptibility locus to chromosome 9q21.32

An estimated 10% of all cutaneous malignant melanoma (CMM) cases are inherited, but the genetics of familial CMM are largely unknown. Ocular malignant melanoma (OMM), which is rare, may be associated with familial CMM. We performed a genome-wide scan of two Danish pedigrees with multiple cases of OMM (N = 10) and CMM (N = 3) and other malignancies (with no germline mutations in CDKN2A, CDK4, BRCA1, and BRCA2) to identify melanoma susceptibility genes. Results of parametric linkage analysis are presented as logarithm of the odds (LOD) scores, and all P values are two-sided. Peak two-point parametric LOD score of 2.2 (P = .0007) at D9S167 on chromosome 9q21 was observed. Targeted analysis of a third Danish family with OMM and CMM patients confirmed 9q21 linkage, providing a combined four-point parametric LOD score of 3.02 (nominal P = .00003 and genome-wide P = .086). Two families shared a common haplotype comprising three adjacent and highly polymorphic markers, limiting the region to less than 5 cM and 3 Mbp at 9q21.32. Expression of RASEF, a known gene in this region, was examined in tumor tissue from 10 sporadic CMM lesions and was found to be decreased in 70% of these tumors compared with RASEF expression in a human reference RNA pool from 10 different cell types and in 10 breast tumors.     

Treatment and prognosis of oral mucosal melanoma

To evaluate the treatment and prognosis of oral mucosal melanoma (OMM) and provide basic data for clinical treatment. Retrospective analysis of clinicopathological data on OMM from January 1976 to December 2005. Survival analysis was performed and Kaplan-Meier analysis was used to compare the effects of clinicopathological factors on survival using SPSS 18.0 software. A Cox model was applied for multivariate analysis. The 3-year and 5-year overall survival (OS) rates of 51 cases of OMM were 35.0% and 20.7%, respectively. Lymph node metastatic sites were predominantly at levels Ib-III (29/31, 93.5%). Patients of age ≥55 years and size ≥4 cm had a lower survival rate than those of aged <55 years and size <4 cm. The 3-year OS and 5-year OS of patients who underwent surgery combined with biotherapy or biochemotherapy (70.1% and 58.4%, respectively) were significantly higher than that of patients who underwent other therapeutic regimens (including surgery, chemotherapy, surgery combined with radiotherapy or surgery combined with chemotherapy) (25.0% and 12.5%, respectively). Multivariate analysis showed that surgery combined with biotherapy or biochemotherapy and neck dissection were effective treatments for OMM. Patients aged ≥55 years had a worse prognosis than those aged <55 years. OMM has a poor prognosis, but multimodality treatment including surgery combined with biotherapy may improve the prognosis. In patients aged ≥55 years with tumor size ≥4 cm, increasing the scope of resection may be effective. Elective levels I-III neck dissection should be considered in TanyNOMO cases.     

Oral premalignant lesions: from a clinical perspective

In this review article, the clinical and histopathological characteristics of oral premalignant lesions, and primarily oral leukoplakia, are noted and the risk factors for malignant transformation of oral leukoplakia are discussed. Malignant transformation rates of oral leukoplakia range from 0.13 to 17.5%. The risk factors of malignant transformation in the buccal mucosa and labial commissure are male gender with chewing tobacco or smoking in some countries such as India, or older age and/or being a non-smoking female in other countries. Some authors have reported that leukoplakia on the tongue or the floor of the mouth showed a high risk of malignant transformation, although others have found no oral subsites at high risk. In concurrence with some authors, the authors of this review view epithelial dysplasia as an important risk factor in malignant transformation; however, there are conflicting reports in the literature. Many authors believe that nonhomogeneous leukoplakia is a high risk factor without exception, although different terms have been used to describe those conditions. The large size of lesions and widespread leukoplakia are also reported risk factors. According to some studies, surgical treatment decreased the rate of malignant transformation; however, many review articles state that no definitive treatment including surgery can decrease the malignant transformation rate of oral leukoplakia because of the lack of randomized control trials of treatment. Tobacco chewing and smoking may be causative agents for cancerization of oral leukoplakia in some groups, and evidence for a role of human papilloma virus in the malignant transformation of oral leukoplakia is inconsistent. Further research to clarify its role in malignant transformation is warranted.     

