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1.
Asian J Endosc Surg ; 16(4): 822-826, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37448191

RESUMO

We report our experience in a patient with adenoma located in the horizontal part of the duodenum, which was effectively treated with the transmesenteric laparoscopic endoscopic cooperative surgery (LECS) approach. This approach, which entails incising the mesentery of the colon, simplified laparoscopic access to the horizontal part of the duodenum, which was minimally mobilized. Thus, the bulb and descending part of the duodenum were fixed to the retroperitoneum, facilitating stable handling of the endoscope and enabled safe and effective excision of an adenoma located in the horizontal part of the duodenum. This approach enabled safe and effective excision of an adenoma located in the horizontal part of the duodenum. The advantages of this method include a secure field of view, lower probability of damage to large vessels, and minimizing the defect to the intestine caused by the incision.

2.
Discov Oncol ; 14(1): 14, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36719602

RESUMO

BACKGROUND: Germline pathogenic variants in the E-cadherin gene CDH1 cause hereditary diffuse gastric cancer (HDGC), which is an autosomal dominant cancer syndrome, accounting for 1-3% of all gastric cancers. HDGC harboring a CDH 1 variant is extremely rare in Japan. METHOD: In this study we report the clinical courses of three cases with HDGC from a single Japanese family. RESULTS: The proband exhibited advanced and metastatic gastric cancer, and was found to have a previously reported heterozygous frameshift variant in CDH1 (NM_004360.3:c.1009_1010del:p.Ser337Phefs*12). Five at-risk relatives underwent presymptomatic molecular testing after careful genetic counseling, and three were molecularly diagnosed as positive for the variant. Esophagogastroduodenoscopy was performed in these relatives revealing abnormal small pale mucosal patches, small ulcerative lesion and no abnormal findings. Moreover, random and targeted biopsies were compatible with pathological diagnosis of HDGC in the three cases, all of which underwent total prophylactic gastrectomy. CONCLUSION: It is critical for the assessment and management of HDGC patients to be actively offered a multidisciplinary and familial-oriented approach. Notably, genetic screening in suspected individuals and familial members is a determining piece for a higher detection rate and the identification of clinical relevant mutations in both low and high-incidence gastric cancer countries.

3.
Technol Cancer Res Treat ; 22: 15330338221146024, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36617975

RESUMO

BACKGROUND: RAS homolog family member A (RhoA), a member of the Rho family of small GTPases, and Vav1, a guanine nucleotide exchange factor for Rho family GTPases, have been reported to activate pathways related to the actin cytoskeleton and regulation of cell shape, attachment, and motility. The interaction between these molecules in lymphoma is involved in malignant signaling, but its function in epithelial malignancy is unknown. Here, we investigated the malignant signal of mutant RhoA in gastric cancer and demonstrated the potential of RhoA G17E/Vav1 as a therapeutic target for diffuse gastric cancer. METHODS: The RhoA mutants R5W, G17E, and Y42C were retrovirally transduced into the gastric cancer cell line MKN74. The stably transduced cells were used for morphology, proliferation, and migration/invasion assays in vitro. MKN74 cells stably transduced with ectopic wild-type RhoA and mutant RhoA (G17E) were used in a peritoneal xenograft assay. RESULTS: The RhoA mutations G17E and Y42C induced morphological changes in MKN74. G17E induced Vav1 expression at the mRNA and protein levels and promoted the migration and invasion of MKN74. An RNA interference assay of Vav1 revealed that RhoA G17E enhanced cancer cell invasion via Vav1. Furthermore, immunoprecipitation revealed that Vav1 and RhoA G17E specifically bind and function together through matrix metalloproteinase -9. In a peritoneal xenograft model of nude mice, RhoA G17E promoted peritoneal dissemination, whereas Vav1 knockdown suppressed it. CONCLUSION: Overall, our findings indicate that RhoA G17E is associated with Vav1 and promoted cancer invasion via matrix metalloproteinase -9 in gastric cancer cells. Thus, RhoA G17E/Vav1 signaling in diffuse gastric cancer may be a useful therapeutic target.


