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Background: The overall incidence of colorectal cancer (CRC) in the United States has steadily decreased. However, the incidence of right-sided CRC remains unchanged for the past two decades. The serrated neoplastic pathway (sessile serrated adenoma/polyp, SSA/P) has been considered an important pathway of colorectal carcinogenesis, especially in the right-sided CRC. The aim of this study was to compare CRC anatomic distribution patterns in a 9-year interval in the general population before and after SSA/P was recognized and treated as a CRC precursor. Methods: The Miraca Life Sciences (MLS) pathology database was queried for all primary CRCs diagnosed between 8/3/2000 to 12/31/2005 (control group) and 1/1/2014 to 12/31/2014 (current group). Patients’ demographics, clinical information, and pathology reports were collected and analyzed. Results: A total of 5,602 patients with 5,685 CRCs were identified, of which 2,728 patients with 2,765 CRCs in current group and 2,874 patients with 2,920 CRCs in control group. Overall, there were no statistical differences in the current group in regards to the anatomical distribution patterns of CRCs in the proximal, right-sided, distal, and left-sided colon or genders compared with the control group (all P>0.05). Among the current group, there were 33 (1.2%) patients with 38 (1.4%) CRCs arising in SSA/Ps [serrated carcinomas (SCAs)], of which 33 (86.8%) were in the right-sided colon and 5 (13.2%) in the left-sided colon. Twenty-three (69.7%) SCA patients were female with significant advanced age than male (76.4 vs. 69.6, P=0.023). Conclusions: The overall current CRC anatomic distribution patterns after SSA/Ps managed as CRC precursor remain the same in the patients’ population from the community-based endoscopy centers in the U.S. It is suggested that the current SSA/P management might need to be further modified.

Background. Human papillomavirus (HPV) infections have been implicated in anogenital neoplasia in both sexes. In this study, the authors postulated that HPV infections induce squamous epithelium to become hyperproliferative and aneuploid. Methods. To test this hypothesis, formalin fixed, paraffin embedded tissues were analyzed for the presence of HPV by in situ hybridization. S-phase fraction and DNA content were evaluated by flow cytometry. Proliferative indices also were analyzed using an antibody to proliferating cell nuclear antigen (PCNA). Results. Human papillomavirus DNA was present in 48.1% of the carcinomas. All but one HPV-positive tumor contained HPV 16/18 DNA. The remaining tumor contained only HPV 6/11. No correlation was found between HPV status, patient age, or tumor differentiation. Thirty-three percent of tumors were aneuploid. Only two patients had aneuploid tumors that were HPV-negative ; these patients received preoperative radiotherapy. The average S-phase fraction was significantly higher (P < 0.01) in HPV-positive versus HPV-negative lesions. The PCNA index for HPV positive tumors was also significantly higher than that observed in negative tumors (p < 0.003). Conclusion. The presence of HPV in tumor cells is significantly associated with an increased proliferative rate and aneuploid status of tumors compared with HPV-negative tumors. These findings are consistent with the fact that viral proteins binding to tumor suppressor gene proteins can deregulate the cell cycle and lead to genomic instability.

Human immunodeficiency virus (HIV), commonly affects the liver and biliary tract, although the types of HIVassociated liver disorders have changed with the recent availability of highly active antiretroviral therapy (HAART) [1, 2]. Before the introduction HAART, mycobacterial infection of the liver was the most commonly diagnosed opportunistic infection. In one study that examined liver biopsies from 501 HIV-positive individuals in the USA, granulomatous hepatitis – usually due to mycobacteria – was the most common finding [3].

The p53 protein is implicated in the control of cell proliferation, differentiation, and death. As part of a study characterizing p53 alterations in colonic mucosa of patients with ulcerative colitis, we identified a unique pattern of basal p53 immunoreactivity.Tissue samples (n=180) from 42 ulcerative colitis patients were evaluated for p53 alterations by immunohistochemistry, loss of heterozygosity analysis, polymerase chain reaction-single-strand conformation polymorphism and direct sequencing. In addition, the expression of the p53- associated proteins p21waf1/cip1 and MDM2 was evaluated immunohistochemically. Three basic patterns of p53 immunoreactivity were observed: (i) isolated immunoreactive cells in the crypt bases; (ii) strongly positive cells confined to the basal half of the glands; and (iii) diffusely staining cells. The basal staining pattern was observed in both non-neoplastic tissues and in some areas of dysplasia, and was associated with normal expression of p21waf1/cip1 in all cases, and with p53 mutation in seven of 11 cases.The basal pattern of p53 expression is associated with mutation in the p53 gene, and appears to be an early change in a subgroup of ulcerative colitis patients. The significance of this pattern of immunoreactivity and the mechanism by which it develops are discussed.

