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BACKGROUND: Pharyngocutaneous fistula formation represents a major postoperative complication following total laryngectomy. We aimed to investigate the risk factors for pharyngocutaneous fistula development after total laryngectomy and to identify factors that lead to severe cases of pharyngocutaneous fistula. METHODS: Patients who underwent total laryngectomy between January 2013 and February 2021 were included in the study and were divided into 2 groups: Those with and without pharyngocutaneous fistula. The severity of pharyngocutaneous fistula was graded using the Clavien-Dindo classification. RESULTS: Patients with pharyngocutaneous fistula experienced longer operative time, greater intraoperative blood loss, greater decrease in perioperative hemoglobin level, and longer postoperative hospitalization. Unlike in lower-severity cases, patients with grade IIIb pharyngocutaneous fistula underwent preoperative radiotherapy or chemoradiotherapy; preoperative treatment was thus a risk factor for higher severity of pharyngocutaneous fistula (odds ratio, 35; P = 0.004). CONCLUSION: Salvage laryngectomy was found to be a predictor of severe pharyngocutaneous fistula development. Prolonged operative time, increased intraoperative blood loss, and decreased postoperative hemoglobin level were found to be predictors of postlaryngectomy pharyngocutaneous fistula formation.
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Fístula Cutânea , Neoplasias Laríngeas , Doenças Faríngeas , Humanos , Estudos Retrospectivos , Laringectomia/efeitos adversos , Perda Sanguínea Cirúrgica , Neoplasias Laríngeas/cirurgia , Fístula Cutânea/epidemiologia , Fístula Cutânea/etiologia , Doenças Faríngeas/etiologia , Doenças Faríngeas/cirurgia , Fatores de Risco , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , HemoglobinasRESUMO
OBJECTIVE: Anorectal transplantation is a challenging procedure but a promising option for patients with weakened or completely absent anorectal function. SUMMARY BACKGROUND DATA: We constructed a canine model of anorectal transplantation, evaluated the long-term outcomes, and controlled rejection and infection in allotransplantation. METHODS: In the pudendal nerve function study, 6 dogs were randomly divided into 2 groups, transection and anastomosis, and were compared with a control using anorectal manometry, electromyography, and histological examination. In the anorectal transplantation model, 4 dogs were assigned to 4 groups: autotransplant, allotransplant with immunosuppression, allotransplant without immunosuppression, and normal control. Long-term function was evaluated by defecography, videography, and histological examination. RESULTS: In the pudendal nerve function study, anorectal manometry indicated that the anastomosis group recovered partial function 6âmonths postoperatively. Microscopically, the pudendal nerve and the sphincter muscle regenerated in the anastomosis group. Anorectal transplantation was technically successful with a 3-stage operation: colostomy preparation, anorectal transplantation, and stoma closure. The dog who underwent allotransplantation and immunosuppression had 2 episodes of mild rejection, which were reversed with methylprednisolone and tacrolimus. The dog who underwent allotransplantation without immunosuppression had a severe acute rejection that resulted in graft necrosis. Successful dogs had full defecation control at the end of the study. CONCLUSIONS: We describe the critical role of the pudendal nerve in anorectal function and the first long-term success with anorectal transplantation in a canine model. This report is a proof-of-concept study for anorectal transplantation as a treatment for patients with an ostomy because of anorectal dysfunction.
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Canal Anal , Reto , Canal Anal/cirurgia , Anastomose Cirúrgica/métodos , Animais , Colostomia , Cães , Eletromiografia , Humanos , Manometria , Reto/cirurgiaRESUMO
Sterically stabilized hybrids of cellulose nanowhiskers (CNWs) and silver nanoparticles (AgNPs) were prepared via poly(ethylene glycol) (PEG) grafting and subsequent reduction of Ag+ counterions by sodium borohydride (NaBH4) for improved dispersion stability after hybridization. The preparation scheme includes surface carboxylation of CNWs using a 2,2,6,6-tetramethyl-1-pyperidinyloxy radical (TEMPO), grafting of monomethoxy PEG (mPEG) via amidation mediated by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride or 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, exchange of countercation of residual carboxyls to Ag+, and deposition of AgNPs via reduction with NaBH4. UV-vis spectroscopy and electron microscopy analyses confirmed the successful deposition of AgNPs. Most of the mPEG-grafted hybrids were stable under the presence of an electrolyte, although some of them were precipitated by the addition of 0.1 M CaCl2. The addition of CaCl2 was also found to trigger discoloration of the hybrids, suggesting the partial dissolution of AgNPs and the formation of water-insoluble AgCl.