Assuntos
Proteínas Proto-Oncogênicas c-vav , Neoplasias Gástricas , Proteína rhoA de Ligação ao GTP , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Movimento Celular/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Nus , Invasividade Neoplásica/genética , Proteínas Proto-Oncogênicas c-vav/genética , Proteínas Proto-Oncogênicas c-vav/metabolismo , Proteína rhoA de Ligação ao GTP/genética , Proteína rhoA de Ligação ao GTP/metabolismo , Neoplasias Gástricas/patologia
4.
ANZ J Surg ; 92(12): 3219-3223, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36074636

RESUMO

BACKGROUND: Laparoscopic colorectal surgery (LCRS) requires a small laparotomy at the umbilicus. The wound is small and inconspicuous, but if the patient develops an umbilical incisional hernia (UIH), the wound is visible and the patient suffers from symptoms of discomfort. However, the incidence of UIH after LCRS and its risk factors are not well understood. The purpose of this study was to investigate the risk factors for UIH after LCRS for colorectal cancer. METHODS: This was a single-centre retrospective study of 135 patients with colorectal cancer, conducted at our hospital from April 2013 to March 2019. The diagnosis of UIH was based on computed tomography and physical examination findings. Preoperative patient data such as enlargement of the umbilical orifice (EUO), subcutaneous fat thickness (SFT) and intraperitoneal thickness (IPT) were collected and analysed using univariate and multivariate analyses for the presence of risk factors for UIH. RESULTS: A total of 135 patients who underwent LCRS were analysed. The incidence of UIH was 20.7%. Univariate analysis revealed significantly high body mass index (BMI) ≥ 25 (P = 0.032), EUO (P < 0.001), SFT ≥18 mm (P = 0.011), and IPT ≥61 mm (P < 0.01) in the UIH group. Multivariate analysis revealed significant differences in EUO (P < 0.001), SFT ≥18 mm (P = 0.046) and IPT ≥61 mm (P = 0.022). CONCLUSION: EUO was the most important risk factor for UIH, followed by IPT and SFT. These findings are predictive indicators of the development of UIH after LCRS and can be assessed objectively and easily with preoperative computed tomography.


Assuntos
Neoplasias Colorretais , Cirurgia Colorretal , Hérnia Umbilical , Hérnia Incisional , Laparoscopia , Humanos , Hérnia Incisional/epidemiologia , Hérnia Incisional/etiologia , Hérnia Incisional/cirurgia , Cirurgia Colorretal/métodos , Umbigo , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Laparoscopia/efeitos adversos , Fatores de Risco , Hérnia Umbilical/epidemiologia , Hérnia Umbilical/cirurgia , Incidência , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/complicações
5.
Intern Med ; 61(5): 709-713, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35228477

RESUMO

A 67-year-old man with a history of esophageal cancer resection was referred to our hospital because of nausea and appetite loss. Laboratory findings showed severe hyponatremia and were compatible with syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Chest computed tomography (CT) revealed a nodule measuring 13 mm in the lower lobe of the right lung. Right thoracotomy was performed, and the histopathological diagnosis was small-cell lung cancer (T1bN0M0; Stage 1b). Although SIADH is frequently associated with small-cell lung cancer, it is extremely rare as the initial clinical feature in stage I small-cell lung cancer.


Assuntos
Hiponatremia , Síndrome de Secreção Inadequada de HAD , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Idoso , Humanos , Hiponatremia/complicações , Síndrome de Secreção Inadequada de HAD/complicações , Síndrome de Secreção Inadequada de HAD/diagnóstico , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/patologia , Masculino , Carcinoma de Pequenas Células do Pulmão/complicações , Vasopressinas
6.
DEN Open ; 2(1): e16, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35310707

RESUMO

Gastric hamartomatous inverted polyp (GHIP) is rare, with few reports of carcinogenesis from GHIP during long-term follow-up. A 51-year-old woman was diagnosed as having a submucosal tumor (SMT) during esophagogastroduodenoscopy (EGD) in 2008. In 2016, although the size and height of the lesion had not changed, she was referred to our hospital for further investigation of the lesion. EGD depicted a gastric SMT of 20 mm in diameter in the greater curvature of the upper gastric body, and a biopsy specimen showed a well to poorly differentiated adenocarcinoma. Following successful laparoscopic total gastrectomy, histopathological examination revealed an intramucosal adenocarcinoma arising in GHIP.

