Long-term outcome of regional cooperation pathway after endoscopic submucosal dissection for early detection of new gastric cancer.

OBJECTIVES: The Cancer Control Act requires the maintenance of regional cooperation pathways (RCP) for cancer treatment. In 2008, we started RCP for early detection of new gastric cancer after endoscopic submucosal dissection (ESD). In gastric cancer treatment, RCP after surgical resection had been widely used, but little is known about RCP after ESD. This study aimed to evaluate the effectiveness of RCP after ESD. METHODS: This study included 465 patients on whom our RCP was implemented from 2008 to 2018. A regional family physician performed surveillance endoscopy at 3 months and 1 year after ESD and annually thereafter. We retrospectively evaluated the cumulative incidence and treatment outcomes of new gastric cancer and compared them with previous reports. RESULTS: During a median follow-up period of 70.5 months (3-120 months), 58 patients developed new gastric cancers, and metachronous gastric cancer was detected in 55 patients more than 1 year after ESD. The 5-year cumulative incidence rate was 9.8%. Three patients did not want treatment. Among the remaining 55 patients, the initial treatment was ESD in 51 and surgical resection in 4. Eventually, 50 patients (48 in the ESD group and 2 in the surgical resection group) fulfilled the pathologic criteria for curative ESD. There were no deaths due to gastric cancer. CONCLUSION: Our study was the first to reveal the incidence of new gastric cancer after ESD using RCP. Most lesions were cured with ESD, and no patients died of gastric cancer. Therefore, we consider RCPs to be an option for surveillance after ESD.

Comparison of proton-based definitive chemoradiotherapy and surgery-based therapy for esophageal squamous cell carcinoma: a multi-center retrospective Japanese cohort study.

BACKGROUND: Proton-based, definitive chemoradiotherapy (P-CRT) for esophageal squamous cell carcinoma (ESCC) previously showed comparable survival outcomes with the surgery-based therapy, i.e., neoadjuvant chemotherapy followed by esophagectomy (NAC-S), in a single-institutional study. This study aimed to validate this message in a Japanese multicenter study. METHODS: Eleven Japanese esophageal cancer specialty hospitals have participated. A total of 518 cases with clinical Stage I-IVA ESCC between 2010 and 2019, including 168 P-CRT and 350 NAC-S patients, were enrolled and long-term outcomes were evaluated. Propensity-score weighting analyses with overlap weighting for confounding adjustment were used. RESULTS: The 3-year overall survival (OS) of the P-CRT group was equivalent to the NAC-S group (74.8% vs. 72.7%, hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.61-1.25). Although, the 3-year P-CRT group progression-free survival (PFS) was inferior to the NAC-S group (51.4% vs. 59.6%, HR 1.39, 95% CI 1.04-1.85), the progression P-CRT group cases showed better survival than the NAC-S group (HR 0.58, 95% CI 0.38-0.88), largely because of salvage surgery or endoscopic submucosal dissection for local progression. The survival advantage of P-CRT over NAC-S was more pronounced in the cT1-2 (HR 0.61, 95% CI 0.29-1.26) and cStage I-II (HR 0.50, 95% CI 0.24-1.07) subgroups, although this trend was not evident in other populations, such as cT3-4 and cStage III-IVA. CONCLUSIONS: Proton-based CRT for ESCC showed equivalent OS to surgery-based therapy. Especially for patients with cT1-2 and cStage I-II disease, proton-based CRT has the potential to serve as a first-line treatment.

Outcomes of definitive carbon-ion radiotherapy for cT1bN0M0 esophageal squamous cell carcinoma.

