Hiroyuki Tsukagoshi

Long-term outcome after endoscopic mucosal resection in patients with esophageal squamous cell carcinoma invading the muscularis mucosae or deeper ☆

BACKGROUND Endoscopic mucosal resection is recommended for squamous cell carcinoma of the esophagus confined to the lamina propria. However, endoscopic mucosal resection is often performed in patients with tumors that invade the muscularis mucosa or upper submucosa to minimize surgical invasiveness, despite the increased risk of lymph node metastasis. This study prospectively evaluated long-term outcome in such patients. METHODS Twenty-six consecutive patients with squamous cell esophageal carcinoma invading the muscularis mucosa or submucosa who underwent endoscopic mucosal resection from June 1992 through March 2000 (extended endoscopic mucosal resection group) were studied. As control group, 44 consecutive patients with esophageal carcinoma invading the muscularis mucosae or upper third of the submucosa and no preoperative evidence of lymph node metastasis who underwent esophagectomy during the same period (surgical resection group) were studied. RESULTS Overall survival rates at 5 years in the extended endoscopic mucosal resection group and surgical resection group were, respectively, 77.4% and 84.5%. There was no significant difference between survival distributions. Cause-specific survival rates at 5 years in extended endoscopic mucosal resection and surgical resection groups were, respectively, 95.0% and 93.5%. Survival curves for the groups were similar. CONCLUSION Although patients were not randomized to extended endoscopic mucosal resection or surgical resection in this study, the results suggest that endoscopic mucosal resection may be safe and effective for management of squamous cell esophageal carcinoma invading the muscularis mucosae or upper submucosa.

Endoscopic clip application for closure of esophageal perforations caused by EMR

BACKGROUND With increasing use of EMR for early stage esophageal carcinoma, the number of cases of iatrogenic esophageal perforation is likely to increase. This study evaluated the results of endoscopic clip application for treatment of perforations caused by EMR in patients with esophageal carcinoma. METHODS Among 185 patients who underwent EMR for esophageal carcinoma, esophageal perforation occurred in 3 patients (1.6%). Metallic clips were immediately applied endoscopically to close the perforations. OBSERVATIONS All 3 patients were observed closely and were managed conservatively (intravenous hyperalimentation, antibiotics) after closure of the perforation. They were discharged without any further serious complication. CONCLUSIONS When esophageal perforation caused by EMR is immediately recognized, endoscopic application of metallic clips is appropriate therapy. However, patients must be carefully monitored for the development of generalized mediastinitis.

A molecular epidemiological study of respiratory viruses detected in Japanese children with acute wheezing illness

BackgroundRecent studies strongly suggest that some respiratory viruses are associated with the induction of acute wheezing and/or exacerbation of bronchial asthma. However, molecular epidemiology of these viruses is not exactly known.MethodsUsing PCR technology, we attempted to detect various respiratory viruses from 115 Japanese children. Furthermore, the detected viruses were subjected to homology, pairwise distance, and phylogenetic analysis.ResultsViruses were detected from 99 (86.1%) patients. Respiratory syncytial virus (RSV) alone and human rhinovirus (HRV) alone were detected in 47 (40.9%) and 36 (31.3%) patients, respectively. Both RSV and HRV were detected in 14 (12.2%) patients. Human metapneumovirus (HMPV) alone and human parainfluenza virus (HPIV) alone were detected in 1 (0.9%) patient each, respectively. Homology and phylogenetic analyses showed that the RSV and HRV strains were classified into genetically diverse species or subgroups. In addition, RSV was the dominant virus detected in patients with no history of wheezing, whereas HRV was dominant in patients with a history of wheezing.ConclusionsThe results suggested that these genetically diverse respiratory viruses, especially RSV and HRV, might be associated with wheezing in Japanese children.

