Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2021.

In Japan, with the increasing prevalence of gastroesophageal reflux disease (GERD) and growing public interest, the Japanese Society of Gastroenterology issued Evidence-based Clinical Practice Guidelines for GERD (1st edition) in 2009 and a revised 2nd edition in 2015. A number of studies on GERD were subsequently conducted in Japan and abroad, and vonoprazan, a potassium-competitive acid blocker (P-CAB), became available for the first time in Japan in February 2015. The revised 3rd edition (Japanese edition), which incorporates new findings and information, was published in April 2021. These guidelines are summarized herein, particularly sections related to the treatment of GERD. The important clinical issues addressed in the present revision are (i) the introduction of treatment algorithms that classify GERD into reflux esophagitis and non-erosive reflux disease, (ii) the clarification of treatment algorithms based on to the severity of reflux esophagitis, and (iii) the positioning of vonoprazan in the treatment for GERD. The present guidelines propose vonoprazan as the initial/maintenance treatment for severe reflux esophagitis. They also recommend vonoprazan or PPI as an initial treatment for mild reflux esophagitis and recommended PPI and proposed vonoprazan as maintenance treatment. These updated guidelines offer the best clinical strategies for GERD patients in Japan and hope that they will be of global use for the diagnosis and treatment for GERD.

Prognostic significance of pathological tumor response and residual nodal metastasis in patients with esophageal squamous cell carcinoma after neoadjuvant chemotherapy followed by surgery.

BACKGROUND: The present study investigated prognostic factors in patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC) among various clinicopathological features related to neoadjuvant chemotherapy (NAC) and surgery, and the indications for additional treatment after surgery were considered. METHODS: A total of 113 patients with clinical stage II or III ESCC, who had undergone NAC followed by a thoracic esophagectomy with a three-field lymphadenectomy were retrospectively reviewed. NAC consisted of either two courses of cisplatin and 5-fluorouracil or three courses of docetaxel, cisplatin and 5-fluorouracil, with a new course beginning every 3 weeks. RESULTS: The overall survival (OS) rate was poorer in the pN-positive group than in the pN-negative group (P < 0.001). In terms of the histological therapeutic effect, the OS rate was poorer in the worse pathological responder group than in the better pathological responder group (P = 0.001). A multivariate analysis examining overall survival suggested that only pN (HR 3.204, P = 0.007) and worse pathological responder (HR 2.347, P = 0.041) were independent prognostic factors. The OS rate was compared among four groups classified according to the different combinations of pN and pathological response. A group of patients with pN-positive and worse pathological response had a significantly poorer outcome than the other groups. CONCLUSIONS: The present study suggested that patients with resectable advanced ESCC undergoing NAC followed by surgery, who have both pN and worse pathological response, have a poor prognosis.

Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2015.

As an increase in gastroesophageal reflux disease (GERD) has been reported in Japan, and public interest in GERD has been increasing, the Japanese Society of Gastroenterology published the Evidence-based Clinical Practice Guidelines for GERD (1st edition) in 2009. Six years have passed since its publication, and there have been a large number of reports in Japan concerning the epidemiology, pathophysiology, treatment, and Barrett's esophagus during this period. By incorporating the contents of these reports, the guidelines were completely revised, and a new edition was published in October 2015. The revised edition consists of eight items: epidemiology, pathophysiology, diagnosis, internal treatment, surgical treatment, esophagitis after surgery of the upper gastrointestinal tract, extraesophageal symptoms, and Barrett's esophagus. This paper summarizes these guidelines, particularly the parts related to the treatment for GERD. In the present revision, aggressive proton pump inhibitor (PPI) maintenance therapy is recommended for severe erosive GERD, and on-demand therapy or continuous maintenance therapy is recommended for mild erosive GERD or PPI-responsive non-erosive GERD. Moreover, PPI-resistant GERD (insufficient symptomatic improvement and/or esophageal mucosal break persisting despite the administration of PPI at a standard dose for 8 weeks) is defined, and a standard-dose PPI twice a day, change in PPI, change in the PPI timing of dosing, addition of a prokinetic drug, addition of rikkunshito (traditional Japanese herbal medicine), and addition of histamine H2-receptor antagonist are recommended for its treatment. If no improvement is observed even after these treatments, pathophysiological evaluation with esophageal impedance-pH monitoring or esophageal manometry at an expert facility for diseases of the esophagus is recommended.