Recently, a polymorphism in the hMSH2 DNA mismatch repair gene has been associated with the development of dysplasia in ulcerative colitis (UC) patients. This polymorphism is of interest because DNA mismatch repair defects result in alterations in microsatellite stability. The current study was designed to determine whether this hMSH2 polymorphism associates with the development of microsatellite instability and dysplasia in UC patients. The hMSH2 genotype of 96 UC patients was determined by direct DNA sequencing. In addition, we examined 363 samples of colonic mucosa from 93 of these UC patients for microsatellite mutation by polymerase chain reaction (PCR) at eight loci. Three cases had insufficient DNA for microsatellite instability studies. The hMSH2 polymorphism was identified in 13 of the 96 patients examined (13.5%). The polymorphism was observed in 7 of 46 patients with dysplasia (15.2%), and in 6 of 50 patients without dysplasia (12.0%). Microsatellite instability was identified in 35 tissue samples (25 regenerative, one indefinite for dysplasia, eight dysplasias, and one invasive carcinoma) from 26 patients. Two patients with microsatellite instability had the hMSH2 alteration. The 11 remaining patients had the hMSH2 polymorphism, but no evidence of microsatellite mutations with any of the markers tested. We were unable to confirm the previously reported findings that the specific germline hMSH2 alteration represents a marker for increased risk of dysplasia in patients with UC, nor is it responsible for the development of microsatellite instability in these patients.

An increased risk of colon cancer has been observed in individuals with long-standing ulcerative colitis (UC). In order to identify molecular genetic markers for the development of neoplasia in UC individuals, we isolated DNA from normal, regenerative, and dysplastic mucosa, as well as from colon carcinomas from UC patients, and evaluated it for the presence of mutations in microsatellite DNA sequences. DNAs isolated from regenerative mucosa displayed microsatellite mutation. These observations suggest that DNA mutation is an early event in the UC disease process.

To study the association of cervical cancer with human papillomaviral (HPV) infection in Uygur women at high risk for development of cervical cancer in Xinjiang.Cervical samples from 65 Uygur women with cervical cancer were collected. HPV DNA types 6/11, 16/18, 31/33/35 were studied by in-situ hybridization, and both consensus and type-specific primers for HPV types 6, 16 and 18 were used in 58 cases by polymerase chain reaction (PCR).HPV DNA was detected in 43.1%, 22.4% and 77.6% of specimens by the in-situ hybridization, PCR using L1 consensus primers and E6 type-specific primers, respectively.E6 type-specific PCR was more sensitive than L1 consesus PCR and in-situ hybridization detection of HPV DNA. These data supported the role of HPV DNA (particularly HPV 16) in the pathogenesis of cervical carcinoma in high risk women living in Xinjiang.

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon characterized by repeated episodes of inflammation and epithelial regeneration. Patients with long-standing UC have an increased risk for the development of dysplasia and subsequent colon carcinoma. Because dysplasia likely results from deregulatec cell proliferation, the authors examined Ki-67 immunoreactivity in tissues from UC patients to examine patterns of proliferation in neoplastic and nonneoplastic lesions.One hundred and eighty-seven specimens were obtained from 41 patients with UC and each lesion evaluated according to the International Classification for Dysplasia in Inflammatory Bowel Disease. All sections were stained with a monoclonal antibody directed against the proliferation marker Ki-67, and evaluated by three observers.Statistically significant differences in the pattern of Ki-67 immunoreactivity were observed between nonneoplastic and neoplastic lesions. In regenerative mucosa, Ki-67 immunoreactivity localized to the bases of the crypts, and the proliferative zone appeared expanded. In dysplasia, Ki-67 staining was prominent in cells in the superficial mucosa, as well as in cells at the crypt bases. In some dysplasias and all invasive carcinomas, Ki-67 staining was diffusely distributed throughout the crypts, suggesting complete deregulation of normal cell proliferation.Cell proliferation is markedly increased in patients with UC, and appears abnormally regulated in neoplastic lesions. Furthermore, Ki-67 staining helps delineate areas of dysplasia in cases in which the distinction from regenerative mucosa is unclear. The increased cell proliferation that occurs in patients with UC may predispose the mucosa to mutational events, thereby increasing cancer risk in these patients.

