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1.
Surg Case Rep ; 10(1): 186, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39138697

RESUMEN

BACKGROUND: An enterocutaneous fistula (ECF) is defined as an abnormal communication between the gastrointestinal tract and skin. ECFs are rarely encountered in clinical practice, yet are frequently difficult to treat. Few reports exist regarding the surgical techniques for the treatment of an ECF. Therefore, we report a case of refractory ECF with concomitant severe adhesions, in which we performed combined laparoscopic adhesiolysis and planned open conversion. CASE PRESENTATION: A 57-year-old female patient underwent a laparotomy for an ovarian cyst in her 20s. At 46 years, adhesiolysis without bowel resection was performed for adhesive small bowel obstruction (SBO). However, her symptoms did not improve. Eighteen days postoperatively, she underwent a reoperation and jejunostomy. An ECF developed post-reoperation; therefore, stoma closure and radical surgery for the ECF were planned. Due to the severe adhesions, only stoma closure was performed, based on intraoperative assessments. The patient was subsequently referred to our hospital. First, skin care around the fistula was provided during an outpatient visit. Appropriate sizing of the stoma pouch was performed, to improve erosions and ulcers. Thereafter, debridement of the perifistula skin and simple closure of the ECF outlet were attempted; however, the ECF recurred shortly thereafter. After 8 years of regular skin care, with the ECF remaining stable, however, manifesting as symptomatic SBO, she underwent laparoscopic adhesiolysis. This procedure was initiated in the epigastric region, where relatively fewer adhesions were anticipated. Post-open conversion, partial resection of the small intestine at four locations, including the fistula site, was performed. Postoperatively, jejunal edema and peristaltic dysfunction, due to narrowing of the superior mesenteric artery occurred. Regular drainage by percutaneous endoscopic gastrostomy was required. However, she improved and was discharged 3 months post-operatively. Three years post-operatively, the ECF and SBO did not recur. CONCLUSIONS: We reported a case of refractory ECF in which we were able to safely perform surgery, by combining laparoscopic adhesiolysis and a planned open conversion. Therefore, the surgical approach used in this case may be an option for securing a safe surgical field, while avoiding collateral damage.

2.
BMC Cancer ; 24(1): 1027, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164626

RESUMEN

BACKGROUND: Local recurrence is common after curative resections of rectal cancer. Surgical resection is considered a primary curative treatment option for patients with locally recurrent rectal cancer (LRRC). LRRC often requires a combined resection of other organs, especially in the case of posterior recurrence, which requires a combined resection of the sacrum, making the surgery highly invasive. Venous thromboembolism (VTE) is one of the lethal complications in the postoperative period, particularly in the field of pelvic surgery. We found no reports regarding the risks of postoperative VTE in surgery for LRRC, a typical highly invasive procedure in the field of colorectal surgery. This study aims to evaluate the risk of postoperative VTE in surgery for LRRC patients. METHODS: From April 2010 to March 2022, a total of 166 patients underwent surgery for LRRC in the pelvic region at our institutions. Clinicopathological background and VTE incidence were compared retrospectively. RESULTS: Among the 166 patients included in the study, 55 patients (33.1%) needed sacral resection. Pharmacological prophylaxis for prevention of VTE was performed in 121 patients (73.3%), and the incidence of VTE was 9.09% (5/55 patients) among those who underwent surgery for LRRC with sacral resection, while it was 1.8% (2/111 patients) in those without sacral resection. In univariate analysis, the combination with sacral resection was identified as a risk factor for VTE in surgery for LRRC (p = 0.047). CONCLUSIONS: This study demonstrates that surgery for LRRC combined with sacral resection could be a significant risk factor for VTE.


