Gastric microbiome signature for predicting metachronous recurrence after endoscopic resection of gastric neoplasm.

BACKGROUND: Changes in gastric microbiome are associated with gastric carcinogenesis. Studies on the association between gastric mucosa-associated gastric microbiome (MAM) and metachronous gastric cancer are limited. This study aimed to identify gastric MAM as a predictive factor for metachronous recurrence following endoscopic resection of gastric neoplasms. METHOD: Microbiome analyses were conducted for 81 patients in a prospective cohort to investigate surrogate markers to predict metachronous recurrence. Gastric MAM in non-cancerous corporal biopsy specimens was evaluated using Illumina MiSeq platform targeting 16S ribosomal DNA. RESULTS: Over a median follow-up duration of 53.8 months, 16 metachronous gastric neoplasms developed. Baseline gastric MAM varied with Helicobacter pylori infection status, but was unaffected by initial pathologic diagnosis, presence of atrophic gastritis, intestinal metaplasia, or synchronous lesions. The group with metachronous recurrence did not exhibit distinct phylogenetic diversity compared with the group devoid of recurrence but showed significant difference in ß-diversity. The study population could be classified into two distinct gastrotypes based on baseline gastric MAM: gastrotype 1, Helicobacter-abundant; gastrotype 2: Akkermansia-abundant. Patients in gastrotype 2 showed higher risk of metachronous recurrence than gastrotype (Cox proportional hazard analysis, adjusted hazard ratio [95% confidence interval]: 5.10 [1.09-23.79]). CONCLUSIONS: Gastric cancer patients can be classified into two distinct gastrotype groups by their MAM profiles, which were associated with different risk of metachronous recurrence.

Effects of Helicobacter pylori eradication for metachronous gastric cancer prevention: a randomized controlled trial.

BACKGROUND AND AIMS: Whether eradication of Helicobacter pylori reduces the incidence of metachronous gastric cancer (MGC) is still debatable. We aimed to evaluate the long-term effect of H pylori eradication on the development of MGC after endoscopic gastric tumor resection. METHODS: We undertook an open-label, prospective, randomized controlled trial at a tertiary hospital in Seoul, Korea. Participants were recruited during April 2005 to February 2011 and followed until December 2016. We assigned 898 patients with H pylori infection treated with endoscopic resection (ER) for gastric dysplasia or early gastric cancer to receive (n =442) or not receive (n =456) eradication therapy using a random-number chart. Eradication group patients received oral omeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg twice daily for a week, whereas control group patients received no H pylori treatment. The primary outcome was the incidence of MGC (intention-to-treat analysis). RESULTS: The 877 patients who attended ≥1 follow-up examination (eradication group, 437; control group, 440) were analyzed. Median follow-up was 71.6 months (interquartile range, 42.1-90.0). MGC developed in 18 (4.1%) eradication and 36 (8.2%) control group patients (log-rank test, P = .01). In our yearly analysis, the effect of eradication showed a significant difference in 5 years after allocation (log-rank test, P = .02). The adjusted hazard ratio for the control group was 2.02 (95% CI, 1.14-3.56; P = .02), compared with the eradication group. CONCLUSIONS: H pylori eradication significantly reduces the incidence of MGC after ER of gastric tumors and should be considered for H pylori-positive gastric tumor patients treated with ER. (Clinical trial registration number: NCT01510730.).

Occurrence of metachronous basal cell carcinomas: a prognostic model.

BACKGROUND: A third of patients with a first basal cell carcinoma (BCC) will develop subsequent (metachronous) BCCs. OBJECTIVES: To study the prognostic effect of the number of previous BCC diagnosis dates a patient has experienced to derive a prediction model to assess the risk of metachronous BCCs that may inform individualized decision making on surveillance. METHODS: We considered participants of north-western European ancestry from a prospective population-based cohort study (Rotterdam Study). After linkage with the Dutch Pathology Registry, 1077 patients with a first BCC were included. Candidate predictors for metachronous BCCs included patient, lifestyle and tumour characteristics. The prognostic model was developed with Fine and Gray regression analysis to account for competing risk of death. We used bootstrapping to correct for within-patient correlation and statistical optimism in predictive performance. RESULTS: Second to fifth BCCs occurred in 293, 122, 58 and 36 patients, with median follow-up times of 3·0, 2·1, 1·7 and 1·8 years after the previous BCC, respectively. The risk of a new BCC was higher for patients with more metachronous BCCs. Having more than one BCC at diagnosis was another strong predictor of metachronous BCCs. Discriminative ability of the model was reasonable with an optimism-corrected c-index of 0·70 at 3 years. CONCLUSIONS: The number of previous BCC diagnosis dates was a strong prognostic factor and should be considered when predicting the risk of metachronous BCCs. When the number of previous BCC diagnosis dates is combined with other readily available characteristics into a prognostic model, patients at high risk of a new BCC can be identified.

