Pembrolizumab plus cisplatin and fluorouracil as induction chemotherapy followed by definitive chemoradiotherapy for patients with cT4 and/or supraclavicular lymph node metastasis (M1Lym) of esophageal squamous cell carcinoma.

Definitive chemoradiotherapy (DCRT) is administered as standard treatment for patients with cT4 and/or M1Lym esophageal squamous cell carcinoma (ESCC); however, its long-term result is inadequate. Although several studies have reported that conversion surgery can improve the survival of these patients, none have identified significantly better long-term survival than that achieved by DCRT. Thus, enhancing DCRT seems important to improve the survival of these patients. A strategy of shrinking tumor volume before DCRT and providing consolidation chemotherapy for systemic control is expected to improve the survival of these patients. Pembrolizumab plus cisplatin and fluorouracil has demonstrated good local control and significant improvement in the survival of patients with advanced esophageal cancer. Based on these results, the following strategy is proposed: This protocol should be applied as induction for these patients; then, DCRT should be provided depending on the initial response; and finally, adjuvant chemotherapy with an immune checkpoint inhibitor should be given to all responders.

Accuracy of preoperative staging of gastric stump cancer.

BACKGROUND: In this study, the accuracy of preoperative staging for gastric stump cancer, which has not been thoroughly investigated since the condition is rare, was investigated using computed tomography and gastroscopic imaging. METHODS: Between February 1994 and April 2018, 49 patients with gastric stump cancer, following subtotal or total gastrectomy, were reviewed retrospectively. Preoperative diagnoses of clinical T and clinical N categories were compared with post-operative pathological diagnoses (pT and pN categories). Positive predictive values, accuracy, sensitivity and specificity were also evaluated. RESULTS: The overall accuracy of T staging was 40.8%. The positive predictive value for cT3/T4 was 96.3%, whereas the positive predictive value for cT1/T2 was 72.7%. The overall accuracy for N staging was 61.2%. The positive predictive value of lymph node positive patients was 73.3%. The positive predictive value and sensitivity of over stage II were 96.6% and 84.8%, respectively. CONCLUSIONS: The accuracy of preoperative diagnosis using both computed tomography and gastroscopy imaging may be feasible for T3/T4 advanced gastric stump cancer, whereas diagnosing T1/2 gastric stump cancer must be carefully considered due to high misdiagnosis rates, relating to depth.

Plasma exosome-encapsulated microRNA-21 and microRNA-92a are promising biomarkers for the prediction of peritoneal recurrence in patients with gastric cancer.

In patients with gastric cancer (GC), peritoneal recurrence is a common risk and associated with poor prognosis. A novel biomarker for the prediction of high-risk peritoneal recurrence in patients with GC is desirable. The present study investigated the effectiveness of exosome-encapsulated microRNAs (ex-miRNAs) as minimally invasive biomarkers in patients with GC that received curative surgery. Recurrence-specific ex-miRNAs were selected following comparison of miRNA microarray data from patients with TNM stage II GC with peritoneal recurrence (n=3) and without peritoneal recurrence following curative surgery (n=3), and three healthy volunteers. In this analysis, exosome-encapsulated miRNA-21 (ex-miR-21) and exosomal miR-92a (ex-miR-92a) exhibited the greatest alterations in expression patterns. Using plasma exosome samples collected from another 129 patients with stage II and III GC, the present study investigated the potential value of ex-miR-21 and ex-miR-92a as biomarkers. Ex-miRNA levels were measured using TaqMan miRNA assays. Ex-miR-21 levels were significantly higher and ex-miR-92a levels were significantly lower in samples from patients with GC compared with healthy controls. The overall survival (OS) and peritoneal recurrence-free survival (PRFS) were poorer in stage II and III patients with high ex-miR-21 levels than in patients with low miR-21 levels. OS and PRFS of stage II and III patients with low ex-miR92a levels were significantly worse than those with high ex-miR92a levels. Cox multivariate analyses indicated that ex-miR-21 and ex-miR-92a were independent prognostic factors for OS and PRFS in stage II and III GC. A negative correlation was detected between expression levels of miR-21 and programmed cell death protein 4 mRNA, and miR-92a and prostaglandin E receptor 4 mRNA. Therefore, ex-miR-21 and ex-miR-92a may function as effective and minimally invasive biomarkers for the prediction of peritoneal recurrence and the prognosis of patients with stage II/III GC.

Exosome­encapsulated microRNA­23b as a minimally invasive liquid biomarker for the prediction of recurrence and prognosis of gastric cancer patients in each tumor stage.

