Risk factors for synchronous or metachronous tumor development after endoscopic resection of gastric neoplasms.

BACKGROUND: Despite many advantages, the development of synchronous or metachronous neoplasm is one of the main concerns with endoscopic resection. We aimed to clarify the independent risk factors for synchronous or metachronous gastric neoplasm. METHODS: We retrospectively reviewed the medical records of all patients who had undergone endoscopic resection for gastric high-grade dysplasia or early gastric cancer between April 2001 and February 2011. RESULTS: Among 971 subjects, 56 synchronous neoplasms and 42 metachronous neoplasms developed during 12-131 months of follow-up. In univariate analysis, age over 65 years, male gender, absence of Helicobacter pylori infection, lower third location, mucosal atrophy, and intestinal metaplasia were related to multiple gastric neoplasms. In multivariate analysis, absence of H. pylori infection [odds ratio (OR) 1.610, 95 % confidence interval (CI) 1.038-2.497)], lower third location (OR 1.704, 95 % CI 1.070-2.713), and intestinal metaplasia (OR 4.461, 95 % CI 1.382-14.401) were independent risk factors for multiple gastric neoplasms. For synchronous neoplasm, primary tumor size less than 1 cm was the only independent risk factor. For metachronous neoplasm, absence of H. pylori infection (OR 2.416, 95 % CI 1.214-4.810) was found to be the only independent risk factor. H. pylori eradication was found to be unrelated to the development of metachronous gastric neoplasms. CONCLUSIONS: For tumors located in the antrum and accompanied by intestinal metaplasia, meticulous endoscopic evaluation with close follow-up after endoscopic resection is recommended.

Association between Fusobacterium nucleatum and patient prognosis in metastatic colon cancer.

Recent evidence suggests that Fusobacterium nucleatum (Fn) is associated with the development and progression of colorectal cancer. We aimed to delineate the clinical implications of Fn in metastatic colon cancer. We performed quantitative polymerase chain reaction (qPCR) using DNA samples from synchronous metastatic colon cancer patients with either formalin-fixed paraffin-embedded (FFPE) archival primary site tumor samples or fresh colon tissues. Progression-free survival (PFS)1 and PFS2 were defined as PFS of first- and second-line palliative settings. qPCR for Fn was successfully performed using 112 samples (FFPE, n = 61; fresh tissue, n = 51). Forty-one and 68 patients had right-sided and left-sided colon cancer, respectively. Patients with Fn enriched right-sided colon cancers had shorter PFS1 (9.7 vs. 11.2 months) than the other subgroups (HR 3.54, 95% confidence interval [CI] 1.05-11.99; P = 0.04). Fn positive right-sided colon was also associated with shorter PFS2 (3.7 vs. 6.7 months; HR 2.34, 95% CI 0.69-7.91; P = 0.04). In the univariate analysis, PFS1 was affected by differentiation and Fn positive right-sided colon cancer. The multivariate analysis showed that differentiation (HR 2.68, 95% CI 1.40-5.14, P = 0.01) and Fn positive right-sided colon (HR 0.40, 95% CI 0.18-0.88, P = 0.02) were associated with PFS1. Fn enrichment in right sided colon was not associated with overall survival (OS). Fn enrichment has significantly worse prognosis in terms of PFS1 and PFS2 in patients with right-sided metastatic colon cancers.

Cancer patterns in nasopharyngeal carcinoma multiplex families in Taiwan.

Genetic and environmental factors have been implicated in the etiology of nasopharyngeal carcinoma (NPC), a tumor known to be closely associated with Epstein-Barr virus (EBV) infection. Studies have reported familial aggregation of NPC and have suggested the possible aggregation of NPC and other cancers. We evaluated familial aggregation of cancer in 358 high-risk families with two or more NPC cases enrolled in a NPC genetics study in Taiwan. Participants were linked to the Taiwan National Cancer Registry to identify incident cancers diagnosed after study enrollment (started in 1996) and before December 31, 2005, or death. In total, 2,870 individuals from the NPC Multiplex Family Study contributed 15,151 person-years over an average of 5.3 years of follow-up. One hundred ten incident cancers were identified. Multiple-primary standardized incidence ratios (MP-SIRs) were computed to evaluate overall cancer risk associated with infectious agents and with other tumors. The overall MP-SIR was 1.3 (95% CI: 1.1-1.6), which was largely explained by an excess in NPC (MP-SIR = 15; 95% CI: 10-23). Exclusion of incident NPC diagnoses led to an overall MP-SIR of 1.0 (95% CI: 0.83-1.3). Similarly, the observed excess risk of cancers associated with infectious agents (MP-SIR = 2.0; 95% CI: 1.5-2.6) was driven by the excess in NPC; exclusion of NPC cases led to a reduced MP-SIR that did not differ from 1.0. Analysis of the largest NPC multiplex family study to date confirms the presence of coaggregation of NPC within families in Taiwan but does not provide evidence for a broader familial syndrome involving NPC and other tumors.