Asunto(s)
Recurrencia Local de Neoplasia , Complicaciones Posoperatorias , Neoplasias del Recto , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/etiología , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/prevención & control , Femenino , Masculino , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Anciano , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de Riesgo , Incidencia , Adulto , Sacro/cirugía , Anciano de 80 o más Años
3.
Gan To Kagaku Ryoho ; 51(6): 608-612, 2024 Jun.
Artículo en Japonés | MEDLINE | ID: mdl-39009515

RESUMEN

The gut microbiome is involved in host physiology, including nutrition, metabolism, and immunity. It was recently known that dysbiosis of the gut microbiome has been implicated in several human diseases such as inflammatory bowel disease. It is altered by environmental factors such as diet, habit and lifestyle and has been directly and indirectly linked to the development and progression of colorectal cancer(CRC). Fusobacterium(F.)nucleatum, which causes periodontal disease, has been shown to play an important role in the initiation and development of CRC, although not as clearly as Helicobacter(H.) pylori in gastric cancer. Therefore, gut bacteria hold promise as a potential therapeutic approach to prevent or treat CRC. Although its clinical usefulness has not yet been demonstrated, future research such as metagenomics may open new avenues for CRC treatment with gut bacteria. Here, we reviewed the role of the gut microbial community in the development, progression, and prevention of colorectal carcinogenesis.


Asunto(s)
Neoplasias Colorrectales , Microbioma Gastrointestinal , Humanos , Neoplasias Colorrectales/microbiología , Neoplasias Colorrectales/terapia , Animales , Disbiosis/microbiología
4.
Surg Case Rep ; 10(1): 111, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38700734

RESUMEN

BACKGROUND: Pouch-related complications (PRCs), such as pelvic abscesses and perianal complex fistulas, can occur after ileal pouch-anal anastomosis (IPAA) in ulcerative colitis (UC). They are often difficult to treat and require salvage surgery. We report two cases of PRC associated with fistulas. CASE PRESENTATION: First case: A 38-year-old man was diagnosed with UC at age 26 years. Four months after the diagnosis of UC, the patient underwent hand-assisted laparoscopic restorative proctocolectomy, IPAA, and ileostomy for acute fulminant UC. Two years after the closure of the ileostomy, the patient developed a perianal abscess and underwent ileostomy reconstruction. He was referred to our department at 35 years of age, because his symptoms did not improve despite repeated seton drainage of a complicated perineal fistula. We diagnosed PRC with a pelvic abscess and complicated pouch fistula and performed salvage surgery. This diagnosis was revised to Crohn's disease. SECOND CASE: A 50-year-old man was diagnosed with UC at age 18 years and was administered high doses of steroids; however, his symptoms did not improve. He underwent restorative proctocolectomy, IPAA, and ileostomy at another hospital. The ileostomy was closed, and his condition stabilized thereafter. At 35 years of age, perianal pain developed, and he was diagnosed with a complicated pouch-perineal fistula. A fistula was observed near the staple line of the ileal end closure on the head side of the pouch. Reconstruction of the ileostomy and seton drainage were performed; however, his symptoms did not improve, and he was referred to our hospital. We diagnosed PRC with a pelvic abscess and a complicated pouch fistula and performed salvage surgery. The resected specimen showed strictures in two locations: at the oral site of the afferent limb (at the pouch) and at the IPAA. Both patients returned to society and are currently outpatients. CONCLUSIONS: We encountered two cases of PRC after IPAA that did not improve with seton drainage or ileostomy. Pouch resection was performed after considering the patient's quality of life and reintegration into society.

5.
Anticancer Res ; 44(2): 695-701, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38307590

RESUMEN

BACKGROUND/AIM: Postoperative venous thromboembolism (VTE) is a well-recognized complication that leads to morbidity and mortality. Lateral lymph node dissection (LLND) for rectal cancer is thought to potentially increase the risk of VTE due to its technical complexity. However, the relationship between LLND and VTE remains inadequately understood. The aim of this study was to elucidate the impact of LLND on the incidence of postoperative VTE. PATIENTS AND METHODS: This is a retrospective analysis of patients who underwent rectal cancer resection between 2010 and 2018 to identify the risk factors associated with postoperative VTE. Patients were divided into two groups: those who underwent surgery with LLND (LLND+ group) and those who underwent surgery without LLND (LLND- group). RESULTS: A total of 543 patients were enrolled in this study, and 113 patients underwent surgery for rectal cancer with LLND. VTE developed in 8 patients (1.47%), with the incidence rates being 4.42% in the LLND+ group and 0.69% in the LLND- group, respectively (p=0.012). Three of 8 patients had developed severe postoperative complications, and the other two patients needed intraoperative repair of the iliac vein during LLND procedure. Multivariate analysis identified the incidence of postoperative complications and LLND as the independent risk factors of VTE. CONCLUSION: Patients undergoing rectal cancer surgery with LLND should be closely monitored for signs of VTE.


