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1.
Artículo en Inglés | MEDLINE | ID: mdl-38694538

RESUMEN

Large ileal lipomas over 2 cm can cause symptoms, that may require a resection. Due to the narrow lumen and thin walls of the ileum, endoscopic treatments can have a high risk of adverse events and require technical expertise, thus surgical resection is currently the mainstay of treatment. To overcome the technical challenges, we developed a novel method to endoscopically resect terminal ileal lipomas. The technique involves extracting the lesion into the cecum, which creates sufficient space to maneuver, and a better field of view. The lipoma is resected with endoscopic mucosal resection or endoscopic submucosal dissection. The appearance of the lipoma protruding out of the ileocecal valve resembles that of a tongue sticking out of the mouth, thus we named this the "tongue out technique". To assess the technical feasibility of this method, we retrospectively analyzed seven cases of terminal ileal lipoma that were endoscopically resected using the "tongue out technique" at NTT Medical Center Tokyo between January 2017 and October 2023. Technical success was 100% and en bloc resection was achieved in all cases. The median size was 31 (14-55) mm. Three cases were resected with endoscopic mucosal resection while endoscopic submucosal dissection was performed on the other four cases. There was one case of delayed post-endoscopic mucosal resection bleeding, which was caused by clip dislodgement. There were no perforations. No recurrence of the lipoma or associated symptoms have been observed. This new technique can allow more ileal lipomas to be treated with minimally invasive and organ-preserving endoscopic procedures.

2.
VideoGIE ; 9(4): 188-190, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38618616

RESUMEN

Video 1Nonexposed endoscopic wall inversion surgery for local resection of microscopic residual tumor after endoscopic submucosal dissection.

3.
DEN Open ; 4(1): e340, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38343421

RESUMEN

A 57-year-old woman with no significant medical history was referred after a colonoscopy for abdominal distension, which revealed a tumor in the lower rectum. Pre-operative colonoscopy showed the tumor was 12 mm in size, located from the anorectal junction to beyond the dentate line, and was diagnosed as high-grade intramucosal neoplasia or shallow submucosal invasive cancer. Endoscopic submucosal dissection was performed, and the lesion was resected en bloc. Pathological examination revealed moderately differentiated tubular adenocarcinoma with tubulovillous adenoma. The stratified squamous epithelium adjacent to the anal side of the lesion showed pagetoid spread of atypical cells with positive horizontal margins. We referred her to a surgeon for radical treatment. The mucosa surrounding the endoscopic submucosal dissection scar was normal on narrow-band imaging magnification. We marked its oral side endoscopically as the resected boundary. Transanal local excision was performed. The horizontal margins were positive because atypical cells had spread into the stratified squamous epithelium of the anorectal side of the lesion. The patient was followed on an outpatient basis. Sixty days postoperatively, residual tumor growth was observed. The second local resection was performed after mapping biopsy. All resection margins were negative, there was no lymphovascular invasion. One year after surgery, no recurrence was observed. Regarding endoscopic findings, there are no reports of endoscopic findings of the rectal mucosa, or the squamous epithelium of the anus of pagetoid spread. Here, we report a review of perianal Paget's Disease that resulted in difficulties in borderline diagnosis of pagetoid spread, resulting in multiple therapeutic interventions.

4.
DEN Open ; 4(1): e338, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38283588

RESUMEN

A 25-year-old man was referred to our center for investigation of a gastric submucosal tumor and an ulcer that had developed on its oral side. Endoscopic ultrasonography findings suggested the presence of an ectopic pancreas, and treatment with an oral proton pump inhibitor was planned for the ulcer. Over the subsequent 3 years, the patient endured recurring epigastric pain and episodes of passing black stools. Emergency endoscopy revealed that the morphology of the gastric submucosal tumor had transformed into a pedunculated polyp-like morphology with a bleeding ulcer at the apex of the lesion. Endoscopic hemostasis using hemostatic forceps was performed. However, the patient continued to pass black stools. In light of the persistent symptoms and unique morphology of the lesion, endoscopic resection was attempted as a curative approach. The lesion was excised by hot snare polypectomy. Post-treatment, the patient exhibited no signs of recurrence, marking a successful resolution. Three months later, a gastroduodenal endoscopy showed that the excised site had undergone scar formation without recurrence of the lesion. This case holds significant clinical value as it demonstrates the efficacy of a minimally invasive treatment strategy in managing repeated bleeding ulcerations of an ectopic pancreas, ultimately achieving a complete cure.