Human papillomavirus (HPV) DNA has been identified in esophageal carcinomas. However, the incidence of HPV varies significantly in different geographic locations. In the current study, neoplasms from two separate geographic regions were analyzed for the presence of HPV DNA:One hundred and ten esophageal squamous cell carcinomas, 83 from Beijing, China and 27 from Cincinnati, Ohio, were examined for the presence of HPV DNA: In situ hybridization and polymerase chain reaction (PCR) using both consensus primers for the HPV L1 gene and type specific primers for the E6 gene of HPV types 6, 16, and 18 were performed.In situ hybridization failed to demonstrate any HPV type (6, 11, 16, 18, 31, 33, or 35) in any tumor specimen. Likewise, PCR using consensus primers for the HPV L1 gene was negative in all samples. Three of the Chinese specimens (4.29%) were positive for HPV using E6 type specific primers. One tumor contained HPV type 6 DNA, whereas the other 2 contained HPV type 16 DNA. One Cincinnati tumor (4.35%) was positive for HPV 16 by type specific primer. None of the specimens contained HPV 18 DNA.The incidence of HPV DNA in esophageal carcinoma specimens from Beijing, China and Cincinnati, Ohio is similar. The incidence of HPV in tumors from Beijing is significantly lower than that reported for those from other regions of China where the incidence of esophageal cancer is higher. Thus, although HPV may play a role in esophageal carcinogenesis, this role may be more pronounced in those regions of the world with a high incidence of the disease, and may be less important in areas with moderate or low risks for esophageal cancer.

This article covers the basic pathologic features of gastric cancer. Gastric cancer is not a single entity but consists of several major tumor types. The risk factors for their development and their pathological features are discussed. The two major forms of gastric cancer, intestinal and diffuse, are described, as are the settings in which they arise. A number of prognostic factors exist for gastric cancer, including traditional pathologic variables such as histological staging grade and tumor type. Some more recent potential markers involve determinants of biologic behavior. The more frequently encountered types are covered, as well as their clinical implications. Finally, a scheme for standardized handling of gastric resection specimens is presented.

Anogenital malignancy has been increasing in incidence in recent decades. There is strong evidence in the literature suggesting that human papillomavirus (HPV) plays a role in the genesis of anogenital neoplasia. In addition, identification of oncogenic HPV types in anogenital carcinomas may have prognostic significance. The method used to detect HPV infection, however, affects the frequency with which viral DNA is identified. We examined tissues from 56 patients with anal squamous cell carcinoma for the presence of HPV DNA by in situ hybridization and polymerase chain reaction using both consensus and type-specific primers to determine if HPV detection varies when different methods are used. In situ hybridization identified the presence of HPV DNA in 41.1% of patients. Polymerase chain reaction using type-specific probes for the HPV E6 gene demonstrated HPV DNA in 46% of anal carcinomas, whereas polymerase chain reaction with consensus primers detected HPV DNA in only 16.3% of cases. All cases containing HPV type 6 were identified with L1 primers, whereas only three of 23 cases containing HPV type 16 were identified. The differences in the rate of HPV detection by the two polymerase chain reactions methods are most likely related to L1 gene loss in cells containing integrated HPV type 16.

