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1.
Langenbecks Arch Surg ; 409(1): 201, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38954011

RESUMEN

PURPOSE: The mortality rate for non-occlusive mesenteric ischemia remains high even after patients survive the acute postoperative period with tremendous treatment efforts, including emergency surgery, which is challenging. The aim of this study was to explore the preoperative risk factors for 90-day postoperative mortality in patients with non-occlusive mesenteric ischemia. METHODS: This single-center, retrospective cohort study included patients diagnosed with non-occlusive mesenteric ischemia who underwent emergency surgery between August 2014 and January 2023. All patients were divided into survival-to-discharge and mortality outcome groups at the 90-day postoperative follow-up. Preoperative factors, including comorbidities, preoperative status of vital signs and consciousness, blood gas analysis, blood test results, and computed tomography, were compared between the two groups. RESULTS: Twenty patients were eligible, and 90-day mortality was observed in 10 patients (50%). The mortality outcome group had significantly lower HCO3- (20.9 vs. 14.6, p = 0.006) and higher lactate (4.4 vs. 9.4, p = 0.023) levels than did the survival outcome group. The median postoperative time to death was 19 [2-69] days, and five patients (50%) died after postoperative day 30, mainly because hemodialysis was discontinued because of hemodynamic instability in patients requiring hemodialysis. CONCLUSION: Low preoperative HCO3- and high lactate levels may be preoperative risk factors for 90-day postoperative mortality in patients with non-occlusive mesenteric ischemia. However, patients on hemodialysis die from discontinuing hemodialysis even after surviving the acute postoperative phase. Therefore, indications for emergency surgery in patients with risk factors for postoperative mortality should be carefully determined.


Asunto(s)
Isquemia Mesentérica , Humanos , Masculino , Femenino , Isquemia Mesentérica/cirugía , Isquemia Mesentérica/mortalidad , Estudios Retrospectivos , Anciano , Factores de Riesgo , Persona de Mediana Edad , Complicaciones Posoperatorias/mortalidad , Anciano de 80 o más Años , Estudios de Cohortes , Periodo Preoperatorio
2.
Int J Cancer ; 152(7): 1425-1437, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36412556

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is resistant to current treatments but lectin-based therapy targeting cell surface glycans could be a promising new horizon. Here, we report a novel lectin-based phototherapy (Lec-PT) that combines the PDAC targeting ability of rBC2LCN lectin to a photoabsorber, IRDye700DX (rBC2-IR700), resulting in a novel and highly specific near-infrared, light-activated, anti-PDAC therapy. Lec-PT cytotoxicity was first verified in vitro with a human PDAC cell line, Capan-1, indicating that rBC2-IR700 is only cytotoxic upon cellular binding and exposure to near-infrared light. The therapeutic efficacy of Lec-PT was subsequently verified in vivo using cell lines and patient-derived, subcutaneous xenografting into nude mice. Significant accumulation of rBC2-IR700 occurs as early as 2 hours postintravenous administration while cytotoxicity is only achieved upon exposure to near-infrared light. Repeated treatments further slowed tumor growth. Lec-PT was also assessed for off-target toxicity in the orthotopic xenograft model. Shielding of intraperitoneal organs from near-infrared light minimized off-target toxicity. Using readily available components, Lec-PT specifically targeted pancreatic cancer with high reproducibility and on-target, inducible toxicity. Rapid clinical development of this method is promising as a new modality for treatment of pancreatic cancer.


Asunto(s)
Lectinas , Neoplasias Pancreáticas , Animales , Ratones , Humanos , Ratones Desnudos , Reproducibilidad de los Resultados , Inmunoterapia/métodos , Línea Celular Tumoral , Fototerapia/métodos , Neoplasias Pancreáticas/tratamiento farmacológico , Ensayos Antitumor por Modelo de Xenoinjerto , Fármacos Fotosensibilizantes/uso terapéutico , Neoplasias Pancreáticas
3.
BMC Cancer ; 23(1): 624, 2023 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-37403011