5.
DEN Open ; 4(1): e335, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38264464

RESUMEN

A 51-year-old woman visited our hospital with the chief complaint of tarry stools. Contrast-enhanced abdominal computed tomography revealed leakage of contrast medium into the lumen of the small intestine. Subsequently, a double-balloon endoscopy was performed, which revealed a submucosal mass-like lesion in the jejunum. Although hemostasis was attempted with clips, complete hemostasis was difficult to achieve, and angiographic embolization was performed. Nevertheless, the anemia progressed, and a small bowel resection was performed. Histopathological examination led to a diagnosis of a ruptured submucosal aneurysm of the small intestine. Endoscopic hemostasis is often difficult to achieve for submucosal aneurysms in the intestine. The submucosal tumor-like finding observed on endoscopy in submucosal aneurysms is termed an "SMT-like sign" and is considered an important finding to diagnose aneurysms.

6.
DEN Open ; 4(1): e328, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38188356

RESUMEN

Objectives: Previous studies of cold snare polypectomy (CSP) for sessile serrated lesions (SSLs) ≥10 mm were performed by experienced endoscopists, and therefore their skills might have significantly influenced results. In this study, we compared the efficacy and safety of CSP for SSLs ≥10 mm between experienced and trainee endoscopists. Methods: In a 1:1 propensity score matched retrospective cohort study, we compared the complete resection rate, en-bloc resection rate, adverse event rate, and procedure time between experienced and trainee groups. Thirteen endoscopists performed CSP, and we defined the experienced group as endoscopists with board certification from the Japan Gastroenterological Endoscopy Society. Results: We examined 616 lesions with SSLs ≥10 mm resected by CSP between February 2018 and May 2022. We excluded 61 lesions from the analysis because they had simultaneously undergone hot snare polypectomy (n = 57) or had been taken over by experienced endoscopists from trainees in the CSP procedure (n = 4). Finally, we identified 217 propensity score-matched pairs (n = 434). Between experienced and trainee groups, the results were complete resection rate (100 vs. 100%; p = 1.00), en-bloc resection rate (73.2 vs. 75.6%; p = 0.24), adverse event rate (3.2 vs. 2.8%; p = 0.77), or procedure time (6.2 vs. 5.9 min; p = 0.64). Conclusions: We have demonstrated the safety and efficacy of CSP for SSLs ≥10 mm performed by experienced and trainee endoscopists.

7.
BMJ Case Rep ; 16(12)2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-38081738

RESUMEN

Wernicke encephalopathy is an emergent neurological disorder caused by vitamin B1 (thiamine) deficiency. Here, we present a case of Wernicke encephalopathy in a male patient in his 70s with normal serum thiamine levels and MRI findings on admission. He had a history of heavy alcohol consumption and a gradual decrease in food intake. On arrival at the hospital, his consciousness was impaired which persisted even after glucose replacement. Moreover, horizontal nystagmus and cerebellar ataxia were observed. Head CT scan and MRI revealed no abnormal findings. Further, his serum thiamine level was within the normal range. The patient was clinically diagnosed with Wernicke encephalopathy, and high-dose thiamine therapy was started. Then, his symptoms improved immediately. Thus, in case of clinical suspicion, treatment for Wernicke encephalopathy must be initiated promptly even in patients with normal serum thiamine levels.


Asunto(s)
Beriberi , Síndrome de Korsakoff , Deficiencia de Tiamina , Encefalopatía de Wernicke , Humanos , Masculino , Beriberi/complicaciones , Síndrome de Korsakoff/etiología , Imagen por Resonancia Magnética , Tiamina , Deficiencia de Tiamina/complicaciones , Deficiencia de Tiamina/diagnóstico , Deficiencia de Tiamina/tratamiento farmacológico , Encefalopatía de Wernicke/diagnóstico por imagen , Encefalopatía de Wernicke/tratamiento farmacológico , Anciano
8.
Endosc Int Open ; 11(10): E976-E982, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37828975