Patterns of regional spread and the value of elective neck treatment for oral mucosal melanoma

Objective To investigate the patterns of regional lymphatic spread and the value of elective neck treatment (ENT) in oral mucosal melanoma (OMM). Methods In this retrospective analysis, 61 OMM patients with no distant metastasis treated in Cancer Hospital of Chinese Academy of Medical Sciences between 1984 and 2016 were recruitred. The regional lymph node distribution of cN+ disease, the value of ENT in cN0 disease, the failure patterns and prognostic factors were retrospectively analyzed. Results Overall, 55.7% of the patients were clinical/pathological cN+. The most frequently involved locations were the level Ⅰ b (76%), followed by level Ⅱ and level Ⅲ. For cN0 patients, the 5-year regional failure-free survival rate was 91.7% in patients who received at least ipsilateral level Ⅰ b-Ⅲ ENT and 52.4% in patients who did not receive at least ipsilateral level Ⅰ b-Ⅲ ENT (P=0.036). The regional failure rate was 6% for patients treated with at least ipsilateral leve Ⅰ b-Ⅲ ENT, while in their counterparts who did not receive at least ipsilateral level Ⅰ b-Ⅲ ENT was 46%(P=0.035). For the regional failure pattern, the most frequently failure sites were level Ⅰ b (93%), level Ⅱ(50%) and level Ⅲ(36%). Conclusions The cervical lymph node metastasis rate is relatively high in OMM patients. The pathway of regional LN spread follows a regular pattern. The most frequently involved regions for clinical/pathological cN+ and regional failure are both level Ⅰ b-Ⅲ. Elective treatment including at least ipsilateral level Ⅰ b-Ⅲ ENT should be recommended for OMM patients with cN0.     

口腔黏膜恶性黑色素瘤颈部淋巴结转移规律及颈部预防治疗的价值

目的 分析口腔黏膜恶性黑色素瘤(OMM)颈部淋巴结转移规律以及颈部预防治疗的价值。方法 回顾性分析中国医学科学院肿瘤医院1984-2016年间收治的61例无远处转移的OMM病例的颈部淋巴结转移规律,颈部预防治疗疗效,失败模式及预后因素。结果 OMM颈部淋巴结转移率为55.7%。Ⅰ b区是最常见的颈部淋巴结转移区域,占颈部淋巴结转移患者的76%,其次是Ⅱ区和Ⅲ区。对于cN0患者,接受至少同侧Ⅰ b-Ⅲ区颈部预防治疗和未接受的5年无区域复发生存率分别为91.7%和52.4%(P=0.036),接受至少同侧Ⅰ b-Ⅲ区颈部预防治疗能将区域失败率由46%降至6%(P=0.035)。发生区域失败患者中93%发生在Ⅰ b区,50%发生在Ⅱ区,36%发生在Ⅲ区。结论 OMM颈部淋巴结转移率较高,淋巴结引流具有一定规律性,最常见转移和复发部位均为Ⅰ b-Ⅲ区。对于cN0的OMM,推荐至少包括同侧颈部Ⅰ b-Ⅲ区的预防治疗。     

Induction of apoptosis in oral cancer cells: agents and mechanisms for potential therapy and prevention

Oral cancer is one of the most disfiguring types of cancer, since the surgical removal of the tumor may result in facial distortion. Oral cancer is also known to exhibit "field cancerization", resulting in the development of a second primary tumor. Furthermore, the five-year survival rate of this disease has remained approximately 50% during the past 30 years. Prevention and early detection/treatment of oral cancer could significantly improve the quality of life for individuals at risk. Recently, the targeted elimination of oral squamous cell carcinoma cells by inducing apoptosis has emerged as a valued strategy to combat oral cancer. Studies utilizing a variety of chemical or biological interventions demonstrated promising results for induction of apoptosis in oral malignant cells. This review summarizes the results of a number of investigations focused specifically on induction of apoptosis in oral cancer cells by synthetic compounds and naturally occurring chemopreventive agents with apoptotic potential.     