RESUMEN

BACKGROUND: Locally advanced pancreatic ductal adenocarcinoma (PDAC), accounting for about 30% of PDAC patients, is difficult to cure by radical resection or systemic chemotherapy alone. A multidisciplinary strategy is required and our TT-LAP trial aims to evaluate whether triple-modal treatment with proton beam therapy (PBT), hyperthermia, and gemcitabine plus nab-paclitaxel is a safe and synergistically effective treatment for patients with locally advanced PDAC. METHODS: This trial is an interventional, open-label, non-randomized, single-center, single-arm phase I/II clinical trial organized and sponsored by the University of Tsukuba. Eligible patients who are diagnosed with locally advanced pancreatic cancer, including both borderline resectable (BR) and unresectable locally advanced (UR-LA) patients, and selected according to the inclusion and exclusion criteria will receive triple-modal treatment consisting of chemotherapy, hyperthermia, and proton beam radiation. Treatment induction will include 2 cycles of chemotherapy (gemcitabine plus nab-paclitaxel), proton beam therapy, and 6 total sessions of hyperthermia therapy. The initial 5 patients will move to phase II after adverse events are verified by a monitoring committee and safety is ensured. The primary endpoint is 2-year survival rate while secondary endpoints include adverse event rate, treatment completion rate, response rate, progression-free survival, overall survival, resection rate, pathologic response rate, and R0 (no pathologic cancer remnants) rate. The target sample size is set at 30 cases. DISCUSSION: The TT-LAP trial is the first to evaluate the safety and effectiveness (phases1/2) of triple-modal treatment comprised of proton beam therapy, hyperthermia, and gemcitabine/nab-paclitaxel for locally advanced pancreatic cancer. ETHICS AND DISSEMINATION: This protocol was approved by the Tsukuba University Clinical Research Review Board (reference number TCRB22-007). Results will be analyzed after study recruitment and follow-up are completed. Results will be presented at international meetings of interest in pancreatic cancer plus gastrointestinal, hepatobiliary, and pancreatic surgeries and published in peer-reviewed journals. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCTs031220160. Registered 24 th June 2022, https://jrct.niph.go.jp/en-latest-detail/jRCTs031220160 .


Asunto(s)
Carcinoma Ductal Pancreático , Hipertermia Inducida , Neoplasias Pancreáticas , Humanos , Albúminas , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma Ductal Pancreático/tratamiento farmacológico , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Gemcitabina , Paclitaxel/uso terapéutico , Neoplasias Pancreáticas/patología , Protones , Neoplasias Pancreáticas
4.
World J Surg ; 47(11): 2816-2824, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37501009

RESUMEN

BACKGROUND: Superior mesenteric artery (SMA) nerve plexus (PLsma) dissection has been performed to achieve R0 resection in pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) in high-volume centers. However, full-extent PLsma preservation in PD is employed in our institution. The feasibility of the PLsma preservation strategy was investigated. METHODS: Between January 2010 and December 2020, 156 patients underwent PLsma preservation PD for PDAC at our institution. Of these, 118 patients had resectable PDAC (R group) and 38 patients had borderline resectable artery (BR-A group). Clinical and oncological outcomes focusing on local recurrence, patient prognoses, and morbidities (including postoperative refractory diarrhea) were retrospectively analyzed and our postoperative outcomes were compared with those of other institutions. RESULTS: Pathological R0 resection by PLsma preservation PD was achieved in 96 R group patients (81.4%) and 27 BR-A group patients (71.1%). The median postoperative hospital stay was 15.0 days in both groups. Local site-only recurrence was observed in 10.2% (12/118) of R-group and 10.5% (4/38) of BR-A-group patients, whereas distant site-only recurrence occurred in 21.2% (25/118) of R-group and 28.9% (11/38) of BR-A-group patients. Median survival times were 64.3 months (R group) and 35.4 months (BR-A group, p = 0.07). Median disease-free survival (DFS) times were 31.0 months (R group) and 12.0 months (BR-A group). No diarrhea requiring opioids was observed in either group. These results were equal or superior to those of PLsma dissection PD in other institutions. CONCLUSIONS: PLsma preservation in PD was feasible compared to PLsma dissection in recurrence and overall survival.

5.
Langenbecks Arch Surg ; 408(1): 139, 2023 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-37016188

RESUMEN

PURPOSE: Even though minor, stoma-related complications significantly impact quality of life, they are often excluded from clinical analyses that compare short-term postoperative outcomes of loop ileostomy and loop colostomy. This study compares stoma-related complications between loop ileostomy and loop colostomy after rectal resection, including minor complications, and discusses the characteristics of diverting stoma types. METHODS: A retrospective review was conducted in patients who underwent diverting stoma construction after rectal resection. Data on patient background and postoperative short-term outcomes, including stoma-related complications and morbidity after stoma closure, were collected and compared between loop ileostomy and loop colostomy groups. Morbidities of all severity grades were targeted for analysis. RESULTS: A total of 47 patients (27 loop ileostomy, 20 loop colostomy) underwent diverting stoma construction following rectal resection. Overall stoma-related complications, incidence of skin irritation, high-output stoma, and outlet obstruction were significantly higher in the loop ileostomy group but high-output stoma and outlet obstruction were absent in the loop colostomy group. Regarding morbidity after stoma closure, operation times and surgical site infections were significantly higher in the loop colostomy group while anastomotic leakage after diverting stoma closure occurred (2 cases; 15%) in the loop colostomy group but not the loop ileostomy group. CONCLUSION: Because stoma-related complications were significantly higher in the loop ileostomy group, and even these minor complications may impair QOL, early loop ileostomy closure is recommended. For loop colostomy, stoma-related morbidities are lower but post-closure leakage is a calculated risk.


