Development Of Metachronous Cancer Research Articles

Long- vs short-segment Barrett's esophagus-derived adenocarcinoma: clinical features and outcomes of endoscopic submucosal dissection.

The incidence of Barrett's esophageal adenocarcinoma (BEA) is increasing, and endoscopic submucosal dissection (ESD) has been frequently performed for its treatment. However, the differences between the characteristics and ESD outcomes between short- and long-segment BEA (SSBEA and LSBEA, respectively) are unclear. We compared the clinicopathological characteristics and short- and long-term outcomes of ESD between both groups. We retrospectively reviewed 155 superficial BEAs (106 SSBEAs and 49 LSBEAs) treated with ESD in 139 patients and examined their clinicopathological features and ESD outcomes. SSBEA and LSBEA were classified based on whether the maximum length of the background mucosa of BEA was < 3cm or ≥ 3cm, respectively. Compared with SSBEA, LSBEA showed significantly higher proportions of cases with the macroscopically flat type (36.7% vs. 5.7%, p < 0.001), left wall location (38.8% vs. 11.3%, p < 0.001), over half of the tumor circumference (20.4% vs. 1.9%, p < 0.001), and synchronous lesions (17.6% vs. 0%, p < 0.001). Compared with SSBEA, regarding ESD outcomes, LSBEA showed significantly longer resection duration (91.0min vs. 60.5min, p < 0.001); a lower proportion of submucosal invasion (14.3% vs. 29.2%, p = 0.047), horizontal margin negativity (79.6% vs. 94.3%, p = 0.0089), and R0 resection (69.4% vs. 86.8%, p = 0.024); and a higher proportion of post-procedural stenosis cases (10.9% vs. 1.9%, p = 0.027). The 5-year cumulative incidence of metachronous cancer in patients without additional treatment was significantly higher for LSBEA than for SSBEA (25.0% vs. 0%, p < 0.001). The clinicopathological features of LSBEA and SSBEA and their treatment outcomes differed in many aspects. As LSBEAs are difficult to diagnose and treat and show a high risk of metachronous cancer development, careful ESD and follow-up or eradication of the remaining BE may be required.

Segmental Colectomy in Ulcerative Colitis.