Recently, exosome­encapsulated microRNAs (miRNAs) have been attracting attention as stable and minimally invasive biomarkers in cancer patients. The aim of the present study was to clarify the value of plasma exosomal microRNA­23b (miR­23b) as a diagnostic and prognostic biomarker in gastric cancer (GC) patients at each tumor stage. We first selected recurrence specific exosomal miRNA by miRNA microarray from 6 GC patients (stage I) with or without recurrence, and 3 healthy volunteers. In this analysis, miR­23b demonstrated the most significant change. Subsequently, we validated the usefulness of miR­23b as a biomarker using the plasma exosome samples collected from 232 GC patients and 20 healthy volunteers. miR­23b levels were evaluated by Taqman microRNA assays. Exosomal miR­23b levels of GC patients were significantly lower than those of the healthy controls. A significant association was revealed between the plasma exosomal miR­23b levels and the expression of miR­23b in primary tumor tissues. Concerning the pathological condition, miR­23b demonstrated a significant association with tumor size, depth of invasion, liver metastasis and TNM stage. The overall survival (OS) rates of low­miR­23b patients were significantly worse than those of high­miR­23b patients at stage I, II, III and IV. The disease­free survival (DFS) rates of low exosomal miR­23b patients were significantly worse than those of high­miR­23b patients at stage I, II and III. Cox multivariate analysis indicated that exosomal miR­23b was an independent prognostic factor for OS and DFS at each tumor stage. Our results revealed that exosomal miR­23b has potential as minimally invasive predictive biomarker for the recurrence and prognosis of GC in patients at all stages.

Two cases of early recurrence after transabdominal preperitoneal inguinal hernia repair.

We performed transabdominal preperitoneal inguinal hernia repair in 46 patients (58 diseases), two of whom experienced early recurrence after mesh repair. Case 1 was a 76-year-old man with a bilateral inguinal hernia (recurrence site, left indirect hernia) after appendectomy. The recurrence occurred 1 month after transabdominal preperitoneal inguinal hernia repair. The mesh was dislocated to the lateral side, and we repaired it using the direct Kugel® patch with an anterior technique. Case 2 was a 79-year-old man with a bilateral inguinal hernia (recurrence site, right direct hernia with an orifice >3 cm) after appendectomy. The recurrence occurred 3 months after transabdominal preperitoneal inguinal hernia repair. The mesh was dislocated to the lateral side, and we repaired it using an ULTRAPRO® Plug with an anterior technique under laparoscopic observation. We believe the recurrences resulted from insufficient internal exfoliation and fixation affected by complicated exfoliation of the preperitoneal space with omental adhesion after intraperitoneal surgery.

Clinical Significance of Area of Psoas Major Muscle on Computed Tomography after Gastrectomy in Gastric Cancer Patients.

BACKGROUND: The measurement of a single abdominal image on computed tomography (CT) can provide an estimate of the total body skeletal muscle. We evaluate the change of the area of the psoas major muscle (PMMA) in a CT which was performed routinely after gastrectomy in gastric cancer. METHODS: A total of 119 gastric cancer patients who underwent gastrectomy were enrolled for the study. A CT image at the top of the iliac crest level was obtained at the following times: 3 postoperative months (POM), 6 POM, 1 postoperative year (POY), 2 POY, 3 POY, and 5 POY. We analyzed the change rate of PMMA after gastrectomy and before or after recurrence. RESULTS: PMMA change after gastrectomy was approximately between -8 and -10% over the 5-year observation period. PMMA in the R2 (macroscopic residual tumor)/recurrence group was lower than that in the no recurrence group, and a significant difference was observed at 2 POY (-21.7 ± 3.6% vs. -7.9 ± 2.3%, p < 0.01). PMMA after freshly diagnosed recurrence had decreased significantly by 14.1 ± 1.8% (p < 0.01). CONCLUSIONS: Evaluation of PMMA change by CT after gastrectomy could assist in the diagnosis of the progression of cancer state in gastric cancer patients.

Seven esophageal perforation cases after aortic replacement/stenting for thoracic aortic dissection or aneurysm.

BACKGROUND: Esophageal perforation after aortic replacement/stenting for aortic dissection or aneurysm is a rare but severe complication. However, its cause, standard treatment, and prognosis are unclear. We analyzed the treatment and outcome retrospectively from seven cases experienced at our hospital. CASE PRESENTATION: The median age of the patients was 70 years (range, 41-86), and six of the seven cases were male. As the first treatment, aortic replacement techniques were performed in five, and thoracic endovascular aortic repair (TEVAR) procedure was performed in two. We evaluated the treatment of the perforation, the cause of death, and the median survival time after reparative surgery (esophagectomy). Initial treatment of the perforation was esophagectomy without reconstruction in six and esophagogastric bypass (later, esophagectomy was performed) in one. Three of seven cases could be discharged from hospital or moved to another hospital, but two of these three cases died of major bleeding on postoperative days 320 and 645. The other four esophagectomy cases died in hospital because of sepsis on postoperative days 14, 30, and 41 and major bleeding on postoperative day 54. The one surviving case was a 65-year-old man who underwent reconstruction, and was still alive without signs of infection at 424 days postoperatively. CONCLUSION: The prognosis of esophageal perforation cases after aortic replacement/stenting for thoracic aortic dissection or aneurysm is poor, though there were some cases with relatively long survival. Therefore, the indication for invasive esophagectomy should be decided carefully. Control of infection including regional infection is essential for successful treatment.