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BACKGROUND: Although stakeholder involvement in policymaking is attracting attention in the fields of medicine and healthcare, a practical methodology has not yet been established. Rare-disease policy, specifically research priority setting for the allocation of limited research resources, is an area where evidence generation through stakeholder involvement is expected to be effective. We generated evidence for rare-disease policymaking through stakeholder involvement and explored effective collaboration among stakeholders. METHODS: We constructed a space called 'Evidence-generating Commons', where patients, family members, researchers, and former policymakers can share their knowledge and experiences and engage in continual deliberations on evidence generation. Ten rare diseases were consequently represented. In the 'Commons', 25 consecutive workshops were held predominantly online, from 2019 to 2021. These workshops focused on (1) clarification of difficulties faced by rare-disease patients, (2) development and selection of criteria for priority setting, and (3) priority setting through the application of the criteria. For the first step, an on-site workshop using sticky notes was held. The data were analysed based on KJ method. For the second and third steps, workshops on specific themes were held to build consensus. The workshop agendas and methods were modified based on participants' feedback. RESULTS: The 'Commons' was established with 43 participants, resulting in positive effects such as capacity building, opportunities for interactions, mutual understanding, and empathy among the participants. The difficulties faced by patients with rare diseases were classified into 10 categories. Seven research topics were identified as priority issues to be addressed including 'impediments to daily life', 'financial burden', 'anxiety', and 'burden of hospital visits'. This was performed by synthesising the results of the application of the two criteria that were particularly important to strengthen future research on rare diseases. We also clarified high-priority research topics by using criteria valued more by patients and family members than by researchers and former policymakers, and criteria with specific perspectives. CONCLUSION: We generated evidence for policymaking in the field of rare diseases. This study's insights into stakeholder involvement can enhance evidence-informed policymaking. We engaged in comprehensive discussions with policymakers regarding policy implementation and planned analysis of the participants' experiences in this project.
Stakeholder involvement is significant for effective policymaking in the field of rare diseases. However, practical methods for this involvement have not yet been established. Therefore, we developed the 'Commons project' to generate valuable policymaking information and explore effective ways for stakeholders' collaboration. This article explains the process and results of 25 continuous workshops, held from 2019 to 2021 with 43 participants, including patients, family members, researchers, and former policymakers. The main achievements of the discussion that took place in the 'Commons' included a presentation of the overview of the difficulties faced by patients with rare diseases and formulation of high priority research topics.First, the difficulties faced by patients with rare diseases were grouped into 10 categories. Second, seven research topics were identified as priority issues including 'impediments to daily life', 'financial burden', 'anxiety', and 'burden of hospital visits'. During the project process, positive effects such as capacity building, opportunities for interactions, mutual understanding, and empathy among the participants, were identified. Beyond the context of the field of rare diseases and science of policy, these findings are useful for the future of society, including co-creation among stakeholders and patient and public involvement. Based on this study's results, we have initiated communications with policy stakeholders in the field of rare diseases, with the aim of policy implementation.