Human papillomavirus (HPV) infections have been implicated in anogenital neoplasia in both sexes. In this study, the authors postulated that HPV infections induce squamous epithelium to become hyperproliferative and aneuploid.To test this hypothesis, formalin fixed, paraffin embedded tissues were analyzed for the presence of HPV by in situ hybridization. S-phase fraction and DNA content were evaluated by flow cytometry. Proliferative indices also were analyzed using an antibody to proliferating cell nuclear antigen (PCNA).Human papillomavirus DNA was present in 48.1% of the carcinomas. All but one HPV-positive tumor contained HPV 16/18 DNA. The remaining tumor contained only HPV 6/11. No correlation was found between HPV status, patient age, or tumor differentiation. Thirty-three percent of tumors were aneuploid. Only two patients had aneuploid tumors that were HPV-negative; these patients received preoperative radiotherapy. The average S-phase fraction was significantly higher (P0.01) in HPV-positive versus HPV-negative lesions. The PCNA index for HPV positive tumors was also significantly higher than that observed in negative tumors (p0.003).The presence of HPV in tumor cells is significantly associated with an increased proliferative rate and aneuploid status of tumors compared with HPV-negative tumors. These findings are consistent with the fact that viral proteins binding to tumor suppressor gene proteins can deregulate the cell cycle and lead to genomic instability.

Nuclear electric propulsion (NEP), compared with chemical and nuclear thermal propulsion (NTP), can effectively deliver the same mass to Mars using much less propellant, consequently requiring less mass delivered to Earth orbit. The lower thrust of NEP requires a spiral trajectory near planetary bodies, which significantly increases the travel time. Although the total travel time is long, the portion of the flight time spent during interplanetary transfer is shorter, because the vehicle is thrusting for much longer periods of time. This has led to the supposition that NEP, although very attractive for cargo missions, is not suitable for piloted missions to Mars. However, with the application of a hybrid approach to propulsion, the benefits of NEP can be utilized while drastically reducing the overall travel time required. Development of a dual‐mode system, which utilizes high‐thrust NTP to propel the spacecraft from the planetary gravitational influence and low‐thrust NEP to accelerate in interplanetary space, eliminates the spiral trajectory and results in a much faster transit time than could be obtained by either NEP or NTP alone. This results in a mission profile with a lower initial mass in low Earth orbit. In addition, the propulsion system would have the capability to provide electrical power for mission applications.

A fully integrated energy‐based approach to mission planning is needed if the Space Exploration Initiative (SEI) is to succeed. Such an approach would reduce the number of new systems and technologies requiring development. The resultant horizontal commonality of systems and hardware would reduce the direct economic impact of SEI and provide an economic benefit by greatly enhancing our international technical competitiveness through technology spin‐offs and through the resulting early return on investment. Integrated planning and close interagency cooperation must occur if the SEI is to achieve its goal of expanding the human presence into the solar system and be an affordable endeavor. An energy‐based mission planning approach gives each mission planner the needed power, yet preserves the individuality of mission requirements and objectives while reducing the concessions mission planners must make. This approach may even expand the mission options available and enhance mission activities.

The direction of the American space program, as defined by President Bush and the National Commission on Space, is to expand human presence into the solar system. Landing an American on Mars by the 50th anniversary of the Apollo 11 lunar landing is the goal. This challenge has produced a level of excitement among young Americans not seen for nearly three decades. The exploration and settlement of the space frontier will occupy the creative thoughts and energies of generations of Americans well into the next century. The return of Americans to the moon and beyond must be viewed as a national effort with strong public support if it is to become a reality. Key to making this an actuality is the mission approach selected. Developing a permanent presence in space requires a continual stepping outward from Earch in a logical progressive manner. If we seriously plan to go and to stay, then not only must we plan what we are to do and how we are to do it, we must address the logistic support infrastructure that will allow us to stay there once we arrive. A fully integrated approach to mission planning is needed if the Space exploration Initiative (SEI) is to be successful. Only in this way can a permanent human presence in space be sustained. An integrated infrastructure approach would reduce the number of new systems and technologies requiring development. The resultant horizontal commonality of systems and hardware would reduce the direct economic impact of SEI while an early return on investment through technology spin‐offs would be an economic benefit by greatly enhancing our international technical competitiveness. If the exploration, development, and colonization of space is to be affordable and acceptable, careful consideration must be given to such things as ‘‘return on investment’’ and ‘‘commercial product potential’’ of the technologies developed. This integrated approach will win the Congressional support needed to secure the financial backing necessary to assure that the President’s long‐range vision of human expansion into the solar system becomes a reality.