Cadaver surgical training and research using donated cadavers in the field of surgery in Japan: an overview of reports from 2012 to 2021.

PURPOSE: Subsequent to the publication of "Guidelines for cadaver dissection in education and research of clinical medicine" in 2012, cadaver surgical training (CST) was implemented in various surgical fields across Japan. This article summarizes the recent progress made in the implementation of CST using donated cadavers, and its associated research, focusing on the field of surgery, and discusses its future direction. METHODS: All reports from 2012 to 2021 registered with the CST Promotion Committee of the Japan Surgical Society were analyzed. There were 292 (24.9%) programs in the field of surgery, including acute care surgery, out of a total of 1173 programs overall. Data were classified by the purpose of implementations and fields of surgery, with subclassification by organ, costs and participation fees. RESULTS: CST and its research were introduced in 27 (33.3%) of a total 81 universities. The total number of participants was 5564 and the major (80%) purpose of the program was to advance surgical techniques. When classified by objectives, 65, 59 and 11% were for mastering operations for malignant disease, minimally invasive surgery, and transplantation surgery, respectively. CONCLUSION: CST in the field of surgery is increasing progressively in Japan, but still with disproportionate dissemination. Further efforts are needed to achieve full adoption.

Guidelines for cadaver dissection in education and research of clinical medicine (The Japan Surgical Society and The Japanese Association of Anatomists).

This article translates the guidelines for cadaver surgical training (CST) published in 2012 by Japan Surgical Society (JSS) and Japanese Association of Anatomists from Japanese to English. These guidelines are based on Japanese laws and enable the usage of donated cadavers for CST and clinical research. The following are the conditions to implement the activities outlined in the guidelines. The aim is to improve medicine and to contribute to social welfare. Activities should only be carried out at medical or dental universities under the centralized control by the department of anatomy under the regulation of Japanese law. Upon the usage of cadavers, registered donors must provide a written informed-consent for their body to be used for CST and other activities of clinical medicine. Commercial use of cadavers and profit-based CST is strongly prohibited. Moreover, all the cadaver-related activities except for the commercial-based ones require the approval of the University's Institutional Review Board (IRB) before implementation. The expert committee organized at each university for the implementation of CST should summarize the implementation of the program and report the details of the training program, operating costs, and conflicts of interest to the CST Promotion Committee of JSS.

Usage of cadavers in surgical training and research in Japan over the past decade.

The "Guidelines for Cadaver Dissection in Education and Research of Clinical Medicine" drafted by the Japan Surgical Society (JSS) and the Japanese Association of Anatomists in 2012 helped dispel legal concerns over cadaver surgical training (CST) and the usage of donated human bodies for research and development (R&D) in the country. Subsequently, in the fiscal year 2018, the Ministry of Health, Labour and Welfare increased the funding for CST, prompting its wider implementation. This study analyzed data obtained in 2012-2021 through the reporting system of the JSS-CST Promotion Committee to map the usage of cadavers for clinical purposes, specifically education and R&D, in Japan. We found that the number of medical universities using cadavers for CST and R&D programs was just 5 in 2012, and it reached 38 for the decade. Thus, about half of Japan's medical universities implemented such programs over the period. Meanwhile, the total number of programs was 1,173. In the clinical field, the highest number of programs were implemented in orthopedics (27%), followed by surgery (21%), and neurosurgery (12%). Based on the purpose, the most common objective of the programs (approximately 70%) was acquiring advanced surgical techniques. Further, the highest number of programs and participants were recorded in 2019 (295 programs, 6,537 participants). Thus, the guidelines helped expand cadaver usage for clinical purposes in Japan. To further promote the clinical usage of cadavers in medical and dental universities throughout Japan, sharing know-how on operating cadaver laboratories and building understanding among the general public is recommended.

Systemic steroid application for treatment of edematous anastomotic stenosis following delta-shaped anastomosis in laparoscopic distal gastrectomy: a case report.