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PURPOSE: In Japan, two courses of CDDP+5-FU (CF) therapy followed by surgery are accepted as a standard treatment for stage II/III esophageal cancer (EC) based on the results of the JCOG9907 trial. To gain a better survival, benefit especially for stage III patients in comparison with CF therapy, a three-arm phase III trial (neoadjuvant setting: CF vs. CF + radiation vs. DOC+CF [DCF]) is ongoing. We have aggressively performed DCF therapy for stage III or IV patients since October 2014. We herein review the outcomes of DCF therapy. METHODS: We retrospectively reviewed the cases of 27 patients with stage III or IV EC (male, n = 24; female, n = 3; median age, 70.0 years) who received DCF therapy. RESULTS: The response rate was 48.1%. Downstaging was achieved over the course of treatment in 14 patients (51.9%). Twenty-six patients transitioned to surgery, with 25 receiving R0 resection. DCF-treated patients who achieved downstaging showed significantly longer relapse-free survival (RFS) than those without downstaging (p = 0.0002). DCF-treated patients with a grade ≥ 1b histological effect showed significantly longer RFS than those with a grade < 1b effect (p = 0.0282). The multivariate analysis showed that downstaging was the only factor significantly associated with RFS in DCF-treated patients. CONCLUSIONS: DCF therapy for stage ≥ III esophageal carcinoma is both feasible and effective. These findings suggest that downstaging and the histological effect might predict the effects of DCF therapy for EC.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Esophageal Neoplasms/therapy , Esophageal Squamous Cell Carcinoma/therapy , Neoadjuvant Therapy/methods , Neoplasm Recurrence, Local/epidemiology , Aged , Cisplatin/administration & dosage , Disease-Free Survival , Docetaxel/administration & dosage , Drug Administration Schedule , Esophageal Mucosa/diagnostic imaging , Esophageal Mucosa/drug effects , Esophageal Mucosa/pathology , Esophageal Mucosa/surgery , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/mortality , Esophageal Squamous Cell Carcinoma/diagnosis , Esophageal Squamous Cell Carcinoma/mortality , Esophageal Squamous Cell Carcinoma/pathology , Esophagectomy , Esophagoscopy , Feasibility Studies , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Japan/epidemiology , Male , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Neoplasm Staging , Pyrimidines , Retrospective StudiesABSTRACT
A 69-year-old man with dyschezia was diagnosed with locally advanced colorectal cancer invading the urinary bladder and pelvis. We performed ileostomy to avoid passage disturbance because curative resection was difficult. The patient received 2 courses of modified FOLFOXIRI plus bevacizumab. The size of the primary tumor and lymph nodes decreased after chemotherapy. High anterior resection with D3 lymph node dissection was performed. Histopathological analysis revealed that the tumor stage was pT3, N0, M0, Stageâ ¡. The patient has been receiving adjuvant chemotherapy with oral UFT/UZEL for 6months. No recurrence has been observed for the past 4 months.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Rectal Neoplasms , Aged , Bevacizumab , Camptothecin/analogs & derivatives , Fluorouracil , Humans , Leucovorin , Male , Neoplasm Recurrence, Local , Organoplatinum Compounds , Rectal Neoplasms/drug therapyABSTRACT
This multicenter phase II N-DOCC-F-C-1701 trial is being planned in order to investigate the efficacy and safety of CPT-11+S-1 +Ramucirumab (IRIS+Rmab), which is anticipated to have a stronger anti-tumor effect than IRIS+Bmab in patients with metastatic colorectal cancer (mCRC) previously treated with oxaliplatin (L-OHP) containing regimen, in consideration of the result of RAISE, FIRIS and some phase II trials of IRIS+Bevacicizumab (Bmab). The number of patients is set at 38 for the statistical analysis, assuming an expected median PFS of 5.0 months (threshold: 3.0 months). The primary endpoint of the study is the progression free survival (PFS), and the secondary endpoints are the overall response rate (ORR), overall survival (OS), adverse events (AE), quality of life (QOL) and review of nausea and vomiting. This trial is registered in the UMIN Clinical Trials Registry as UMIN000028170. We intend to start conducting the trial in September 1, 2017. If this trial meets the endpoint, IRIS+Rmab might be supported as a new optional standard regimen for mCRC.
Subject(s)
Antibodies, Monoclonal, Humanized , Colorectal Neoplasms , Oxaliplatin , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Colorectal Neoplasms/drug therapy , Drug Resistance, Neoplasm , Humans , Irinotecan/therapeutic use , Oxaliplatin/pharmacology , Oxaliplatin/therapeutic use , Quality of Life , Thiazoles , RamucirumabABSTRACT
