Pedunculated early colorectal cancer with nodal metastasis: a case report.

BACKGROUND: Pedunculated polyps are more likely to be amenable to complete resection than non-pedunculated early colorectal cancers and rarely require additional surgery. We encountered a patient with a pedunculated early colorectal cancer that consisted of poorly differentiated adenocarcinoma with lymphatic invasion. We performed an additional bowel resection and found nodal metastasis. CASE PRESENTATION: A 43-year-old woman underwent colonoscopy after a positive fecal occult blood test. The colonoscopist found a 20-mm pedunculated polyp in the descending colon and performed endoscopic resection. Histopathologic examination revealed non-solid type poorly differentiated adenocarcinoma. The lesion invaded the submucosa (3500 µm from the muscularis mucosa) and demonstrated lymphatic invasion. In spite of the early stage of this cancer, the patient was considered at high risk for nodal metastasis. She was referred to our institution, where she underwent bowel resection. Although there was no residual cancer after her endoscopic resection, a metastatic lesion was found in one regional lymph node. The patient is undergoing postoperative adjuvant chemotherapy, and there has been no evidence of recurrence 3 months after the second surgery. CONCLUSIONS: Additional bowel resection is indicated for patients with pedunculated polyps and multiple risk factors for nodal metastasis, such as poorly differentiated adenocarcinoma and lymphatic invasion. We encountered just such a patient who did have a nodal metastasis; herein, we report her case history with a review of the literature.

Determining the difference in the efficacy and safety of self-expandable metallic stents as a bridge to surgery for obstructive colon cancer among patients in the CROSS 0 group and those in the CROSS 1 or 2 group: a pooled analysis of data from two Japanese prospective multicenter trials.

PURPOSE: This study compared the feasibility and safety of endoscopic placement of self-expandable metallic stents (SEMSs) as a bridge to surgery (BTS) between patients with obstructive colorectal cancer (CRC) classified as ColoRectal Obstruction Scoring System (CROSS) 0 and those with CROSS 1 or 2. METHODS: We conducted a post hoc analysis of two prospective, observational, single-arm multicenter clinical trials and performed a pooled analysis of the data. In total, 336 consecutive patients with malignant colorectal obstruction underwent SEMS placement. The primary endpoint was clinical success, defined as resolution of symptoms and radiological findings within 24 h. Secondary endpoints were technical success and adverse events. RESULTS: High clinical (98.0% vs. 98.4%) and technical (96.7% vs. 97.8%) success rates were observed in both groups (CROSS 0 vs. CROSS 1 or 2). The adverse event rate was low. The mean stricture length was lower (3.8 ± 1.2 cm vs. 4.4 ± 1.8 cm) and laparoscopic surgery more common (56.7% vs 52.2%) in the CROSS 0 group than in the CROSS 1 and 2 group. CONCLUSION: This study was the first to compare the degree of stricture in different CROSS groups and demonstrated comparable results with respect to the short-term efficacy and safety of SEMS placement as a BTS for obstructive CRC in CROSS 0, 1, and 2 patients.

Usefulness of the endoscopic surgical skill qualification system in laparoscopic colorectal surgery: short-term outcomes: a single-center and retrospective analysis.

BACKGROUND: The use of laparoscopic surgery has become widespread, and many surgeons are striving to acquire the necessary techniques for it. The Endoscopic Surgical Skill Qualification System (ESSQS), established by the Japan Society for Endoscopic Surgery, serves to maintain and improve the quality of laparoscopic surgery in Japan. In this study, we aimed to determine whether ESSQS certification is useful in maintaining and improving the quality of surgical techniques and in standardization of laparoscopic surgery in Japan. METHODS: This retrospective study used data from the Institute for Integrated Medical Sciences, Tokyo Women's Medical University, Japan. From January 2016 to October 2017, 241 patients with colorectal cancer underwent laparoscopic surgery. Of them, 220 patients were selected and divided into two groups on the basis of surgery performed by an ESSQS-qualified surgeon (QS group) (n = 170) and a non-ESSQS-QS (NQS) (n = 50). We compared the short-term results in the two groups and examined those before and after propensity score matching (PSM). RESULTS: Mean operation time was longer in the NQS group than in the QS group. Furthermore, mean blood loss was significantly less in the QS group. These were similar before and after PSM. The rate of conversion to open surgery was significantly higher in the NQS group before PSM. However, the rate of postoperative complications was not different between the two groups. CONCLUSIONS: A laparoscopic procedure performed by ESSQS-QS often leads to good short-term outcomes. Thus, the ESSQS system works and is potentially useful in maintaining and improving the quality of surgical techniques and in standardization of laparoscopic surgery in Japan.