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OBJECTIVE: Concurrent chemoradiotherapy is the standard treatment for locally advanced non-small cell lung cancer. In the current aging society, the establishment of an ideal treatment strategy for locally advanced non-small cell lung cancer in the elderly is warranted. To assess the efficacy of concurrent chemoradiotherapy with carboplatin and vinorelbine in elderly patients with locally advanced non-small cell lung cancer. PURPOSE: To assess the efficacy of concurrent chemoradiotherapy with carboplatin and vinorelbine in elderly patients with locally advanced non-small cell lung cancer. METHODS: This multicenter, phase II study included patients with physiologically or medically unresectable stage I-III NSCLC, who were ≥70 years old. The patients received carboplatin (AUC 2) and vinorelbine (15 mg/m2) both on day 1, 8, 22 and 29 concurrently with radiotherapy (2.0 Gy/day, 30 fractions, total 60 Gy). The primary endpoint was the objective response rate. The secondary endpoints were the progression-free survival, overall survival and the incidence of adverse events. RESULTS: 50 patients were accrued (42 men and 8 women). The median age was 77 years (range, 70-89 years) and the clinical stage was I/II/III in 3/7/40, respectively. Forty-seven patients completed the planned treatment. The response was complete remission in 4, partial response in 31, stable disease in 12 and progressive disease in 3, giving an objective response rate of 70% (95% confidence interval: 55.4-82.1). Frequent high Grade 3 or higher adverse events were hematologic, but no treatment deaths were noted. The median and 2-year progression-free survival were 8.4 months and 21.1% (95% confidence interval: 9.5-32.7%), respectively, and the median and 2-year overall survival were 15.4 months and 41.1% (95% confidence interval: 27.0-55.2), respectively. CONCLUSION: Concurrent chemoradiotherapy with carboplatin and vinorelbine showed an acceptable objective response rate and safety in elderly patients.
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Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia , Neoplasias Pulmonares/terapia , Vinorelbina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Indução de Remissão , Análise de SobrevidaRESUMO
BACKGROUND AND OBJECTIVES: Tattoo removal by laser has been mostly performed using Q-switched laser, which has nanosecond pulse width. In recent years, the efficacy of treatment with picosecond pulse width laser has also been reported. STUDY DESIGN/MATERIALS AND METHODS: Using a picosecond-domain, neodymium-doped yttrium-aluminum-garnet laser with a potassium-titanyl-phosphate frequency-doubling crystal, we performed a retrospective clinical study with combination treatment using pulse widths of 750 ps and 2 ns. The number of treatments was compared with the Kirby-Desai score. Tissue changes immediately after laser irradiation at 2 ns and 750 ps were compared using an electron microscope. RESULTS: The combination treatment using pulse widths of 2 ns and 750 ps was safe and more effective than the Q-switched neodymium-doped yttrium-aluminum-garnet laser treatment. Tattoo removal was possible with significantly fewer treatment numbers than the Kirby-Desai score, without adverse events. The results from the scanning electron microscope revealed that ink particles irradiated by 750 ps were more dispersed than those by 2 ns. CONCLUSIONS: The combination treatment with pulse widths of 2 ns and 750 ps and 1064 nm and 532 nm wavelengths using the neodymium-doped yttrium-aluminum-garnet laser was safe and effective and can be a useful option for tattoo removal. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
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Lasers de Estado Sólido/uso terapêutico , Terapia com Luz de Baixa Intensidade/instrumentação , Tatuagem , Adulto , Feminino , Humanos , Tinta , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Ascaris lumbricoides or roundworm is one of the key soil-transmitted helminths affecting humans. A small number of infections continue to occur in Japan, suggesting plant foodstuff contamination as the source of infection. To understand the current status of ascariasis incidence and to identify potential sources of infection, we extensively surveyed the available literature and collected data from testing facilities that examined clinical samples or foodstuffs. We observed that from 2002 onwards, there was a decrease in the number of ascariasis cases reported in scientific journals. Data from a clinical testing facility indicated that the number of detected cases declined remarkably from 2009. Foodstuff testing facilities reported that 11 of 10,223 plant foodstuff specimens were contaminated with anisakid nematodes but not with Ascaris. Imported kimchi was suspected as the most probable source of ascarid nematode infection, as one Ascaris egg-positive sample was detected among 60 kimchi samples in a testing facility. Therefore, the sources of Ascaris infection are still not fully known and need to be clarified to establish preventive countermeasures to safeguard Ascaris infections that continue to occur in Japan.