Objective In the treatment of advanced and recurrent colorectal cancer (ARCC), FOLFOXIRI regimens have been proven to be significantly superior to FOLFIRI in terms of the progression-free survival (PFS), response rate (RR), and overall survival (OS). Furthermore, the Tribe trial showed that the RR and PFS rates in patients who received bevacizumab (Bmab) +FOLFOXIRI were superior to those in patients treated with Bmab+FOLFIRI. A phase III trial of panitumumab (Pmab) +FOLFOXIRI is currently ongoing. A modified FOLFOXIRI regimen is also widely used to reduce adverse events. In our department, we introduced modified FOLFOXIRI+α (mFOLFOXIRI+α) in 2015. The present study reviewed the efficacy and safety of mFOLFOXIRI+α. Methods Eligible patients were retrospectively reviewed, and their results were compared to those of patients treated with other regimens (OTHERS) (n=134) to demonstrate the efficacy of this treatment. Patients: Between February 2015 and November 2018, 12 patients with ARCC (male/female=6/6; average age, 60.7 years old) received mFOLFOXIRI+α (Bmab: 10, Pmab: 1, alone: 1). Results The median PFS in the mFOLFOXIRI+α and OTHERS groups was 565 and 322 days, respectively (p=0.0544). The RR in the mFOLFOXIRI+α and OTHERS groups was 66.7% and 31.3%, respectively (p=0.0135). The conversion rate (Conv R) in the mFOLFOXIRI+α and OTHERS groups was 50.0% and 12.7%, respectively (p=0.0007). While 58% of patients treated with FOLFOXIRI+α developed grade ≥3 leukopenia, the incidence of febrile neutropenia (FN) was only 17%. In all patients with symptoms due to the tumor burden, the symptoms subsided with mFOLFOXIRI+α treatment. Conclusion Based on the RR, Conv R, and symptom palliation ability, mFOLFOXIRI+α was suggested to be a viable candidate for first-line treatment for patients with ARCC, especially those with a high tumor burden.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Camptothecin/analogs & derivatives , Colorectal Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab/adverse effects , Camptothecin/administration & dosage , Camptothecin/adverse effects , Camptothecin/therapeutic use , Colorectal Neoplasms/pathology , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Fluorouracil/therapeutic use , Humans , Leucovorin/administration & dosage , Leucovorin/adverse effects , Leucovorin/therapeutic use , Male , Middle Aged , Neoplasm Recurrence, Local , Neoplasm Staging , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Organoplatinum Compounds/therapeutic use , Panitumumab , Progression-Free Survival , Retrospective StudiesABSTRACT
Superior mesenteric artery syndrome can lead to duodenal obstruction due to vascular compression. We treated a patient with superior mesenteric artery syndrome by performing a complete laparoscopic duodenojejunostomy with a linear stapled closure of the common enterotomy. A 72-year-old woman presented with nausea, vomiting, and weight loss. CT revealed superior mesenteric artery syndrome. Conservative management was not effective. Because the patient required a surgical bypass for long-term relief, a laparoscopic duodenojejunostomy was performed. In past cases, hand-sewn sutures were made through a small incision to avoid stenosis when the common enterotomy was closed. For our patient, we closed the common enterotomy with a linear stapler in a complete laparoscopic maneuver. We performed the closure after placing several temporary sutures to minimize the amount of intestinal wall to be removed. Laparoscopic duodenojejunostomy is a minimally invasive procedure, and a linear stapled closure of a common enterotomy is a safe surgical technique that reduces invasiveness.
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Laparoscopy , Superior Mesenteric Artery Syndrome , Aged , Anastomosis, Surgical , Duodenostomy , Female , Humans , Jejunostomy , Superior Mesenteric Artery Syndrome/surgeryABSTRACT
BACKGROUND AND AIMS: The aim of this study is to exploratively evaluate the effect of Tsumura Daikenchuto Extract Granules (DKT, TJ-100) on abdominal symptoms, body weight, and nutritional function following colorectal cancer surgery. METHODS: The subjects included 20 patients for curative resection of colorectal cancer. A TJ-100 administration group (n = 10) and non-administration group (n = 10) were randomized and compared. In the administration group, TJ-100 was administered from 2 days prior to surgery up to 12 weeks following surgery. The endpoints included body weight gain, Gastrointestinal Symptom Rating Scale (GSRS), and blood biochemical factors. For the purpose of observing safety, drug adverse events were evaluated including liver function tests. RESULTS: Excluding one patient, we compared 9 cases in the administration group and 10 cases in the non-administration group. No obvious adverse events were observed in any of the cases. In the comparison of body weight gain, the TJ-100 administration group showed significantly higher values at 2, 4, and 12 weeks following the surgery. There was a tendency for lower stable GSRS scores in the administration group overall, with no statistically significant difference. CONCLUSION: It is suggested that TJ-100 can be safely administered in the perioperative period for cases undergoing colorectal cancer surgery, potentially preventing weight loss during the early postoperative period.