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.

Infections among long-term survivors of childhood and adolescent cancer: a report from the Childhood Cancer Survivor Study.

BACKGROUND: Little is known about infections among adult survivors of childhood cancer. The authors report the occurrence of infections and risk factors for infections in a large cohort of survivors of childhood cancer. METHODS: The Childhood Cancer Survivor Study cohort was used to compare incidence rates of infections among 12,360 5-year survivors of childhood cancer with the rates of 4023 siblings. Infection-related mortality of survivors was compared with that of the US population. Demographic and treatment variables were analyzed using Poisson regression to determine the rate ratios (RRs) and corresponding 95% confidence intervals (CIs) for associations with infectious complications. RESULTS: Compared with the US population, survivors were at an increased risk of death from infectious causes (standardized mortality ratio [SMR], 4.2; 95% CI, 3.2-5.4), with the greatest risk observed among females (SMR, 3.2; 95% CI, 1.5-6.9) and among those who had been exposed to total body irradiation (SMR, 7.8; 95% CI, 1.8-33.0). Survivors also reported higher rates than siblings of overall infectious complications (RR, 1.3; 95% CI, 1.2-1.4) and higher rates of all categories of infection. CONCLUSIONS: Survivors of childhood cancer remain at elevated risk for developing infectious-related complications, and they have a higher risk of infection-related mortality years after therapy. Further investigation is needed to provide insight into the mechanisms for the observed excess risks.

Effect of Helicobacter pylori eradication on metachronous gastric cancer after endoscopic resection of gastric tumors: a meta-analysis.

BACKGROUND: Although endoscopic resection is widely accepted as the curative treatment modality for early gastric cancer, secondary metachronous cancer may subsequently develop in the residual gastric mucosa. The preventive effect of Helicobacter pylori eradication on the development of metachronous gastric cancer in such cases remains controversial. The aim of this study was to determine the effect of H. pylori eradication on the development of metachronous gastric cancer after endoscopic resection of gastric neoplasm by a meta-analysis of all relevant studies. MATERIALS AND METHODS: We performed a systematic literature search of PubMed, EMBASE, Google Scholar, and the Cochrane Library without language restrictions through March 31, 2014. We included all relevant articles, including prospective, observational, and retrospective studies. Pooled estimates (odds ratios with 95% confidence intervals) were obtained using a random effects model. RESULTS: Thirteen studies were considered to be appropriate for this meta-analysis. Compared with the control group, the pooled odds ratio in the eradication group was 0.42 (95% confidence interval, 0.32-0.56), and there was no heterogeneity across the studies (p = .853, I(2) = 0%). Subgroup analysis of three prospective trials also showed a lower incidence of metachronous cancer in the eradication group (odds ratio, 0.39; 95% confidence interval, 0.20-0.75). There was no evidence of publication bias in this meta-analysis. CONCLUSION: Helicobacter pylori eradication reduces the occurrence of metachronous gastric cancer in patients who have undergone endoscopic resection.

MALT lymphoma and Kaposi sarcoma in an HIV-negative patient.

A 77-year-old caucasian man presented on March 2005 with important epigastric pain without any other significant history of gastritis. Patient refers a history of cutaneous Kaposi's sarcoma (KS) treated since 1974 with surgical excision or oncovorin topical injection. He underwent endoscopic evaluation showing a 1.5-cm ulcerated area at the gastric angulus, associated with edematous and erythematous nodular mucosa (Fig. 1).