Efficacy and short-term outcomes of preoperative chemoradiotherapy with intermittent oral tegafur-uracil plus leucovorin in Japanese rectal cancer patients: a single center experience retrospective analysis.

BACKGROUND: Various types of preoperative chemoradiotherapy (CRT) have been established for rectal cancer; thus, Physicians will need to refine the selection of appropriate preoperative CRT for different patients since there are various treatment regimens. Oral tegafur-uracil (UFT) plus leucovorin (LV) is commonly used to treat rectal cancer in Japan. Oral chemotherapy offers patients many potential advantages. Since 2008, we have been performing preoperative CRT with intermittent oral UFT plus LV in locally advanced rectal cancer patients to prevent postoperative local recurrence. Here, in a retrospective analysis, we evaluated the efficacy and short-term outcomes of preoperative CRT with intermittent oral UFT plus LV. METHODS: We analyzed data from 62 patients with locally advanced rectal cancer, including 31 patients who underwent preoperative CRT between 2009 and 2013 (the CRT group) and 31 patients who were treated with surgery alone between 2001 and 2008 (the non-CRT group). Clinicopathologically, both groups included patients with rectal cancer at clinical tumor stages III-IV or clinical node stages 0-III. In the CRT group, curative operations were performed ≥8 weeks after CRT. Patients were concomitantly treated with 2 cycles of oral UFT (300 mg/m2/day, days 1-14 and 29-42) plus LV (75 mg/day, days 1-14 and 29-42) and 45 Gy of radiotherapy. Chemotherapy was repeated every 28 days, followed by a 2-week break. RESULTS: The completion rate of CRT was high at 94% (n = 29/31). The downstaging rate of CRT was 61% (n = 19/31). The pathological complete response rate was 6.5% (n = 2/31). Significant differences were observed in the 3-year local recurrence rate between the two groups (P < 0.05). CONCLUSIONS: Preoperative CRT with intermittent oral UFT plus LV appears to be a tolerable and effective treatment for Japanese patients with rectal cancer. A further investigation of a diversification of preoperative CRT for Japanese rectal cancer patients is required.

Application of regenerative medical technology using tissue-engineered cell sheets for endoscopic submucosal dissection of esophageal neoplasms.

We have developed a technique for endoscopic transplantation of cultured autologous oral mucosal epithelial cell sheets to an esophageal ulcer following endoscopic submucosal dissection (ESD). The epithelial cell sheets successfully prevented esophageal stricture after ESD. Key technology is that epithelial cell sheets cultured from oral mucosal tissue and attached proteins can be harvested using cell sheet technology and can be transplanted to a wound site without the use of adhesive material. This regenerative procedure can promote the epithelialization of ulceration safely and effectively. In the near future, the development of advanced endoscopic treatment of regenerative medicine shows promise.

Primary esophageal mucosa-associated lymphoid tissue lymphoma treated by endoscopic submucosal dissection.

Primary esophageal mucosa-associated lymphoid tissue (MALT) lymphoma is rare. There have been few reports about early primary esophageal MALT lymphoma being treated endoscopically. The clinical profile of primary esophageal MALT lymphoma is currently unclear, so it is important to accumulate more information about early esophageal MALT lymphoma. To achieve early detection of esophageal MALT lymphoma, we need more accurate knowledge and information about the macroscopic and morphological features of this tumor. Endoscopic resection is one of the most effective treatments. With respect to the lateral and vertical margins of the resected specimen, endoscopic submucosal dissection (ESD) may be superior to endoscopic mucosal resection for treating early esophageal MALT lymphoma. Here we report the macroscopic appearance of the tumor which is the first successful case of ESD for early esophageal MALT lymphoma.