RESUMEN

Background and study aims Endoscopic treatment strategies for small superficial duodenal epithelial neoplasia (SDET) have not been established, and the R0 resection rates of all previously reported endoscopic techniques are somewhat low. Furthermore, no reports of cap-assisted endoscopic mucosal resection (EMRC), which is reportedly associated with a relatively high R0 resection rate, have been evaluated in sufficient numbers of patients. Therefore, we assessed the efficacy and safety of EMRC for SDETs ≤ 10 mm in a retrospective cohort study. Patients and methods We examined a prospectively maintained database and identified 248 consecutive patients (248 lesions) who had undergone endoscopic resection for SDETs ≤ 10 mm between January 2017 and June 2022. Our treatment strategy was consistent, with EMRC indicated for all SDETs ≤ 10 mm without non-lifting signs. The primary endpoint was the R0 resection rate. Results Overall, 20 lesions had non-lifting signs and were selected for endoscopic submucosal dissection, while the remaining 228 lesions were treated with EMRC. As a result of EMRC, the median tumor size was 5 mm, and the mean procedure time was 5 minutes. Most of the lesions (89.2%) were located in the descending part. The R0 resection rate was 97.4% (222/228 cases), and the en bloc resection rate was 99.6%. Only seven patients(3.1%) experienced adverse events (6 patients, delayed bleeding; 1 patient, acute pancreatitis), which were successfully managed without surgical intervention. Furthermore, no recurrences were observed. Conclusions We have demonstrated that EMRC is an effective and safe treatment for SDETs ≤ 10 mm that do not have non-lifting signs.

9.
VideoGIE ; 8(9): 379-381, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37719943

RESUMEN

Video 1Presentation of a newly invented transparent silicon attachment, the static electricity fastening tape hood, and its creation process, durability, and usefulness for various endoscopic procedures.

10.
J Med Case Rep ; 17(1): 92, 2023 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-36915159

RESUMEN

BACKGROUND: Perigastric abscess caused by delayed perforation after endoscopic submucosal dissection is a very rare complication. In principle, delayed perforation after endoscopic submucosal dissection is treated surgically. Herein, we report a case of perigastric abscess caused by delayed perforation after gastric endoscopic submucosal dissection that was treated conservatively, without perforation closure, and in which the patient was discharged from hospital in a short period. CASE PRESENTATION: A-74-year-old Asian man was diagnosed with having early gastric cancer on follow-up endoscopy and was admitted to our hospital for endoscopic resection. Endoscopic submucosal dissection was performed without intraoperative complications. On postoperative day 2, the patient complained of a slight abdominal pain localized to the epigastric region and a small amount of melena. A computed tomography scan revealed the presence of free air in the peritoneal cavity, and a little fluid collection abutting the dorsal area of the stomach. An endoscopy examination showed a deep ulcer with the accumulation of pus, suggesting a perforation in the post-endoscopic submucosal dissection ulcer. We diagnosed a perigastric abscess, caused by delayed perforation after endoscopic submucosal dissection, and opted for conservative treatment, leaving the perforation site open to allow spontaneous drainage from the abscess into the stomach. A follow-up computed tomography scan revealed an encapsuled and localized perigastric abscess on postoperative day 5, and the disappearance of the free air and the regression of the perigastric abscess on postoperative day 7. A follow-up endoscopy examination on postoperative day 7 showed the closure of the perforation. Finally, surgery was avoided, and the patient was discharged on postoperative day 14, after a relatively short hospital stay. CONCLUSION: Regarding the treatment of perigastric abscess, caused by delayed perforation after endoscopic submucosal dissection, leaving the perforation site open to allow spontaneous drainage may shorten the conservative treatment period.


Asunto(s)
Resección Endoscópica de la Mucosa , Neoplasias Gástricas , Masculino , Humanos , Absceso/etiología , Absceso/terapia , Resección Endoscópica de la Mucosa/efectos adversos , Tratamiento Conservador , Úlcera , Estómago , Neoplasias Gástricas/cirugía , Endoscopía Gastrointestinal , Resultado del Tratamiento
12.
Endosc Int Open ; 11(1): E3-E10, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36618874