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Ascaríase , Ascaris lumbricoides , Parasitologia de Alimentos , Animais , Ascaríase/epidemiologia , Ascaríase/prevenção & controle , Humanos , Incidência , Japão/epidemiologia , SoloRESUMO
AIM: To evaluate the clinical and molecular characteristics of hepatitis E virus (HEV) infection in Mie Prefecture, Japan, from 2004 through 2018. METHODS: The clinical information of hepatitis E cases was collected from 21 medical institutions in Mie Prefecture. The nucleotide sequences of infecting HEV strains were determined for cases with available serum samples. The origins or transmission routes were inferred from phylogenetic analyses of the nucleotide sequences. RESULTS: Fifty-three patients were diagnosed with HEV infection. The number of cases increased each year through 2012 and then decreased. Analyses of the clinical characteristics of the cases indicated that even mild cases were detected in the latter 10 years of the study. Nucleotide sequence analyses were undertaken on 38 of the 53 cases. The HEV subtype 3e (HEV-3e) strains identified for 13 cases were closely related to a swine HEV-3e strain that was isolated from the liver of a pig bred in Mie Prefecture. The number of cases infected with the indigenous Mie HEV-3e strains increased until 2012 but have not been reported since 2014. In the latter half of the study, cases involving various HEV strains of different genotypes and subtypes emerged. CONCLUSIONS: The disappearance of indigenous Mie HEV-3e strains appeared to be the primary cause for the decrease in hepatitis E cases in Mie Prefecture. The disappearance might have been associated with improved hygienic conditions on pig farms or the closure of contaminated farms. The results suggest that indigenous HEV strains can be eradicated by appropriate management.
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BACKGROUND AND AIM: We aimed to examine the validity of the Japanese version of SARC-F questionnaire (SARC-F-J) that employs the diagnostic criteria for sarcopenia established by the Japan Society of Hepatology in patients with chronic liver disease. METHODS: Subjects were outpatients at the Department of Hepatology at the Japanese Red Cross Ise Hospital, Japan. Evaluations were performed using the following self-administered questionnaires: SARC-F-J, Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC), the Japanese version of the Falls Efficacy Scale (FES), and Kaigo-Yobo Checklist (CL). Based on the diagnostic criteria of the Japan Society of Hepatology, we diagnosed sarcopenia from the skeletal muscle index calculated using the iliopsoas muscle area at the third lumbar vertebra on computed tomography and from grip strength. To evaluate construct validity, we calculated the sensitivity, specificity, and positive and negative predictive values of SARC-F-J that used the diagnostic criteria of the Japan Society of Hepatology as reference. Furthermore, to evaluate convergent validity, we calculated Pearson's correlation coefficients between SARC-F-J and TMIG-IC, FES, and CL. RESULTS: A total of 140 subjects were included in the analysis set. Sensitivity and specificity were 16.3% and 45.0% and 95.3% and 90.8% for men and women, respectively. The positive predictive value was 81.8% for both, whereas the negative predictive value was 47.1% and 64.5% for men and women, respectively. A significant correlation was seen between SARC-F-J and TMIG-IC, FES, and CL. CONCLUSIONS: We believe that the SARC-F-J is a valid tool for patients with chronic liver disease.