Endoscopic treatment of anastomotic leakage after colorectal surgery by using polyglycolic acid sheets and fibrin glue.

We describe the case of a 66-year-old man with an anastomotic fistula after rectal surgery, which was treated colonoscopically using polyglycolic acid sheets and fibrin glue. Polyglycolic acid sheets and fibrin glue have been used in thoracic surgery and otolaryngology to reinforce sutures and prevent air leakage. There have been recent reports of their use in endoscopic surgery for the closure of intraoperative perforations after endoscopic submucosal dissection and for fistula closure after upper gastrointestinal tract surgery. However, anastomotic fistulas in colorectal surgery are difficult to visualize endoscopically and may be difficult to suture with clips due to fibrosis. Polyglycolic acid sheets can be easily trimmed, and the fistula can be easily filled using these sheets; moreover, using fibrin glue to fix the sheets may enable fistula closure in areas that are difficult to visualize endoscopically.

A New Self-Expandable Metallic Stent with Low Axial Force and a High Axial Force Zero-Border Shows a Very Low Perforation Rate in Malignant Colorectal Obstruction: A Japanese Multicenter Prospective Study.

Background: Recently, there has been a significant increase in the utilization of self-expandable metallic stents (SEMSs) for treating malignant colorectal obstructions through colorectal stenting. The mechanical properties of SEMSs are usually considered to affect clinical outcomes of patients with malignant colorectal obstructions. Methods: This single-arm, prospective, multicenter study of SEMS with a lower axial force and high axial force zero-border included 200 patients with malignant colorectal obstruction. Technical and clinical success, stent patency, and adverse events associated with SEMS placement were evaluated. Results: One patient was excluded, and 199 patients were evaluated. The treatment intent was bridge-to-surgery in 129 and palliation in 70 patients. Technical and clinical success rates were 99.5% and 97.0%, respectively. The percentage of the ColoRectal Obstruction Scoring System scores of 3 or higher improved significantly from 19.2% before placement to 93.9% after placement. Clinical success was not achieved in five patients due to insufficient stent expansion in four patients and stent occlusion in one patient. Only one patient underwent emergency surgery for perforation of the proximal colon, far from where the stent was placed; the rescue procedure was not performed, despite no improvement in proximal dilatation due to insufficient stent expansion. Among the palliation cohort, 15 patients received chemotherapy, including molecular-targeted agents such as bevacizumab. There were no fatal cases related to stent placement. Conclusions: For management of malignant colorectal obstruction, this newly developed SEMS with low axial force and a high axial force zero-border showed high technical and clinical success rates, and an extremely low perforation rate (0.5%).

Prevention of esophageal stricture after endoscopic submucosal dissection using tissue-engineered cell sheets.

BACKGROUND & AIMS: The use of esophageal endoscopic submucosal dissection (ESD) to remove superficial esophageal neoplasms is gradually becoming more common in Japan. However, large-scale esophageal ESD often requires subsequent multiple balloon dilations to prevent postoperative esophageal stricture. We investigated the safety and efficacy of endoscopic transplantation of tissue-engineered autologous oral mucosal epithelial cell sheets in preventing formation of strictures after ESD. METHODS: We performed an open-label, single-arm, single-institute study. We collected specimens of oral mucosal tissue from 9 patients with superficial esophageal neoplasms. Epithelial cell sheets were fabricated ex vivo by culturing isolated cells for 16 days on temperature-responsive cell culture surfaces. After a reduction in temperature, these sheets were endoscopically transplanted directly to the ulcer surfaces of patients who had just undergone ESD. All patients were monitored by endoscopy once a week until epithelialization was complete. RESULTS: Autologous cell sheets were successfully transplanted to ulcer surfaces using an endoscope. Complete re-epithelialization occurred within a median time of 3.5 weeks. No patients experienced dysphagia, stricture, or other complications following the procedure, except for one patient who had a full circumferential ulceration that expanded to the esophagogastric junction. CONCLUSIONS: Sutureless, endoscopic transplantation of carrier-free cell sheets composed of autologous oral mucosal epithelial cells safely and effectively promotes re-epithelialization of the esophagus after ESD. Patients in this study did not experience any serious complications. This procedure might be used to prevent stricture formation following ESD and improve patients' quality of life. Further study will be needed to show that stricture formation can be prevented.