7.
Asian J Endosc Surg ; 15(2): 363-367, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34672101

RESUMO

Radical surgical procedures for malignant diseases of the pelvis result in a large pelvic defect that requires soft tissue reconstruction. The mesentery can be used for pelvic floor reconstruction when debridement with intestinal resection is required. A 75-year-old woman was diagnosed with sacral necrosis, infection and sepsis after carbon ion radiotherapy for sacral chordoma. She underwent sacral debridement three times, which resulted in a large pelvic defect of 14 × 13 cm. Surgery was performed to completely resect the necrotic tissue. We performed extended debridement of sacrum and adjacent tissue around the rectum and anus. Since it was impossible to preserve the anus, laparoscopic left hemicolectomy, abdominosacral resection, and left-sided mesocolic leaf repair for the pelvic defect, and reconstructed the pelvis and buttocks using a gluteal thigh flap were performed. Indocyanine green fluorescent (ICG) imaging was used to detect the margin of the pelvic floor and necrotic tissue and the blood flow of the left-sided mesocolic leaf flap. Left-sided mesocolic leaf reconstruction is useful for large pelvic defects. ICG imaging enabled the detection of the resection margins and the blood flow of the mesocolic leaf.


Assuntos
Laparoscopia , Procedimentos de Cirurgia Plástica , Idoso , Feminino , Humanos , Necrose/patologia , Necrose/cirurgia , Pelve/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Sacro/patologia , Sacro/cirurgia , Retalhos Cirúrgicos
8.
Case Rep Surg ; 2021: 5683621, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733565

RESUMO

BACKGROUND: Tension-free repair using mesh has become the standard treatment for abdominal wall incisional hernias. However, its postoperative complications reportedly include mesh infection, adhesions, and fistula formation in other organs. Here, we report an extremely rare case of mesh migration into the neobladder and ileum with entero-neobladder and neobladder-cutaneous fistulas. Case Presentation. An 80-year-old male who had undergone radical cystectomy 5 years ago and abdominal wall incisional hernia repair 3 years ago presented with fever and abdominal pain. Computed tomography (CT) scan revealed mesh migration into the neobladder and ileum. He was treated conservatively with antibiotics for a month but did not show improvement; hence, he was transferred to our hospital. He was diagnosed with mesh migration into the neobladder and ileum with complicated fistula formation. He underwent mesh removal, partial neobladder resection, and partial small bowel resection. He developed superficial incisional surgical site infection, which improved with drainage and antibiotics, and he was discharged 40 days after the surgery. CONCLUSIONS: We reported a rare case of mesh migration into the neobladder and ileum with fistula formation. Successful conservative treatment cannot be expected for this condition because mesh migration into the intestinal tract causes infection and fistula formation. Hernia repair requires careful placement of the mesh such that it does not come into contact with the intestinal tract. Early surgical intervention is important if migration into the intestinal tract is observed.

9.
Surg Case Rep ; 7(1): 218, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581917

RESUMO

BACKGROUND: Neurofibromatosis type 1 is an autosomal dominant inherited disease associated with multiple skin neurofibromas or other neurogenic tumors, such as nodular plexiform neurinoma or cerebrospinal tumor. Gastrointestinal stromal tumors are often complicated in patients with neurofibromatosis type 1, although involvement of the appendix is rare, and there have been few reports of appendiceal ganglioneuroma. CASE PRESENTATION: The patient was a 29-year-old man diagnosed with neurofibromatosis type 1 based on physical findings and his family history. During the follow-up of neurofibromatosis, computed tomography was performed to detect neurological tumors, such as neurofibromas in the brain, spinal cord, and gastrointestinal tract. Computed tomography showed a markedly thickened appendix wall, and an appendiceal tumor was suspected. Laparoscopic appendectomy was performed, and a 50 × 35 mm appendiceal submucosal tumor was resected with a negative resection margin. At histopathological examination, the tumor was diagnosed as ganglioneuroma; it showed short spindle-shaped cells and ganglion cells diffusely infiltrated into the proper muscle layer and fibrous tissue that grew around nerve cells. The patient was discharged on the 5th postoperative day without postoperative complications and was doing well at 13 months following the operation. CONCLUSIONS: Gastrointestinal stromal tumor and neurofibroma are the most common gastrointestinal tumors associated with neurofibromatosis type 1, but ganglioneuroma of the appendix is rare. Appendiceal neurogenic tumors should be considered in patients with neurofibromatosis type 1, and surgical resection is necessary because of the risk of malignancy.