BACKGROUND: Delta-shaped anastomosis is a common method of intracorporeal gastroduodenostomy in totally laparoscopic distal gastrectomy. One common postoperative complication of this procedure is anastomotic stenosis, and endoscopic balloon dilatation is a major remedy for such complications. Other treatment strategies are necessary to manage unsuccessful endoscopic balloon dilatation. CASE PRESENTATION: We present a case where systemic steroid treatment was applied in sustained anastomotic stenosis after endoscopic balloon dilatation. We performed delta-shaped anastomosis in laparoscopic distal gastrectomy to treat early-stage gastric cancer in a patient. The patient experienced abdominal pain post-surgery; subsequent investigation revealed edematous anastomotic stenosis. The stenosis sustained even after endoscopic balloon dilatation and local steroid injection. Consequently, we applied systemic steroid treatment. CONCLUSION: Systemic steroid treatment improved the stenosis and no recurrence was observed. These results suggest that systemic steroid application could be useful to treat anastomotic stenosis.

Multiple gastrointestinal stromal tumors caused by a novel germline KIT gene mutation (Asp820Gly): a case report and literature review.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract; most of them have gain-of-function mutations of the KIT gene. There have been rare cases of families with multiple GISTs, that had autosomal dominant germline KIT mutations. Here, we present a case of multiple GISTs caused by a novel germline KIT mutation. Intraoperatively, the main tumor was present in the body of the stomach, and multiple small nodules were detected mainly in the upper and middle part of the gastric wall; several nodules were also present in the small bowel wall. The main tumor and surrounding nodules were resected. DNA sequencing of the tumor tissue, adjacent normal mucosal tissue, and peripheral blood leukocytes revealed that the patient had germline Asp820Gly mutation in exon 17 of the KIT gene. This is the first case with germline Asp820Gly mutation in exon 17 of the KIT gene.

Comparing the Incidences of Occult Contralateral Hernia under Laparo-Endoscopic Techniques and of Contralateral Metachronous Hernia after a Unilateral Groin Hernia Repair in Open Technique.

The aim of this study was to evaluate the utility of immediate repair of a contralateral occult hernia at the same time as incipient hernia repair. A total of 693 patients were diagnosed preoperatively with a unilateral groin hernia from January 2006 to December 2017. The open technique was used for 541 patients, and the laparo-endoscopic technique was used for 152 patients. The incidences of occult contralateral hernia confirmed during surgery under laparo-endoscopic techniques and those of contralateral metachronous hernia after a unilateral groin hernia repair with open technique were compared. Fifty-one (9.4%) of 541 patients underwent a contralateral metachronous hernia repair after unilateral groin hernia repair. Twenty-three (15.1%) of 152 patients had occult contralateral hernias using laparo-endoscopic techniques. There was a significant difference in the incidence of contralateral metachronous hernia and that of occult contralateral hernia (P = 0.02). It is concluded that finding and repairing an occult contralateral hernia at the time of laparo-endoscopic technique has the advantage of avoiding a second operation. However, it has been considered overtreatment to repair all patients with an occult contralateral hernia.

[A Case of Interstitial Pneumonitis Induced by TAS-102 for Liver and Lung Metastasis of Colorectal Cancer].

A 78-year-old man who developed metastatic liver and lung cancer after undergoing surgery for rectal and sigmoid colon cancer was treated with TAS-102 as fourth-line chemotherapy. He developed high fever and dyspnea and was referred to the emergency room 16 days after receiving the first course of TAS-102. Chest X-ray and computed tomography examinations showed bacterial pneumonia. He was treated with tazobactam/piperacillin, but developed severe dyspnea 4 days later. A diffuse ground-glass appearance was observed in both the lungs on chest X-ray examination, and drug-induced interstitial pneumonitis was suspected. Oxygenation and respiratory support were immediately administered, and steroid pulse therapy with methylprednisolone at 1,000mg/day was initiated. His symptoms and radiographic findings dramatically improved. The TAS102-J003 trial, a double-blind phase 2 trial, showed that interstitial pneumonitis occurs at a rate of only 0.9%, but can lead to severe complications, as observed in the present case. The possibility of interstitial pneumonitis should always be considered when a patient develops a fever and respiratory disorder during treatment containing TAS-102.