Depth of submucosal invasion in the sessile and superficial types of submucosal invasive colorectal carcinoma: objective versus subjective measurement.

BACKGROUND/AIMS: When endoscopic resection (ER) is performed for submucosal invasive colorectal carcinoma (SICC), it may be difficult to determine whether to perform follow-up observation or surgical resection with lymph node dissection. The Japanese Guidelines provide guidelines for additional treatment after ER. Depth of submucosal invasion (SM depth) is measured in the same manner for both the sessile type and the superficial type. We compared the SM depth in the sessile and superficial types of SICC. METHODOLOGY: Among patients who underwent surgical resection of SICC between 1990 and 2010, this study included 118 consecutive patients with SICC. The SM depth in the sessile and superficial macroscopic morphological types was evaluated on the basis of both objective and subjective measurement of SM depth. RESULTS: The SM depth overall was significantly greater in the sessile type (p < 0.0001). In SM1 cancer, no significant difference was seen between the two groups. In SM2 and SM3 cancer, SM depth in the sessile type was significantly greater than that in the superficial type (p < 0.0001). CONCLUSIONS: In the basis of subjective measurement of SM depth, it was suggested that the sessile and superficial types of SICC may need to be evaluated separately to determine the correlation.

Transplantation of hybrid adipose-derived stem cell sheet with autologous peritoneum: An in vivo feasibility study.

Introduction: In regenerative medicine, cell sheet engineering has various advantages, including the retention of cells at the transplantation site for a longer period and the local delivery of growth factors and cytokines. Adipose-derived stem cell (ASC) is widely used owing to their various functions such as wound healing, immunomodulation, and nerve regeneration, in addition to their ability to differentiate into adipocytes, chondrocytes, and osteoblasts. ASC sheet generated using cell sheet engineering is considered effective in preventing anastomotic leakage, a serious postoperative complication in gastrointestinal surgery. However, the ASC sheet is too soft, thin, and brittle to handle with laparoscopic forceps during the operation. Therefore, we considered using the peritoneum, which is stiff and easy to collect while operating, as an alternative support. In this study, we explored the feasibility of using the peritoneum as a support for the precise transplantation of ASC sheets during surgery. Methods: ASCs were isolated from the subcutaneous fat of the inguinal region of Sprague-Dawley (SD) transgenic rats expressing green fluorescent protein. ASCs were cultured until passage 3, seeded in temperature-responsive culture dishes, and the resulting ASC sheet was harvested at more than 80% confluency. Non-transgenic SD rats were used for transplant experiments. The wall peritoneum was harvested from SD rats following laparotomy, and hybrid adipose-derived stem cell (HASC) sheet was prepared by laminating the peritoneum with ASC sheet. The cell sheets were transplanted on the backs of SD rats following the incision. On post-transplantation days 3 and 7, the specimens were extracted. ASC and HASC sheets were then compared macroscopically and histopathologically. Results: HASC sheet transplantation was macroscopically and histopathologically more effective than ASC sheet transplantation. The peritoneum provided sufficient stiffness as a support for precise transplantation. Conclusion: The newly developed HASC sheet, which combine the advantages of ASC sheet with those of the peritoneum, could be more useful for clinical application than the ASC sheet alone.

Multiple Small Bowel Gastrointestinal Stromal Tumors Associated with Neurofibromatosis Type 1 that Were Not Detected by Endoscopy: A Case Report.