Cisplatin and 4-hexylresorcinol synergise to decrease metastasis and increase survival rate in an oral mucosal melanoma xenograft model: a preliminary study

The present study was undertaken to examine the effects of cisplatin plus 4-hexylresorcinol (4-HR) combination therapy on oral mucosal melanoma (OMM) using cultured primary OMM cells in a tumour xenograft model. Cultured primary OMM cells were used for the MTT assay and DNA microarray. OMM cells were implanted into the submandibular glands of nude mice. The mice were then treated with cisplatin only or cisplatin plus 4-HR. Tumour size changes, survival rate and tumour metastasis were compared between the two groups by observation, micro-positron emission tomography (PET) and histological examination. In the MTT assay, the cisplatin plus 4-HR group showed significantly higher inhibition of OMM cell growth compared to the other groups (p?<?0.05). DNA microarray results showed significant inhibition of matrix metalloproteinase (MMP)-2 gene expression upon 4-HR application. The necropsy and micro-PET results showed that the mice from the cisplatin-only group had more distant metastases than the mice from the cisplatin plus 4-HR combination group (p?=?0.002). MMP-2 expression was lower in the primary tumours in the cisplatin plus 4-HR combination group than in the cisplatin-only group (p?<?0.001). Overall survival was longer in mice from the cisplatin plus 4-HR combination group than in the cisplatin-only group (p?=?0.049). In conclusion, the combined effect of cisplatin and 4-HR resulted in fewer metastases and longer survival than cisplatin-only treatment in the OMM xenograft model.     

NRAS and BRAF mutation frequency in primary oral mucosal melanoma

Oral mucosal melanoma (OMM) is a fatal sarcoma of unknown etiology. Histological morphology and genetic events are distinct from those of its cutaneous counterpart. Mutation and up-regulation of c-kit has been identified in OMM which may activate downstream molecules such as RAS and RAF. These molecules are involved in the mitogen-activated protein kinase (MAPK) pathway leading to tremendous cell proliferation and survival. NRAS and BRAF mutation and protein expression have been studied in other melanoma subtypes. The purpose of this study was to determine RAS protein expression and NRAS and BRAF mutation in 18 primary OMM cases using immunohistochemistry and mutation analysis. Results showed that RAS is intensely expressed in both in situ and invasive OMMs. However, NRAS mutation was only observed in 2/15 polymerase chain reaction (PCR) amplified cases both of which were silent mutations. On the other hand, BRAF missense mutations were observed only in 1/15 cases with PCR amplification. NRAS and BRAF mutations were independent from previously reported c-kit mutations. The classical V600E BRAF mutation was not found; instead a novel V600L was observed suggesting that the oncogenic event in OMM is different from that in skin melanoma. The low frequency of NRAS and BRAF mutations indicate that these genes are not common, but probable events in OMM pathogenesis, most likely independent of c-kit mutation.     

Laser surgery as a treatment for oral leukoplakia

Various treatment procedures for oral leukoplakia have been reported. However, after some treatments, oral leukoplakia show recurrence and/or malignant transformation, even following complete resection. Furthermore, patients with oral leukoplakia may develop new lesions in other oral cavity locations. Laser surgery for oral mucosal lesions has been reported to have many advantages, and it is widely used in the treatment of oral leukoplakia. In previous studies, recurrence and malignant transformation from the lesion have occasionally been observed following laser surgery. We reviewed the records of oral leukoplakia patients treated with laser surgery to assess its clinical usefulness. It has been reported that the rate of recurrence was 7.7–38.1%, while malignant transformation was 2.6–9% for oral leukoplakia treated with laser surgery. In the present study, there was 29.3% recurrence and 1.2% malignant transformation after laser surgery. This was similar to previous findings. This suggests that non-homogeneous leukoplakia on nonkeratinized epithelia, i.e. the tongue mucosa has a high risk for malignant transformation, so lesions should be excised after detecting abnormal epithelia using vital tissue staining. The wound healing process after laser surgery was satisfactory and no significant complications were observed. Management of oral leukoplakia prevents not only recurrence and malignant transformation, but also postoperative dysfunction: laser surgery is an excellent procedure that is able to overcome these problems.     