Resection of a Submucosal Tumor-Like Superficial Carcinoma in Middle Thoracic Esophagus Concomitant with Mucosal Adenocarcinoma and Submucosal Squamous Cell Carcinoma: A Case Report and Review of Literature.

A 67-year-old man was pointed out mucosal irregularity on health check-up and was referred to our institution. Diagnostic examinations were performed and an aggregated type 0-IIa lesion having 3 small protrusions was recognized in the middle thoracic esophagus. Endoscopic biopsy led to diagnosis of esophageal cancer concomitant with adenocarcinoma and squamous cell carcinoma. Thoracic esophagectomy with 3-fields lymph node dissection was performed via a right thoracoabdominal approach and reconstructed with stomach roll. Three submucosal tumors like small protrusions were recognized in resected specimen. One of them was well differentiated tubular adenocarcinoma which occupied in mucosal layer. The other two were moderately differentiated squamous cell carcinoma. They existed very near but no connection was recognized by serial section. The adenocarcinoma existing in middle esophagus is very rare. Almost all of them were submucosal or advanced cancers. When we searched with the ICHUSHI database (a domestic medical literature database service provided by the NPO Japan Medical Abstracts Society) and the PubMed database, there was no report of mucosal adenocarcinoma occurred in middle thoracic esophagus in the past 10 years. Then this report was thought to be the first report of mucosal adenocarcinoma in middle thoracic esophagus in the world.

A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907).

BACKGROUND: Patients with esophageal carcinoma receiving postoperative chemotherapy showed superior disease-free survival than those receiving surgery alone in a Japan Clinical Oncology Group trial (JCOG9204). The purpose of this study was to evaluate optimal perioperative timing-that is, before or after surgery-for providing chemotherapy in patients with locally advanced esophageal squamous cell carcinoma. METHODS: Eligible patients with clinical stage II or III, excluding T4, squamous cell carcinoma were randomized to undergo surgery followed (group 1) or preceded (group 2) by chemotherapy consisting of two courses of cisplatin plus 5-fluorouracil. The primary end point was progression-free survival. RESULTS: We randomized 330 patients, with 166 assigned to group 1 and 164 to group 2, between May 2000 and May 2006. The planned interim analysis was conducted after completion of patient accrual. Progression-free survival did not reach the stopping boundary, but overall survival in group 2 was superior to that of group 1 (P = 0.01). Therefore, the Data and Safety Monitoring Committee recommended early publication. Updated analyses showed the 5-year overall survival to be 43% in group 1 and 55% in group 2 (hazard ratio 0.73, 95% confidence interval 0.54-0.99, P = 0.04), where the median follow-up of censored patients was 61.6 months. Concerning operative morbidity, renal dysfunction after surgery in group 2 was slightly higher than in group 1. CONCLUSIONS: Preoperative chemotherapy with cisplatin plus 5-fluorouracil can be regarded as standard treatment for patients with stage II/III squamous cell carcinoma.

[Infectious complications after esophageal surgery].

The incidence of wound infection, which is an intrasurgical field infection, is lower than the incidence of pneumonia, which is an extrasurgical field infection, after esophageal cancer surgery. Several trials predicting postoperative infectious complications have been reported. One measured the phytohemagglutinin- and concanavalin A-induced proliferation of peripheral blood mononuclear cells in patients; one measured the white blood cell (WBC) count 2 h after surgery and the decrease in WBC count on first postoperative day; and another showed that the decrease in serum IgG2 level can predict the occurrence of methicillin-resistant Staphylococcus aureus (MRSA) infections. Useful strategies for managing infectious complications have also been reported. Applying mupirocin calcium hydrate ointment to the nasal cavity decreases the incidence of MRSA infections. Autologous blood collection reduces the need for allogeneic transfusion in patients undergoing resection of esophageal cancer, and avoidance of allogeneic transfusion may reduce the risk of postoperative infection. The total exposure to preoperative chemoradiotherapy should be limited to 40 Gy or less to prevent postoperative pneumonia.