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Idioma , Hepatopatias/complicações , Sarcopenia/diagnóstico , Sarcopenia/etiologia , Inquéritos e Questionários , Doença Crônica , Feminino , Força da Mão , Humanos , Japão , Masculino , Músculo Esquelético/diagnóstico por imagem , Valor Preditivo dos Testes , Sarcopenia/fisiopatologia , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios XRESUMO
Sterically stabilized chitin nanowhiskers (ChNWs) were prepared by surface grafting monomethoxy poly(ethylene glycol) (mPEG) via reductive amination of primary amino groups on ChNWs and terminal aldehydes on mPEG. The amount of grafted mPEG was determined to be 0.2-0.3 g/g ChNWs, by conductometric titration, from the decrease in amino groups after grafting. ChNWs with controlled amounts of surface amino groups were obtained by deacetylation; however, this did not cause a drastic change in the amount of grafted mPEG. Grafting was confirmed by Fourier-transform infrared spectroscopy; however, X-ray diffractometry indicated no sign of mPEG. Thermogravimetry indicated a higher amount of mPEG than that from titration, suggesting an overestimation due to the facilitated combustion of grafted samples. In contrast to ungrafted samples, all grafted samples were stable in the presence of electrolytes. However, liquid-crystalline phase separation of grafted ChNWs was not observed, possibly owing to the high viscosity of the concentrated sample.
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Materiais Biocompatíveis/química , Quitina/química , Nanopartículas/química , Polietilenoglicóis/química , Aminação , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria , Viscosidade , Difração de Raios XRESUMO
AIM: Uterine transplantation (UTx) is a potential option for child-bearing in women with uterine infertility. Recovery of uterine function after allogeneic UTx in non-human primates has not been reported. The objective of this study is to establish the functional uterine transplant model in non-human primates. METHODS: Uteri of two cynomolgus monkeys were simultaneously removed, cooled at 4°C and perfused with heparin saline. The uteri were interchanged with each other and then orthotopically transplanted. Immunosuppressive protocols included use of three agents (tacrolimus, mycophenolate mofetil and methylprednisolone) in case 1 and two agents (tacrolimus and methylprednisolone) in case 2. Transabdominal ultrasonography, vaginoscopy and biopsy of the transplanted uterine cervix were routinely conducted to monitor rejection after surgery. RESULTS: The blood concentration of tacrolimus decreased 11 days after surgery and evidence of rejection was found in biopsy of the uterine cervix in both cases. The suspected rejection disappeared 23 days after surgery in case 1 and temporary menstruation resumed at 3 months after surgery. In case 2, blood flow to the uterine artery gradually decreased and the uterus resulted in atrophy due to ischemia, which has been triggered by rejection. CONCLUSION: Allogeneic UTx in the cynomolgus monkeys resulted in temporary recovery of menstruation with three immunosuppressants and uterine atrophy with two immunosuppressants. This preliminary experience suggests that recovery of uterine function after allogeneic UTx in non-human primates is possible but more experiments are required.
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Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Útero/transplante , Animais , Quimioterapia Combinada , Feminino , Macaca fascicularis , Menstruação , Transplante Homólogo , Útero/imunologia , Útero/fisiologiaRESUMO
A sterically stabilized aqueous suspension of "charge-free" cellulose nanowhiskers was prepared by hydrochloric acid hydrolysis of cotton powders and subsequent surface grafting of monomethoxy poly(ethylene glycol) (mPEG). The preparation scheme included carboxylation of the terminal hydroxyl groups in mPEG via oxidation with silica gel particles carrying 2,2,6,6-tetramethyl-1-pyperidinyloxyl (TEMPO) moieties and subsequent esterification between terminal carboxyls in mPEG and surface hydroxyl groups of cellulose nanowhiskers, mediated by 1,1'-carbonyldiimidazole (CDI) in dimethyl sulfoxide or dimethylacetamide. Some of the prepared PEG-grafted samples showed remarkable flow birefringence and enhanced stability after 24 h, even in 0.1 M NaCl, suggesting successful steric stabilization by efficient mPEG grafting. Actual PEG grafting via ester linkages was confirmed by attenuated total reflectance-Fourier transform infrared spectrometry. In a typical example, the amount of grafted mPEG was estimated as ca. 0.3 g/g cellulose by two measurements, i.e., weight increase after grafting and weight loss after alkali cleavage of ester linkages. Transmission electron microscopy indicated unchanged nanowhisker morphology after mPEG grafting.