Spontaneous tumors in dogs and cats: Models for the study of cancer biology and treatment

Spontaneous tumors in dogs and cats are appropriate and valid model tumor systems available for testing cancer therapeutic agents or studying cancer biology. The pet population is a vastly underutilized resource of animals available for study. Dogs and cats develop spontaneous tumors with histopathologic and biologic behavior similar to tumors that occur in humans. The tumors with potential relevance for human cancer biology include osteosarcoma, mammary carcinoma, oral melanoma, oral squamous cell carcinoma, nasal tumors, lung carcinoma, soft tissue sarcomas, and malignant non-Hodgkin's lymphoma.Canine osteosarcoma is a malignant aggressive bone tumor with a 90% matastasis rate after surgical amputation. Its predictable metastatic rate and pattern and its relative resistance to chemotherapy make this tumor particularly attractive for studying anti-metastasis approaches. Canine and feline malignant mammary tumors are fairly common in middle-aged animals and have a metastatic pattern similar to that in women; that is, primarily to regional lymph nodes and lungs. Chemotherapy has been minimally effective, and these tumors may be better models for testing biological response modifiers.Oral tumors, especially melanomas, are the most common canine malignant tumor in the oral cavity. Metastasis is frequent, and the response to chemotherapy and radiation has been disappointing. This tumor can be treated with anti-metastatic approaches or biological response modifiers. Squamous cell carcinomas, especially in the gum, are excellent models for radiation therapy studies.Nasal carcinomas are commonly treated with radiation therapy. They tend to metastasize slowly, but have a high local recurrence rate. This tumor is suitable for studying radiation therapy approaches.Primary lung tumors and soft tissue sarcomas are excellent models for studying combined modality therapy such as surgery with chemotherapy or biological response modifiers.Finally, non-Hodgkin's lymphoma is a common neoplastic process seen in the dog. These tumors respond to combination chemotherapy and have great potential as a model for newer chemotherapeutic agents and biological response modifiers.This paper will further elaborate on the relative merits of each tumor type as a model for human cancer therapy and biology.     

Oral leukoplakia: a Clinicopathological review

Leukoplakia is the most common premalignant or potentially malignant lesion of the oral mucosa. It seems preferable to use the term leukoplakia as a clinical term only. When a biopsy is taken, the term leukoplakia should be replaced by the diagnosis obtained histologically. The annual percentage of malignant transformation varies in different parts of the world, probably as a result of differences in tobacco and dietary habits. Although epithelial dysplasia is an important predictive factor of malignant transformation, it should be realized that not all dysplastic lesions will become malignant. On the other hand non-dysplastic lesions may become malignant as well. In some parts of the world the tongue and the floor of the mouth can be considered to be high-risk sites with regard to malignant transformation of leukoplakia, while this does not have to be the case in other parts of the world. The cessation of tobacco habits, being the most common known aetiological factor of oral leukoplakia, has been shown to be an effective measure with regard to the incidence of leukoplakia and, thereby, the incidence of oral cancer as well. Screening for oral precancer may be indicated in individuals at risk.     

Alternative Therapeutic Approach in the Treatment of Oral Pyogenic Granuloma

Pyogenic granulomas (PGs) in the oral cavity present as an inflammatory hyperplasia usually caused by trauma, hormonal imbalance, chronic irritation, or as the response to a wide variety of drugs. PGs with atypical presentation and behavior may clinically mimic malignant tumors. Thus, histological examination is required to rule out cancer development. Lesions in the oral cavity have been described to be either an isolated entity or present in multiple forms and with multiple recurrences. Conservative surgical excision is the standard choice of treatment in almost every scenario. However, the severity of the lesions and the affected sites often challenge surgical treatment. In this report, we describe the clinical scenario of a recurrent PG, where surgical excision of the lesion was questioned. As an alternative, we describe a noninvasive approach with lesional steroid injections.Key Words: Gingiva, Pyogenic granuloma, Oral cavity, Steroids, Swelling     

Correlation between p53 gene mutations and circulating antibodies in betel- and tobacco-consuming North Indian population