Benefits of intracorporeal gastrointestinal anastomosis following laparoscopic distal gastrectomy.

BACKGROUND: Laparoscopic gastrectomy has recently been gaining popularity as a treatment for cancer; however, little is known about the benefits of intracorporeal (IC) gastrointestinal anastomosis with pure laparoscopic distal gastrectomy (LDG) compared with extracorporeal (EC) anastomosis with laparoscopy-assisted distal gastrectomy (LADG). METHODS: Between June 2000 and December 2011, we assessed 449 consecutive patients with early-stage gastric cancer who underwent LDG. The patients were classified into three groups according to the method of reconstruction LADG followed by EC hand-sewn anastomosis (LADG + EC) (n = 73), using any of three anastomosis methods (Billroth-I (B-I), Billroth-II (B-II) or Roux-en-Y (R-Y); LDG followed by IC B-I anastomosis (LDG + B-I) (n = 248); or LDG followed by IC R-Y anastomosis (LDG + R-Y) (n = 128)). The analyzed parameters included patient and tumor characteristics, operation details, and post-operative outcomes. RESULTS: The tumor location was significantly more proximal in the LDG + R-Y group than in the LDG + B-I group (P < 0.01). Mean operation time, intra-operative blood loss, and the length of post-operative hospital stay were all shortest in the LDG + B-I group (P < 0.05). Regarding post-operative morbidities, anastomosis-related complications occurred significantly less frequently in with the LDG + B-I group than in the LADG + EC group (P < 0.01), whereas there were no differences in the other parameters of patients' characteristics. CONCLUSIONS: Intracorporeal mechanical anastomosis by either the B-I or R-Y method following LDG has several advantages over at the LADG + EC, including small wound size, reduced invasiveness, and safe anastomosis. Although additional randomized control studies are warranted to confirm these findings, we consider that pure LDG is a useful technique for patients with early gastric cancer.

Functional outcomes according to the size of the gastric remnant and type of reconstruction following laparoscopic distal gastrectomy for gastric cancer.

BACKGROUND: In gastric cancer, various methods of gastric resection and reconstruction have been devised according to the location of the primary tumor and the depth of invasion. The functional outcomes of patients treated by laparoscopy-assisted or totally laparoscopic distal gastrectomy were compared with respect to the approach, size of the remnant stomach, and type of reconstruction. METHODS: Patients who required distal gastrectomy to treat early-stage cancer between May 2000 and December 2008 were treated by one of the four following procedures: Billroth Type I (B-1) reconstruction for 1/2 remnant stomach (1/2B1ML) or B-1 for 1/3 remnant stomach (1/3B1ML), through a mini-laparotomy following laparoscopy-assisted surgery; intra-corporeal B-1 for 1/2 remnant stomach (1/2 B1IC); or intra-corporeal Roux-en-Y for 1/3 remnant stomach (1/3RYIC). The primary outcome measure was digestive function, assessed by body weight, food intake, and degree of abdominal symptoms. The secondary outcome was morbidity. RESULTS: The 1/2B1ML (n = 27) and 1/2B1IC (n = 56) groups were significantly superior to the 1/3 resection groups in terms of the preservation of body weight. The 1/3B1ML (n = 29) and 1/3RYIC (n = 64) groups were associated with significantly decreased food intake compared with the 1/2B1ML group. Endoscopy revealed a greater incidence of esophagitis and gastritis among the 1/3B1ML patients compared with the 1/3RYIC patients. There were no operative deaths, and no differences in morbidity between the groups. CONCLUSION: Patients with early-stage cancer actually benefit from 1/2 gastrectomy rather than the typical 2/3 gastrectomy. B-1 reconstruction is appropriate for patients with large gastric remnants, and intra-corporeal reconstruction in experienced hands is associated with no apparent disadvantages, while offering a favorable cosmetic result.

Histoculture drug response assay predicts the postoperative prognosis of patients with esophageal cancer.