10.
ANZ J Surg ; 91(10): 2074-2080, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34339097

RESUMO

BACKGROUND: Adhesive small bowel obstruction (ASBO) is one of the major causes of postoperative morbidity. Non-surgical management is generally applied to non-strangulated ASBO. Several factors have been reported to affect the response to non-surgical management in patients with ASBO. However, the association between sex differences and non-strangulated ASBO remains unclear. This study aimed to elucidate the effect of sex differences in non-strangulated postoperative ASBO. METHODS: We divided 139 patients with a first episode of non-strangulated postoperative ASBO into two groups: male group (n = 83) and female group (n = 56). Clinical features and prognosis were compared between the two groups. RESULTS: Female patients had lower proportions of oesophageal/gastric malignancies (P = 0.044) and colorectal malignancies (P = 0.030) and a higher proportion of uterine/ovarian malignancies (P < 0.001) than male patients did. More female patients required surgical management than male patients (P = 0.003) did. Hospital length of stay (LOS) was longer (P = 0.046) in the female group than in the male group. Multiple logistic regression analysis showed that the female sex was associated with an increased risk of the need for surgical management (odds ratio 5.318, P = 0.006). Cox proportional hazards regression analysis revealed that the female sex was positively associated with increased LOS (hazard ratio 0.687, P = 0.045). CONCLUSION: Female sex was associated with failure of non-surgical management and increased LOS in patients with non-strangulated postoperative ASBO.


Assuntos
Obstrução Intestinal , Caracteres Sexuais , Adesivos , Feminino , Humanos , Obstrução Intestinal/cirurgia , Masculino , Estudos Retrospectivos , Aderências Teciduais/complicações , Aderências Teciduais/epidemiologia , Resultado do Tratamento
11.
Oncology ; 99(10): 632-640, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34280933

RESUMO

INTRODUCTION: Patients with unresectable or recurrent gastric cancer who have an objective response (OR) to nivolumab monotherapy are expected to have a good long-term prognosis. However, the OR rate for nivolumab treatment is low at 11%, and there is a need for biomarkers to predict the treatment response. This study aimed to analyze the significance of systemic inflammation-related variables and clinicopathologic characteristics as predictive markers of response to nivolumab monotherapy in patients with advanced gastric cancer. METHODS: In this retrospective cohort study, we enrolled 71 consecutive patients who received nivolumab monotherapy for unresectable or recurrent gastric cancer. Receiver operating characteristic curve analysis was performed to determine the cutoff values of systemic inflammation-related variables, predictors of treatment response, and other prognostic factors related to nivolumab therapy. We focused on systemic inflammation-related variables measured before nivolumab induction and 2 weeks after its first administration and performed multivariate analysis to assess whether they could be used as prognostic factors. RESULTS: Multivariate analysis revealed that a lymphocyte-to-monocyte ratio (LMR) of ≤3.28 after 2 weeks of initial nivolumab treatment (2wLMR) is a statistically significant predictor of treatment response (p = 0.012). The progression-free survival (PFS) rate of patients with liver metastasis was significantly worse than that of the other patients (1-year PFS: 0.0 vs. 24.4%, respectively; p = 0.005). The overall survival (OS) of patients with a low 2wLMR was significantly longer than that in patients with a high 2wLMR (1-year OS: 37.4 vs. 18.9%, respectively; p = 0.022). CONCLUSIONS: Thus, the 2wLMR could be a useful biomarker to predict response to nivolumab treatment and the prognosis of unresectable and recurrent gastric cancer.


Assuntos
Linfócitos/patologia , Neutrófilos/patologia , Neoplasias Gástricas/sangue , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nivolumabe , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia
12.
Mol Clin Oncol ; 15(1): 148, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34094546

RESUMO

Colorectal cancer with a Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) gene mutation is considered to be resistant to anti-EGFR agents. G12D is the most common KRAS mutation in colorectal cancer, followed by G12V and G13D. According to clinical and basic research data, patients with colorectal cancer exhibiting G12D and G12V KRAS mutations are resistant to anti-EGFR agents; however, this is not true of G13D and other minor mutations, which are still not well understood. The current study focused on minor KRAS mutations (G12A, G12C, G12S, Q61H and A146T) and evaluated whether these were resistant to anti-EGFR antibodies using a mix culture assay. The results demonstrated that all KRAS mutations, including minor mutations, were resistant to two anti-EGFR agents: Cetuximab and panitumumab. The combined effect of MEK and BCL-XL inhibition on colorectal cancer cells with KRAS minor mutations were subsequently evaluated. The combined effect of MEK and BCL-XL inhibitors was confirmed in all KRAS minor mutations. The sensitivity of AMG510, a novel KRAS G12C selective inhibitor, was also assessed. The mix culture assay revealed that AMG510 selectively exerted an antitumor effect on colon cancer cells with a G12C KRAS mutation. The combination of MEK and BCL-XL inhibition markedly enhanced the effect of AMG510 in colon cancer cells. The current study suggested that AMG510 may have potential clinical use in combination with MEK and BCL-XL inhibitors in the treatment of patients with colorectal cancer exhibiting the G12C KRAS mutation.