We treated a 39-year-old Japanese man who was admitted for an abdominal mass. He had had neurofibroma-like skin lesions since childhood. Computed tomography and endoscopic ultrasound results were consistent with a tumor in the small intestine. Although the tumor was undetectable by single-balloon endoscopy, the patient's background and imaging results led us to suspect a gastrointestinal stromal tumor (GIST). He also met the diagnostic criteria for neurofibroma type 1 (NF1). We performed a surgical removal of the tumor, and the biopsy results led to a definitive diagnosis of GIST. Small bowel GISTs should be considered in cases of NF1.

Fabricated autologous epidermal cell sheets for the prevention of esophageal stricture after circumferential ESD in a porcine model.

BACKGROUND: Endoscopic submucosal dissection (ESD) is an accepted treatment for early esophageal carcinoma. However, resection of a large mucosal area, as with circumferential ESD, induces severe stricture formation. OBJECTIVE: To evaluate the efficacy of cultured autologous epidermal cell sheets to prevent severe esophageal constriction after circumferential ESD. DESIGN: Animal study. SETTING: University institute. INTERVENTION: Eight pigs underwent circumferential esophageal ESD while under general anesthesia. In 4 pigs, fabricated autologous epidermal cell sheets were endoscopically transplanted to the central ESD sites immediately after the ESD. The other 4 pigs underwent circumferential ESD only. Necropsy and histological assessment were performed at 1 and 2 weeks post-ESD. MAIN OUTCOME MEASUREMENTS: Weight gain, degree of mucosal constriction, and histological assessments. RESULTS: All pigs in the control group showed severe esophageal constriction after 2 weeks. The control and transplanted groups had weight gains of -10.3% and 0.3% (P = .03), respectively, and the mean degrees of constriction were 88% and 56% (P < .01), respectively. Early re-epithelialization and mild fibrosis in the muscularis were observed in the transplanted group. LIMITATIONS: Animal study, small sample size. CONCLUSIONS: Fabricated autologous skin epidermal cell sheets would be useful in preventing severe esophageal constriction after circumferential ESD.

Usefulness of clip traction in the early phase of esophageal endoscopic submucosal dissection.

BACKGROUND: The usefulness of clip traction in endoscopic submucosal dissection (ESD) for early esophageal carcinoma was investigated. METHODS: A total of 87 patients who underwent ESD for esophageal squamous cell carcinoma were included in the study. The hook knife method was used for ESD. Twenty patients underwent ESD without clip traction (non-clip group) and 67 underwent procedures in which clip traction was used (clip group). A clip with a string was attached to the oral edge of the lesion after mucosal incision in the clip group. RESULTS: ESD was successful in all cases. Wide exposure of the submucosal tissue below the lesion was obtained by applying tension to the clip traction. The duration of ESD was shorter in the clip group, and there was a significant difference in duration between the non-clip and clip groups. There were no complications of ESD in the clip group, but muscle layer injury occurred in three patients in the non-clip group. CONCLUSION: Clip traction shortens operating time and is safer in esophageal ESD. Clip traction is recommended as a useful auxiliary procedure.

[Regenerative medicine using cell-sheet engineering].

We have developed a novel strategy for regenerative medicine to recover tissue functions using temperature-responsive cell culture surfaces. To overcome the disadvantages of conventional methods such as the usage of single-cell suspension injections and biodegradable polymer scaffolds, we use transplantable cell sheets fabricated with temperature-responsive culture surfaces for cell delivery. Here, we summarize our progress in promoting regenerative medicine using cell-sheet engineering with respect to research and regulatory systems and describe recent challenges in the standardization of cell-sheet engineering.

Multiple intestinal lymphangiomas with episodic hemorrhage requiring partial laparoscopic resection: a case report.