Alterations in p53 tumour suppressor gene and its expression may be implicated in the pathogenesis of betel- and tobacco-related oral cancer. There is wide regional variation in betel- and tobacco-consuming habits in different parts of the Indian subcontinent. The purpose of this study was to determine the correlations between p53 gene mutations, protein accumulation and serum antibodies in oral precancer and cancer. We analysed 30 potentially malignant oral lesions (leukoplakia) and 30 oral squamous cell carcinomas (SCCs) from northern India because the betel quid-consuming habits are different from those prevalent in other regions of India. p53 mutations were analysed by polymerase chain reaction amplification of genomic DNA and direct sequencing, p53 protein accumulation by immunohistochemical analysis and circulating p53 antibodies by ELISA. p53 gene mutations, analysed within exons 5-9, were observed in five out of 30 (17%) potentially malignant oral lesions and seven out of 30 (23%) oral SCCs. All the mutations were base substitution mutations. Three missense and two nonsense mutations were observed in potentially malignant oral lesions, while six missense and one nonsense mutations were identified in oral SCCs. The probable hot spots for the mutations were identified at codons 126, 136 and 174, which have not been observed thus far. A good correlation was observed between p53 missense mutation, p53 antibodies and p53 protein accumulation in matched potentially malignant and malignant oral lesions. All the potentially malignant and cancerous lesions harbouring missense mutations showed accumulation of p53 protein and the majority of these patients showed circulating p53 antibodies suggesting that serological detection of p53 antibodies may serve as a surrogate marker for p53 alterations in oral lesions.     

Head and neck irradiation in childhood: increased risk of developing thyroid disease

A nodule of the thyroid in a patient with a history of prior irradiation to the head and neck area in childhood is more likely to be malignant than a nodule in the general population. Thirty-two of 144 such patients (22%) who came to surgery were found to have a carcinoma of the thyroid. A relative short-term (6 mo) trial with suppressive therapy with a thyroactive agent may be helpful in selecting out those nodules that may be malignant. Although considerable controversy continues to exist as to the proper surgical treatment, our current surgical management involves performing a total extracapsular thyroidectomy.     

Diagnosis of Oral Cancers by Targeting VPAC Receptors: Preliminary Report

Introduction: Oral cancer is a major health problem. The study of exfoliative cytology material helps in the differentiation of premalignant and malignant alterations of oral lesions. The objective of this study was to assess the feasibility of detecting oral cancer by targeting genomic VPAC (combined vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide) receptors expressed on malignant oral cancer cells. Patients & Methods: All patients with suspected oral cavity cancers/lesions formed the study group. The samples from the oral cavity lesion or suspicious area were collected with a cytology brush. The harvested material was examined for malignant cells by 1. the standard PAP stain and 2. targeting the VPAC receptors on the cell surface using a fluorescent microscope. Similarly, malignant cells were identified from cells shed in oral gargles. Results: A total of 60 patients with oral lesions were included in the study. The histopathological diagnosis was squamous cell carcinoma in 30 of these. The VPAC receptor positivity both on the brush cytology staining as well oral gargle staining was more sensitive than the brush cytology PAP staining. The accuracy of the various techniques was as follows, brush cytology PAP staining at 86.67%, brush cytology VPAC staining at 91.67% and oral gargle VPAC staining at 95%. Conclusions: This preliminary study validates our belief that malignant cells in the saliva can be identified by targeting the VPAC receptors. The test is simple, easy, non-invasive and reliable in the detection of oral cancers.     