Asunto(s)
Cirugía Colorrectal , Neoplasias del Recto , Humanos , Colostomía/efectos adversos , Ileostomía/efectos adversos , Calidad de Vida , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Anastomosis Quirúrgica/efectos adversos
6.
Int J Clin Oncol ; 28(6): 748-755, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36928515

RESUMEN

BACKGROUND: Although the transmediastinal approach as a radical esophagectomy for esophageal carcinoma patients has attracted attention, its advantages over the transthoracic approach remain unclear. This study aimed to evaluate the efficacy of transmediastinal esophagectomy (TME) in terms of postoperative respiratory complications compared to that of open transthoracic esophagectomy (TTE). METHODS: We reviewed patients with thoracic and abdominal esophageal carcinoma who underwent TME or TTE between February 2014 and November 2021. We compared postoperative respiratory complications as the primary outcome. The secondary outcomes included perioperative operation time, blood loss, postoperative complications, and the number of harvested mediastinal lymph nodes. RESULTS: Overall, 60 and 54 patients underwent TME and TTE, respectively. The baseline characteristics were similar between the two groups, except for age and histological type. There were no intraoperative lethal complications in either group. The incidence of respiratory complications was significantly lower in the TME group than in the TTE group (6.7 vs. 22.2%, p = 0.03). The TME group had a shorter operation time (403 vs. 451 min, p < 0.01), less blood loss (107 vs. 253 mL, p < 0.01), and slightly higher anastomotic leakage (11.7 vs. 5.6%, p = 0.33). The number of harvested lymph nodes was similar in both groups (24 vs. 26, p = 0.10). Multivariate analysis revealed that TME is an independent factor in reducing respiratory complications (odds ratio = 0.27, p = 0.04). CONCLUSIONS: TME for esophageal carcinoma was performed safely. TME was superior to TTE in terms of postoperative respiratory complications; however, the relatively higher frequency of anastomotic leakage should be considered and requires further evaluation.


Asunto(s)
Carcinoma , Neoplasias Esofágicas , Humanos , Escisión del Ganglio Linfático/efectos adversos , Fuga Anastomótica , Esofagectomía/efectos adversos , Complicaciones Posoperatorias/epidemiología , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/patología , Carcinoma/cirugía , Estudios Retrospectivos
7.
Surg Today ; 52(10): 1423-1429, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35737123

RESUMEN

PURPOSE: General surgeons are at high risk for work-related musculoskeletal disorders (WRMSDs), especially in their neck and back. The prevalence and risk factors for surgeons' WRMSDs in Japan have not been well surveyed. METHODS: A cross-sectional questionnaire survey on WRMSDs was conducted among general surgeons in Japan. Surgeons were asked about the presence and degree of neck, shoulder, and back disability in relation to open and laparoscopic surgery. RESULTS: The questionnaire was sent to 174 general surgeons in 21 hospitals and 106 (60.9%) responded. The prevalence of WRMSDs in the last month was 65.1%, and the prevalence at least once in a lifetime was 79.2%. The rate of WRMSDs of the neck and back was higher after open surgery (44.3%, 42.5%) than after laparoscopic surgery (28.2%, 31.1%), but there was no marked difference in shoulder pain. Age was the strongest risk factor for WRMSDs, and the pain scores, prevalence of chronic pain, and rate of WRMSD-related absence from work tended to increase with age. CONCLUSION: A questionnaire survey of surgeons in Japan showed that about 80% of surgeons suffer from WRMSDs. Countermeasures for WRMSDs among surgeons are urgently desired to ensure that limited numbers of surgeons work in the operating theatre throughout their career. CLINICAL TRIAL REGISTRATION: Registry name: a survey of surgeons' musculoskeletal pain associated with performing surgery. University of Tsukuba Institutional Review Board registration number: 1519.


Asunto(s)
Enfermedades Musculoesqueléticas , Enfermedades Profesionales , Cirujanos , Estudios Transversales , Humanos , Japón/epidemiología , Enfermedades Musculoesqueléticas/complicaciones , Enfermedades Musculoesqueléticas/epidemiología , Enfermedades Profesionales/epidemiología , Prevalencia , Encuestas y Cuestionarios
8.
BMC Surg ; 22(1): 274, 2022 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-35836157

RESUMEN

BACKGROUND: Pancreatic fistula remains the biggest problem in pancreatic surgery. We have previously reported a new pancreatojejunostomy method using an inter-anastomosis drainage (IAD) suction tube with Blumgart anastomosis for drainage of the pancreatic juice leaking from the branched pancreatic ducts. This study aimed to evaluate the postoperative outcomes of our novel method, in pancreatojejunostomy and investigate the nature of the inter-anastomosis space between jejunal wall and pancreas parenchyma. METHODS: This retrospectively study consist of 282 pancreatoduodenectomy cases, including 86 reconstructions via the Blumgart method plus IAD (B + IAD group) and 196 cases reconstructed using the Blumgart method alone (B group). Postoperative outcomes and the amylase value and the volume of the drainage fluids were compared between the two groups. The IAD tube was placed to collect amylase-rich fluid from the inter-anastomosis space during operative procedure between the jejunal wall and pancreatic stump. RESULTS: The daily IAD drainage volume and the amylase level was significantly higher in patients with a soft pancreas (vs hard pancreas; 16.5 vs. 10.0 mL/day, p = 0.012; 90,900 vs. 1634 IU/L, p < 0.001, respectively). The mean amylase value of IAD collection in 86 cases of B + IAD group was 63,100 IU/L. The incidence of clinically relevant pancreatic fistula grade B and C (23.2% vs. 23.0%, p = 0.55) and the hospital stay was similar between the groups (median 17 vs. 18 days, p = 0.55). In 176 patients with soft pancreas, the incidence of pancreatic fistula grade B and C (33.3% vs. 35.3%, p = 0.67) and the hospital stay was also similar between the groups (median 22.5 vs. 21 days, p = 0.81). CONCLUSIONS: Positive effect of the IAD method observed in the pilot cases was not reproduced in the current study. IAD tube objectively demonstrated the existence of amylase-rich discharge at the anastomosis site, and countermeasures to eliminate this liquid are highly desired for preventing pancreatic fistula, especially in patients with soft pancreatic texture. Trial registration Retrospectively registered.