BACKGROUND: A recent phase I/II study determined the optimal dose of definitive carbon-ion radiotherapy (CIRT) for cT1bN0M0 esophageal cancer. This study aimed to further confirm the efficacy and feasibility of the recommended dose fractionation of CIRT with long-term follow-up results in a larger sample size. METHODS: This single center retrospective study evaluated patients with cT1bN0M0 esophageal squamous cell carcinoma treated with the recommended dose fractionation of 50.4 Gy relative biological effectiveness in 12 fractions, between 2012 and 2022. RESULTS: Thirty-eight patients underwent CIRT at our hospital. Although eight (21.1%) patients were older than 80 years, 15 (39.5%) had high surgical risk, and seven (18.4%) were at high risk for chemotherapy, all patients underwent CIRT as scheduled. Grade 3 esophagitis occurred in eight (21.1%) patients and grade 3 pneumonia in one (2.6%) patient in this study, but no grade 4 adverse events occurred. The only grade 3 late adverse event was pneumonia in one patient (2.6%). The 5-year overall survival rate, local control rate, and disease-free survival rates were 76.6% (95% CI, 90.9-62.4), 74.9% (95% CI, 90.7-59.0), and 66.4% (95% CI, 83.3-49.5), respectively. Additionally, post CIRT recurrence was as follows: seven (18.4%) patients had recurrence in another part of the esophagus, three (7.9%) in the primary site, three (7.9%) in lymph nodes outside the irradiated area, and one (2.6%) patient had liver metastasis. CONCLUSIONS: Our study demonstrates that CIRT using the recommended dose fractionation is feasible and effective for cT1bN0M0 esophageal squamous cell carcinoma.

MicroRNAs associated with postoperative outcomes in patients with limited stage neuroendocrine carcinoma of the esophagus.

Esophageal neuroendocrine carcinoma (E-NEC) is an aggressive disease with a poor prognosis. The present study aimed to assess the role of surgery in the treatment of patients with resectable E-NEC, and identify a microRNA (miRNA/miR) signature in association with positive postoperative outcomes. Between February 2017 and August 2019, 36 patients with E-NEC who underwent curative surgery at the Japan Neuroendocrine Tumor Society partner hospitals were enrolled in the study. A total of 16 (44.4%) patients achieved disease-free survival (non-relapse group), whereas 20 (55.6%) patients developed tumor relapse (relapse group) during the median follow-up time of 36.5 months (range, 1-242) after surgery with a 5-year overall survival rate of 100 and 10.8%, respectively (P<0.01). No clinicopathological parameters, such as histological type or TNM staging, were associated with tumor relapse. Microarray analysis of 2,630 miRNAs in 11 patients with sufficient quality RNA revealed 12 miRNAs (miR-1260a, -1260b, -1246, -4284, -612, -1249-3p, -296-5p, -575, -6805-3p, -12136, -6822-5p and -4454) that were differentially expressed between the relapse (n=6) and non-relapse (n=5) groups. Furthermore, the top three miRNAs (miR-1246, -1260a and -1260b) were associated with overall survival (P<0.01). These results demonstrated that surgery-based multidisciplinary treatment is effective in a distinct subpopulation of limited stage E-NEC. A specific miRNA gene set is suggested to be associated with treatment outcome.

Large esophageal gastrointestinal stromal tumors resected thoracoscopically after oral imatinib therapy: a report of two cases.

Esophageal gastrointestinal stromal tumors (GISTs) are very rare, accounting for 2-5% of all GISTs. As with other GISTs, the principle of surgical treatment is complete resection with negative margins. In addition to biological grades of GISTs itselves, local recurrence due to capsular damage is a known risk. We describe two cases of massive esophageal GISTs that were successfully resected thoracoscopically after 2 months administration of 400 mg imatinib, with some discussion of the literature. Case 1, the patient was a 51-years-old man. After treated with 400 mg of imatinib as preoperative chemotherapy for 2 months, we performed surgery that included right thoracoscopic subtotal esophagectomy, gastric tube reconstruction, and jejunostomy. The resection specimen and histopathology were esophageal GIST-LtMtAeG, 110 × 95 mm. The postoperative course was uneventful, and was discharged on postoperative day 14. The patient has been recurrence free for 11 months postoperatively. Case 2, the patient was a 70-years-old man. After treated with 400 mg of imatinib as preoperative chemotherapy for 2 months, we performed surgery that included right thoracoscopic subtotal esophagectomy, gastric tube reconstruction, and jejunostomy. The resection specimen and histopathology were esophageal GIST-LtAeG, 90 × 52 mm. The postoperative course was uneventful, and was discharged on postoperative day 14. The patient has been recurrence free for 9 months postoperatively.