A new type of human papillomavirus associated with oral focal epithelial hyperplasia.

Lesions from 10 patients suffering from focal epithelial hyperplasia (FEH) of the oral mucosa, including those of 4 Greenlandic Eskimos, were investigated for the presence of human papillomavirus (HPV) DNA sequences by blot hybridization experiments. Two distinct HPVs were detected in the DNA extracted from these lesions, and their genomes were molecularly cloned and characterized. One of these HPVs, detected in 4 patients, was found to be identical with HPV13, whose association with FEH was already known. The other one, detected in 6 patients, was only weakly related to HPV13 and to the other HPVs associated with lesions of the mucous membranes, and constituted a new HPV type, tentatively named HPV32. Lesions from other types of oral papillomas, obtained from 14 additional patients, were also analyzed. Human papillomavirus DNA sequences were detected in the DNA preparations extracted from 5 specimens: HPV6 DNA in a condyloma and in a papilloma, 2 as yet uncharacterized HPV DNAs in 2 papillomas, and HPV32 DNA in a papilloma which showed histologic similarities to FEH. Thus, it seems likely that FEH of the oral mucosa is a disease associated with 2 specific HPVs--HPV13 and HPV32.

Squamous cell carcinoma of the lung in a nonsmoking, nonirradiated patient with juvenile laryngotracheal papillomatosis. Evidence of human papillomavirus-11 DNA in both carcinoma and papillomas.

Malignant transformation of laryngeal juvenile papillomatosis most often occurs in patients with previous radiation therapy or smoking histories. We report the case of a 35-year-old, nonsmoking, nonirradiated man who developed squamous cell carcinoma of the lung with a 33-year history of laryngotracheal juvenile papillomatosis. Postmortem examination showed pulmonary cavitating papillomatosis and chest wall, vertebrae, and peribronchial lymph node involvement by tumor. Molecular studies (Southern blot, polymerase chain reaction) showed extrachromosomal human papillomavirus-11 (HPV11) DNA in both carcinoma and two laryngotracheal squamous cell papillomas, including one excised 20 years previously. Our observation is analogous to the previously reported cases of spontaneous (not related to irradiation or smoking) malignant transformation of juvenile laryngotracheal papillomatosis. Although HPV11 viral infection likely played a role in the malignant transformation, other less likely factors, such as drugs given for treatment and radiography performed throughout the illness, should be considered. Repeated pulmonary infections and the host immune response are additional considerations.

Human papillomavirus type 16 in bowenoid papulosis, intraoral papillomas, and squamous cell carcinoma of the tongue.

A 33-year-old immunosuppressed man developed bowenoid papulosis on his genitalia, velvety papules and plaques in his mouth, and invasive squamous cell carcinoma of his tongue. All three lesions were positive for human papillomavirus type 16 (HPV-16). The case provides further circumstantial evidence for a role of HPV-16 in epithelial neoplasia. The possible roles of a second HPV infection and of immunosuppression are also discussed.

Carcinoma ex-papilloma: histologic and virologic studies in whole-organ sections of the larynx.

A patient with adult-onset recurrent respiratory papillomatosis (RRP), initially diagnosed at age 28 years, was treated with radiation therapy due to the rapid regrowth of lesions. Following 6 years of apparently inhibited growth, papilloma recurred, and squamous carcinoma was diagnosed from a laryngeal biopsy. A spontaneous laryngocutaneous fistula developed, and laryngectomy was performed 14 years after irradiation. The laryngectomy specimen was snap frozen and representative tissues were stored frozen for viral studies. The larynx was whole-organ sectioned for histologic examinations; residual papilloma, as well as carcinoma, was observed. Koilocytosis and other virus-associated histologic changes were also found. HPV capsid antigen was present in papilloma, carcinoma, and clinically normal epithelium. HPV nucleic acids, conforming to HPV type 6, were present in keratin pearls and dysplastic cells. According to prior reports, carcinoma developing in preexisting papilloma arises from juvenile-onset RRP. Irradiated papilloma develop cancer at about 10 years, and the patients rarely survive. Nonirradiated cases develop cancer after 30 years, and some develop papilloma in the hypopharynx and trachea, but most patients survive. Irradiation is not an obligatory precursor for malignant transformation of cancer; however, until now there have been no case reports of favorable outcome after irradiation of papilloma.