Segmental colectomy in ulcerative colitis is performed in select patients who may be at increased risk for postoperative morbidity. To identify patients with ulcerative colitis who underwent segmental colectomy and assess their postoperative and long-term outcomes. Retrospective case series. A tertiary care IBD center. Patients with ulcerative colitis who underwent surgery between 1995 and 2022. Segmental colectomy. Postoperative complications, early and late colitis, metachronous cancer development, completion proctocolectomy-free survival rates, and stoma at follow-up. Fifty-five patients were included (20 [36.4%] women; age 67.8 (57.4-77.1) years at surgery; BMI 27.7 (24.2-31.1) kg/m 2 ; median follow-up 37.3 months). Thirty-two patients (58.2%) had ASA score of 3, 48 (87.3%) had at least 1 comorbidity, and 48 (87.3%) had Mayo endoscopic subscores of 0 to 1. Patients underwent right hemicolectomy (n = 28; 50.9%), sigmoidectomy (n = 17; 30.9%), left hemicolectomy (6; 10.9%), low anterior resection (n = 2; 3.6%), or a nonanatomic resection (n = 2; 3.6%) for endoscopically unresectable polyps (n = 21; 38.2%), colorectal cancer (n = 15; 27.3%), symptomatic diverticular disease (n = 13; 23.6%), and stricture (n = 6; 10.9%). Postoperative complications occurred in 16 patients (29.1%; n = 7 [12.7%] Clavien-Dindo class III-V). Early and late postoperative colitis rates were 9.1% and 14.5%, respectively. Metachronous cancer developed in 1 patient. Four patients (7.3%) underwent subsequent completion proctocolectomy with ileostomy. Six patients (10.9%) had a stoma at follow-up. Two- and 5-year completion proctocolectomy-free survival rates were 91% and 88%, respectively. Retrospective study and small sample size. Segmental colectomy in ulcerative colitis is associated with low postoperative complication rates, symptomatic early colitis and late colitis rates, metachronous cancer development, and the need for subsequent completion proctocolectomy. Therefore, it can be safe to consider select patients, such as the elderly with quiescent colitis and other indications, for colectomy. See Video Abstract . ANTECEDENTES:La colectomía segmentaria en la colitis ulcerosa se realiza en pacientes seleccionados que pueden tener un mayor riesgo de morbilidad posoperatoria.OBJETIVO:Identificar pacientes con colitis ulcerosa sometidos a colectomía segmentaria y evaluar sus resultados postoperatorios y a largo plazo.DISEÑO:Serie de casos retrospectivos.AMBIENTE:Un centro de atención terciaria para enfermedades inflamatorias intestinales.PACIENTES:Pacientes con colitis ulcerosa intervenidos quirúrgicamente entre 1995 y 2022.INTERVENCIÓN(S):Colectomía segmentaria.PRINCIPALES MEDIDAS DE RESULTADO:Complicaciones postoperatorias, colitis temprana y tardía, desarrollo de cáncer metacrónico, tasas de supervivencia sin proctocolectomía completa y estoma en el seguimiento.RESULTADOS:Se incluyeron cincuenta y cinco pacientes [20 (36,4%) mujeres; 67,8 (57,4-77,1) años de edad al momento de la cirugía; índice de masa corporal 27,7 (24,2-31,1) kg/m2; mediana de seguimiento 37,3 meses]. La puntuación ASA fue III en 32 (58,2%) pacientes, 48 (87,3%) tenían al menos una comorbilidad y 48 (87,3%) tenían una subpuntuación endoscópica de Mayo de 0-1. Los pacientes fueron sometidos a hemicolectomía derecha (28, 50,9%), sigmoidectomía (17, 30,9%), hemicolectomía izquierda (6, 10,9%), resección anterior baja (2, 3,6%) o resección no anatómica (2, 3,6%) para; pólipos irresecables endoscópicamente (21, 38,2%), cáncer colorrectal (15, 27,3%), enfermedad diverticular sintomática (13, 23,6%) y estenosis (6, 10,9%). Se produjeron complicaciones postoperatorias en 16 (29,1%) pacientes [7 (12,7%) Clavien-Dindo Clase III-V]. Las tasas de colitis posoperatoria temprana y tardía fueron del 9,1% y el 14,5%, respectivamente. Un paciente desarrolló cáncer metacrónico. A 4 (7,3%) pacientes se les realizó posteriormente proctocolectomía completa con ileostomía. Seis (10,9%) pacientes tenían estoma en el seguimiento. Las tasas de supervivencia sin proctocolectomía completa a dos y cinco años fueron del 91% y 88%, respectivamente.LIMITACIONES:Estudio retrospectivo, tamaño de muestra pequeño.CONCLUSIONES:La colectomía segmentaria en la colitis ulcerosa se asocia con bajas tasas de complicaciones postoperatorias, tasas de colitis sintomática temprana y tasas de colitis tardía, desarrollo de cáncer metacrónico y la necesidad de una posterior proctocolectomía completa. Por lo tanto, puede ser seguro considerar pacientes seleccionados, como los ancianos con colitis inactiva y otras indicaciones de colectomía. (Traducción-Dr. Yolanda Colorado ).

Impact of endoscopic surveillance on mortality of metachronous esophageal and head and neck cancer after esophageal endoscopic resection.

As more superficial esophageal cancer (EC) patients are being treated with endoscopic resection (ER), it is important to understand the outcomes, including survival data, of patients who develop metachronous EC and head and neck cancer (HNC). We aimed to evaluate the long-term surveillance and survival outcomes of metachronous EC and HNC after esophageal ER. This study included 627 patients who underwent ER of superficial esophageal squamous cell carcinoma from 2008 to 2016 and were generally followed by annual or biannual esophagogastroduodenoscopy up to 2019 at Osaka International Cancer Institute. Data on metachronous cancer development and causes of death were collected from an integrated database of hospital-based cancer registry and Vital Statistics of Japan. During a median (range) follow-up period of 67.4 (3.8-142.7) months, 230 patients (36.7%) developed 500 metachronous ECs and 126 patients (20.1%) developed 239 metachronous HNCs, post-ER of index EC. The 3-year, 5-year, and 7-year cumulative incidences were 25.8%, 36.0%, and 43.6% for metachronous EC and 10.9%, 16.0%, and 26.9% for metachronous HNC, respectively. No patients died of metachronous EC, and only seven patients (1.1%) died of metachronous HNC. The 3-year, 5-year, and 7-year disease-specific survival rates were 99.8%, 99.6%, and 98.6%, respectively. The incidences of metachronous EC and HNC increase with time over 5years after esophageal ER; therefore, surveillance endoscopy should be continued over 5years. Endoscopic surveillance is useful for survivors after esophageal ER given the high incidence and extremely low mortality of metachronous EC and HNC.