Asunto(s)
Fístula Pancreática , Pancreatoyeyunostomía , Amilasas , Anastomosis Quirúrgica/métodos , Drenaje/efectos adversos , Humanos , Fístula Pancreática/epidemiología , Fístula Pancreática/etiología , Fístula Pancreática/prevención & control , Jugo Pancreático , Pancreaticoduodenectomía/métodos , Pancreatoyeyunostomía/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control
9.
Int J Mol Sci ; 23(8)2022 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-35457034

RESUMEN

Localization of tumors during laparoscopic surgery is generally performed by locally injecting India ink into the submucosal layer of the gastrointestinal tract using endoscopy. However, the location of the tumor is obscured because of the black-stained surgical field and the blurring caused by India ink. To solve this problem, in this study, we developed a tissue-adhesive porphyrin with polycations consisting of quaternary ammonium salt groups. To evaluate the ability of tissue-adhesive porphyrin in vivo, low-molecular-weight hematoporphyrin and tissue-adhesive porphyrin were injected into the anterior wall of the exposed stomach in rats. Local injection of low-molecular-weight hematoporphyrin into the anterior wall of the stomach was not visible even after 1 day because of its rapid diffusion. In contrast, the red fluorescence of the tissue-adhesive porphyrin was visible even after 7 days due to the electrostatic interactions between the positively-charged moieties of the polycation in the tissue-adhesive porphyrin and the negatively-charged molecules in the tissue. In addition, intraperitoneal injection of tissue-adhesive porphyrin in rats did not cause adverse effects such as weight loss, hepatic or renal dysfunction, or organ adhesion in the abdominal cavity. These results indicate that tissue-adhesive porphyrin is a promising fluorescent tissue-marking agent.


Asunto(s)
Porfirinas , Adhesivos Tisulares , Animales , Colorantes , Hematoporfirinas , Polielectrolitos , Compuestos de Amonio Cuaternario , Ratas
10.
Cancer Sci ; 112(9): 3722-3731, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34115906

RESUMEN

The rBC2LCN lectin, known as a stem cell marker probe that binds to an H type 3 fucosylated trisaccharide motif, was recently revealed to also bind to pancreatic ductal adenocarcinoma (PDAC) cells. A lectin-drug conjugate was generated by fusing rBC2LCN with a cytocidal toxin, and it showed a strong anticancer effect in in vitro and in vivo PDAC models. However, it is unclear which molecules are carrier proteins of rBC2LCN on PDAC cells. In this study, we identified a rBC2LCN-positive glycoprotein expressed in PDAC. Tumor lysates of PDAC patient-derived xenografts (PDXs) were coprecipitated with rBC2LCN lectin and analyzed by liquid chromatography-mass spectrometry. A total of 343 proteins were initially identified. We used a web-based database to select five glycoproteins and independently evaluated their expression in PDAC by immunohistochemistry (IHC). Among them, we focused on carcinoembryonic antigen 5 (CEA) as the most cancer-specific carrier protein in PDAC, as it showed the most prominent difference in expression rate between PDAC cells (74%) and normal pancreatic duct cells (0%, P > .0001). rBC2LCN lectin and CEA colocalization in PDAC samples was confirmed by double-staining analysis. Furthermore, rBC2LCN-precipitated fractions were blotted with an anti-CEA polyclonal antibody (pAb), and CEA pAb-precipitated fractions were blotted with rBC2LCN lectin. The results demonstrate that CEA is in fact a ligand of rBC2LCN lectin.


Asunto(s)
Antígeno Carcinoembrionario/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Proteínas Portadoras/metabolismo , Lectinas/metabolismo , Neoplasias Pancreáticas/metabolismo , Animales , Anticuerpos/inmunología , Antígeno Carcinoembrionario/inmunología , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Femenino , Proteínas Ligadas a GPI/inmunología , Proteínas Ligadas a GPI/metabolismo , Xenoinjertos , Humanos , Inmunohistoquímica/métodos , Inmunoprecipitación/métodos , Ligandos , Ratones , Ratones Endogámicos ICR , Ratones SCID , Trasplante de Neoplasias , Neoplasias Pancreáticas/patología
11.
Liver Transpl ; 27(5): 719-734, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33277780