EMR combined with chemoradiotherapy: a novel treatment for superficial esophageal squamous-cell carcinoma

BACKGROUND Esophagectomy or chemoradiotherapy (CRT) are the procedures of choice for patients with superficial esophageal squamous-cell carcinoma. However, esophagectomy is highly invasive, and CRT is associated with the risk of local failure. A study was conducted of a novel treatment, EMR combined with CRT, for patients with superficial esophageal carcinoma. EMR was performed for the purpose of complete local tumor control and chemoradiotherapy was performed for regional and distant control. METHODS EMR combined with CRT was performed for patients with esophageal carcinoma invading the muscularis mucosae or upper submucosa who refused esophagectomy. The planned treatment after EMR was 40 to 46 Gy of external beam radiation to the mediastinum, including the supraclavicular fossa or cardia. Chemotherapy was given during weeks 1 and 5 (5-fluorouracil, 700 mg/m(2) per 24 hours in a 120-hour infusion, and cisplatin 15 mg/m(2) per day intravenously on days 1 to 5). RESULTS During the study period, 16 patients underwent EMR combined with CRT (EMR plus CRT group) and 39 patients with similar stage cancer underwent esophagectomy (surgical resection group). None of the patients in the EMR plus CRT group have had local recurrence or metastasis. Overall survival rates at 5 years in the EMR plus CRT and surgical resection groups were estimated to be, respectively, 100% and 87.5%. CONCLUSIONS Although this study was not randomized, the results suggest that EMR combined with CRT is a safe and effective method for treating patients with superficial esophageal carcinoma. The results were equivalent or, in view of the lower degree of invasiveness, superior to surgical resection.

Factors Associated With Risk for Colorectal Cancer Recurrence After Endoscopic Resection of T1 Tumors

BACKGROUND & AIMS More information is needed on the long-term outcomes of patients who undergo endoscopic resection of colorectal tumors. We evaluated recurrence of colorectal cancer (CRC) after endoscopic resection or a combination of endoscopic research and surgery for T1 colorectal tumors. METHODS We conducted a retrospective study of 389 patients with T1 CRC treated by endoscopic resection from January 1989 to December 2008 in Sapporo, Japan. We compared outcomes between patients who underwent subsequent surgery (ER + SURG, n = 205) and those who did not (ER only, n = 184) and statistically adjusted baseline differences between the groups according to the propensity scores. RESULTS There was almost no risk of cancer recurrence among patients without indications for surgery recommended by the Japanese Society for Cancer of the Colon and Rectum (these indications include tumors with vertical margins, deep submucosal invasion, lymphatic or venous invasion, poor differentiation, or high-grade budding). Among patients with indications for surgery, the cumulative risks of recurrence (CRRs) were 3.7% in the ER + SURG group and 20.1% in the ER only group (P = .001). However, the patients with only deep submucosal invasion had a low CRR, even without surgery (2.3% in the ER + SURG group and 3.4% in the ER only groups, P = .867). In contrast, patients with indications for surgery other than deep submucosal invasion (high-risk patients) had much better outcomes when they also underwent surgery (CRRs: 5.8% in the ER + SURG group vs 58.0% in the ER only group, P < .001). CONCLUSIONS On the basis of a retrospective study of patients who underwent endoscopic resection for T1 CRC, those with tumors with only submucosal invasion are at low risk for cancer recurrence. However, patients with other high-risk tumor features have greater risks for cancer recurrence and benefit from subsequent surgery.

Phase I/II study of docetaxel/cisplatin/fluorouracil combination chemotherapy against metastatic esophageal squamous cell carcinoma.