Study of the level of tumor markers and mutations in the BRCA1/2 genes in breast cancer patients with metachronous tumors.

e12563 Background: Primary multiple malignant tumors are more common in women with breast cancer (BC). However, the difference in the frequency of mutations in the BRCA1/2 genes in metachronous BC tumors has not been fully studied, and there are also conflicting data on the increase in the level of specific tumor markers in this category of patients. Methods: The survey included 58 patients with BC with II-III clinical stages of the disease, of which metachronous tumors in terms of 6 months or more were found in 26 (44.8%) patients, among them metachronous cancer of the second breast - in 14 (53 .8%), cancer of the body of the uterus - in 7 (26.9%) and ovarian cancer - in 5 (19.2%) patients. In the control group of 32 (55.2%) patients with initially diagnosed BC, with the same stages of the disease. Tumor markers were determined in the peripheral venous blood of patients using reagent kits for ELISA analysis produced in Russia. The study of mutations in the BRCA1/2 genes was performed using sequencing on the Illumina MiSeq platform in tumor samples from waxed histological blocks. Library sequencing was performed using MiSeq Reagent Kit v2. Results: ELISA analysis of the level of tumor markers in patients with BC showed that with the development of metachronous cancer, the studied markers were more common than in the control group. In patients with metachronous tumors, elevated levels of CA-125 occurred in 10 (38.5%) patients, CA-15-3 - in 8 (30.8%), CA-19-9 - in 4 (15.4%), AFP - in 5 (19.2%), CEA - in 6 (23.1%). In the control group, CA-125 was found in 6 (18.8%) patients, CA-15-3 - in 5 (15.6%), CA-19-9 - in 2 (6.3%), AFP - in 1 (3.1%), CEA - in 2 (6.3%). Excess levels significant for diagnosis were observed for CA-125 and CA-15-3 in both groups of patients, but in the group of patients with BC with metachronous tumors, these figures were approximately 2 times higher. In the rest of the patients, the oncomarkers under consideration did not reach values significant for diagnosis. The total incidence of patients with clinically significant germline variants in the BRCA1/2 genes in the control group was 5 (15.6%), of which there were predominantly patients with an increased frequency in the population (5382insC, 4154del4, C61G). The total incidence of BC patients with metachronous tumors with germline and somatic variants in the BRCA1/2 genes was 16 (61.5%), with an increased frequency in the same population, mainly in patients with germline mutations. Conclusions: Dynamic study of the level of tumor markers CA-125 and CA-15-3 and CA-19-9 may be useful in the preventive examination of patients with a history of BC as an early diagnosis of the development of metachronous tumors in this category of patients. The most important diagnostic unfavorable factor in the development of metachronous tumors in the examined BC patients was germline mutations in the BRCA1/2 genes.

The necessity of intensive surveillance colonoscopy for patients with a remaining right colon after resection of colorectal cancer: a retrospective cohort study.

To clarify how often postoperative surveillance colonoscopy should be undertaken based on the risk factors for the development of metachronous cancer (MC) and advanced adenoma (AA) after surgery for colorectal cancer. We collected data of consecutive patients who underwent curative resection for primary colorectal cancer between 2005 and 2012, with preoperative colonoscopy and surveillance colonoscopy at 1year after surgery (406 patients, mean age: 69years, 59% male). The detection rates of AA (with villous features, > 10mm or high-grade dysplasia) and MC by surveillance colonoscopy were the primary outcomes. At 5years, colonoscopy was performed as postoperative surveillance an average of 3.2 times. AA and MC were detected in 57 (14.0%) and 18 patients (4.4%), respectively. Both lesions were more common in the right colon (n = 43) than in the left colon (n = 28). The detection rate did not differ to a statistically significant extent according to the number of colonoscopies performed for surveillance (p = 0.21). However, after left-sided colectomy, both types of lesions were more commonly detected in those who received ≥ 3 colonoscopies than in those with one or two colonoscopies (p = 0.04). A remaining right colon after left-sided colectomy was associated with a higher risk of developing AA and MC. Physicians should consider performing surveillance colonoscopy more frequently if the right colon remains after surgery.