Asunto(s)
Neoplasias del Recto , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Estudios Retrospectivos , Resultado del Tratamiento , Escisión del Ganglio Linfático/efectos adversos , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/patología , Neoplasias del Recto/patología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Recurrencia Local de Neoplasia/patología
6.
Anticancer Res ; 43(11): 5061-5066, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37909970

RESUMEN

BACKGROUND/AIM: Locally recurrent rectal cancer (LRRC) involving the upper sacrum is generally considered a contraindication for curative surgery. In the surgical management of LRRC, sacrectomy is frequently performed to secure clear resection margins. Nonetheless, the indications for high sacrectomy remain controversial due to potential postoperative complications, questions about radicality, and the increased complexity of the operation. Furthermore, comprehensive studies addressing this issue are notably absent. This study aimed to assess the feasibility, safety, and surgical prognosis in high sacrectomy for LRRC. PATIENTS AND METHODS: All patients with LRRC who required concomitant sacrectomy, but did not include the inferior margin of the second sacral vertebra, between 2003 and 2014, were reviewed retrospectively. RESULTS: Eight patients with a median age of 59 years were included in this study. The proximal resection line for sacral bone resection was the central part of the S1 vertebra in one patient, lower edge of the S1 vertebra in six patients, and central part of the S2 vertebra in one patient. Negative margin resection was achieved in five out of the eight patients. The median operative time was 922 min, and the median operative blood loss volume was 6,370 ml. Major complications included pelvic abscess (n=5), ileus (n=1), and pulmonary vein embolism (n=1), none of which proved fatal during the postoperative period. Both the 5-year local re-recurrence-free survival rate and the 5-year distant metastasis-free survival rate were 50% (4/8). CONCLUSION: High sacrectomy is safe and feasible to achieve negative margins in patients with LRRC.


Asunto(s)
Neoplasias del Recto , Sacro , Humanos , Persona de Mediana Edad , Sacro/cirugía , Estudios Retrospectivos , Neoplasias del Recto/cirugía , Complicaciones Posoperatorias , Pérdida de Sangre Quirúrgica , Márgenes de Escisión
7.
bioRxiv ; 2023 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-37790498

RESUMEN

KRAS G12C inhibitor (G12Ci) has produced encouraging, albeit modest and transient, clinical benefit in pancreatic ductal adenocarcinoma (PDAC). Identifying and targeting resistance mechanisms to G12Ci treatment is therefore crucial. To better understand the tumor biology of the KRAS G12C allele and possible bypass mechanisms, we developed a novel autochthonous KRAS G12C -driven PDAC model. Compared to the classical KRAS G12D PDAC model, the G12C model exhibit slower tumor growth, yet similar histopathological and molecular features. Aligned with clinical experience, G12Ci treatment of KRAS G12C tumors produced modest impact despite stimulating a 'hot' tumor immune microenvironment. Immunoprofiling revealed that CD24, a 'do-not-eat-me' signal, is significantly upregulated on cancer cells upon G12Ci treatment. Blocking CD24 enhanced macrophage phagocytosis of cancer cells and significantly sensitized tumors to G12Ci treatment. Similar findings were observed in KRAS G12D -driven PDAC. Our study reveals common and distinct oncogenic KRAS allele-specific biology and identifies a clinically actionable adaptive mechanism that may improve the efficacy of oncogenic KRAS inhibitor therapy in PDAC. Significance: Lack of faithful preclinical models limits the exploration of resistance mechanisms to KRAS G12C inhibitor in PDAC. We generated an autochthonous KRAS G12C -driven PDAC model, which revealed allele-specific biology of the KRAS G12C during PDAC development. We identified CD24 as an actionable adaptive mechanisms in cancer cells induced upon KRAS G12C inhibition and blocking CD24 sensitizes PDAC to KRAS inhibitors in preclinical models.