RESUMEN

Background and study aims Endoscopic submucosal dissection (ESD) of pharyngeal cancers with conventional endoscopes often is difficult, not only because of the narrow working space, but also because endoscope maneuverability in the pharynx is poor due to interference from the endotracheal tube and/or hyoid bone. However, we hypothesized that those problems could possibly be resolved by use of an ultrathin endoscope for ESD of superficial pharyngeal cancer. The aim of this prospective interventional study was to investigate the feasibility of ESD for superficial pharyngeal cancer using an ultrathin endoscope. Patients and methods This feasibility study was conducted at NTT Medical Center Tokyo between June 2020 and September 2021, and data from a total of 20 consecutively superficial pharyngeal cancers were analyzed. The primary outcome measure was the R0 resection rate. The ESD completion rate, en bloc resection rate, procedure time, and frequency of intraoperative and postoperative adverse events (AEs) were also evaluated as secondary outcome measures. Results Data from 16 patients with 20 lesions were included in the analysis. All of the lesions were successfully resected by ultrathin endoscope ESD, and the en bloc and R0 resection rates were 100 % and 85.0 % (17/20), respectively; the procedure time was 37.8 ±â€Š28.2 minutes. No intraoperative or postoperative AEs were encountered in any cases. Conclusions ESD using an ultrathin endoscope is feasible for superficial pharyngeal cancers and has potential to be a safe and effective treatment option for these cancers.

13.
DEN Open ; 3(1): e197, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36582763

RESUMEN

While duodenal neoplasms of the gastric phenotype are uncommon and their natural history is unknown, gastric neoplasms of gastric phenotype reportedly grow rapidly and can invade the submucosa. Several studies suggest that duodenal neoplasms of gastric phenotype might have a high risk of deep invasion and lymph node metastasis. Duodenal neoplasms of gastric phenotype might also have a high biological malignancy and likely require early treatment if detected. Here, we report two cases of intramucosal duodenal carcinoma with a gastric phenotype that grew rapidly but was successfully resected endoscopically.

15.
J Med Case Rep ; 16(1): 416, 2022 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-36372896

RESUMEN

BACKGROUND: Gastric mixed neuroendocrine-non-neuroendocrine neoplasms are rare malignant tumors. The lack of specific findings makes it difficult to diagnose endoscopically. We report the case of early gastric mixed neuroendocrine-non-neuroendocrine neoplasms treated by endoscopic submucosal dissection. CASE PRESENTATION: An 81-year-old Japanese female underwent esophagogastroduodenoscopy for screening and was treated with endoscopic submucosal dissection for the diagnosis of early gastric cancer. Histopathologically, the lesion was diagnosed as mixed neuroendocrine-non-neuroendocrine neoplasms (tubular adenocarcinoma 2 60%, endocrine cell carcinoma 40%), pT1b(submucosa (SM) 900 µm), pUL(-), Ly(+), v(-), pHM0, pVM0. After additional surgical resection without adjuvant chemotherapy, she has had no recurrences or metastases for 3 years. CONCLUSIONS: Comparing narrow-band imaging magnified endoscopic findings with pathological findings, the depressed area with a lack of surface structure was consistent with the neuroendocrine cell carcinoma component, while narrow-band imaging magnification findings showed non-network vessels. In this case, we examined endoscopic findings of early stage mixed neuroendocrine-non-neuroendocrine neoplasms in detail and compared it with the pathological findings. We believe that these endoscopic findings contribute to the diagnosis of mixed neuroendocrine-non-neuroendocrine neoplasms and can lead to its early detection.


Asunto(s)
Adenocarcinoma , Carcinoma Neuroendocrino , Resección Endoscópica de la Mucosa , Células Neuroendocrinas , Tumores Neuroendocrinos , Neoplasias Gástricas , Femenino , Humanos , Anciano de 80 o más Años , Mucosa Gástrica/patología , Células Neuroendocrinas/patología , Resección Endoscópica de la Mucosa/métodos , Tumores Neuroendocrinos/patología , Neoplasias Gástricas/patología , Adenocarcinoma/patología , Carcinoma Neuroendocrino/patología
16.
Clin Gastroenterol Hepatol ; 20(2): e132-e138, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-33152541

RESUMEN

BACKGROUND & AIMS: Cold snare polypectomy (CSP) has become the standard resection method for small colorectal polyps (<10 mm). Sessile serrated lesions (SSL) have low prevalence of advanced histology irrespective of size, and thus could be amenable to CSP. In this study, we evaluated the safety and efficacy of CSP for SSLs ≥10 mm. METHODS: Between November 2018 and January 2020, we prospectively enrolled 300 consecutive patients who underwent CSP for 474 SSLs ≥10 mm. To delineate SSL borders, indigo carmine chromoendoscopy and/or image-enhanced endoscopy was conducted. Piecemeal CSP (pCSP) was performed in cases where en-bloc resection was difficult. Biopsy specimens were obtained from the margins of the post-polypectomy defect to confirm complete resection. Surveillance colonoscopy was performed to screen for local recurrence. RESULTS: All lesions were successfully resected using CSP without submucosal injection. The median diameter of the resected lesions was 14 mm, and pCSP was used to resect 106 (22%) lesions. Post-polypectomy biopsies revealed residual serrated tissue in only one case (0.2%). Adverse events included immediate bleeding in 8 (3%) patients; no delayed bleeding events occurred, irrespective of the use of antithrombotic drugs. During a 7-month median follow-up period, surveillance colonoscopies were performed for 384 lesions (81%), and no local recurrences were detected. CONCLUSIONS: CSP without submucosal injection is a safe and effective treatment for SSLs ≥10 mm. UMIN Clinical Trials, Number: UMIN000034763.