Abstract 2185: Genetic analysis of metachronous pancreatic cancers

Abstract [Introduction] Early detection of pancreatic cancer is a key to curable surgery. However, many patients are diagnosed with an advanced disease and even in those who have an early stage tumor successfully resected, the development of metachronous cancer in the residual pancreas prevents a long-term survival. Thus, it is important to control metachronous tumors to improve clinical outcomes, whose pathogenesis, however, is poorly understood. In this study, we aimed to reveal the origin of metachronous tumors using an unbiased detection of somatic mutations in primary and metachronous tumors as well as adjacent precursor lesions. [Methods] Serially obtained formalin-fixed paraffin-embedded surgical specimens from 12 patients who had undergone curative surgery for an early-stage pancreatic cancer were subjected to laser microdissection for enrichment of tumor and precancerous components, from which DNA was extracted and analyzed for somatic mutations using whole-exome sequencing (WES) with matched normal DNA. Based on shared and private mutations across different samples, we interrogated history of clonal evolution of these lesions. [Results] Pathology for resected primary cancer was margin-negative in all patients. The median interval between the initial and second surgery was 34.6 months (12 - 65.1 months). Paired primary and metachronous cancers were analyzed in all 12 patients. An additional 5 pancreatic intraepithelial neoplasia (PanIN) samples were also analyzed in one case. We identified a median of 86 (range: 40-145) and 20 (14-42) somatic mutations using WES in cancers and PanIN lesions, respectively. None of the patients have known pathogenic germline variants. All samples had one or more driver mutations. In each patient, all driver mutations and many passenger mutations were shared between primary and metachronous cancer samples, suggesting that those metachronous tumors are evolutionally closely related to the primary cancer, despite long years before recurrence. Negative pathology of the margins at the initial surgery suggested that those metachronous lesions originated from distant dissemination or metastasis, rather than contiguous, intraductal invasion. By contrast, none of the mutations other than hotspot KRAS mutations were shared between precursor lesions and cancer samples. Despite multiple independent clones in the precancerous lesion, all metachronous tumors originated from the primary lesions in this study. [Conclusions] Our study suggests that even early pancreatic cancer might be disseminated within the pancreas and give rise to metachronous cancers, suggesting the importance of close monitoring of recurrence in the residual pancreas. Citation Format: Tomonori Hirano, Nobuyuki Kakiuchi, Yasuhide Takeuchi, Tomomi Nishimura, Toshihiko Masui, Sachiko Minamiguhi, Hironori Haga, Kenichi Chiba, Hiroko Tanaka, Yuichi Shiraishi, Satoru Miyano, Uza Norimitsu, Yuzo Kodama, Hiroshi Seno, Seishi Ogawa. Genetic analysis of metachronous pancreatic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2185.

Risk factors of metachronous recurrence after endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma.

Esophageal endoscopic submucosal dissection (ESD) can be a curative treatment for superficial esophageal squamous cell carcinoma (SESCC). However, it is unclear whether the development of metachronous recurrence after ESD may be explained based on several risk factors. This study aimed to assess the incidence and the risk factors of metachronous recurrence of SESCC after ESD. This retrospective analysis was conducted at Samsung Medical Center, Seoul, Korea, from April 2007 to May 2018. Two hundred and fifty-three SESCC patients treated with ESD were followed using surveillance endoscopy after the procedure. Risk factors for metachronous esophageal SCC were analyzed using the Kaplan-Meier method and Cox’s proportional hazards model. Metachronous esophageal SCCs were found in 21 (8.3%) of the 253 patients. Six patients (2.4%) with extraesophageal recurrence such as lymph node metastasis confirmed by imaging were excluded from patients with metachronous recurrence and data were censored from the recurrence date. Univariate analysis revealed that the presence of many (>10) irregularly shaped multiform Lugol-voiding lesions (LVLs) around the main lesion, margin of the main LVL, and tumor differentiation were risk factors for the development of metachronous cancer. Multivariate analysis also revealed that many (>10) LVLs (hazard ratio [HR], 6.32; 95% confidence interval [CI], 1.62–24.72; p = 0.047) and unclear or spiculated margin of the main LVL (HR, 6.51; 95% CI, 1.44–29.42; p = 0.029) were associated with the risk of metachronous recurrence. Metachronous esophageal SCC develops in patients treated with ESD for SESCC. A risk assessment is important for surveillance before and after ESD for SESCC. Number of LVLs and tumor edge type are associated with an increased risk of metachronous cancer in SESCC. Patients will benefit from careful endoscopic surveillance when endoscopists pay attention to these tumor characteristics.