8.
Cancer Diagn Progn ; 3(5): 597-600, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37671313

RESUMEN

Background/Aim: Recently, robotic surgery for rectal cancer has become a common minimally invasive surgery. In addition, the technology of augmented and mixed reality is applied in various living environments, including medicine. We successfully performed robotic surgery for rectal cancer with three-dimensional (3D) images as mixed reality (MR) using HoloLens2. Case Report: The patient was diagnosed with rectal cancer by colonoscopy and a positron-emission computed-tomography scan, and we performed robot-assisted anterior resection. The operator used HoloLens2 and performed the surgery while visualizing 3D images of pelvic anatomy with the location of the rectal cancer as hologram. The operation was performed completely and safely, and she was discharged 11 days after surgery with no postoperative complications. Conclusion: This case presents the usefulness of a MR system offering organ visualization as hologram during surgery.

9.
Surg Case Rep ; 9(1): 149, 2023 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-37610526

RESUMEN

BACKGROUND: As the number of patients with inflammatory bowel disease (IBD) increases, the incidence of IBD-related colorectal cancer (CRC) is also on the rise. Crohn's disease (CD)-related CRC has been reported to have a poorer prognosis than sporadic CRC, and the early detection of CD-related CRC is difficult. Japanese patients with CD are reported to have a higher frequency of anorectal cancer than the Western population; however, methods for early diagnosis have not yet been established because of perianal pain during the examination. CASE PRESENTATION: We report a case of CD-related anal fistula cancer that was detected early by surveillance examination under anesthesia (EUA). The patient was a 37-year-old man, diagnosed with CD at the age of 15 years and started medical treatment. However, due to poor disease control, the intestinal tract remained highly inflamed and the patient continued to have over 10 bowel movements per day. He was referred to our hospital for surgical treatment after a colonoscopy (CS), which revealed multiple active ulcers and stenoses. Since three perianal seton drainage tubes had been placed around his anus since the age of 33 years, we decided to perform an EUA to rule out cancer coexistence in the anorectal region. After a random biopsy of the rectum by CS under general anesthesia, we resected and curetted multiple perianal fistulas as much as possible and reinserted the seton drainage tubes. Pathological examination of the fistula tract revealed adenocarcinoma in one tract, indicating the coexistence of anal fistula cancer. Based on the diagnosis of multiple intestinal stenoses and anal fistula cancer due to CD, we performed hand-assisted laparoscopic total colectomy, rectal amputation, extensive perineal resection, and reconstruction using a left rectus abdominis flap. CONCLUSION: In a long-term CD patient with anorectal lesions, we performed an EUA to diagnose the coexistence of anal fistula cancer at an early stage, and surgical resection was achieved. EUA is effective for the early detection and treatment of CD-related CRC and may contribute to an improved prognosis.

10.
Gan To Kagaku Ryoho ; 50(3): 351-353, 2023 Mar.
Artículo en Japonés | MEDLINE | ID: mdl-36927906

RESUMEN

In cases of pancreatic cancer with anatomical variations of the hepatic artery, it is important to evaluate the hemodynamics of each case for surgical indication. We report the case of a 68-year-old man with locally advanced pancreatic cancer and an aberrant right hepatic artery who underwent distal pancreatectomy with celiac axis resection(DP-CAR). He was admitted to our institute due to abdominal discomfort. A CT scan showed pancreatic cancer invading the common hepatic artery. He underwent chemoradiotherapy with a diagnosis of locally advanced pancreatic cancer. After the tumor downstaging, we performed DP-CAR, which included a gastroduodenal artery and a proper hepatic artery resection. Even though delayed gastric emptying was observed after the operation, he was discharged on postoperative day 36.


Asunto(s)
Arteria Hepática , Neoplasias Pancreáticas , Masculino , Humanos , Anciano , Arteria Hepática/cirugía , Arteria Hepática/patología , Pancreatectomía , Arteria Celíaca/cirugía , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas
11.
Gan To Kagaku Ryoho ; 50(1): 113-115, 2023 Jan.
Artículo en Japonés | MEDLINE | ID: mdl-36760004

RESUMEN

FOLFIRI plus ramucirumab(RAM)therapy has been reported to be effective and safe in the RAISE trial as second-line treatment for unresectable colorectal cancer. It is hypothesized that RAM may be effective in patients with PD treated with FOLFIRI plus bevacizumab(Bev)due to different mechanism of action from that of Bev, which is also an angiogenesis inhibitor. From January 2017 to December 2021, we conducted a retrospective study of 6 patients who had PD with 5-FU, oxaliplatin, irinotecan, or Bev as first or second-line treatment at our institution and who received FOLFIRI plus RAM in later line treatment. The 6 cases consisted of 3 patients in the third-line treatment, 1 patient in the fourth-line treatment, and 2 patients in the sixth-line treatment. The anti-tumor effect was PD in all cases in the third-line and fourth-line treatment, but the 2 patients of sixth-line treatment were controlled diseases.