Primary esophageal cancer treated by esophagectomy with distal pancreatectomy: a report of three cases.

Esophagectomy and pancreatectomy are recognized as highly invasive procedures with relatively high complication rates; therefore, careful indication decisions are required. The depth of tumors invading adjacent organs, such as the aorta, vertebral body, and trachea, is defined as T4, and are estimated to have a low survival rate even after treatment. Conversely, pancreatic invasion of esophageal cancer is uncommon and not clearly defined as T4. Thus, it is often difficult to decide on a treatment strategy for locally advanced esophageal cancer. In this study, we describe three cases of esophagectomy with combined resection of the pancreas and spleen for esophageal cancer or esophagogastric junction cancer with invasion of the pancreatic body or tail. To the best of our knowledge, this is the first report of esophagectomy and combined resection of the pancreas and spleen in multiple patients from a single institution.

Efficacy of thoracotomy and thoracoscopic-assisted esophageal surgery in conversion and salvage surgeries: a retrospective study.

BACKGROUND: The esophagus has no serosa; therefore, esophageal cancer may quickly invade its adjacent organs. In recent years, reports of conversion surgery (CS) and salvage surgery (SS) have described resection of esophageal cancer previously considered unresectable, with the addition of intensive preoperative chemotherapy or chemoradiotherapy. Currently, there is no established method for determining whether tumor excision is possible. Additionally, differences in surgical approaches between facilities may influence outcome after resection. However, the option for resection is considered a significant factor in determining a patient's prognosis. METHODS: Patients who were diagnosed with advanced-stage (T3 or higher) squamous cell carcinoma of the esophagus and subsequently underwent resection with CS or SS were included in the study. Resection was performed through a small thoracotomy using a thoracoscope. Clinicopathologic factors, such as complete resection rate (R0) and prognosis, were investigated. RESULTS: A total of 49 surgeries were conducted: 39 CS and 10 SS cases. The male-to-female ratio was 37:12. R0:R1:R2 equals 42:3:4, and the R0 resection rate was 85.7%. The 5-year survival rates for CS and SS cases were 69.2% and 32.1%, respectively. The 5-year survival rates for R0, R1, and R2 resections were 63.4%, 0.0%, and 25.0%, and those for R0 and R1 + 2 resections were 63.4% and 14.3%, respectively, indicating that the prognosis for R0 resection cases was significantly better (P = 0.001 and P = 0.001, respectively). Regarding chemotherapy for CS, 29 patients received 5-FU and cisplatin therapy, whereas 10 patients received 5-FU, cisplatin, and docetaxel (DCF) therapy. After 2015, the ratio of DCF was significantly high, and the R0 resection rate was 100% in patients who received DCF therapy. CONCLUSIONS: In this study, a satisfactory R0 rate was achieved using the magnifying effect of the thoracoscope while ensuring safety during thoracotomy. TRIAL REGISTRATION: This was a single-center cohort study wherein clinical data were retrospectively registered. This study was approved by the Chiba Cancer Center review board (H29-262). All procedures adhered to the ethical standards of the responsible committee on human experimentation and the Helsinki Declaration of 1964 and its later amendments.

A right pulmonary vein abnormality treated with 3D CT assistance in thoracoscopic surgery for esophageal cancer: a case report.