BACKGROUND: Lymphangioma is a non-epithelial tumor marked by aggregates of abnormally dilated lymphatics. Mesenteric occurrences account for < 1% of all cases, and < 0.05% involve the gastrointestinal tract. Most are confined to children, rarely affecting adults. CASE PRESENTATION: Herein, we describe an elderly Japanese woman with anemia, hypoalbuminemia, and episodic bleeding due to multiple intestinal lymphangiomas. Abdominal computed tomography revealed multiple low-density defects of mesentery, with areas of intermediate (T1 images) or high (T2 images) signal intensity similarly dispersed in magnetic resonance scanning sequences. Single-balloon enteroscopy was undertaken, enabling identification and tattooing of a small intestinal bleeding source. Laparoscopy-assisted resection at this site served to control related hemorrhage, removing a histologically confirmed hemolymphangioma. Having recovered uneventfully, the patient remained stable 2 months postoperatively. CONCLUSIONS: Although rare in adults, mesenteric or gastrointestinal lymphangiomas must be considered in a setting of anemia and hypoalbuminemia. Complete resection is advantageous to improve patient symptoms, but limited resection of multiple lesions may be equally effective.

Fabrication and validation of autologous human oral mucosal epithelial cell sheets to prevent stenosis after esophageal endoscopic submucosal dissection.

OBJECTIVES: Human oral mucosal epithelial cells derived from 7 healthy volunteer donors were cultured in a clean room in a cell-processing center (CPC) according to good manufacturing practice guidelines. Cell culture and fabricated transplantable epithelial cell sheets were validated for treating ulcers after endoscopic mucosal dissection. METHODS: The clonal growth and morphology of the human oral mucosal epithelial cells seeded on temperature-responsive surfaces were observed. During the cultivation, sterilization tests were performed to validate the environment in the CPC. To validate the purity and morphology of fabricated epithelial cell sheets, cell sheets harvested from temperature-responsive surfaces by temperature reduction were examined by histology and flow cytometry. RESULTS: Human oral mucosal epithelial cells were successfully cultured and harvested as continuous cell sheets from temperature-responsive culture inserts without any animal-derived materials. During the cultivations, the sterile environment in the CPC was confirmed. The results of histological and flow cytometry analysis showed the high reproducibility of stratification and the purity of the fabricated human oral mucosal epithelial cell sheets. CONCLUSIONS: The method for fabricating epithelial cell sheets shown in this study was suitable for the validation for clinical trials and suggested usability of the fabricated cell sheets.

[Ileocecal resection for idiopathic intussusception in an adult].

A 60-year-old woman presented with abdominal pain and bloody stools. On examination, there was muscular guarding and rebound tenderness in the right abdomen. Abdominal ultrasonography and CT showed a concentric structure in the ascending colon and ascites. Emergency surgery was performed with a preoperative diagnosis of idiopathic intussusception. At operation, an intussusception was not seen, but ileocecal resection was performed to remove a possible tumor. No lesion that could have caused intussusception was identified in the resected bowel segment, so the condition was idiopathic.

Laparoscopic appendectomy for appendiceal intussusception assisted by colonoscopy: A case report.

INTRODUCTION: Appendiceal intussusception sometimes results from appendiceal cancer. Ileocecal resection instead of appendectomy is often chosen as a treatment as it is technically difficult to resect the appendix alone without causing dissemination of appendiceal cells to the abdominal cavity. Herein, we present the first report of a case in which appendiceal intussusception was treated by resection of the appendix alone via simultaneous colonoscopy and laparoscopy. PRESENTATION OF CASE: A 40-year-old man underwent laparoscopic appendectomy for appendiceal intussusception. Since a neoplastic cause could not be completely ruled out, we planned to carry out oncologically safe appendectomy that would not expose the tumor to the abdominal cavity. The resection was performed in the lumen of the cecum rather than in the abdominal cavity to prevent dissemination of appendiceal cells to the peritoneal cavity during surgery. Histopathologic examination revealed chronic inflammation of the appendix but no malignancy. The postoperative course was uneventful. DISCUSSION: Here, we present a case in which laparoscopic resection of the mesoappendix and colonoscopy-assisted resection of the appendix were performed in combination in a patient with appendiceal intussusception. When the possibility of malignancy is low, this maneuver may prevent patients from undergoing ileocecal resection with lymph node dissection as it prevents exposure of the abdominal cavity to the tumor. CONCLUSION: Simultaneous performance of laparoscopy and intraoperative colonoscopy is feasible and, from an oncological viewpoint, may be preferable when the cause of appendiceal intussusception is unknown or malignancy is not suspected.