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Short bowel syndrome (SBS) is a morbid and mortal condition characterized in most patients by insufficient intestinal surface area. Current management strategies are inadequate, but tissue-engineered small intestine (TESI) offers a potential therapy. A barrier to translation of TESI is the generation of scalable mucosal surface area to significantly increase nutritional absorption. Fibroblast growth factor 10 (Fgf10) is a critical growth factor essential for the development of the gastrointestinal tract. We hypothesized that overexpression of Fgf10 would improve the generation of TESI. Organoid units, the multicellular donor tissue that forms TESI, were derived from Rosa26(rtTA/+), tet(o)Fgf10/(-) or Fgf10(Mlc-nlacZ-v24) (hereafter called Fgf10(lacZ)) mice. These were implanted into the omentum of NOD/SCID γ-chain-deficient mice and induced with doxycycline in the case of tet(o)Fgf10/(-). Resulting TESI were explanted at 4 weeks and studied by histology, quantitative RT-PCR and immunofluorescence. Four weeks after implantation, Fgf10 overexpressing TESI was larger and weighed more than the control tissues. Within the mucosa, the villus height was significantly longer and crypts contained a greater percentage of proliferating epithelial cells. A fully differentiated intestinal epithelium with enterocytes, goblet cells, enteroendocrine cells and Paneth cells was identified in the Fgf10-overexpressing TESI, comparable to native small intestine. ß-Galactosidase expression was found in both the epithelium and the mesenchyme of the TESI derived from the Fgf10(LacZ) duodenum. However, this was not the case with TESI generated from jejunum and ileum. We conclude that Fgf10 enhances the formation of TESI.
Subject(s)
Fibroblast Growth Factor 10/metabolism , Intestine, Small/metabolism , Tissue Engineering/methods , Animals , Cell Differentiation , Cell Proliferation , Intestinal Mucosa/cytology , Intestinal Mucosa/metabolism , Mice, Transgenic , Organ SizeABSTRACT
The first issue of Nature Medicine published 20 years ago featured an article that reported Japan's critical situation regarding clinical trials, calling for major reform. Twenty years later, Japan has enacted three laws to promote the use of regenerative medicine as a national policy. The first law to be enacted was the Regenerative Medicine Promotion Act, which represents the country's determination to work toward the promotion of regenerative medicine. Subsequently, the Pharmaceuticals, Medical Devices, and Other Therapeutic Products Act (PMD Act) and the Act on the Safety of Regenerative Medicine (RM Act) came into effect. The PMD Act created a new category for regenerative medicine products, and established the process for obtaining approval for cell therapy and other regenerative therapies through the implementation of clinical trials. The RM Act specified the regulations that doctors, review committees, and cell culture/processing facilities must adhere to when providing regenerative medicine in medical care, not only in clinical research but also in private practice. Previously, researchers in regenerative medicine only had a set of guidelines to follow for conducting clinical research. Now, with the enactment of the RM Act, all areas for improvement that had been enumerated 20 years ago-such as the lack of appropriate review committees and governmental control-have been addressed by law, creating a system that gives the highest priority to patient safety. In this paper, we present the particularly noteworthy points of the RM Act, along with the actual current conditions of regenerative medicine in Japanese medical care.
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INTRODUCTION: Generating tissue-engineered small intestine (TESI) from mature intestinal cells has been established in a mouse model. The purpose of this study was to generate TESI from Lgr5 stem cells in vivo. METHODS: We used Lgr5-EGFP mice for intestinal crypt isolation. After seven days, cultured crypts with Lgr5 stem cells were seeded onto a biodegradable polymer and implanted into omentum of NOD/SCID mice. RESULTS: Engineered intestinal epithelium was generated from Lgr5 stem cells after four weeks of in vivo implantation. Intestinal epithelium was immunohistochemically positive for Paneth cells, enteroendocrine cells, goblet cells, microvilli of the absorptive enterocytes and Ki67. CONCLUSION: Our observations suggest that transplanted Lgr5 stem cells can differentiate into the intestinal epithelium in vivo with further proliferative activity.