Asunto(s)
Camptotecina , Neoplasias Colorrectales , Humanos , Estudios Retrospectivos , Camptotecina/uso terapéutico , Fluorouracilo/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Bevacizumab/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucovorina/uso terapéutico
12.
Ann Surg Oncol ; 28(8): 4720-4732, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33393034

RESUMEN

BACKGROUND: Anticancer drugs generate excessive reactive oxygen species (ROS), which can cause cell death. Cancer cells can resist this oxidative stress, but the mechanism of resistance and associations with chemoresistance are unclear. Here, we focused on Sirtuin 3 (SIRT3), a deacetylating mitochondrial enzyme, in oxidative stress resistance in colorectal cancer (CRC). METHODS: To evaluate SIRT3-related changes in mitochondrial function, ROS (mtROS) induction, and apoptosis, we used the human CRC cell lines HT29 and HCT116 transfected with short-hairpin RNA targeting SIRT3 and small interfering RNAs targeting superoxide dismutase 2 mitochondrial (SOD2) and peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1α). In 142 clinical specimens from patients with CRC, we also assessed the association of SIRT3 protein levels (high/low) and prognosis. RESULTS: SIRT3 expression correlated with mtROS generation and apoptosis induction in cells treated with anticancer agents. Suppressing SIRT3 increased mtROS levels and cell sensitivity to anticancer agents. SIRT3 knockdown decreased SOD2 expression and activity, and suppressing SOD2 also improved sensitivity to anticancer drugs. In addition, SIRT3 was recruited with PGC-1α under oxidative stress, and suppressing SIRT3 decreased PGC-1α expression and mitochondrial function. PGC-1α knockdown decreased mitochondrial activity and increased apoptosis in cells treated with anticancer drugs. In resected CRC specimens, high vs low SIRT3 protein levels were associated with significantly reduced cancer-specific survival. CONCLUSIONS: SIRT3 expression affected CRC cell chemoresistance through SOD2 and PGC-1α regulation and was an independent prognostic factor in CRC. SIRT3 may be a novel target for CRC therapies and a predictive marker of sensitivity to chemotherapy.


Asunto(s)
Neoplasias Colorrectales , Resistencia a Antineoplásicos , Sirtuina 3 , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Humanos , Mitocondrias/metabolismo , Estrés Oxidativo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Especies Reactivas de Oxígeno/metabolismo , Sirtuina 3/genética , Sirtuina 3/metabolismo , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo
13.
Cancer Res ; 81(2): 332-343, 2021 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-33158812

RESUMEN

Cellular dedifferentiation is a key mechanism driving cancer progression. Acquisition of mesenchymal features has been associated with drug resistance, poor prognosis, and disease relapse in many tumor types. Therefore, successful targeting of tumors harboring these characteristics is a priority in oncology practice. The SWItch/Sucrose non-fermentable (SWI/SNF) chromatin remodeling complex has also emerged as a critical player in tumor progression, leading to the identification of several SWI/SNF complex genes as potential disease biomarkers and targets of anticancer therapies. AT-rich interaction domain-containing protein 1A (ARID1A) is a component of SWI/SNF, and mutations in ARID1A represent one of the most frequent molecular alterations in human cancers. ARID1A mutations occur in approximately 10% of pancreatic ductal adenocarcinomas (PDAC), but whether these mutations confer a therapeutic opportunity remains unclear. Here, we demonstrate that loss of ARID1A promotes an epithelial-mesenchymal transition (EMT) phenotype and sensitizes PDAC cells to a clinical inhibitor of HSP90, NVP-AUY922, both in vitro and in vivo. Although loss of ARID1A alone did not significantly affect proliferative potential or rate of apoptosis, ARID1A-deficient cells were sensitized to HSP90 inhibition, potentially by promoting the degradation of intermediate filaments driving EMT, resulting in cell death. Our results describe a mechanistic link between ARID1A defects and a quasi-mesenchymal phenotype, suggesting that deleterious mutations in ARID1A associated with protein loss exhibit potential as a biomarker for patients with PDAC who may benefit by HSP90-targeting drugs treatment. SIGNIFICANCE: This study identifies ARID1A loss as a promising biomarker for the identification of PDAC tumors that are potentially responsive to treatment with proteotoxic agents.