RESUMEN

Living donor liver transplantation (LDLT) is sometimes associated with impaired regeneration and severe ischemia/reperfusion injury (IRI) in the graft, resulting in small-for-size syndrome (SFSS). Platelets were previously reported to stimulate liver regeneration in models of hepatectomy, but the evidence in partial liver transplantation (LT) is lacking. In this study, a rat model of partial LT was used, and the impact of thrombopoietin (TPO)-induced perioperative thrombocytosis on graft regeneration, IRI, and survival was investigated. In experiment 1, a 30% partial LT was performed. Under thrombocytosis, SFSS was attenuated, as shown by decreased levels of serum aminotransferases, bilirubin, and ascites. Serum hepatocyte regeneration-related cytokines, including insulin-like growth factor-1, hepatocyte growth factor, interleukin 6 (IL6), and tumor necrosis factor α (TNF-α), were elevated. In addition, the proliferative signaling pathways, Ki-67-labeling index, proliferating cell nuclear antigen (PCNA)-labeling index, mitotic index, and liver/body weight ratio were increased under thrombocytosis. The platelet-induced regeneration was independent of TPO because increases in the Ki-67-labeling and PCNA-labeling indexes were eliminated after reducing platelet counts by antiplatelet serum in rats administered with TPO. For IRI, thrombocytosis did not aggravate oxidative stress or downstream signaling pathways, necrosis, or apoptosis in the graft. After Kupffer cell (KC) depletion, the platelet-induced attenuation of serum aminotransferases, increased serum levels of IL6 and TNF-α, and proliferation-related signaling pathways were eliminated. Moreover, platelet accumulation in the graft decreased substantially. In experiment 2, a 20% partial LT was performed, and thrombocytosis improved postoperative survival. In conclusion, our results suggested that thrombocytosis stimulated graft regeneration and prolonged survival without aggregating IRI after partial LT, and KCs vitally contributed to platelet-derived regeneration. Platelet therapies to increase perioperative platelet counts may improve the outcomes after LDLT.


Asunto(s)
Regeneración Hepática , Trasplante de Hígado , Animales , Plaquetas , Hepatectomía , Humanos , Hígado , Trasplante de Hígado/efectos adversos , Donadores Vivos , Ratas
12.
Xenotransplantation ; 28(4): e12702, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34145650

RESUMEN

BACKGROUND: The human-to-rat hematopoietic stem cell transplantation (HSCT) model is rare, unlike its human-to-mouse counterpart. The rat models are desired, especially in areas of physiology, toxicology, and pharmacology. In addition to lymphocytes, macrophages are also considered to be important for xenotransplantation. We generated a rat xenotransplantation model to prove the role of macrophages as a xenotransplantation barrier. METHODS: Immunodeficiency in SRG rats, which are Sprague-Dawley (SD) rats lacking Rag2 and Il2rg, was confirmed by flow cytometry and spleen immunostaining. Human umbilical cord blood was collected after scheduled cesarean section at the University of Tsukuba Hospital. Cord blood mononuclear cells (CB-MNCs) were transplanted into the SRG rats administered several injections of clodronate liposome (CL), which cause macrophage depletion. Survival of human cells was observed by flow cytometry. Rat macrophage phagocytosis assay was performed to check the species-specific effects of rat macrophages on injected human/rat blood cells. RESULTS: SRG rats were deficient in T/B/NK cells. Without CL pretreatment, human CB-MNCs were removed from SRG rats within 7 hours after transplantation. The rats pretreated with CL could survive after transplantation. Prolonged survival for more than 4 weeks was observed only following a one-time CL injection. Rat macrophages had a species-specific potential for the phagocytosis of human blood cells in vivo. CONCLUSION: In human-to-rat HSCT, the short period of early macrophage control, leading to macrophage immunotolerance, is important for engraftment. The generated model can be useful for the creation of future xenotransplantation models or other clinical research.


Asunto(s)
Cesárea , Células Madre Hematopoyéticas , Animales , Femenino , Humanos , Macrófagos , Ratones , Ratones SCID , Embarazo , Ratas , Ratas Sprague-Dawley , Trasplante Heterólogo
13.
Int J Clin Oncol ; 26(10): 1856-1863, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34241725