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To demonstrate whether reactive oxygen and free radical measuring are appropriate to evaluate short-term surgical stress after laparoscopic colectomy. The subjects consisted of 22 cases (laparoscopic surgery, 16; and laparotomy, 6) that underwent surgery for colon cancer. The reactive oxygen metabolites (ROM) value in the blood were measured perioperatively. The average ROM values immediately prior to surgery, immediately following surgery, and 1 day following surgery were 360.1, 316.0, and 346.7 U.CARR, respectively, meaning that ROM declined immediately following surgery compared with immediately prior to surgery (P < 0.05), while a tendency was observed for these values to increase again 1 day following surgery. In the comparison of pain control 1 day following surgery, a significantly lower value was indicated in the epidural anesthesia group (n = 12) compared with the fentanyl intravenous injection group (n = 10). Moreover, no significant change was observed in the surgical stress level in a comparison of patient background items such as age, sex, and so forth, laparoscopic surgery, and laparotomy. The low-invasiveness of laparoscopic surgery was not indicated in the ROM value 1 day following surgery, probably because pain control offsets the level of surgical stress using this method.
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Colectomy , Colonic Neoplasms/surgery , Laparoscopy , Reactive Oxygen Species/blood , Female , Humans , Male , Pain ManagementABSTRACT
BACKGROUND: Survival of human immunodeficiency virus (HIV)-infected patients has improved due to the widespread use of anti-retroviral therapy. However, mortality has increased when HIV-infected patients are co-infected with hepatitis C virus (HCV), and the liver disease in such patients is rapidly progressive compared with that in HCV monoinfected patients. Therefore, accurate staging of the liver disease is critical when determining appropriate treatment. AIM: To clarify the efficacy of acoustic radiation force impulse (ARFI) elastography for the evaluation of liver fibrosis and hepatic functional reserve in HIV/HCV co-infected patients. METHODS: The correlation of shear wave velocity (Vs), measured by ARFI elastography, with liver fibrosis or hepatic functional reserve was analyzed. RESULTS: Vs was significantly correlated with platelet count, splenic volume, hyaluronic acid, type IV collagen, and LHL15 (receptor index: uptake ratio of the liver to the liver plus heart at 15min) in 99mTc-GSA (technetium-99m-diethylenetriaminepentaacetic acid-galactosyl human serum albumin) scintigraphy. CONCLUSION: ARFI elastography was useful for the staging of liver disease in HIV/HCV co-infected patients and it facilitated minimally invasive and accessible evaluation of fibrosis and functional reserve.
Subject(s)
Coinfection/complications , Elasticity Imaging Techniques/methods , HIV Infections/complications , Hepatitis C/complications , Liver Diseases/diagnosis , Liver Diseases/etiology , Liver Function Tests/methods , Adult , Disease Progression , Fibrosis , Humans , Liver/pathology , Liver Diseases/pathology , Middle AgedABSTRACT
Chronic idiopathic colonic pseudo-obstruction (CICP) is characterized by the chronic disturbance of colonic motility without mechanical obstruction, any underlying disease or medication. Currently, there are no established medical treatments for CICP. A 62-year-old female who had undergone right hemicolectomy for splenic flexure syndrome caused by idiopathic megacolon was referred to our hospital with relapse, experiencing palpitation and abdominal fullness. She was diagnosed with CICP according to findings of marked dilation of the colon without mechanical obstruction, dilation of other parts of the gastrointestinal tract, or underlying disease. The dilated colon was surgically removed by hand-assisted laparoscopic subtotal colectomy, followed by cecorectal anastomosis. Histopathologically, there was no degeneration or lack of ganglion cells in Auerbach's plexus. The patient has experienced no severe symptoms after undergoing the present operation.
Subject(s)
Anastomosis, Surgical/methods , Colectomy/methods , Colonic Pseudo-Obstruction/surgery , Hand-Assisted Laparoscopy/methods , Cecum/surgery , Chronic Disease , Colonic Pseudo-Obstruction/pathology , Female , Humans , Middle Aged , Rectum/surgery , Recurrence , Syndrome , Treatment OutcomeABSTRACT
INTRODUCTION: To detect a small number of malignant cells, we used a highly sensitive detection system that measures the expression levels of cytokeratin (CK) 19 messenger RNA by reverse transcription-loop-mediated isothermal amplification (RT-LAMP). MATERIALS AND METHODS: We evaluated the clinical relevance of our novel diagnostic method with an RT-LAMP assay using CK19 as a target gene for the detection of free cancer cells in peritoneal lavage and assessed the clinical significance of the molecular diagnosis by survival analysis and frequency of recurrence, with a median follow-up period of 39 mo. We observed 52 patients with gastric cancer who underwent gastrectomy, bypass operation, and exploratory laparotomy. RESULTS: Those 52 patients, who were subjected to both RT-LAMP and cytologic examination, were divided into the following three groups: (1) patients positive by cytology and RT-LAMP (CY+/LAMP+) (n = 9), (2) patients positive by LAMP and negative by cytology (CY-/LAMP+) (n = 12), and (3) patients negative by both cytology and LAMP (CY-/LAMP-) (n = 31). All patients with simultaneous peritoneal dissemination and positive cytology were positive on RT-LAMP. The results of RT-LAMP were statistically significant for recurrence by univariate analysis (P < 0.005). Cytology-positive cases had a very poor prognosis, and RT-LAMP-positive cases had a worse prognosis than RT-LAMP-negative cases. CONCLUSIONS: Our findings suggest that CK19 RT-LAMP would be useful as an intraoperative diagnostic modality to detect patients with a high risk of recurrence even after clinically curative surgery, who thus require proper adjuvant therapy.