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.

SPORADIC AND HEREDITARY FORMS OF MULTIPLE PRIMARY MALIGNANT TUMORS IN CHILDREN

The article presents the features of the clinical manifestation of multiple primary sporadic and heritable malignant tumors in 104 children who observed at Pediatric Oncology and Hematology Research Institute of «NN Blokhin's National Medical Research Center of Oncology» from 1998 to 2012. The age of patients at the time of occurrence of the second malignant tumor ranged from 2.8 to 28 years and averaged 15.6 years. The second neoplasia occurred significantly more frequently in the group of primary hemoblastosis, compared with the group of solid tumors - 8.7% versus 3.4%, respectively (p &lt;0.0001). In children with multiple primaries, were found tumors that occur in common the most frequency. Retinoblastoma patients have an increased risk of developing sarcoma. Patients with Hodgkin's lymphoma have an increased risk of developing leukemia. In surviving children after treatment of the first neoplasia the thyroid, bone tissue and breast have a specific risk for the development of metachronous cancer and are target organs for control. Children with new hematopoietic tumors may be candidates for metachronous development of leukemia and bone tissue tumors. The using methods Next Generation Sequencing (NGS) and Multiplex Ligation-dependent Probe Amplification (MLPA) revealed germinal mutations in 12 children with of multiple primary tumors. The mutations in the TP53, RB1, CHEK2, FANCN/PALB2, MLH1, PMS2 genes identified in patients were associated with hereditary syndromes and an increased risk of developing second tumors, among which: sarcomas, brain tumors, hematopoietic tumors were the most frequent. It was shown that the second tumors can appear at the any age. Children who survived the treatment of the first tumor in later life should be monitored annually. Clinical management of children with multiple primary tumors requires a multidisciplinary approach.

Long-term clinical outcomes of endoscopic vs. surgical resection for early gastric cancer with undifferentiated histology.

The efficacy of endoscopic submucosal dissection (ESD) for undifferentiated early gastric cancer (UD EGC) is controversial due to the relatively high risk of lymph node metastasis. We compared long-term clinical outcomes of UD EGC between ESD and surgical resection groups. We retrospectively reviewed the medical records of patients with UD EGC treated by either ESD or surgical resection between January 2007 and December 2014. Long-term clinical outcomes were compared between the two groups in terms of survival. A total of 1147 patients were enrolled with median follow-up duration of 59.1 months. ESD and surgical resections were performed in 126 and 1021 patients respectively. Additional surgery was performed in 22 patients after ESD. There were no significant differences in overall survival [total, p = 0.641; propensity score matching (PSM), p = 0.330; expanded criteria, p = 0.512]. Although the disease-free survival rate was lower in ESD group because of the higher rate of metachronous cancer development (total, p < 0.001; PSM, p = 0.001), the difference was not significant in the group within expanded criteria (p = 0.071). ESD could be a comparable treatment option with surgical resection for UD EGC within expanded criteria in terms of long-term survival. It is mandatory to establish a meticulous indication of ESD for UD EGC considering the risk of lymph node metastasis.

CLINICAL AND IMMUNOHISTOCHEMICAL FEATURES OF PRIMARY BREAST CANCER AND METACHRONOUS OVARIAN AND ENDOMETRIAL TUMORS

In the study, 63patients with ВС, who developed metachronous EC (n = 47) or OC (n = 16) were enrolled. Expression of estrogen receptor(ER), progesterone receptor (PR), HER/2neu was assessed using immunohistochemical approach. BC in patients with metachronous EC and OC was characterized by a different frequency of molecular subtypes with the dominance of luminal A (36%) and B (43%) subtypes. In primary BC, we have established a correlation between ER expression and regional lymph nodes status (r = -0.50, p &lt; 0.05); negative correlation between HER2/neu expression and tumor stage (r = -0.48, p &lt; 0.05); between the molecular subtype of BC and its size (r = -0.33, p &lt;0.05), the molecular subtype of primary BC and metastases in regional lymph nodes (r = 0.27, p &lt;0.05). In the patients with luminal subtype BC metachronous tumors developed with the highest frequency (OC- 50%, EC- 50%). After treatment of primary BC metachronous tumors developed at different period: EC (22.2%)- most often in 3-5years, OC (11.0%)- after 10years and more. Our data evidence on the clinical significance of the individual characteristics of the BC, especially its molecular subtype, and the need to calculate the personalized risk of development of metachronous tumors of the reproductive system in patients with the BC.