Preventing Metachronous Gastric Cancer after the Endoscopic Resection of Gastric Epithelial Neoplasia: Roles of Helicobacter pylori Eradication and Aspirin.

Whether Helicobacter pylori eradication actually reduces the risk of metachronous gastric cancer (MGC) development remains a controversial question. In this review, we addressed this topic by reviewing the results of clinical investigations and molecular pathological analyses of the roles of H. pylori eradication and aspirin administration in the prevention of MGC. In regard to the clinical studies, the results of meta-analyses and randomized control trials differ from those of retrospective studies: the former trials show that H. pylori eradication has a preventive effect on MGC, while the latter studies do not. This discrepancy may be at least partly attributable to differences in the follow-up periods: H. pylori eradication is more likely to prevent MGC over a long-term follow-up period (≥5 years) than over a short-term follow-up period. In addition, many studies have shown that aspirin may have an additive effect on MGC-risk reduction after H. pylori eradication has been achieved. Both H. pylori eradication and aspirin use induce molecular alterations in the atrophic gastritis mucosa but not in the intestinal metaplasia. Unfortunately, the molecular pathological analyses of these interventions have been limited by short follow-up periods. Therefore, a long-term prospective cohort is needed to clarify the changes in molecular events caused by these interventions.

Helicobacter pylori Infection following Endoscopic Resection of Early Gastric Cancer.

The role of Helicobacter pylori (H. pylori) infection in patients following endoscopic resection of early gastric cancer (EGC) remains unclear. This article presents a review of literature published in the past 15 years. H. pylori-mediated persistent methylation levels are associated with the development of metachronous gastric cancer. The methylation of certain specific genes can be used to identify patients with a high risk of metachronous gastric cancer even after H. pylori eradication. H. pylori eradication after endoscopic resection should be performed as early as possible for eradication success and prevention of metachronous precancerous lesions. Although whether the eradication of H. pylori could prevent the development of metachronous cancer after endoscopic resection is controversial, several meta-analyses concluded that H. pylori eradication could reduce the incidence of metachronous gastric cancer significantly. In addition, H. pylori eradication in gastric cancer survivors after endoscopic resection could reduce healthcare cost and save lives in a cost-effective way. Taken together, H. pylori eradication after endoscopic resection of EGC is recommended as prevention for metachronous precancerous lesions and metachronous gastric cancer.

Impact of Prior Malignancy on Survival Outcomes of Stage IV Pancreatic Adenocarcinoma: SEER-Based Cohort.

PURPOSE: Pancreatic cancer is one of the most fatal malignancies and the fourth leading cause of cancer-related mortality in the USA. Most clinical trials involving pancreatic adenocarcinoma (PAC) patients exclude subjects with a prior malignancy because of the possible effect of prior malignancies on survival. However, no data in the medical literature support this assumption. In this paper, we aim to study the impact of having a prior malignancy on the survival outcomes of stage IV PAC. METHODS: We used the surveillance, epidemiology, and end results database to review patients with stage IV PAC diagnosed between 1973 and 2014. We calculated overall and pancreatic cancer-specific survival of these patients using unadjusted Kaplan-Meier test and multivariable covariate-adjusted Cox models. RESULTS: We reviewed 66,874 stage IV PAC patients, of which 4942 had a prior malignancy. Kaplan-Meier and Cox models showed that a history of prior malignancy did not cause significant difference in overall survival (HR = 0.938, 95%CI = 0.880-1.000, p = .052). However, a prior malignancy was associated with a better pancreatic cancer-specific survival (HR = 0.855, 95% CI = 0.796-0.918, p < .001). CONCLUSION: A prior malignancy before stage IV PAC was not associated with worse survival outcomes. Researchers should take these results into consideration when including/excluding patients to improve the generalizability and accuracy of their results.

Characteristics of Primary and Metachronous Gastric Cancers Discovered after Helicobacter pylori Eradication: A Multicenter Propensity Score-Matched Study.