Introduction: More effective regimens are urgently needed for squamous cell carcinoma of esophagus (SCCE), therefore, we conducted a phase I/II trial of a combination of docetaxel, platinum, and fluorouracil (TPF) for treating metastatic SCCE. Methods: This phase I/II trial (n = 12/39) was conducted in our institute from April 2005 to June 2008. Progression-free survival (PFS) and overall survival were analyzed by the Kaplan-Meier method. Results: The recommended dose of docetaxel was determined to be 50 mg/m2 in phase I. In phase II with a mean follow-up period of 13.3 months, the objective response rate was 66.6%, a median survival period of 13 months and PFS of 7 months was achieved, and the 1-year survival and PFS rates were 52.9% and 19.6%, respectively. Grade 3/4 toxicities of leukopenia, neutropenia, and anorexia were observed in 53.8%, 43.6%, and 25.6%, respectively. Conclusions: A TPF regimen against metastatic SCCE was well tolerated and achieved a favorable objective response rate and survival benefit compared with other recently reported regimens. Randomized phase III trials of the TPF regimen are warranted and urgently required.

Genetic analysis of attachment glycoprotein (G) gene in new genotype ON1 of human respiratory syncytial virus detected in Japan

We studied the evolution of the G gene in the new genotype ON1 of RSV detected from patients with acute respiratory infection in Japan. Phylogenetic analyses and the evolutionary timescale were obtained by the Bayesian MCMC method. We also analyzed p‐distance and positive selection sites. A new genotype ON1 emerged around 2001. The evolution rate was rapid (3.57 × 10−3 substitutions/site per year). The p‐distance was short and no positive selection site was found in the present strains. These results suggested that a new genotype ON1 of RSV‐A emerged approximately10 years ago and spread to some countries with a high evolution rate.

Molecular epidemiological study of human rhinovirus species A, B and C from patients with acute respiratory illnesses in Japan

Recent studies suggest that human rhinovirus species A, B and C (HRV-ABCs) may be associated with both the common cold and severe acute respiratory illnesses (ARIs) such as bronchiolitis, wheezy bronchiolitis and pneumonia. However, the state and molecular epidemiology of these viruses in Japan is not fully understood. This study detected the genomes of HRV-ABCs from Japanese patients (92 cases, 0-36 years old, mean±sd 3.5±5.0 years) with various ARIs including upper respiratory infection, bronchiolitis, wheezy bronchiolitis, croup and pneumonia between January and December 2010. HRV-ABCs were provisionally type assigned from the pairwise distances among the strains. On phylogenetic trees based on the nucleotide sequences of the VP4/VP2 coding region, HRV-A, -B and -C were provisionally assigned to 14, 2 and 12 types, respectively. The present HRV-A and -C strains had a wide genetic diversity (>30 % divergence). The interspecies distances were 0.230±0.063 (mean±sd, HRV-A), 0.218±0.048 (HRV-B) and 0.281±0.105 (HRV-C), based on nucleotide sequences, and 0.075±0.036 (HRV-A), 0.049±0.022 (HRV-B) and 0.141±0.064 (HRV-C) at the deduced amino acid level. Furthermore, HRV-A and -C were the predominant species and were detected throughout the seasons. The results suggested that HRV-A and -C strains have a wide genetic divergence and are associated with various ARIs in Japan.

Molecular evolution of human respiratory syncytial virus attachment glycoprotein (G) gene of new genotype ON1 and ancestor NA1

We conducted a comprehensive genetic analysis of the C-terminal 3rd hypervariable region of the attachment glycoprotein (G) gene in human respiratory syncytial virus subgroup A (HRSV-A) genotype ON1 (93 strains) and ancestor NA1 (125 strains). Genotype ON1 contains a unique mutation of a 72 nucleotide tandem repeat insertion (corresponding to 24 amino acids) in the hypervariable region. The Bayesian Markov chain Monte Carlo (MCMC) method was used to conduct phylogenetic analysis and a time scale for evolution. We also calculated pairwise distances (p-distances) and estimated the selective pressure. Phylogenetic analysis showed that the analyzed ON1 and NA1 strains formed 4 lineages. A strain belonging to lineage 4 of ON1 showed wide genetic divergence (p-distance, 0.072), which suggests that it might be a candidate new genotype, namely ON2. The emergence of genotype NA1 was estimated to have occurred in 2000 (95% of highest probability density, HPD; 1997-2002) and that of genotype ON1 in 2005 (95% HPD; 2000-2010) based on the time-scaled phylogenetic tree. The evolutionary rate of genotype ON1 was higher than that of ancestral genotype NA1 (6.03×10(-3) vs. 4.61×10(-3) substitutions/site/year, p<0.05). Some positive and many negative selection sites were found in both ON1 and NA1 strains. The results suggested that the new genotype ON1 is rapidly evolving with antigenic changes, leading to epidemics of HRSV infection in various countries.