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Celulose/química , Nanoestruturas/química , Polietilenoglicóis/química , Esterificação , Microscopia Eletrônica de Transmissão , Oxirredução , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Lateral chest wall perforator flaps, such as the lateral intercostal artery perforator flap, lateral thoracic artery perforator flap, and thoracodorsal artery perforator flap, have been used for volume replacement oncoplastic breast-conserving surgery (VR-OPBCS) in the lateral and central breast. However, there are cases in which these perforators are missing or too thin, making it difficult to raise a flap for partial breast reconstruction. A 58-year-old woman underwent VR-OPBCS for breast cancer in the lower quadrant of the right breast. Preoperative imaging studies did not identify lateral thoracic artery perforator or thoracodorsal artery perforator but identified a well-developed superficial thoracic artery perforator (STAP). A flap based on the STAP was dissected, and partial breast reconstruction was performed. The flap survived with no complications. No deformity of the lower breast or displacement of the nipple-areola complex was observed 8 months after the completion of postoperative radiotherapy. The STAP flap can be used as an alternative to VR-OPBCS when other lateral chest wall perforator flaps are unavailable.
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OBJECTIVE: The differences in speech function between groin flap reconstruction and anterolateral thigh (ALT) flap reconstruction after hemiglossectomy have not been clarified to date. This study aimed to compare Japanese speech intelligibility after hemiglossectomy reconstruction using groin and ALT flaps of similar thickness. METHODS: Data of patients who underwent hemiglossectomy reconstruction with groin or ALT flaps between April 2010 and March 2020 were collected from the medical chart database. The ALT flap was the first choice for hemiglossectomy reconstruction, and a groin flap was used when the ALT flap was >10 mm. Cases in which speech intelligibility assessments based on Hirose's 10-point scoring system, the TKR speech test, and the Japanese speech intelligibility test for 100 monosyllables were performed after 6 months postoperatively were extracted. The per-patient scores for each assessment were initially compared between the two flap groups. Then, the results of the Japanese speech intelligibility test for 100 monosyllables were reanalyzed on a syllable-by-syllable basis. RESULTS: Among the 44 hemiglossectomy patients who underwent free-flap reconstruction during the study period, 14 (seven each in the groin flap and ALT flap groups) underwent all three conventional speech intelligibility assessments after 6 months postoperatively. The two groups showed no significant difference in postoperative speech intelligibility in any of the three patient assessment methods. However, in intergroup comparisons based on per-syllable accuracy for each of the 100 monosyllables, the groin flap group showed 19 syllables with a significantly higher accuracy, whereas the ALT flap group showed one such syllable. In particular, five out of the six alveolar consonants (/t/ and /d/) were more accurately articulated in the groin flap group. Per-syllable accuracy was significantly higher in the groin flap group (74.6% vs. 66.7%; 95% confidence interval: 4.6-11.1, p < 0.001). CONCLUSION: In patients undergoing hemiglossectomy reconstruction, our new analysis method, which compared intelligibility by syllables, showed that the groin flap yielded higher speech intelligibility than the ALT flap. This difference was evident at all four articulation points involving the tongue, whereas there was no significant difference at the two articulation points without tongue involvement.
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Retalhos de Tecido Biológico , Neoplasias da Língua , Humanos , Inteligibilidade da Fala , Coxa da Perna/cirurgia , Virilha , População do Leste Asiático , Neoplasias da Língua/cirurgia , DeglutiçãoRESUMO
BACKGROUND: There is no consensus on the postoperative outcomes of tongue reconstruction. Therefore, the authors developed a novel risk model for predicting dysphagia after tongue reconstruction. METHODS: This retrospective study was conducted by the Oral Pharyngeal Esophageal Operation and Reconstruction Analytical, or OPERA, group across 31 cancer centers and university hospitals in Japan. A total of 532 patients [390 (73.3%) men and 142 (26.7%) women; median age at surgery, 60 years (range, 15 to 88 years)] who were diagnosed with oral tongue squamous cell carcinoma and underwent tongue reconstruction following glossectomy between 2009 and 2013 were included. Independent risk factors were identified using univariate regression analysis and converted to a binary format for multivariate analysis. An integer value was assigned to each risk factor to calculate a total score capable of quantifying the risk of feeding tube dependence. RESULTS: Overall, 54 patients (10.2%) required a feeding tube at the time of evaluation. Predictive factors for feeding tube dependence were advanced age, lower American Society of Anesthesiologists physical status, low body mass index, lower serum albumin, comorbid hypertension and diabetes, extended tongue defect, resection beyond the tongue, laryngeal suspension, postoperative radiation therapy, and no functional teeth. In multivariate logistic regression analysis, age greater than or equal to 58.5 years, postoperative radiation therapy, wider tongue defect, and body mass index less than 21.27 kg/m 2 earned 6, 4, 3, and 2 points, respectively, for a maximum total score of 15. CONCLUSION: The authors' risk model provides a mathematical tool for estimating the individual risk of postoperative feeding tube dependence before tongue reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.