BACKGROUND/AIMS: Gastric cancers develop even after successful Helicobacter pylori eradication. We aimed to clarify the characteristics of early gastric cancers discovered after H. pylori eradication. METHODS: A total of 1,053 patients with early gastric cancer treated by endoscopic submucosal dissection were included. After matching the propensity score, we retrospectively investigated the clinicopathological features of 192 patients, including 96 patients who had undergone successful H. pylori eradication (Hp-eradicated group) and 96 patients who had active H. pylori infection (Hp-positive group). RESULTS: In the Hp-eradicated group, early gastric cancers were discovered 1 to 15 years (median, 4.1 years) after H. pylori eradication. Compared with Hp-positive patients, Hp-eradicated patients showed a more frequently depressed configuration (81% vs 53%, respectively, p<0.0001) and a higher trend toward submucosal invasion (18% vs 8%, respectively, p=0.051). A multivariable analysis revealed the macroscopic depressed type to be characteristics of early gastric cancers after H. pylori eradication. Among patients in the Hp-eradicated group, metachronous cancers showed less frequent depressed lesions (68% vs 84%, respectively, p=0.049) and smaller tumor sizes (median, 11 mm vs 14 mm, respectively, p=0.014) than primary cancers. CONCLUSIONS: Early gastric cancers after H. pylori eradication are characterized by a depressed configuration. Careful follow-up endoscopies are necessary after H. pylori eradication.

Mycosis fungoides with coccidioidomycosis.

Mycosis fungoides is an indolent, epidermotropic, cutaneous T-cell lymphoma of helper/memory T cells that presents as heterogeneous, papulosquamous patches, plaques, and tumors. We present a patient with mycosis fungoides and infection with Coccidioides immitis of the skin, which has not been previously reported.

Helicobacter pylori Eradication Prevents Metachronous Gastric Neoplasms after Endoscopic Resection of Gastric Dysplasia.

PURPOSE: There is insufficient data about the role of eradication of H. pylori after endoscopic resection (ER) for gastric dysplasia. The aim was to investigate the benefit of H. pylori eradication after ER in patients with gastric dysplasia to prevent metachronous gastric neoplasms. MATERIALS AND METHODS: We retrospectively reviewed 1872 patients who underwent ER of gastric dysplasia. We excluded patients with a follow-up period of <2 years or who had not undergone tests for active H. pylori infection. A total of 282 patients were enrolled. The patients were categorized into those without active H. pylori infection (H. pylori-negative group, n = 124), those who successfully underwent H. pylori eradication (eradicated group, n = 122), and those who failed or did not undergo H. pylori eradication (persistent group, n = 36). RESULTS: Metachronous recurrence was diagnosed in 36 patients, including 19 in the H. pylori-negative group, 10 in the eradicated group, and 7 in the persistent group. The cumulative incidence of metachronous recurrence was significantly lower in the H. pylori-eradicated group in comparison with either of the H. pylori-persistent (non-eradicated or failed) groups (p = 0.039). Similarly, the incidence of metachronous recurrence was significantly lower in the H. pylori-eradicated group compared with the H. pylori-negative group (p = 0.041). CONCLUSION: Successful H. pylori eradication may reduce the development of metachronous gastric neoplasms after ER in patients with gastric dysplasia.

Second genital primary squamous neoplasms in vulvar carcinoma: viral and histopathologic correlates.

OBJECTIVE: To determine whether vulvar squamous cell carcinomas associated with certain morphologic features and/or human papillomavirus (HPV) nucleic acids were more likely to be associated with other genital primary squamous neoplasms. METHODS: We surveyed 169 invasive squamous cell carcinomas of the vulva and correlated associated vulvar intraepithelial neoplasia (VIN), invasive growth patterns resembling VIN (intraepithelial-like or basaloid), and the presence of HPV nucleic acids by in situ hybridization with a history of a second primary squamous neoplasm of the genital tract. RESULTS: Twenty-two patients (13%) had a history of a second primary. An intraepithelial growth pattern or an associated VIN correlated significantly with HPV, at P = .0005 and P = .007, respectively, and with a second primary, at P = .077 and P = .009, respectively. When HPV-positive, the same histologic variables correlated with a second primary at P = .099 and P = .25, respectively. Compared with cases lacking both these histologic features and HPV, they correlated with multifocal disease at P = .01 and P = .003. CONCLUSIONS: The findings of HPV nucleic acids, tumor growth patterns, and associated VIN are interrelated and confer risk of other genital primary neoplasms in women with vulvar carcinoma. This supports the concept that subsets of vulvar carcinoma may be distinguished not only by morphology and HPV DNA, but also by a distinctly different risk of a second genital primary neoplasm.