RESUMEN

BACKGROUND: This is the first study to compare the long-term outcomes between neoadjuvant chemotherapy + surgery and definitive chemoradiotherapy with proton beam therapy for locally advanced esophageal squamous cell carcinoma. METHODS: We reviewed patients with clinical stage IB-III esophageal squamous cell carcinoma (UICC 7th edition) who underwent neoadjuvant chemotherapy + surgery or definitive chemoradiotherapy with proton beam therapy (2009-2017). Overall survival, progression-free survival, and recurrence or regrowth rates were compared between the two treatment groups. Subgroup analyses of overall survival according to baseline characteristics were also performed. RESULTS: Forty-three patients received neoadjuvant chemotherapy + surgery (median follow-up 47.4 months) and 60 received definitive chemoradiotherapy with proton beam therapy (median follow-up 51.5 months). Baseline characteristics were similar between the groups except for sex, tumor location, and cT classification. The neoadjuvant chemotherapy + surgery and definitive chemoradiotherapy with proton beam therapy groups had similar 3-year overall survival rates (73.1% and 61.7%, respectively, hazard ratio: 0.88, 95% confidence interval 0.49-1.58, p = 0.66), 3-year progression-free survival rates (46.5% and 45%, respectively, hazard ratio: 1.03, 95% confidence interval 0.62-1.70, p = 0.92), and recurrence or regrowth rates (53.5% vs. 50.0%, p = 0.84). In the subgroup analysis, favorable survival was observed after definitive chemoradiotherapy with proton beam therapy for cT1-2 disease (hazard ratio 2.58, 95% confidence interval 0.84-7.99) and after neoadjuvant chemotherapy + surgery for cT3 or higher disease (hazard ratio 0.32, 95% confidence interval 0.15-0.67, p-for-interaction = 0.002). CONCLUSIONS: Long-term outcomes were comparable between the treatments. The choice of the treatment according to cT classification might affect survival.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Neoplasias de Cabeza y Cuello , Quimioradioterapia , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/radioterapia , Esofagectomía , Humanos , Terapia Neoadyuvante , Recurrencia Local de Neoplasia , Protones , Estudios Retrospectivos
14.
BMC Surg ; 21(1): 198, 2021 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-33874921

RESUMEN

BACKGROUND: Persistent pancreatic leakage (PL) due to disconnected pancreatic duct syndrome (DPDS) is associated with severe morbidity and mortality and it usually treated with internal drainage. However, in cases without localized fistula formation, internal drainage is challenging to perform. We report an original one-stage surgical approach for nonlocalized persistent PL, namely, the "intentional internal drainage tube method". CASE PRESENTATION: A 49-year-old woman whose main pancreatic duct was penetrated during endoscopic retrograde cholangiopancreatography experienced severe PL. Peritoneal lavage and a second operation involving central pancreatectomy failed to relieve the symptoms, and nonlocalized PL persisted due to DPDS. Although we attempted a radical resection of the pancreatic remnants as a third strategy, the highly inflamed tissue and massive bleeding prevented the completion of the procedure. We sutured the pancreatic head margin and performed a pancreaticojejunostomy to the distal margin. Because these two cut margins could possibly be the source of the persistent PL, we created a hole at the Roux-en-Y jejunal limb, and a silicone drainage tube was inserted into the peritoneal space via this hole. Postoperatively, we continuously suctioned the intentional internal drainage tube, and the residual PL cavity gradually diminished. Even after removal of the tube, the residual PL drained internally into the jejunum through this hole. CONCLUSIONS: We present this intentional internal drainage tube method as a novel alternative approach for the management of nonlocalized PL consequential of DPDS. Due to the simplicity and minimally invasive nature of this method, we propose this technique may also be used to treat various types of nonlocalized persistent PL or be used prophylactically for central pancreatectomy.


Asunto(s)
Drenaje , Conductos Pancreáticos , Femenino , Humanos , Persona de Mediana Edad , Conductos Pancreáticos/cirugía , Fístula Pancreática/etiología , Fístula Pancreática/cirugía , Pancreatoyeyunostomía , Estudios Retrospectivos , Resultado del Tratamiento
15.
Cancer Sci ; 111(12): 4548-4557, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33058342

RESUMEN

Drug resistance represents an obstacle in colorectal cancer (CRC) treatment because of its association with poor prognosis. rBC2LCN is a lectin isolated from Burkholderia that binds cell surface glycans that have fucose moieties. Because fucosylation is enhanced in many types of cancers, this lectin could be an efficient drug carrier if CRC cells specifically present such glycans. Therefore, we examined the therapeutic efficacy and toxicity of lectin drug conjugate therapy in CRC mouse xenograft models. The affinity of rBC2LCN for human CRC cell lines HT-29, LoVo, LS174T, and DLD-1 was assessed in vitro. The cytocidal efficacy of a lectin drug conjugate, rBC2LCN-38 kDa domain of pseudomonas exotoxin A (PE38) was evaluated by MTT assay. The therapeutic effects and toxicity for each CRC cell line-derived mouse xenograft model were compared between the intervention and control groups. LS174T and DLD-1 cell lines showed a strong affinity for rBC2LCN. In the xenograft model, the tumor volume in the rBC2LCN-PE38 group was significantly reduced compared with that using control treatment alone. However, the HT-29 cell line showed weak affinity and poor therapeutic efficacy. No significant toxicities or adverse responses were observed. In conclusion, we demonstrated that rBC2LCN lectin binds CRC cells and that rBC2LCN-PE38 significantly suppresses tumor growth in vivo. In addition, the efficacy of the drug conjugate correlated with its binding affinity for each CRC cell line. These results suggest that lectin drug conjugate therapy has potential as a novel targeted therapy for CRC cell surface glycans.