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Carcinoma/secondary , Neoplastic Cells, Circulating/pathology , Peritoneal Lavage/methods , Reverse Transcriptase Polymerase Chain Reaction/methods , Stomach Neoplasms/secondary , Adult , Aged , Biomarkers, Tumor/genetics , Carcinoma/genetics , Carcinoma/mortality , DNA, Neoplasm/analysis , Female , Humans , Intraoperative Period , Keratin-19/genetics , Male , Middle Aged , Molecular Diagnostic Techniques/methods , RNA, Messenger/analysis , Sensitivity and Specificity , Stomach Neoplasms/genetics , Stomach Neoplasms/mortalityABSTRACT
Anastomotic leakage is a serious complication that can occur after colorectal surgery. Several risk factors for anastomotic leakage have been reported based on the findings of prospective and retrospective studies, including patient characteristics, the use of neoadjuvant therapy, the tumor location, intraoperative events, etc. However, as these risk factors affect each other, the statistical results have differed in each study. In addition, differences in surgical methods, including laparoscopy versus laparotomy or stapling anastomosis versus handsewn anastomosis, may influence the incidence of anastomotic leakage. This mini-review summarizes the results of reported papers to clarify the current evidence of risk factors for anastomotic leakage.
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Anastomotic Leak/etiology , Colorectal Neoplasms/surgery , Anastomosis, Surgical/methods , Anastomotic Leak/epidemiology , Chemoradiotherapy, Adjuvant , Digestive System Surgical Procedures/methods , Female , Forecasting , Humans , Incidence , Laparoscopy , Laparotomy , Male , Neoadjuvant Therapy , Risk Factors , Surgical Stapling , Suture TechniquesABSTRACT
BACKGROUND: Although hepatectomy procedures should be designed to provide both curability and safety, minimal invasiveness also should be pursued. METHODS: We analyzed the data related to our method for laparoscopy-assisted open resections (hybrid method) through a short upper midline incision for various types of hepatectomies. Of 215 hepatectomies performed at Nagasaki University Hospital between November 2009 and June 2012, 102 hepatectomies were performed using hybrid methods. RESULTS: A hybrid method was applicable for right trisectionectomy in 1, right hemihepatectomy in 32, left hemihepatectomy in 29, right posterior sectionectomy in 7, right anterior sectionectomy in 1, left lateral sectionectomy in 2, and segmentectomy in 7 patients, and for a minor liver resection in 35 patients (12 combined resections). The median duration of surgery was 366.5 min (range 149-709) min, and the median duration of the laparoscopic procedure was 32 min (range 18-77) min. The median blood loss was 645 g (range 50-5,370) g. Twelve patients (12 %) developed postoperative complications, including bile leakage in three patients, wound infections in two patients, ileus in two patients, and portal venous thrombus, persistent hyperbilirubinemia, incisional hernia, local liver infarction each in one patient. There were no perioperative deaths. CONCLUSIONS: Our method of hybrid hepatectomy through a short upper midline incision is considered to be applicable for all types of hepatectomy and is a reasonable approach with no abdominal muscle disruption, which provides safe management of the hepatic vein and parenchymal resection even for patients with bilobular disease.