Asunto(s)
Pólipos del Colon , Biopsia , Pólipos del Colon/patología , Colonoscopía/métodos , Humanos , Márgenes de Escisión , Estudios Prospectivos
17.
Clin J Gastroenterol ; 14(5): 1443-1447, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34264499

RESUMEN

Primary appendiceal cancer is rare, and difficult to diagnose pre-operatively because lack of specific symptoms. This report presents a rare case of synchronous colon and appendiceal cancer. A 50-year-old man was referred to our hospital due to endoscopic submucosal resection (ESD) for early cecal cancer. ESD was performed, and the pathological examination revealed tubular adenocarcinoma with deep submucosal invasion. Laparoscopic ileocecal resection was performed as additional resection after ESD of cecal cancer. There were no obvious abnormalities around the ileocecal region in the preoperative examination. Postoperative pathological examination incidentally revealed a mucosal papillary adenocarcinoma of the appendix, with no residual lesion in the ESD scar. The patient was discharged on the seventh postoperative day. Synchronous appendiceal and colon cancer is extremely rare in past reports. Here, we report the case details and review previous case reports.


Asunto(s)
Neoplasias del Apéndice , Apéndice , Neoplasias del Ciego , Laparoscopía , Neoplasias del Apéndice/diagnóstico , Neoplasias del Apéndice/cirugía , Neoplasias del Ciego/cirugía , Colectomía , Humanos , Masculino , Persona de Mediana Edad
18.
Exp Physiol ; 106(9): 1961-1970, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34216158

RESUMEN

NEW FINDINGS: What is the central question of this study? Does Enterococcus faecium strain R30 (R30), a new lactic acid bacterial strain for supplementation, attenuate shifts in the typology of whole muscle fibres from slow- to fast-twitch by altering the autonomic nervous system in atrophied skeletal muscles? What is the main finding and its importance? R30 supplementation may attenuate the shifts in the typology of whole muscle fibres from slow- to fast-twitch fibres by upregulating peroxisome proliferator-activated receptor-γ coactivator-1α and activating the calcineurin-nuclear factor of activated T-cells signalling pathway, thus ameliorating the decrease in muscle endurance associated with disuse. ABSTRACT: Enterococcus faecium strain R30 (R30), a new lactic acid bacterial strain for supplementation, was hypothesized to attenuate shifts in the typology of whole muscle fibres from slow- to fast-twitch fibres in atrophied skeletal muscles. We further postulated that the prevention of slow-to-fast fibre shifts would suppress the decreased muscle endurance associated with atrophy. To evaluate the protective effects of R30, we analysed slow-to-fast fibre shifts and disuse-associated reduced muscle endurance. R30 was administered to rats with an acclimation period of 7 days before hindlimb unloading (HU) for 2 weeks. The composition ratio of the fibre type and the expression levels of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), calcineurin and nuclear factor of activated T-cells (NFAT) were measured. Muscle endurance was evaluated at the end of the 2-week HU period in an in situ environment. R30 supplementation suppressed the slow-to-fast fibre switch and decreased the HU-induced expression of PGC-1α proteins and the deactivation of the calcineurin-NFAT pathway. Furthermore, R30 prevented a decrease in HU-associated muscle endurance in calf muscles. These results indicate that R30 supplementation may attenuate the shifts in the typology of whole muscle fibres from slow- to fast-twitch fibres via the upregulation of PGC-1α and the activation of the calcineurin-NFAT signalling pathway, thereby ameliorating the decrease in muscle endurance associated with disuse.