Asunto(s)
Antineoplásicos/farmacología , Proteínas de Unión al ADN/metabolismo , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Isoxazoles/farmacología , Neoplasias Pancreáticas/tratamiento farmacológico , Resorcinoles/farmacología , Factores de Transcripción/metabolismo , Animales , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Proliferación Celular , Proteínas de Unión al ADN/genética , Femenino , Humanos , Ratones , Ratones Desnudos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Pronóstico , Factores de Transcripción/genética , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
14.
Cancer Res ; 79(7): 1426-1437, 2019 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-30765602

RESUMEN

Given that cancer stem cells (CSC) play a key role in drug resistance and relapse, targeting CSCs remains promising in cancer therapy. Here we show that RAB5/7, which are involved in the endolysosomal pathway, play key roles in the maintenance of CSC survival via regulation of the mitophagic pathway. Inhibition of RAB5/7 efficiently eliminated colorectal CSCs and disrupted cancer foci. In addition, we identified mefloquine hydrochloride, an antimalarial drug, as a novel RAB5/7 inhibitor and promising colorectal CSC-targeting drug. Endolysosomal RAB5/7 and LAMP1/2 mediated parkin-dependent mitochondrial clearance and modulated mitophagy through lysosomal dynamics. In a patient-derived xenograft (PDX) model of colon cancer, treatment with mefloquine resulted in suppression of mitophagic PINK1/PARKIN and increased mitochondrial disorder and mitochondria-induced apoptosis without apparent side effects. These results suggest that the combination of mefloquine with chemotherapeutic agents in the PDX model potentially disrupts the hierarchy of colorectal cancer cells and identify endolysosomal RAB5/7 and LAMP1/2 as promising therapeutic targets in CSCs. SIGNIFICANCE: These findings show that endosomal/lysosomal RAB5 and RAB7, which regulate mitophagy, are essential for the survival of colon cancer stem cells.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/7/1426/F1.large.jpg.


Asunto(s)
Neoplasias Colorrectales/metabolismo , Endosomas/metabolismo , Lisosomas/metabolismo , Células Madre Neoplásicas/metabolismo , Proteínas de Unión al GTP rab/metabolismo , Proteínas de Unión al GTP rab5/metabolismo , Animales , Antígenos CD/metabolismo , Antineoplásicos/farmacología , Línea Celular Tumoral , Neoplasias Colorrectales/patología , Humanos , Lisosomas/efectos de los fármacos , Mefloquina/farmacología , Ratones , Ratones Endogámicos NOD , Ratones SCID , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/patología , Proteínas de Unión a GTP rab7
15.
Surg Today ; 49(6): 482-487, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30594951

RESUMEN

PURPOSE: High-output syndrome (HOS) is a complication of ileostomy, which can affect quality of life significantly; however, its exact cause remains unknown. The aim of this study was to establish the frequency, as well as the preoperative and intraoperative factors predictive of HOS. METHODS: The subjects of this study were 164 consecutive patients who underwent colorectal cancer surgery with ileostomy construction at our institute between January, 2011 and August, 2018. Thirteen patients with postoperative complications reported as causes of HOS, including intraperitoneal abscess, paralytic ileus, and outlet obstruction, were excluded. We used a logistic regression analysis to identify the factors predictive of HOS. RESULTS: HOS developed in 36 of the 151 patients (23.8%). There were significantly more diabetic patients in the HOS group (P = 0.03), but other patient factors such as age, gender, body mass index, and use of daily laxatives were not significantly different between the groups. The HOS group had significantly more cases of total proctocolectomy (P = 0.04), but other surgical factors such as operative time, and blood transfusion were not significantly different between the two groups. CONCLUSIONS: These results indicate that diabetes and total proctocolectomy are preoperative predictors of HOS, allowing for the possibility of early intervention via post-surgical treatment.