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Hepatectomy/methods , Laparoscopy/methods , Laparotomy/methods , Liver Diseases/surgery , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Postoperative Complications , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Although some reports have shown the safety and efficacy of conversion from Prograf to Advagraf in liver transplantation, there have been no reports showing the change of immune function after conversion. The aim of this study is not only to analyze the safety and efficacy of conversion from Prograf to Advagraf, but also to evaluate the immune function using the ImmuKnow assay. MATERIAL AND METHODS: Of the 168 living donor liver transplantation (LDLT) patients, 21 recipients whose liver function was stable after discharge in outpatient clinic and who agreed to conversion from Prograf to Advagraf were enrolled in this study. Liver, renal, and immune functions were retrospectively reviewed. RESULTS: There were no significant differences in liver and renal function after conversion from Prograf to Advagraf. The intracellular adenosine triphosphate levels before and after conversion were 263±157 and 256±133 ng/ml, respectively, and there was also no significant difference in immune function. None of the recipients showed adverse effects, rejection, or severe infection during the study. It should be further noted that none of the recipients had to increase the dose of Advagraf, while five of 21 recipients (24%) were able to reduce the dose of Advagraf during this study. CONCLUSIONS: Conversion from Prograf to Advagraf in LDLT can be performed safely and effectively without affecting liver, renal, and immune function.
Subject(s)
Immunosuppressive Agents/administration & dosage , Liver Transplantation , Tacrolimus/administration & dosage , Adenosine Triphosphate/metabolism , Adolescent , Adult , Aged , Blood Glucose/metabolism , Child , Child, Preschool , Delayed-Action Preparations , Female , Glomerular Filtration Rate , Humans , Kidney/physiopathology , Liver/immunology , Liver/physiopathology , Living Donors , Male , Middle Aged , Transplantation Immunology , Young AdultSubject(s)
Donor Selection/methods , False Positive Reactions , HIV Antibodies/blood , Influenza Vaccines/adverse effects , Liver Transplantation , Adult , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/therapy , Female , Hepatitis B/complications , Hepatitis B/therapy , Humans , Liver Neoplasms/complications , Liver Neoplasms/therapy , Living Donors , RNA, Viral/analysis , RNA, Viral/bloodABSTRACT
Here, we describe the use of a mouse model as a living bioreactor for the generation of tissue-engineered small intestine. Small intestine is harvested from donor mice with subsequent isolation of organoid units (a cluster of mesenchymal and epithelial cells). Some of these organoid units contain pluripotent stem cells with a preserved relationship with the mesenchymal stem cell niche. A preparation of organoid units is seeded onto a biodegradable scaffold and implanted intraperitoneally within the omentum of the host animal. The cells are nourished initially via imbibition until neovascularization occurs. This technique allows the growth of fully differentiated epithelium (composed of Paneth cells, goblet cells, enterocytes and enteroendocrine cells), muscle, nerve, and blood vessels of donor origin. Variations of this technique have been used to generate tissue-engineered stomach, large intestine, and esophagus. The variations include harvest technique, length of digestion, and harvest times.
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Bioreactors , Intestine, Small/growth & development , Organoids/transplantation , Tissue Engineering/methods , Animals , Intestine, Small/cytology , Mice , Polyglycolic Acid , Tissue ScaffoldsABSTRACT
PURPOSE: Tissue-engineered small intestine (TESI) represents a potential cure for short bowel syndrome (SBS). We previously reported full-thickness intestine formation using an organoid units-on-scaffold approach in rodent and swine models. Transplanted intestinal xenografts have been documented to survive from human fetal tissue but not from postnatal tissue. We now present the first report of human TESI from postnatal tissue. METHODS: Organoid units (OU) were prepared from human small bowel resection specimens, loaded onto biodegradable scaffolds and implanted into NOD/SCID gamma chain-deficient mice. After 4 weeks, TESI was harvested and immunostained for ß2-microglobulin to identify human tissue, villin for enterocytes, lysozyme for Paneth cells, chromogranin-A for enteroendocrine cells, mucin-2 for goblet cells, smooth muscle actin and desmin to demonstrate muscularis, and S-100 for nerves. RESULTS: All TESI was of human origin. Immunofluorescence staining of human TESI reveals the presence of all four differentiated cell types of mature human small intestine, in addition to the muscularis and the supporting intestinal subepithelial myofibroblasts. Nerve tissue is also present. CONCLUSIONS: Our technique demonstrates survival, growth, and differentiation of postnatally derived human small intestinal OU into full thickness TESI in murine hosts. This regenerative medicine strategy may eventually assist in the treatment of SBS.