Predicting response to chemotherapy would provide patients suffering from malignant tumor with not only more favorable outcomes, but also reduction of adverse events, and would enable chemotherapy tailored to individual patients. The purpose of this retrospective study was to evaluate the utility of histoculture drug response assay (HDRA) with the MTT endpoint. Subjects comprised 53 consecutive patients diagnosed with esophageal cancer, with 15 patients receiving preoperative chemoradiotherapy (CRT) followed by surgery (CRT group; n=15) and 38 patients undergoing surgery (surgery group; n=38), including 17 patients with histological lymph node metastasis who received postoperative chemotherapy. Tumor samples obtained from patients were used for HDRA with MTT endpoint and correlations of sensitivity from HDRA with MTT endpoint to clinical response to preoperative CRT, accuracy of in vitro sensitivity test, and clinical outcomes based on HDRA sensitivity were analyzed. HDRA was able to evaluate 379 of 424 assays (89.3%). In the CRT group, no significant correlation was confirmed between efficacy rate of 5-fluorouracil or cisplatin and histological findings in resected specimens after CRT. Efficacy rates of several anticancer agents using HDRA in the surgery group were observed in the range of 0.0-44.8%. On examination of clinical outcomes in the surgery group, in which patients with stage III received adjuvant chemotherapy, chemosensitivity-negative patients tended to display worse prognosis than chemosensitivity-positive patients. HDRA with MTT endpoint probably predicts the postoperative prognosis of patients with esophageal cancer.

Proteomics-based identification of autoantibody against heat shock protein 70 as a diagnostic marker in esophageal squamous cell carcinoma.

Detection of novel tumor-related antigens and autoantibodies in cancer patients is expected to facilitate the diagnosis of early-stage malignant tumor and establish effective new immunotherapies. The purpose of this study was to identify novel tumor antigens in an esophageal squamous cell carcinoma (ESCC) cell line (TE-2) and related autoantibodies in sera from patients with ESCC using a proteomics-based approach. TE-2 proteins were separated by two-dimensional polyacrylamide gel electrophoresis, followed by Western blot analysis in which sera from patients with ESCC, healthy controls and patients with other cancers were tested for primary antibodies. Positive spots were excised from silver-stained gels and analyzed by matrix-assisted laser disorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). Sera from patients with ESCC yielded multiple spots, one of which was identified as heat shock protein 70 (Hsp70) by MALDI-TOF/TOF-MS. Concentrations of serum Hsp70 autoantibody were significantly higher for patients with ESCC (mean, 0.412+/-0.096 mg/ml) than for patients with gastric (0.236+/-0.112 mg/ml, P<0.001) or colon cancer (0.231+/-0.120 mg/ml, P<0.001) or healthy individuals (0.207+/-0.055 mg/ml, P<0.001) by enzyme-linked immunosorbent assay. We have identified an autoantibody against Hsp70 in ESCC patients. The proteomic approach implemented herein offers a powerful tool for identifying novel serum markers that may display clinical utility against cancer.

Proteomics-based approach identifying autoantibody against peroxiredoxin VI as a novel serum marker in esophageal squamous cell carcinoma.

PURPOSE: Detection of novel tumor-related antigens and autoantibodies will aid in diagnosis of early-stage cancer and in development of more effective immunotherapies. The purpose of this study was to identify novel tumor antigens in an esophageal squamous cell carcinoma (ESCC) cell line (TE-2) and related autoantibodies in sera from patients with ESCC using a proteomics-based approach. EXPERIMENTAL DESIGN: TE-2 proteins were separated by two-dimensional PAGE, followed by Western blot analysis in which sera of patients with ESCC, healthy controls, and patients with other cancers were tested for primary antibodies. Positive spots were excised from silver-stained gels and analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS). RESULTS: Sera from patients with ESCC yielded multiple spots, one of which was identified as peroxiredoxin (Prx) VI by MALDI-TOF/TOF MS. Western blot analysis against recombinant Prx VI showed reactivity in sera from 15 of 30 (50%) patients with ESCC and 2 of 30 (6.6%) healthy individuals. Autoantibody against Prx VI was found in sera from 1 of 30 (3.3%) patients with other types of cancer (colon cancer). CONCLUSION: We have identified for the first time an autoantibody against Prx VI in ESCC patients. The proteomic approach implemented here offers a powerful tool for identifying novel serum markers that may display clinical usefulness against cancer.