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Carcinoma de Células Escamosas , Transtornos de Deglutição , Neoplasias de Cabeça e Pescoço , Neoplasias da Língua , Masculino , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/cirurgia , Estudos Retrospectivos , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Japão/epidemiologia , Neoplasias da Língua/cirurgia , Neoplasias da Língua/complicações , Neoplasias da Língua/patologia , Língua/cirurgia , Glossectomia/efeitos adversos , Neoplasias de Cabeça e Pescoço/cirurgiaRESUMO
Background: Multivisceral transplantation of pelvic organs would be a potential treatment for severe pelvic floor dysfunction with fecal and urinary incontinence, extensive perineal trauma, or congenital disorders. Here, we describe the microsurgical technique of multivisceral transplantation of pelvic organs, including the pelvic floor, in rats. Donor operation: We performed a perineal (including the genitalia, anus, muscles, and ligaments) and abdominal incision. The dissection progressed near the pelvic ring, dividing ligaments, muscles, external iliac vessels, and pudendal nerves, allowing pelvic floor mobilization. The aorta and vena cava were isolated distally, preserving the internal iliac and gonadal vessels. The graft containing the skin, muscles, ligaments, bladder, ureter, rectum, anus and vagina, uterus and ovarian (female), or penile, testis and its ducts (male) was removed en bloc, flushed, and cold-stored. Recipient operation: The infrarenal aorta and vena cava were isolated and donor/recipient aorta-aorta and cava-cava end-to-side microanastomoses were performed. After pelvic floor and viscera removal, we performed microanastomoses between the donor and the recipient ureter, and the rectum and pudenda nerves. The pelvic floor was repositioned in its original position (orthotopic model) or the abdominal wall (heterotopic model). We sacrificed the animals 2 h after surgery. Results: We performed seven orthotopic and four heterotopic transplantations. One animal from the orthotopic model and one from the heterotopic model died because of technical failure. Six orthotopic and three heterotopic recipients survived up to 2â h after transplantation. Conclusion: The microsurgical technique for pelvic floor transplantation in rats is feasible, achieving an early survival rate of 81.82%.
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Based on the analysis of exudates from injured adipose tissue, we prepared a mixture containing the injury-associated growth factors at the same proportion as the exudates, named adipose injury cocktail (AIC). We hypothesized that AIC induces a series of regenerating and angiogenic processes without actual wounding. The purpose of this study is to elucidate the therapeutic potentials of AIC. AIC preferentially activated adipose-derived stem/progenitor/stromal cells (ASCs) to proliferate, migrate, and form networks compared with vascular endothelial cells, whereas vascular endothelial growth factor did not induce mitogenesis or chemotaxis in human ASCs. Each component growth factor of AIC was differently responsible for the ASC activation. AIC-treated ASCs tended to differentiate into adipocytes or vessel-constituting cells rather than into other cell types. In ischemic adipose tissues of mice, induced by either a surgical intervention or diabetes, AIC administration enhanced proliferation, especially of CD31(-)/CD34(+) ASCs, and mitigated tissue hypoxia by increasing capillary density and reducing fibrogenesis. These results suggest that AIC may have therapeutic potentials for various ischemic/hypoxic conditions by inducing adipose remodeling and neovascularization through activation of ASCs and other cells. Treatment with AIC has many advantages over cell-based therapies regarding morbidity, cost, and physical risks and may be used as an alternative therapy for improving tissue oxygen.