Asunto(s)
Neoplasias Colorrectales/cirugía , Diabetes Mellitus , Ileostomía/efectos adversos , Complicaciones Posoperatorias , Proctocolectomía Restauradora , Estomas Quirúrgicos/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Predicción , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Gestión de Riesgos , Síndrome , Adulto Joven
16.
Oncol Lett ; 14(2): 1595-1601, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28789384

RESUMEN

Surgeons are increasingly being faced with the challenge of treating elderly patients with colon cancer. The present study therefore aimed to compare the short-term outcomes of single-port laparoscopic surgery (SILS) for elderly patients with colon cancer (≥70 years) with those in younger patients (41-69 years; control group). Among 100 patients with colorectal cancer who had been treated with single-port laparoscopic surgery between January 2011 and December 2014, 56 (56.0%) were ≥70 years of age. The results of treatment and short-term outcomes in the elderly group (n=56) were retrospectively compared with the younger patients in the control group (n=44). The sex distribution, body mass index, history of prior surgery and the American Society of Anesthesiologists physical status classification were similar between the groups. Onodera's prognostic nutritional index demonstrated significant differences between the elderly and control groups (38.3 vs. 49.8; P<0.05). No significant differences were observed in the mean length of surgery (219.5±73.5 vs. 201.4±76.5 min; P=0.43), estimated blood loss (32.2±74.5 vs. 36.1±90.2 ml; P=0.10), postoperative complications (10.9 vs. 7.1%; P=0.78), length of postoperative hospital stay (9.6±12.5 vs. 7.3±3.0 days; P=0.23) or number of harvested lymph nodes (21.8±24.3 vs. 22.5±11.3; P=0.87) between the elderly and control groups. In conclusion, the results of the present study demonstrate that SILS may be carried out feasibly in elderly patients with colon cancer.

17.
Am J Case Rep ; 17: 899-904, 2016 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-27895320

RESUMEN

BACKGROUND Graft thrombosis is the main cause of early graft loss after transplantation. In Japan, pancreases available for transplantation are frequently from marginal donors due to diverse backgrounds in the population. However, marginal tissues increase the risk of early thrombosis in the graft. CASE REPORT Here, we describe a 41-year-old woman with type 1 diabetes mellitus who underwent a simultaneous pancreas-kidney transplantation. The pancreas was retrieved from a 34-year-old man who had experienced severe hemodynamic instability. The pancreaticoduodenal graft was implanted in the recipient iliac fossa with enteric drainage. Although the patient had not shown any physical signs or alterations in substances that might indicate functional loss of the pancreas graft, a Doppler ultrasound analysis detected a major thrombus in the pancreas graft on day 7 after surgery. A thrombectomy was performed with a radiological emergent intervention. After percutaneous direct thrombolysis, the patient received adjuvant thrombolytic therapy. Thereafter, the postoperative course was uneventful and the pancreas graft remained functional. CONCLUSIONS Early detection and treatment of thromboses are required to avoid graft failure and graft pancreatectomy. This case study demonstrates that early detection of severe thrombus with Doppler ultrasound in a grafted pancreas did not increase the risk of graft failure.


Asunto(s)
Oclusión de Injerto Vascular/diagnóstico por imagen , Trasplante de Riñón , Trasplante de Páncreas , Trombosis/diagnóstico por imagen , Ultrasonografía Doppler , Adulto , Índice de Masa Corporal , Diabetes Mellitus Tipo 1/complicaciones , Diagnóstico Precoz , Femenino , Oclusión de Injerto Vascular/cirugía , Humanos , Trasplante de Páncreas/efectos adversos , Cuidados Posoperatorios , Factores de Riesgo , Trombectomía , Trombosis/cirugía , Resultado del Tratamiento , Ultrasonografía Doppler/métodos
18.
Oncol Lett ; 12(2): 1465-1470, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27446454