Segmental resection is a safe oncological alternative to total proctocolectomy in elderly patients with ulcerative colitis and malignancy

The standard approach for the surgical management of colorectal cancer (CRC) in the setting of ulcerative colitis (UC) involves total proctocolectomy (TPC). However, some patients also undergo a partial resection (PR). This may be an attractive option in older patients with a high risk for surgery. The aim of this study was to compare the risk of metachronous cancer after PR or TPC for CRC in the setting of UC. This was a retrospective cohort study conducted through the Nationwide Veterans Affairs Healthcare System (VA). Patients who had UC and underwent a PR or TPC for CRC were followed from the time of their surgery to their most recent clinical follow-up. The primary outcome was development of metachronous cancer in the PR group. Secondary outcomes included surgical and medical outcomes. Fifty-nine patients were included: 24 (40.7%) underwent PR and 35 (59.3%) underwent TPC. The median age at cancer diagnosis was 73.0 and 61.7years in PR and TPC groups, respectively (P<0.0005). Amongst patients undergoing PR, 15 (60%) had no active UC at the time of surgery, whereas in patients undergoing TPC, at the time of surgery eight (23.5%) had no active UC (P=0.005). No patient who underwent a partial colectomy developed a metachronous cancer in the retained colonic segment during the follow-up period (median 7years). Our study suggests that PR for CRC in the setting of UC may be a viable option in a selected cohort of patients, especially among the elderly.

Long-Term Effects of Helicobacter pylori Eradication on Metachronous Gastric Cancer Development.

Background/AimsGastric mucosal atrophy and intestinal metaplasia due to Helicobacter pylori infection are the main precursor lesions of gastric cancer. The aim of this study was to evaluate the long-term effects of H. pylori eradication on the progression of precancerous lesions to metachronous cancer after endoscopic resection of early gastric cancer (EGC).MethodsPatients who underwent endoscopic resection of EGC were retrospectively reviewed. Changes in precancerous lesions and development of metachronous cancer were compared according to H. pylori eradication and final infection status.ResultsIn total, 565 patients were followed for over 5 years after endoscopic resection of EGC. The grade of atrophy on corpus was significantly lower in the H. pylori-eradicated group than in the persistent group during follow-up (p=0.029). In patients <70 years of age, the cumulative incidence rate of metachronous cancer was significantly lower in the H. pylori-eradicated group than in the persistent group (p=0.018). Age was an independent risk factor for metachronous cancer development.ConclusionsH. pylori eradication might prevent the development of metachronous cancer in patients <70 years of age by delaying the progression of precancerous lesions after endoscopic resection of EGC.

Prevention of Gastric Cancer: Eradication of Helicobacter Pylori and Beyond.

Although its prevalence is declining, gastric cancer remains a significant public health issue. The bacterium Helicobacter pylori is known to colonize the human stomach and induce chronic atrophic gastritis, intestinal metaplasia, and gastric cancer. Results using a Mongolian gerbil model revealed that H. pylori infection increased the incidence of carcinogen-induced adenocarcinoma, whereas curative treatment of H. pylori significantly lowered cancer incidence. Furthermore, some epidemiological studies have shown that eradication of H. pylori reduces the development of metachronous cancer in humans. However, other reports have warned that human cases of atrophic metaplastic gastritis are already at risk for gastric cancer development, even after eradication of these bacteria. In this article, we discuss the effectiveness of H. pylori eradication and the morphological changes that occur in gastric dysplasia/cancer lesions. We further assess the control of gastric cancer using various chemopreventive agents.

The Effect of Helicobacter pylori Eradication on the Metachronous Neoplasm after Endoscopic Resection for Gastric Dysplasia.