BACKGROUND: Anomalous bifurcation of the right superior pulmonary vein is an important anomaly that should be recognized not only in respiratory and cardiac surgeries, but also in esophageal surgery for the safe performance of surgery. We report a case in which thoracoscopic esophagectomy was safely performed using preoperative three-dimensional computed tomography (3D CT) imaging. CASE PRESENTATION: An 81-year-old male patient received an upper gastrointestinal endoscopy, which revealed a 20-cm incisor at the entrance, 43-cm EGJ, and 30-mm large type 1 + IIc lesion between the 23-cm and 26-cm incisors; biopsy showed squamous cell carcinoma (SCC). Contrast-enhanced CT showed wall thickening in the anterior wall of the upper thoracic esophagus, without evidence of multi-organ invasion or lymph node metastasis. In addition, a break in the right pulmonary vein passing dorsal to the right main bronchus and flowing directly into the left atrium was observed, and 3D CT was performed preoperatively to confirm the 3D positioning. Positron emission tomography (PET)-CT showed a high degree of accumulation (SUVmax 19.95) in the upper thoracic esophagus. The patient was diagnosed with upper thoracic esophageal cancer, cT2N0M0 cStage II, and underwent thoracoscopic subtotal esophagectomy (three-region dissection) and gastric tube reconstruction. The dorsal inflow of the pulmonary vein in the right main bronchus, which was recognized on preoperative CT, was confirmed and preserved. The pathological diagnosis was basaloid squamous cell carcinoma, pT1b(SM1)N0(0/58)M0 pStage I. The postoperative course was uneventful, and the patient was discharged on postoperative day 20. CONCLUSIONS: The anomalous bifurcation of the pulmonary vein in the right upper lobe area required attention because of its potential to cause massive bleeding and difficulty in securing the operative field if misidentified and damaged during surgery. Although it is not frequently encountered, it is the bifurcation anomaly that esophageal surgeons must bear in mind due to its severe consequences. Preoperative image-reading and intraoperative manipulation of this vessel are imperative for surgical safety.

CA19-9-producing esophageal adenocarcinoma originating from the esophageal cardia of the mid-thoracic esophagus: a case report.

BACKGROUND: Although there are many studies on primary esophageal adenocarcinoma arising from Barrett's esophagus or ectopic gastric mucosa, reports on adenocarcinoma arising from esophageal cardiac glands are extremely rare. Herein, we report a case of mid-thoracic cancer antigen 19-9 (CA 19-9)-producing primary esophageal adenocarcinoma, which presumably originated from the cardiac glands. CASE PRESENTATION: A 74-year-old man was referred to our department with advanced esophageal cancer, which initially presented with dyspepsia. Serum levels of cancer antigen 19-9 (CA 19-9) were elevated (724.89 U/ml). Upper gastrointestinal endoscopy revealed a type 2 tumor on the posterior wall of the mid-thoracic esophagus approximately 29-32 cm from the incisor. Mucosal biopsy was consistent with a diagnosis of adenocarcinoma. Contrast-enhanced computed tomography showed a circumferential wall thickening in the mid-thoracic esophagus without enlarged lymph nodes or distant metastasis. Positron emission tomography-computed tomography showed accumulation in the primary tumor, but no evidence of lymph node or distant metastasis. According to these findings, the adenocarcinoma was staged as cT3N0M0, thereby, requiring subtotal esophagectomy with lymph node dissection. Postoperative course was uneventful. Histopathologic analysis revealed a 50 × 40 mm moderately differentiated adenocarcinoma with invasion to the thoracic duct and lymph node metastasis at #108(1/4), #109R(1/3), and #109L(1/3). After surgery, the stage was revised to moderately differentiated pT4apN2pM0 (pStage III). Immunostaining revealed expression of CA19-9 and suggested esophageal cardiac gland origin of the tumor. Three months after the surgery, the patient showed no recurrence and is undergoing outpatient observation. CONCLUSIONS: We experienced a case of mid-thoracic CA19-9-producing primary esophageal adenocarcinoma, which was presumed to have originated in the esophageal cardiac glands. Due to the scarcity of studies regarding this condition, specific management needs to be further clarified.

Surgical resection of undifferentiated pleomorphic sarcoma (UPS) with jejunal perforation, a suspected case of metastasis of lung cancer.

Undifferentiated pleomorphic sarcoma (UPS) in the gastrointestinal tract is rare. According to the diagnostic criteria after the World Health Organization 2013 reclassification, there has been only one case of UPS with perforation of the gastrointestinal tract. A 71-year-old man who was undergoing outpatient chemotherapy at the department of respiratory medicine of our hospital for lung cancer and brain metastasis, was admitted to our hospital with sudden high fever and abdominal pain. A computed tomography scan showed free air in the abdominal cavity with thickening of part of the jejunal wall. We suspected jejunal metastasis of lung cancer and performed emergency surgery for acute peritonitis due to gastrointestinal perforation in the same area. A Bormann type 2 tumour was found in the jejunum with perforation. The histopathological diagnosis was UPS. Ten months have passed since the surgery, and there has been no recurrence of UPS and no significant change in lung cancer. Primary UPS of the gastrointestinal tract is rare, and cases with perforation are extremely rare. Currently, ten months have passed since the surgery, and no recurrence has been observed. We encountered a case of UPS in which it was difficult to distinguish metastasis from lung cancer to the jejunum, and the emergency surgery gave us the chance to confirm the definitive diagnosis and save the patient's life.