Asunto(s)
Enterococcus faecium , Animales , Suplementos Dietéticos , Enterococcus faecium/metabolismo , Suspensión Trasera/fisiología , Músculo Esquelético/fisiología , Atrofia Muscular/patología , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Ratas
19.
J Gastroenterol Hepatol ; 36(11): 3170-3176, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34142381

RESUMEN

BACKGROUND AND AIM: Although the frequency of endoscopic diagnosis of superficial non-ampullary duodenal epithelial tumors (SNADETs) has been increasing in recent years, no criteria for the endoscopic diagnosis of these tumors have been established yet. The aim of this study was to assess the usefulness of endocytoscopy for diagnosis SNADETs and to establish new criteria. METHODS: This prospective study was conducted at the NTT Medical Center Tokyo from May 2019 to July 2020, and a total of 100 consecutive SNADETs were enrolled. All the endocytoscopic images of the lesions and surrounding normal mucosa were classified into three groups according to the degree of structural atypia and the nuclear morphology and size. The endocytoscopic diagnoses using endocytoscopic classification was compared with the final histopathological diagnoses. RESULTS: Data of 93 patients with 98 lesions were included in the analysis. The preoperative diagnosis by endocytoscopy coincided with the final histopathological diagnosis in 85 (86.7%) of 98 SNADETs. In addition, the sensitivity and specificity for VCL 4/5 were 87.7% and 85.4%, respectively. In contrast, the accuracy, sensitivity, and specificity of preoperative diagnosis by biopsy were 64.3%, 50.9%, and 82.9%, respectively. Preoperative diagnosis by endocytoscopy showed significantly superior accuracy and sensitivity as compared with preoperative biopsy diagnosis (P < 0.001, respectively). CONCLUSIONS: This new classification (endocytoscopic classification) allows prediction of the tumor histopathology in real time, during endocytoscopy without biopsy, and is expected to be of help in determining the appropriate therapeutic strategies for individual cases of SNADETs. (Clinical trial registration number: UMIN000038643.).


Asunto(s)
Neoplasias Duodenales , Neoplasias Glandulares y Epiteliales , Neoplasias Duodenales/clasificación , Neoplasias Duodenales/diagnóstico por imagen , Endoscopía , Humanos , Neoplasias Glandulares y Epiteliales/clasificación , Neoplasias Glandulares y Epiteliales/diagnóstico por imagen , Estudios Prospectivos
20.
Pharm Res ; 38(6): 1093-1106, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33961188

RESUMEN

PURPOSE: The clinical application of gemcitabine (GEM) is limited by its pharmacokinetic properties. The aim of this study was to characterize the stability in circulating plasma, tumor targeting, and payload release of liposome-encapsulated GEM, FF-10832. METHODS: Antitumor activity was assessed in xenograft mouse models of human pancreatic cancer. The pharmacokinetics of GEM and its active metabolite dFdCTP were also evaluated. RESULTS: In mice with Capan-1 tumors, the dose-normalized areas under the curve (AUCs) after FF-10832 administration in plasma and tumor were 672 and 1047 times higher, respectively, than after using unencapsulated GEM. The tumor-to-bone marrow AUC ratio of dFdCTP was approximately eight times higher after FF-10832 administration than after GEM administration. These results indicated that liposomal encapsulation produced long-term stability in circulating plasma and tumor-selective targeting of GEM. In mice with Capan-1, SUIT-2, and BxPC-3 tumors, FF-10832 had better antitumor activity and tolerability than GEM. Internalization of FF-10832 in tumor-associated macrophages (TAMs) was revealed by flow cytometry and confocal laser scanning microscopy, and GEM was efficiently released from isolated macrophages of mice treated with FF-10832. These results suggest that TAMs are one of the potential reservoirs of GEM in tumors. CONCLUSION: This study found that FF-10832 had favorable pharmacokinetic properties. The liposomal formulation was more effective and tolerable than unencapsulated GEM in mouse xenograft tumor models. Hence, FF-10832 is a promising candidate for the treatment of pancreatic cancer.


Asunto(s)
Antimetabolitos Antineoplásicos/sangre , Desoxicitidina/análogos & derivados , Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos/métodos , Neoplasias Pancreáticas/sangre , Ensayos Antitumor por Modelo de Xenoinjerto/métodos , Animales , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/síntesis química , Línea Celular Tumoral , Desoxicitidina/administración & dosificación , Desoxicitidina/sangre , Desoxicitidina/síntesis química , Estabilidad de Medicamentos , Femenino , Humanos , Liposomas , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos ICR , Ratones Desnudos , Neoplasias Pancreáticas/tratamiento farmacológico , Resultado del Tratamiento , Gemcitabina
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