Helicobacter pylori (Hp) infection is an important risk factor for gastric carcinogenesis. Although several studies have investigated the effect of Hp eradication on the development of metachronous neoplasm after endoscopic resection of the gastric dysplasia, the evidence is still insufficient to make a clear conclusion. The aims of this study was to evaluate the risk factors for the development of metachronous neoplasm after endoscopic resection of gastric dysplasia and to investigate the effect of Hp eradication. Between 2005 and 2011, a total of 887 patients underwent endoscopic resection for gastric dysplasia. Among them, 521 patients who had undergone tests for Hp infection and been followed-up for at least one year were included in the final analyses. Of the 292 Hp-positive patients, 116 patients were successfully eradicated, while 176 failed or did not undergo eradication. During a mean follow-up of 59.1 months (range 12-125 months), metachronous neoplasm had developed in 63 patients (12.1%, dysplasia in 38, carcinoma in 25). In multivariate analyses, age ≥65 (hazard ratio [HR]=2.247, 95% confidence interval [CI] 1.297-3.895), tumor size (HR=1.283, 95% CI 1.038-1.585), synchronous lesion (HR=2.341, 95% CI 1.244-4.405), family history of gastric cancer (HR=3.240, 95% CI 1.776-5.912), and smoking (HR=1.016, 95% CI 1.003-1.029) were risk factors for metachronous neoplasm after endoscopic resection of gastric dysplasia. However, Hp eradication was not associated with metachronous neoplasm (HR=0.641, 95% CI 0.297-1.384). Hp eradication was not shown to be associated with the development of metachronous cancer after endoscopic resection of gastric dysplasia.

Endoscopic features associated with development of metachronous gastric cancer in patients who underwent endoscopic resection followed by Helicobacter pylori eradication

The preventive effect of Helicobacter pylori (HP) eradication on metachronous gastric cancer development after endoscopic resection remains controversial. The aim of this study was to identify specific endoscopic features that correlated with the risk of metachronous gastric cancer development after endoscopic submucosal dissection (ESD) using both endoscopic findings before ESD and changes of findings after HP eradication. This retrospective study investigated 122 consecutive patients who underwent ESD for early gastric cancer and successful HP eradication after ESD. Endoscopic findings linked with HP before ESD and changes after HP eradication were evaluated according to the development of metachronous cancer. Most patients showed severe atrophy and intestinal metaplasia (IM) before ESD (97% and 83%, respectively). Improvement of spotty redness, improvement of diffuse redness, emergence of patchy redness, and emergence of map-like redness were frequent findings after HP eradication (52%, 50%, 54%, and 32%, respectively). Kaplan-Meier curves indicated that patients without IM before ESD never developed metachronous cancer, while patients with emergence of map-like redness after HP eradication were significantly more likely to develop metachronous cancer (log-rank test, p = 0.031 and p < 0.001, respectively). Multivariate analysis indicated that emergence of map-like redness after HP eradication was the only predictive factor for development of metachronous cancer (hazard ratio, 3.61; 95% confidence interval, 1.41-9.21; p = 0.007). Absence of IM before ESD and emergence of map-like redness after HP eradication were useful endoscopic findings in the negative and positive prediction of metachronous gastric cancer developing after ESD.

Morbidity among long-term survivors after pancreatoduodenectomy for pancreatic adenocarcinoma.

Because pancreatoduodenectomy for pancreatic adenocarcinoma is focused on disease-free and overall survival, morbidity among long-term survivors is not well described. This study sought to evaluate outcomes for long-term survivors of pancreatic cancer after pancreatoduodenectomy. The authors identified 29 patients from their prospectively collected database of patients with pancreatic adenocarcinoma who had undergone pancreatoduodenectomy and were without evidence of disease during at least 3 years of follow-up evaluation. Demographics, treatment, and pathologic characteristics were collected for review. Data with regard to long-term sequelae also were collected, focusing on those complications requiring additional procedures and on the development of metachronous cancers. The median follow-up period was 83 months, with 62 % of patients still alive. All patients received an R0 resection, and 34 % of the patients had N1 disease. For 42 % of the patients, no significant subsequent sequelae occurred. In the four remaining patients (14 %), ascites developed, requiring repeated paracentesis or Denver shunt, with a median time to development (MTD) of 63 months. Six patients (21 %) experienced a biliary stricture requiring stent placement (MTD, 56 months). One patient experienced portal venous thrombosis requiring a venous stent (MTD, 52 months), and four patients (14 %) experienced clinically significant ulcers (MTD, 52 months). With regard to metachronous cancers, two patients experienced subsequent lymphomas (MTD, 92 months). Long-term survivors among patients who undergo pancreatoduodenectomy for pancreatic adenocarcinoma can experience significant late sequelae, which often manifest more than 3 years after surgery. As such, continued follow-up evaluation and counseling are warranted.

Morbidity in long-term survivors after pancreatoduodenectomy for pancreatic adenocarcinoma.