Human papillomavirus identified by nucleic acid hybridization in concomitant nasal and genital papillomas.

Presence of human papillomavirus (HPV) as the etiologic agent in nearly all upper respiratory tract recurrent papillomas is well-established. The technique of nucleic acid hybridization now allows specific typing of HPV with a high degree of accuracy. This article reports a series of nine consecutive patients treated for nasal papillomas over the past 9 years. Eight of these patients had a personal history of genital papillomas (seven patients) or exposure (one patient). With the use of in situ hybridization and autoradiographic technique on paraffin-embedded tissue sections, HPV RNA type 6/11 was expressed in eight of nine nasal papillomas, and corresponding HPV types were also found in the two cases with which concurrent anogenital papilloma tissue was also available for analysis. Human papillomavirus RNA types 16 and 18 were not detected in any of the specimens. Signals of HPV messenger RNA type 6/11 were stronger in the fungiform areas than in the inverted areas of papillomas.

Human papillomavirus infection in papillomas and nondiseased respiratory sites of patients with recurrent respiratory papillomatosis using the polymerase chain reaction.

We examined human papillomavirus (HPV) infection in biopsy specimens and cellular scrapes that were taken from respiratory papillomas and six nondiseased sites from the respiratory tract of seven patients. Human papillomavirus was detected by polymerase chain reaction amplification, followed by DNA hybridization with probes for specific HPV types. All papillomas (100.0%, n = 5) were positive only for HPV type 6 or 11. In the nondiseased site specimens, 61.3% (19/31) of the specimens were positive, again only for HPV type 6 or 11. Among the nondiseased site specimens from the cervical trachea, intrathoracic trachea, and bronchus, 80% to 100% were HPV positive compared with only 25% to 50% of HPV infection detected in the nasopharynx, posterior tonsillar pillar, and aryepiglottic fold. These results support the tenet that HPV infection is present in clinically normal respiratory tract tissue and that the reservoir site of reinfection is more commonly in the lower airway. However, patients with upper-airway involvement were more likely to be diagnosed as having severe disease.

Inhibitory effect of intestinal bacteria on spontaneous multiple polyps in the small intestine of gnotobiotic BALB/c mice.

The incidence of multiple polyps and number of polyps per mouse were significantly lower in conventionalized (CVz), and chloroform-resistant bacteria (CRB)- or fusiform bacteria (FB)-associated mice than in germfree (GF) BALB/c mice. The concentration of fecal fatty acids was also higher in mice associated with either CRB or FB than in GF mice. The incidence of multiple polyps and number of polyps per mouse were significantly correlated with the concentration of fatty acids in the feces of CVz and CRB-GB mice. This study demonstrated that inhibition of multiple polyps in the small intestine of BALB/c mice was affected by the production of intestinal fatty acids.

Electron microscopy of intestinal adenomatosis in the blue fox, Alopex lagopus.

Scanning electron microscopy of adenomatous intestinal tissue in the blue fox revealed an irregular surface topography of the colon with increased diameter of the crypt openings and prominent ridge formations between crypts. The ileum showed villous atrophy and fusion. Microvilli were short and irregular. Small ulcerations of intestinal mucosa were seen. Freeze-fracture revealed curved intracellular organisms in the altered epithelial cells. Transmission electron microscopy showed features associated with immaturity and high protein synthesis. Filamentous extensions from the basolateral plasma membrane of altered epithelial cells sometimes penetrated the basal lamina. The cytoplasm contained numerous polyribosomes, nuclei had many indentations and large and irregular nucleoli. Intracellular bacteria, with morphology corresponding to Campylobacter spp. were found in the apical epithelial cytoplasm. No host-cell-derived membrane was seen to surround the bacteria.

C cell hyperplasia and carcinoma developing in sheep with experimentally-induced lymphosarcoma.

Two cases of C cell hyperplasia and one case of C cell carcinoma of the thyroid glands were bilaterally recognized in 11 sheep with experimentally-induced lymphosarcoma. The serum calcium concentration in the C cell carcinoma case was slightly increased above the normal concentration of around 9 mg per dl. Bilateral C cell hyperplasia also developed in the thyroid lobes of the C cell carcinoma case. Immunohistochemically, hyperplastic C cells and tumour cells were positive for calcitonin, calcitonin gene-related peptide, chromogranin A and neurone-specific enolase. No amyloid deposition nor multiple endocrine neoplasia was demonstrated in any of the cases. Ultrastructurally, many secretory granules were observed in the cytoplasm of neoplastic cells constituting the C cell carcinoma and in the hyperplastic C cells.