Laparoscopic ileo-transverse bypass may contribute to achieving curative resection for locally advanced right colon cancer: a case report.

BACKGROUND: The strategy for treating obstructive colon cancers with metastatic lesions remains unclear. Herein, we report a case of laparoscopic ileo-transverse colon bypass (LITB) before preoperative chemotherapy for an obstructive right colon cancer. CASE PRESENTATION: A 59-year-old woman was referred to our institution (Department of Gastroenterological Surgery, Chiba Cancer Center) for liver tumors detected on ultrasound. The clinical diagnosis was ascending colon cancer with multiple liver metastases. Based on the criteria of the International Union against Cancer Committee, 8th edition, the staging was confirmed as cT4aN1M1a(H), cStage IV. Although the primary tumor in the ascending colon extended beyond the colonic wall, curative resection was possible for both primary and metastatic tumors. We planned to administer chemotherapy before the radical surgery to obtain tumor-free resection margins; however, as the obstruction was fatal, LITB was prioritized and performed using five ports. An intracorporeal side-to-side anastomosis was performed between the ileum, 25 cm from the terminal ileum, and the transverse colon. The patient was discharged on postoperative day 18 without any complications. After LITB, for preoperative chemotherapy, five courses of capecitabine plus oxaliplatin (CapeOX) + bevacizumab were administered. Six weeks after the preoperative chemotherapy, right hemicolectomy with D3 lymph node dissection and right hepatectomy were performed. Pathological findings of the resected specimen confirmed curative resection of both lesions, and a favorable effect of chemotherapy was obtained. The patient has been alive for over 8 months after the surgery, with no evidence of cancer recurrence. CONCLUSIONS: This case report demonstrates the effectiveness of LITB for obstructive right colon cancer in patients who need preoperative chemotherapy.

[Intracorporeal Anastomosis in Laparoscopic Colectomy with Blood Flow Confirmation by Fluorescence Angiography].

We verified the significance of intestinal blood flow evaluation by indocyanine green(ICG)fluorescence during intracorporeal anastomosis in laparoscopic colectomy which was performed from July 2019 to December 2019 in our institute. For 11 cases of intracorporeal anastomosis, we examined the patient background, surgical results such as operation time and blood loss, evaluation of intraoperative ICG blood flow, and perioperative complications. In all cases, after the mesentery treatment in the abdominal cavity and before the intestinal incision, the blood flow of the planned anastomosis site was evaluated by ICG fluorescence observation. No cases were required to be changed the anastomosis site. The average operation time was 240 minutes and the average blood loss was 10 mL. There were no perioperative complications such as anastomotic leakage, stenosis, bleeding, nor wound infection. It was suggested that the intraoperative evaluation of ICG blood flow during intracorporeal anastomosis in laparoscopic colectomy may contribute to the suppression of complications such as anastomotic leakage.

[A Study of Laparoscopic Stoma Creation for Patients with Colorectal Cancer].

There are few reports on laparoscopic stoma creation; we report here our experience with laparoscopic stoma creation. PATIENTS AND METHODS: Seven patients who underwent laparoscopic stoma creation between April 2019 and December 2019 were studied and their clinical outcome was evaluated retrospectively. Operation approach: We performed a colostomy in the transverse colon. At first, we insert a 12 mm first port into the site of stoma marking. And more, we insert three 5 mm ports on the opposite side of the first port. We remove the adhesions of the intestinal tract and create a colostomy. RESULT: We changed open method 2 cases out of 7 cases due to extensive adhesion. In laparoscopically, we had an operation time of 97 (42-130) minutes and a blood loss of 5(2-40) mL. We had no postoperative complications or stoma problems. CONCLUSION: Laparoscopic stoma creation was useful due to few postoperative complications and can be rapidly transferred to chemotherapy.