RESUMEN

The safety of single-incision laparoscopic surgery (SLS) in elderly patients with colorectal cancer has not been established. The aim of the current study was to compare the outcomes of SLS and multi-port laparoscopic surgery (MLS) and to assess the feasibility of SLS in colorectal cancer patients aged ≥70 years. A retrospective case-control study of colon cancer patients undergoing elective surgical intervention between 2011 and 2014 was conducted. A total of 129 patients with colon cancer underwent surgery and were included in the analysis. Data regarding patient demographics, surgical variables, oncological outcomes and short-term outcomes were evaluated for statistical significance to compare MLS (n=79) and SLS (n=50) in colon cancer patients. No significant differences were observed in patient characteristics. No case required re-admission within 30 days post surgery. The mean surgery times were similar for the MLS and SLS groups when cases with left and right hemicolectomies were combined (207.7 and 215.9 min, respectively; P=0.47). In addition, overall perioperative outcomes, including blood loss, number of lymph nodes harvested, size of the surgical margin and complications, were similar between these groups. Thus, we suggest that SLS can be performed safely in elderly patients with colon cancer.

19.
Gan To Kagaku Ryoho ; 42(4): 511-3, 2015 Apr.
Artículo en Japonés | MEDLINE | ID: mdl-25963704

RESUMEN

A 78-year-old-man visited a nearby doctor for treatment of hepatitis C and high blood pressure.He was diagnosed with right hydronephrosis by abdominal echography conducted in follow-up of hepatitis C treatment in November 2011; he was then introduced to our hospital for close inspection and medical treatment.We observed wall hyperplasia and narrowing of the lumen in the central sigmoid part by contrast-enhanced computed tomography (CT).The right ureter at the L4/5 level showed wall hyperplasia and a deep color, and the right ureter, renal pelvis, and calix were expanded on the head side. By examination for CF, we observed a type 2 lesion in the sigmoid colon, and a biopsy showed well-differentiated adenocarcinoma. Based upon these findings, he was diagnosed with synchronous sigmoid colon cancer (cT4aN0M0, cStage II) and ureter cancer (cT2N0M0, cStage II); we performed laparotomy sigmoidectomy(D3 dissection)and full extraction of the right kidney urinary tract (lymph node dissection in front of the vena cava, the latter outside and between the aorta and vena cava). The postoperative course was particularly uneventful, and the patient was discharged from the hospital on day 38 after the operation. More than 2 years after the surgery, the patient exhibits no sign of sigmoid colon cancer or ureter cancer recurrence.


Asunto(s)
Adenocarcinoma/cirugía , Neoplasias Primarias Múltiples/cirugía , Neoplasias del Colon Sigmoide/cirugía , Neoplasias Ureterales/cirugía , Anciano , Colectomía , Humanos , Hidronefrosis/etiología , Masculino , Nefrectomía , Neoplasias del Colon Sigmoide/patología , Neoplasias Ureterales/complicaciones
20.
Int Surg ; 100(3): 417-22, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25785320

RESUMEN

We prove the safety and feasibility of single-incision plus 1 port (SILS+1) laparoscopic total mesorectal excision (TME) + lateral pelvic lymph node dissection (LPLD) via a medial umbilical approach for rectal cancer. Only a few reports have been published about single-incision multiport laparoscopic low anterior resection with LPLD. Recently, minimally invasive surgery such as single-incision plus 1 port (SILS + 1) for advanced rectal cancer has been reported as safe and feasible. To our knowledge, this is the first reported case of SILS + 1 used for LPLD. A wound protector was inserted through a 30-mm transumbilical incision. Next, a single-port access device was mounted to the wound protector and 3 ports (5 mm each) were placed. A 12-mm port was inserted in the right lower quadrant. Super-low anterior resection of the rectum and bilateral LPLD and temporary ileostomy were performed with SILS + 1, with a blood loss of 50 mL and a total surgical time of 525 minutes. The time for right lateral dissection was 74 minutes; the time for left lateral dissection was 118 minutes. The total number of dissected lymph nodes was 57 and the number of lateral lymph nodes dissected was 21 (8 left pelvic lymph nodes, 13 right pelvic lymph nodes). No postoperative anastomotic insufficiency or voiding dysfunction was observed. We have documented the safety and feasibility of SILS + 1-TME + LPLD via a medial umbilical approach for rectal cancer.


Asunto(s)
Laparoscopía/métodos , Escisión del Ganglio Linfático/métodos , Neoplasias del Recto/cirugía , Recto/cirugía , Anciano , Humanos , Ligamentos/cirugía , Metástasis Linfática , Masculino , Pelvis , Neoplasias del Recto/patología , Ombligo/cirugía
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