Triple cancers in the urogenital area of a patient with aplastic anemia.

Three epithelial neoplastic lesions, perineal Bowenoid papulosis, uterine cervical carcinoma, and bladder transitional cell carcinoma, which occurred in a mildly immunosuppressed patient who had aplastic anemia were studied for human papillomavirus (HPV) infection. In the Bowenoid papulosis, HPV type 16 DNA was identified by polymerase chain reaction (PCR) and by in situ hybridization (ISH). In contrast, in the uterine cervical carcinoma, HPV 16 was not detected, although possibly another unidentified type of HPV in the lesion was suggested by the ISH findings. In the bladder transitional cell carcinoma, neither papillomavirus genus-specific (PGS) antigen nor HPV DNA was found.

Human papillomavirus, type 16, DNA in multicentric anogenital neoplasia associated with idiopathic panmyelopathy. A case report.

A 27-year-old woman suffering from panmyelopathy for six years presented with a cervical low grade squamous intraepithelial lesion (SIL), vulvar high grade SIL and perianal squamous cell carcinoma with an inguinal metastasis. Southern blot hybridization with 32P-labeled human papillomavirus (HPV) DNA revealed HPV 16 DNA in varying copy numbers in material from the four locations. HPV 16 genomes persisting after surgery on the perianal tumor area were no longer detectable after betatron radiotherapy.

Human papillomavirus type 11 DNA in squamous cell carcinomas and pre-existing multiple laryngeal papillomas.

The case histories of 4 patients are presented, who developed an invasive squamous cell carcinoma from pre-existing multiple laryngeal papillomatosis (two juvenile-onset and two adult-onset) during a long latency period. A series of 14 routinely processed, paraffin-embedded biopsies obtained from these patients (including both benign papillomas and carcinomas) were analysed using in situ DNA-hybridization technique with 35S-labelled Human papillomavirus (HPV) DNA probes of HPV types, 6, 11, 16, 18 and 30. The lesions were also assessed by indirect immunoperoxidase (IP-PAP) technique to demonstrate the expression of HPV structural proteins. On light microscopy, morphology was consistent with HPV infection in all 14 biopsies. HPV antigen expression could not be demonstrated in any of the papillomas or carcinomas, however. HPV 11 DNA was present in high copy numbers in both the benign and malignant lesions of 2 patients, both presenting with the juvenile-onset disease. The present findings provide support for the role of HPV as an etiological agent in laryngeal squamous cell carcinoma, most probably acting synergistically with chemical or physical carcinogens (one patient received irradiation and 2 others were smokers). It seems clear that an infection by the 'low risk' HPV types 6 and 11 by no means excludes the possibility of developing a laryngeal malignancy, so far ascribed to the 'high risk' type HPV 16 only.

Vulvar neoplasia associated with other primary malignancies.

It is recognized that a significant number of patients with vulvar neoplasia have had previous, concurrent, or subsequent genital tract neoplasia. This has resulted in speculation that there may be a common etiology and, in particular, of the possibility of an infection element. Among 59 cases of vulvar cancer diagnosed at the National Taiwan University Hospital from 1976 to 1991, there were seven cases (12%) associated with other primary malignancies. Carcinoma of the cervix was the most frequent other primary cancer (6/7, 86%). The possible role of human papilloma virus infection in genital neoplasia is discussed.

HPV 16-positive bowenoid papulosis and squamous-cell carcinoma of the anus in an HIV-positive man.

A homosexual man in stage IV of HIV infection, who suffers from HPV 16-positive bowenoid papulosis of the anal region, is described. In one area the patient developed an HPV 16-positive squamous-cell carcinoma of the anus. Bowenoid papulosis represents a squamous-cell carcinoma in situ, and usually follows a benign clinical course. The possibility exists that immunocompromised individuals are at higher risk to develop cancer on the basis of bowenoid papulosis.

Juvenile and adult laryngeal papillomata: classification by in-situ hybridization for human papillomavirus.

We report the application of an in-situ hybridization technique for the demonstration of human papillomavirus (HPV) employing a biotin-streptavidin-polyalkaline phosphatase complex to paraffin processed tissue from a series of patients with laryngeal papillomata. All cases of juvenile papillomata, whether solitary or multiple, proved positive for HPV types 6 and/or type 11. However, only two cases of adult solitary papillomata and five cases of adult multiple papillomata were positive for HPV type 6 and/or type 11. All papillomata were negative for HPV types 16 and 18. Five specimens of normal vocal cord epithelium were uniformly negative for all four HPV types.