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Tecido Adiposo/metabolismo , Hipóxia/prevenção & controle , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Isquemia/prevenção & controle , Células-Tronco Mesenquimais/citologia , Neovascularização Fisiológica/fisiologia , Tecido Adiposo/lesões , Adulto , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Separação Celular , Citometria de Fluxo , Humanos , Hipóxia/metabolismo , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Isquemia/metabolismo , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Neovascularização Fisiológica/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Estromais/citologia , Células Estromais/efeitos dos fármacosRESUMO
BACKGROUND: For women with congenital uterine infertility, or for those who have undergone hysterectomy, uterine transplantation is one of the potential treatments to regain fertility. In this study, we utilized a primate model of uterine transplantation, and evaluated the patency of our microsurgical anastomoses, and the perfusion of the transplanted uterus. METHODS: Two female cynomolgus monkeys underwent surgery. We anastomosed two arteries and one vein in Case 1 and two arteries and two veins in Case 2. The arteries used were the uterine arteries and the anastomosis was done to the external iliac artery. We used one of the ovarian veins in both animals, but resected the ovary from the Fallopian tube. Uterine arterial blood flow and uterine size were determined by intraoperative indocyanine green (ICG) angiography and ultrasonography. The biopsy of the uterine cervix was performed after surgery. RESULTS: ICG angiography showed that the unilateral uterine artery perfused the bilateral uterine bodies and cervix. In Case 1, ICG angiography showed the occlusion of one of the anastomosed arteries during the operation and the uterus appeared atrophied 2 months after operation. In Case 2, the transplanted uterus survived and normal menstruation occurred. The animal achieved a natural pregnancy and was delivered by the Caeserean section due to early separation of the placenta. The newborn suffered fetal distress. CONCLUSIONS: These results show the anastomosis of at least the bilateral uterine arteries and the unilateral ovarian vein is required for uterus transplantation. This is the first report of a natural pregnancy in a primate following uterine autotransplantation.
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Útero/imunologia , Útero/transplante , Anastomose Cirúrgica , Angiografia/métodos , Animais , Biópsia , Velocidade do Fluxo Sanguíneo , Feminino , Verde de Indocianina/farmacologia , Macaca fascicularis , Transplante Autólogo , Ultrassonografia Doppler/métodos , Útero/irrigação sanguínea , Útero/patologiaRESUMO
OBJECTIVE: Uterine transplantation experiments have been performed in various animal species for future clinical applications of uterine transplantation for permanent uterine factor infertility in humans. The aim of this study was to confirm the feasibility of uterine auto-transplantation in cynomolgus monkeys by developing new surgical techniques. METHODS: Two female cynomolgus monkeys underwent surgery under general anesthesia. The uterus with vascular grafts and the vaginal wall was removed, and back-table preparation was performed using heparinized saline. The uterus with vascular grafts and the vaginal wall was anastomosed with the vaginal stump and blood vessels in the pelvis, respectively. The auto-transplant uterine function was evaluated by confirming engraftment of the uterus by laparotomy, endometrial proliferation by transabdominal ultrasonography and periodical menstruation. RESULTS: The first animal died due to acute renal failure 2 days after the operation. Second-look laparotomy in the second animal at 40 days after the operation indicated there was no congestion in the uterus, and the uterus showed the typical red color of a normal uterus. Thereafter, endometrial proliferation was observed by transabdominal ultrasonography and periodical menstruation was confirmed, indicating re-established uterine function. CONCLUSION: This is the preliminary report of uterine auto-transplantation in cynomolgus monkeys. This study demonstrates the feasibility of uterine auto-transplantation by using new surgical technique in cynomolgus monkeys. Accumulation of basic experimental data in non-human primates is required prior to performing the procedure in humans.
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Transplante Autólogo/métodos , Útero/transplante , Animais , Feminino , Procedimentos Cirúrgicos em Ginecologia/métodos , Macaca fascicularisRESUMO
We have described a procedure to minimize surgical wounds, in which lymph vessels and skin venules are identified by indocyanine green (ICG) lymphography and the AV300 noncontact visualization system (AccuVein, Cold Spring Harbor, NY), respectively. This approach allows accurate decisions regarding sites of incision for lymphatic venous anastomosis (LVA). This method was applied in a patient with right upper-limb lymphedema after breast cancer therapy. The low-invasive procedure can be used before and during surgery. The incision size is minimal, and the incision site is at the joint area. Thus, we aim to establish this approach as a standard method for identifying lymph vessels and veins that are suitable for LVA. This innovative vascular-imaging machine makes LVA less invasive and more effective without side effects.