Gastric tube cancer after esophagectomy for esophageal squamous cell cancer and its relevance to Helicobacter pylori.

BACKGROUND/AIMS: Improvement of surgical skills and postoperative management has allowed longer postoperative survival for patients with esophageal cancer, among those some develop gastric tube cancer. We analyzed the characteristics of such patients we encountered as well as of reported cases of Japan. Furthermore, we investigated if Helicobacter pylori plays a role in carcinogenesis of the gastric tube in our cases. METHODOLOGY: We analyzed the clinicopathological features of our 8 patients with gastric tube cancer from 1991 to 2000 as well as the status of H. pylori on the gastric tube biopsy. Moreover the features of gastric tube cancer from domestic reported cases up to the year 2000 were also summarized. RESULTS: According to the review of our cases, the frequent tumor location was the distal portion of the gastric tube. Seventy-eight percent were detected in early stage during postoperative follow-up, 71% of those were treated endoscopically. No cases showed H. pylori positivity. From the previous domestic reports, early cancer is increasing as the screening becomes popular. Type 0-IIa and 0-IIc were the most popular images for early cancer, while type 2 and 3 were for advanced cancer. CONCLUSIONS: The carcinogenesis of the gastric tube seemed not to be related to H. pylori. Subdermal route of reconstruction at esophagectomy seemed superior regarding early recognition of gastric tube cancer and easiness of its treatment.

Tracheobronchial involvement of laryngeal papillomatosis at onset.

A case of adult onset laryngeal papillomas with tracheal and bronchial involvement present at onset is presented. The presence of human papilloma virus (HPV) DNA type 6/11 is demonstrated by in situ hybridization.

Efficacy of Helicobacter pylori eradication for the prevention of metachronous gastric cancer after endoscopic resection for early gastric cancer.

Helicobacter pylori (H. pylori) plays an important role in gastric carcinogenesis, as the majority of gastric cancers develop from H. pylori-infected gastric mucosa. The rate of early gastric cancer diagnosis has increased in Japan and Korea, where H. pylori infection and gastric cancer are highly prevalent. Early intestinal-type gastric cancer without concomitant lymph node metastasis is usually treated by endoscopic resection. Secondary metachronous gastric cancers often develop because atrophic mucosa left untreated after endoscopic treatment confers a high risk of gastric cancer. The efficacy of H. pylori eradication for the prevention of metachronous gastric cancer remains controversial. However, in patients who undergo endoscopic resection of early gastric cancer, H. pylori eradication is recommended to suppress or delay metachronous gastric cancer. Careful and regularly scheduled endoscopy should be performed to detect minute metachronous gastric cancer after endoscopic resection.

Second primary cancer arising from the neovulva following reconstruction with myocutaneous flaps.

Myocutaneous flaps have been used for vulvar reconstruction following radical vulvectomy. For over 15 years the most common complications related to these flaps are sloughing of the skin and donor site wound infection. A new malignancy arising from the skin of the neovulva is an unusual occurrence. Two cases are presented. The skin of the neovulva may be exposed to the same neoplastic carcinogens that caused the initial lesion. In both patients, the polymerase chain reaction method failed to detect the presence of human papillomavirus DNA in either the initial lesion or the recurrent cancer.

Localized, late-onset, high-grade lymphoma following bone marrow transplantation: response to combination chemotherapy.

Non-Hodgkin's lymphoma is the commonest secondary cancer following bone marrow transplantation (BMT). We report the case of a 42-year-old man who developed a laryngeal high-grade B-cell lymphoma 5 years following a matched T depleted BMT for CML. Polymerase chain reaction (PCR) analysis using the microsatellite marker Cyp 19 demonstrated the donor origin of involved tissue. Epstein-Barr virus (EBV) genomic sequences were identified by PCR. Although EBV related B-cell lymphoproliferative disorders (BLPD) post BMT are difficult to treat, there was a complete remission in this patient following three courses of chemotherapy (CHOP) administered with G-CSF. This case of late-onset BLPD appears clinically distinct from the well-defined, aggressive, early post-transplant BLPD.