CT and MR features of sclerosing mesenteritis mimicking a mesenteric metastasis from the carcinoid tumor.

Sclerosing mesenteritis is a rare and benign inflammatory entity characterized by fibrofatty thickening of the mesentery. To our knowledge, there are only a few reports on the features of sclerosing mesenteritis on magnetic resonance (MR) imaging and computed tomography (CT). In this present case, MR imaging demonstrated tissue characterization of fibrosis, and partial maximum intensity projection (MIP) and three-dimensional angiography images obtained using multislice CT clearly revealed the extent of the tumor and the vascular appearance affected by the mass. However, a mesenteric metastasis from the carcinoid tumor may show such imaging features. Therefore, when encountering such a case, we suggest that a tentative diagnosis of sclerosing mesenteritis be made, followed by a biopsy for intraoperative histopathologic analysis to avoid aggressive surgery.

Preoperative esophageal cancer staging: magnetic resonance imaging of lymph node with ferumoxtran-10, an ultrasmall superparamagnetic iron oxide.

BACKGROUND: Accurate detection of metastasis to lymph nodes is an essential component of the approach to treatment. The purpose of this study was to evaluate the utility of magnetic resonance imaging with ferumoxtran-10 in diagnosing lymph node metastasis in esophageal cancer. STUDY DESIGN: Sixteen patients with esophageal cancer who were scheduled for surgical lymph node dissection were enrolled. All patients underwent MRI scanning before and 24 hours after intravenous administration of ferumoxtran-10, an ultrasmall, superparamagnetic iron oxide. The presence or absence of metastasis was identified in lymph nodes by their enhancement patterns. Nonmalignant nodes contained macrophages that phagocytosed ferumoxtran-10. Metastatic nodes exhibited a decrease in phagocytic activity, and consequently showed little or no uptake of ferumoxtran-10. So we subdivided the enhancement patterns into the following three patterns: (A) node having an overall low signal intensity, (B) node having an area of high signal intensity, and (C) node having an overall high signal intensity. We identified that patterns (B) and (C) were metastatic patterns. The imaging results were compared with histopathologic findings. RESULTS: Of the 408 resected lymph nodes, imaging results of 133 nodes could be compared with histopathologic findings. Twenty-four lymph nodes had histopathologic metastases. Using our enhancement criteria, sensitivity was 100%, specificity was 95.4%, and accuracy was 96.2% for diagnosis of metastatic nodes. CONCLUSIONS: Ferumoxtran-10 is useful for characterizing benign or malignant lymph nodes in esophageal cancer patients based on the defined enhancement criteria.

[A case of recurrent rectal cancer responding to weekly low-dose CPT-11/isovorin/5-fluorouracil].

We report the case of 66-year-old male with recurrent rectal cancer which responded to chemotherapy using CPT-11, Isovorin, and 5-fluorouracil (5-FU). CPT-11 was administered at 40 mg (90 min i.v.) x 3 day/week, and Isovorin and 5-FU were administered at 25 mg (bolus) and 250 mg (continuous) x 5 day/week by intraarterial infusion. Three cycles of this weekly regimen resulted in regression of tumors in the iliac region with remission of the lameness caused by iliac pain. The serum CEA level decreased from 13.1 ng/ml to 0.5 ng/ml. The patient has undergone 13 cycles of the regimen modified for outpatients (CPT-11 at 40 mg x 3 day/week plus Isovorin at 25 mg and 5-FU at 250 mg 1 day/week) with inhibitions of tumor regrowth and improved serum CEA level for more than 12 months. The current case suggests that weekly low-dose CPT-11/Isovorin/5-FU may have a potent therapeutic effect against recurrent rectal cancer.