Palliative management of malignant antro-pyloric strictures. Gastroenterostomy vs. endoscopic stenting. A randomized prospective trial

BACKGROUND: Gastroenterostomy was the palliative treatment of choice in patients with malignant unresectable gastric outlet obstruction. Palliative endoscopic treatment of malignant gastric outlet obstruction with endoluminal self-expanding metallic stents is nowadays a well-established procedure. PATIENTS AND METHODS: Eighteen patients referred for treatment with diagnosis of malignant strictures of the antro-pyloric tract presenting at an advanced unresectable stage. The patients were randomly assigned into two treatment groups (endoscopic vs. surgery) according to random-number tables. The length of procedure, morbidity and mortality rate, restoration of oral intake and gastric emptying at 8, 15 days and 3 months from treatment and hospital stay were assessed. RESULTS: Endoscopic group: The median length of procedure was 40 minutes. No death and one minor complication (11.1%) was reported. Mean time for oral intake was 2.1 days. Gastric emptying was satisfactory in 88.9% after 8 days and in 100% of patients after 15 days and 3 months. The median hospital stay was 3.1 days. Surgery group: The median length of the operation was 93 minutes. No mortality was reported. One patient (11.1%) developed anastomotic bleeding which required relaparotomy. Mean time for oral intake was 6.3 days. Gastric emptying was satisfactory in 66.7% of patients after 8 days, in 88.9% after 15 days and in 100% after 3 months. The median hospital stay was 10 days. CONCLUSION: There were no statistically significant differences between the 2 groups even with respect to morbidity, mortality, delayed gastric emptying and clinical outcomes at 3-month follow-up. Endoscopic stenting was significantly more effective with respect to operative time, restoration of oral intake and median hospitalization. Our results would suggest that endoscopically placed metal stents offer an effective alternative to surgical palliation in patients with unresectable malignant strictures.     

Long-term treatment outcome of oral premalignant lesions

The purpose of the present retrospective study was to learn the long-term outcome of oral premalignant lesions, leukoplakia and erythroplakia, with or without surgical intervention and to relate the outcome to factors supposed to be significant for malignant development including clinical type, demarcation, size, site, presence of epithelial dysplasia, smoking and surgery. A total of 269 lesions in 236 patients were included. Ninety-four lesions were surgically removed, 39 lesions (41%) being homogenous and 46 (49%) non-homogenous leukoplakias whereas nine (5%) were erythroplakias. Seventy-three percent of the lesions were associated with tobacco habits. The mean size of the lesions was 486 mm(2), and 71% of the lesions showed a degree of epithelial dysplasia. After excision the defects were closed primarily by transposition of mucosal flaps or they were covered by free mucosal or skin grafts. A few defects were left for secondary healing. After surgical treatment the patients were followed (mean 6.8 yrs, range 1.5-18.6 yrs), and new biopsies taken in case of recurrences. One hundred and seventy five lesions had no surgical intervention, 149 lesions (85%) being homogenous and 20 (11%) non-homogenous leukoplakias, and 6 (3%) erythroplakias. Eighty-one percent of the lesions were associated with smoking. The mean size of the lesions was 503 mm(2) and 21 of the lesions (12%) exhibited epithelial dysplasia. Sixty-five lesions were not biopsied. These patients were also followed (mean 5.5 yrs, range 1.1-20.2 yrs), and biopsies taken in case of changes indicative of malignant development. All patients were encouraged to quit smoking and candidal infections were treated. The possible role of different variables for malignant development was estimated by means of logistic regression analysis. Following surgical treatment 11 lesions (12%) developed carcinoma after a mean follow-up period of 7.5 yrs. Non-homogenous leukoplakia accounted for the highest frequency of malignant development, i.e. 20%, whereas 3% of the homogenous leukoplakias developed carcinomas. Surgically treated lesions with slight, moderate, severe and no epithelial dysplasia developed carcinoma with similar frequencies, i.e. 9-11%. Without surgical intervention 16% of the 175 lesions disappeared whereas seven lesions (4%) developed carcinoma after a mean observation period of 6.6 yrs. The highest frequency of malignant development (15%) was seen for non-homogenous leukoplakias, this figure being 3% for homogenous leukoplakias. Fourteen percent of lesions with slight epithelial dysplasia developed malignancy and 2% of lesions with no dysplasia showed malignant transformation. Logistic regression analysis showed a seven times increased risk (OR = 7.0) of non-homogenous leukoplakia for malignant development as compared with homogenous leukoplakia and a 5.4 times increased risk for malignant development for lesions with a size exceeding 200 mm(2). No other examined variables including presence of any degree of epithelial dysplasia, site, demarcation, smoking and surgical intervention were statistically significant factors for malignant development.