Sequence and phylogenetic analyses of Saffold cardiovirus from children with exudative tonsillitis in Yamagata, Japan.

(Received 15 February 2010 ; accepted 23 May 2010 ) To the Editor, Saffold cardiovirus (SAFV) of the genus Cardiovirus and family Picornaviridae was recently recovered from faecal specimens of an infant with fever of unknown origin [1]. SAFV has also been detected in children with diseases such as gastroenteritis, respiratory tract infection, and non-polio acute fl accid paralysis [2 – 5]. However, the epidemiology and pathogenicity of SAFV is not exactly known. In this study, we detected SAFV in children with exudative tonsillitis and conducted sequence and phylogenetic analyses. We obtained nasopharyngeal swabs from 37 patients with typically exudative tonsillitis between August and December 2009. Informed consent was obtained from the parents of all subjects for the donation of the nasopharyngeal samples used in this analysis. Initially, we sought to isolate or detect pathogens from these samples using cell culture methods, quick immunochromatography (as used to detect Streptococcus), and polymerase chain reaction (PCR; as used to detect Epstein – Barr virus [6]). To isolate various viruses, we used 7 different cell lines (Vero E6, HEp-2, HEL, MDCK, GMK, HMV-II, and RD18S cells) [7,8]. These cells may be sensitive to the various agents of exudative tonsillitis – parainfl uenza viruses, infl uenza viruses, herpes simplex viruses, adenovirus, and respiratory syncytial virus [7,8]. However, these pathogens were not isolated or detected from the samples provided. Next, we attempted to detect SAFV using a nested reverse transcriptase PCR (RT-PCR). We extracted RNA from the samples and amplifi ed the VP1 coding region of SAFV by nested RT-PCR. Primer sets were newly designed by Primer Express ® version 1.5 software (Applied Biosystems LLC, Foster City, CA, USA) [9]. Primer sequences were as follows: 5 ′ -HAA RCA RGR YTG GAR YTT YNT NAT GTT-3 ′ (primer 315F) and 5 ′ DGG BCK DGG RCA RWA VAC YCT CAT-3′ (primer 738R) as outer primers, and 5 ′ -AAR CAR GRY TGG ARY TTY DTH ATG TTY TC-3′ (primer 316F) and 5 ′ -RTT RKK RAA RTY NGM RDA NCY RTT RAA CCA-3 ′ (primer 621R) as inner primers. Reverse transcription was performed for 10 min at 30 ° C, 45 min at 37 ° C, and 5 min at 95 ° C using random hexamers (TAKARA BIO Inc., Otsu, Japan). First and nested PCR conditions were as follows: 5 min at 94 ° C, followed by 40 cycles at 94 ° C for 30 s, 50 ° C for 30 s, and 72 ° C for 1 min, ending with elongation for an additional 10 min at 72 ° C. To prevent carryover contamination of nested-PCR, we took general precautions as previously described [10,11]. As a result, we obtained amplicons from 9 children who showed typical exudative tonsillitis symptoms, including fever ( 38 ° C). They lived in Yamagata Prefecture, Japan and were aged between 2 and 7 y (mean standard deviation, 3.8 1.6 y). Fever lasted for 1 to 3 days (1.8 0.7 days). Amplicons were sequenced and aligned (453 bp) [3,5,12]. Next, we performed phylogenetic LETTER TO THE EDITOR