Cell-free microRNA-1246 in different body fluids as a diagnostic biomarker for esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma is a malignant tumor with unfavorable prognosis. In this study, we investigated the usefulness of microRNA (miR)-1246 detection in various body fluids as a biomarker for this disease. A total of 72 patients with esophageal squamous cell carcinoma were enrolled, and their blood, urine, and saliva samples were collected prior to treatment. Reverse transcription-polymerase chain reaction of miR-1246 was performed, and pre- and postoperative and intraday fluctuations in its expression were examined. The expression of miR-1246 in the blood and urine was significantly higher in the patients with esophageal squamous cell carcinoma than in 50 healthy control subjects. Receiver operating characteristic curves showed that the area under the curve values were 0.91 (sensitivity 91.7%, specificity 76.0%), 0.82 (sensitivity 90.3%, specificity 62.0%), and 0.80 (sensitivity 83.3%, specificity 66.0%) in the serum, urine, and saliva, respectively. A relatively high diagnostic performance of miR-1246 was observed in all samples, which was better than that of the existing biomarkers squamous cell carcinoma antigen, carcinoembryonic antigen, and cytokeratin 19 fragment. No clear correlation was observed in the levels of miR-1246 expression among the three body fluids. Postoperatively, serum samples displayed significantly decreased miR-1246 levels. Although not significant, changes in the miR-1246 levels were observed at all collection times, with large fluctuations in the saliva. Meanwhile, serum miR-1246 expression was found to be associated with the disease prognosis. The results indicate that the levels of miR-1246 in the urine, saliva, and serum are a useful biomarker for esophageal squamous cell carcinoma and support the use of urine samples instead of blood samples for noninvasive diagnosis.

CD133 prevents colon cancer cell death induced by serum deprivation through activation of Akt-mediated protein synthesis and inhibition of apoptosis.

During the early phase of tumorigenesis, primary malignant cells survive within a low nutrition environment caused by a poorly organized vascular system. Here, we sought to determine the functional significance of CD133 in the survival of cancer cells under nutrient-poor conditions. Knockdown and overexpression experiments demonstrated that CD133 suppresses colon cancer cell death induced by serum deprivation through activation of Akt-mediated anti-apoptosis and protein synthesis pathways. Furthermore, serum deprivation increased the amount of endogenous CD133 protein, which was regulated at least in part by phosphoinositide 3-kinase. Thus, it is highly likely that CD133 contributes to the acquisition/maintenance of the resistance to stress arising from nutrient deficiency in early avascular tumor tissues.

Multipanel assay of 17 tumor-associated antibodies for serological detection of stage 0/I breast cancer.

Because the production of tumor-associated antibodies (TAA) is a humoral immune response in cancer patients, serum autoantibodies may be detected even in patients with early-stage tumors. Seventeen recombinant proteins with tags in Escherichia coli (p53, RalA, p90, NY-ESO-1, HSP70, c-myc, galectin-1, Sui1, KN-HN-1, HSP40, PrxVI, p62, cyclin B1, HCC-22-5, annexin II, HCA25a, and HER2) were applied as capturing antigens in sandwich ELISA to measure serum IgG levels. Sera from 73 healthy donors and 386 patients with breast cancer, including 182 stage 0/I patients, were evaluated using cutoff values for each TAA equal to the mean +3 SD of the serum levels of healthy controls. The positive TAA rates were relatively high for p53 (10%) and RalA (10%). The positive rates of all TAA of stage 0/I were similar to those of all patients. Even in the stage 0/I patients, 24% showed that two or more TAA were positive, and the positive rate of a five-TAA combination assay was 37%. The positivity rate was significantly higher for the non-luminal type than for the luminal type (P = .003). Logistic analysis showed that seropositivity (positive for one or more TAA) in breast cancer patients was independent from any TNM factor or disease stage and was significantly associated with histological grade in the multivariate analysis (P = .007). TAA in breast cancer patients may be useful for early detection. However, seropositivity of breast cancer reflects the tumor characteristics but not the disease stage.