Asunto(s)
ADP Ribosa Transferasas/uso terapéutico , Adenocarcinoma/tratamiento farmacológico , Toxinas Bacterianas/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Exotoxinas/uso terapéutico , Inmunoconjugados/uso terapéutico , Lectinas/uso terapéutico , Factores de Virulencia/uso terapéutico , ADP Ribosa Transferasas/efectos adversos , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Animales , Toxinas Bacterianas/efectos adversos , Burkholderia cenocepacia/química , Línea Celular Tumoral , Supervivencia Celular , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Portadores de Fármacos , Exotoxinas/efectos adversos , Fucosa/metabolismo , Fucosiltransferasas/metabolismo , Células HT29 , Xenoinjertos , Humanos , Inmunoconjugados/efectos adversos , Técnicas In Vitro , Lectinas/aislamiento & purificación , Lectinas/metabolismo , Ratones , Proteínas Recombinantes de Fusión/efectos adversos , Proteínas Recombinantes de Fusión/análisis , Proteínas Recombinantes de Fusión/uso terapéutico , Carga Tumoral , Factores de Virulencia/efectos adversos , Exotoxina A de Pseudomonas aeruginosa
16.
J Anus Rectum Colon ; 8(2): 70-77, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38689778

RESUMEN

Objectives: Surgical-site infections (SSIs) are the most common complication after stoma closure. We propose a new method for wound closure using the subcutaneous large-bite buried suture (SLBS) technique and a closed suction drain (CSD). In this study, we aimed to investigate the efficacy of a combination of the SLBS technique and a CSD to prevent superficial SSIs following stoma closure. Methods: We retrospectively analyzed patients who underwent stoma closure between January 2019 and July 2022. Primary closure of the stomal site was performed using the SLBS technique and a CSD for wound closure. The CSD was placed until postoperative day 7. The occurrence of superficial postoperative SSIs was also evaluated. Results: In total, 67 patients were included in the study. Within 30 days postoperatively, nine patients (13%) developed superficial SSIs. Considering the type of stoma, only 1 (2%) of 45 patients with ileostomy showed superficial SSIs, whereas 8 (36%) of 22 patients with colostomy showed superficial SSIs. Univariate analysis of the risk factors associated with the occurrence of superficial SSIs revealed that colostomy (p < 0.001) and hand-sewn anastomosis were significant risk factors (p = 0.019). Multivariate analysis of the risk factors associated with the occurrence of superficial SSIs revealed that colostomy was significant risk factor (p = 0.003). Conclusions: This new method of stoma closure is feasible for preventing superficial SSIs, especially in ileostomy closure.

17.
World J Gastroenterol ; 30(14): 2006-2017, 2024 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-38681122

RESUMEN

BACKGROUND: The success of liver resection relies on the ability of the remnant liver to regenerate. Most of the knowledge regarding the pathophysiological basis of liver regeneration comes from rodent studies, and data on humans are scarce. Additionally, there is limited knowledge about the preoperative factors that influence postoperative regeneration. AIM: To quantify postoperative remnant liver volume by the latest volumetric software and investigate perioperative factors that affect posthepatectomy liver regeneration. METHODS: A total of 268 patients who received partial hepatectomy were enrolled. Patients were grouped into right hepatectomy/trisegmentectomy (RH/Tri), left hepatectomy (LH), segmentectomy (Seg), and subsegmentectomy/nonanatomical hepatectomy (Sub/Non) groups. The regeneration index (RI) and late regeneration rate were defined as (postoperative liver volume)/[total functional liver volume (TFLV)] × 100 and (RI at 6-months - RI at 3-months)/RI at 6-months, respectively. The lower 25th percentile of RI and the higher 25th percentile of late regeneration rate in each group were defined as "low regeneration" and "delayed regeneration". "Restoration to the original size" was defined as regeneration of the liver volume by more than 90% of the TFLV at 12 months postsurgery. RESULTS: The numbers of patients in the RH/Tri, LH, Seg, and Sub/Non groups were 41, 53, 99 and 75, respectively. The RI plateaued at 3 months in the LH, Seg, and Sub/Non groups, whereas the RI increased until 12 months in the RH/Tri group. According to our multivariate analysis, the preoperative albumin-bilirubin (ALBI) score was an independent factor for low regeneration at 3 months [odds ratio (OR) 95%CI = 2.80 (1.17-6.69), P = 0.02; per 1.0 up] and 12 months [OR = 2.27 (1.01-5.09), P = 0.04; per 1.0 up]. Multivariate analysis revealed that only liver resection percentage [OR = 1.03 (1.00-1.05), P = 0.04] was associated with delayed regeneration. Furthermore, multivariate analysis demonstrated that the preoperative ALBI score [OR = 2.63 (1.00-1.05), P = 0.02; per 1.0 up] and liver resection percentage [OR = 1.02 (1.00-1.05), P = 0.04; per 1.0 up] were found to be independent risk factors associated with volume restoration failure. CONCLUSION: Liver regeneration posthepatectomy was determined by the resection percentage and preoperative ALBI score. This knowledge helps surgeons decide the timing and type of rehepatectomy for recurrent cases.