307 Background: Because the focus of pancreatoduodenectomy for pancreatic adenocarcinoma is placed on disease-free and overall survival, morbidity in long-term survivors is not well described. We sought to evaluate outcomes of long-term survivors of pancreatic cancer after pancreatoduodenectomy. Methods: We identified 30 patients from our prospectively collected database of patients with pancreatic adenocarcinoma who had undergone pancreatoduodenectomy, and who were without evidence of disease with at least 40 months of follow-up. Demographics, treatment and pathologic characteristics were collected for review. Data with regards to long-term sequelae were also collected, particularly those complications requiring additional procedures and the development of metachronous cancers. Results: The median length of follow up was 83 months, with 60% of patients still alive. Half the patients were male, and the median age at diagnosis was 70 years. With regard to treatment, 80% of patients received chemoradiation, with half of these patients receiving it in the neoadjuvant setting. All patients received an R0 resection, although two patients required at least partial resection of the superior mesenteric or portal veins. Thirty-three percent of patients had N1 disease. Forty-four percent of patients did not have any significant subsequent sequelae. In the remainder, four patients (13%) developed ascites requiring repeated paracentesis or Denver shunt, with median time to development (MTD) of 63 months. Six patients (20%) developed a biliary stricture requiring stent placement (MTD 56 months), one patient developed portal venous thrombosis requiring a venous stent (MTD 52 months), and 3 patients (10%) experienced clinically significant gastric anastomotic ulcers (MTD 47 months). With regards to metachronous cancers, 2 patients developed subsequent lymphomas (MTD 92 months). Conclusions: Long-term survivors of patients who undergo pancreatoduodenectomy for pancreatic adenocarcinoma can develop significant late sequelae, which often can manifest more than three to five years after surgery. Continued follow-up and counseling is warranted.

Metachronous gastric cancer after successful Helicobacter pylori eradication.

The high incidence of gastric cancer in Japan initially resulted in establishment of a country-wide gastric cancer screening program to detect early and treatable cancers. In 2013 countrywide Helicobacter pylori (H. pylori) eradication was approved coupled with endoscopy to assess for the presence of chronic gastritis. Current data support the notion that cure of the infection in those with non-atrophic gastritis will prevent development of gastric cancer. However, while progression to more severe damage is halted in those who have already developed, atrophic gastritis/gastric atrophy remain at risk for subsequent development of gastric cancer. That risk is directly related to the extent and severity of atrophic gastritis. Methods to stratify cancer risk include those based on endoscopic assessment of the atrophic border, histologic grading, and non-invasive methods based on serologic testing of pepsinogen levels. Continued surveillance is required because those with atrophic gastritis/gastric atrophy retain considerable gastric cancer risk even after H. pylori eradication. Those who have already experienced a resectable early gastric cancer are among those at highest risk as metachronous lesions are frequent even after H. pylori eradication. We review the role of H. pylori and effect of H. pylori eradication indicating the incidence and the predictive factors on development of metachronous cancer after endoscopic therapy of early gastric cancer. Studies to refine risk markers to stratify for risk, surveillance methods, intervals, and duration after successful H. pylori eradication, and whether adjuvant therapy would change risk are needed.

Metachronous colorectal cancer: A competing risks analysis with consideration for a stratified approach to surveillance colonoscopy

The incidence of metachronous cancer will become an important clinical consideration as the life expectancy of the population increases and as rates of curative resection improve. To assess the pattern of metachronous cancer development following curative resection of colorectal cancer in an unselected patient population offered postoperative colonoscopic surveillance. Prospective clinical follow-up after curative colorectal cancer resection and surveillance colonoscopy with or without polypectomy in accordance with the national guidelines. Actuarial analysis and competing risk analysis were performed to account for death and recurrence and to stratify for age, gender, stage, and tumor site. Five hundred thirty-eight patients with median follow-up 4 years 2 month (0-16) years. Fifteen patients (3%) developed metachronous cancer, at a median time interval of 90 months from primary resection. Thirteen metachronous cancer patients (87%, 13/15) underwent one to five surveillance colonoscopies: nine patients were asymptomatic at time of diagnosis of metachronous cancer. Competing risks analysis suggests that the adjusted cumulative incidence in males aged 55 is 4% at 10 years compared with 1% in females aged 85 years old. A patient aged under 65 at the time of the primary curative resection carries a 2% 5-year risk of metachronous cancer, implying that 3 year surveillance colonoscopy is justified. Whereas patients aged over 75 carry less than a 2% 10-year risk, implying that it is seldom warranted to repeat the colonoscopy more frequently than every 5 years. A stratified approach to the frequency of surveillance colonoscopy requires further consideration.