Asunto(s)
Hepatectomía , Regeneración Hepática , Hígado , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Bilirrubina/sangre , Hepatectomía/métodos , Hepatectomía/efectos adversos , Hígado/cirugía , Neoplasias Hepáticas/cirugía , Tamaño de los Órganos , Periodo Posoperatorio , Periodo Preoperatorio , Estudios Retrospectivos , Albúmina Sérica/análisis , Albúmina Sérica/metabolismo , Factores de Tiempo , Resultado del Tratamiento
18.
Surg Case Rep ; 10(1): 122, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38743303

RESUMEN

BACKGROUND: Superior mesenteric venous thrombosis (SMVT) is mostly treated with anticoagulation therapy; however, SMVT can lead to irreversible bowel ischemia and require bowel resection in the acute or subacute phase. CASE PRESENTATION: We report four cases of SMVT that required careful observation and bowel resection. Case 1: A 71-year-old man presented with abdominal pain, diarrhea, and vomiting that showed a completely occluded SMV with thrombus and small bowel ischemia. Case 2: A 47-year-old man presented with abdominal pain, peritoneal irritation symptoms, and a completely occluded SMV with thrombus, ischemia of the small bowel, and massive ascites. Case 3: A 68-year-old man presented with abdominal pain and vomiting for several days and showed a partially occluded SMV with a thrombus, bowel ischemia, and massive ascites. Case 4: A 68-year-old man presented with acute abdominal pain and a partially occluded SMV with thrombus and bowel edema without ischemic changes. Anticoagulation therapy was administered; however, 3 days later, abdominal pain and bowel ischemia worsened. Bowel resection was performed in all cases. CONCLUSIONS: Most idiopathic SMVT cases can be treated with anticoagulation therapy or endovascular thrombectomy. However, in cases with peritoneal irritation signs, these treatments may be ineffective, and bowel resection may be required.

19.
Ann Gastroenterol Surg ; 7(5): 832-840, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37663963

RESUMEN

Aim: To investigate the risk factors for postoperative delirium among elderly patients undergoing elective surgery for gastroenterological cancer. Methods: From May 2020 to March 2022, patients ≥75 years old with gastroenterological cancer who underwent radical surgery were enrolled. The geriatric assessment, including evaluations of frailty, physical function, nutrition status, and cognitive function, was conducted preoperatively. The confusion assessment method was used to diagnose postoperative delirium. A multivariate logistic regression analysis was used to determine risk factors for postoperative delirium. Results: A total of 158 patients were eligible for inclusion in this study. Of these 53 patients (34%) developed postoperative delirium. In the univariate analysis, the age, regular use of sleeping drugs and benzodiazepine, Charlson Comorbidity Index score, performance status, Fried's frailty score, Vulnerable Elders Survey-13 score, grip weakness, Short Physical Performance Battery (SPPB) score, Mini Nutritional Assessment Short-Form score, and Mini-Mental State Examination score were statistically associated with the incidence of postoperative delirium. In the multivariate analysis, a SPPB score ≤9, Mini Nutritional Assessment score ≤11, a Mini-Mental State Examination score ≤24, and regular use of benzodiazepine were found to be independent preoperative risk factors for postoperative delirium. Conclusion: Certain findings during the preoperative geriatric assessment, especially low SPPB, Mini Nutritional Assessment Short-Form and Mini-Mental State Examination scores, and regular use of benzodiazepine were risk factors for postoperative delirium in elderly patients undergoing gastroenterological surgery.

20.
World J Gastroenterol ; 28(9): 897-908, 2022 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-35317052

RESUMEN

Platelets are anucleate fragments mainly involved in hemostasis and thrombosis, and there is emerging evidence that platelets have other nonhemostatic potentials in inflammation, angiogenesis, regeneration and ischemia/reperfusion injury (I/R injury), which are involved in the physiological and pathological processes during living donor liver transplantation (LDLT). LDLT is sometimes associated with impaired regeneration and severe I/R injury, leading to postoperative complications and decreased patient survival. Recent studies have suggested that perioperative thrombocytopenia is associated with poor graft regeneration and postoperative morbidity in the short and long term after LDLT. Although it is not fully understood whether thrombocytopenia is the cause or result, increasing platelet counts are frequently suggested to improve posttransplant outcomes in clinical studies. Based on rodent experiments, previous studies have identified that platelets stimulate liver regeneration after partial hepatectomy. However, the role of platelets in LDLT is controversial, as platelets are supposed to aggravate I/R injury in the liver. Recently, a rat model of partial liver transplantation (LT) was used to demonstrate that thrombopoietin-induced thrombocytosis prior to surgery accelerated graft regeneration and improved the survival rate after transplantation. It was clarified that platelet-derived liver regeneration outweighed the associated risk of I/R injury after partial LT. Clinical strategies to increase perioperative platelet counts, such as thrombopoietin, thrombopoietin receptor agonist and platelet transfusion, may improve graft regeneration and survival after LDLT.


Asunto(s)
Trasplante de Hígado , Animales , Plaquetas , Humanos , Regeneración Hepática/fisiología , Trasplante de Hígado/efectos adversos , Donadores Vivos , Transfusión de Plaquetas/efectos adversos , Ratas
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