14.
Asian J Endosc Surg ; 14(3): 624-627, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32875728

RESUMO

INTRODUCTION: Perianal Paget's disease is associated with adenocarcinoma and can spread to the perianal skin. It often requires extensive resection of the perianal skin and rectum. Many studies have shown the efficacy of laparoscopic abdominoperineal resection for lower rectal cancer. However, extensive resection of the dorsal side of the perineal skin is difficult in the lithotomy position. We report a laparoscopic abdominosacral approach using the jackknife position for perianal Paget's disease. MATERIALS AND SURGICAL TECHNIQUE: Surgery was started using the lithotomy position, and total mesorectal excision with central lymphadenectomy was performed laparoscopically. Pelvic floor muscles were divided 2 cm away from the rectum. The sigmoid colon was then divided with a linear stapler, and a terminal colostomy was made. The sacral approach was then followed with the patient placed in a jackknife position. A skin incision was made 1-2 cm from the negative margin confirmed by preoperative mapping biopsy and resected en-bloc. We used this approach in two patients with a mean operative time of 483 minutes, including 53.5 minutes for the position change. All tumor margins, including the skin, were cancer-free, and primary wound closure was possible in both of the cases. Both patients were doing well without any recurrence 10 and 13 months postoperatively. CONCLUSION: Laparoscopic abdominosacral resection is safe and effective and facilitates extensive perineal skin resection, especially on the dorsal side, with a less invasive laparoscopic procedure.


Assuntos
Neoplasias do Ânus/cirurgia , Laparoscopia , Doença de Paget Extramamária/cirurgia , Neoplasias Retais , Canal Anal , Humanos , Recidiva Local de Neoplasia , Posicionamento do Paciente , Períneo/cirurgia , Neoplasias Retais/cirurgia , Reto/cirurgia , Sacro/cirurgia , Pele
15.
Asian J Surg ; 44(1): 292-297, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32732062

RESUMO

BACKGROUND: /Objective: The feces sign has been reported as a possible predictive factor for non-operative treatment of small bowel obstruction. However, its relationship with prognosis of non-emergency adhesive small bowel obstruction remains unclear. This study aimed to clarify the relationship between the feces sign and prognosis of non-emergency adhesive small bowel obstruction. METHODS: Ninety-two patients with non-emergency adhesive small bowel obstruction with the transitional zone visible on computed tomography were included. Patients were categorized into two groups: feces sign positive (n = 40) and negative (n = 52). Clinical features and prognosis were compared between the two groups. Cox proportional hazards regression models incorporating the feces sign were used to analyze odds of diet resumption and discharge. RESULTS: Patients with feces sign were younger (p = 0.015), had a higher body mass index (p = 0.027), and a lower white blood cell count (p = 0.019) on admission. More patients with feces sign were successfully treated with fasting and/or nasogastric tube placement (p < 0.001), and no patient with feces sign suffered from recurrent obstruction after diet resumption. Kaplan-Meier analysis showed that patients with feces sign took less time for diet resumption (p = 0.007) and discharge (p = 0.004) than those without it. Using Cox proportional hazards regression model, the feces sign was reported as an independent predictor of diet resumption (odds ratio 1.685, p = 0.018) and discharge (odds ratio 1.861, p = 0.007). CONCLUSIONS: The feces sign is associated with improved odds for diet resumption and discharge.


Assuntos
Ingestão de Alimentos , Fezes , Obstrução Intestinal/diagnóstico , Obstrução Intestinal/terapia , Intestino Delgado , Fatores Etários , Idoso , Jejum , Feminino , Humanos , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/fisiopatologia , Intubação Gastrointestinal , Tempo de Internação , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Prognóstico , Tomografia Computadorizada por Raios X
16.
Int J Oncol ; 57(5): 1179-1191, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32901840

RESUMO

KRAS­mutant colorectal cancer (CRC) is a highly malignant cancer with a poor prognosis, however specific therapies targeting KRAS mutations do not yet exist. Anti­epidermal growth factor receptor (EGFR) agents, including cetuximab and panitumumab, are effective for the treatment of certain patients with CRC. However, these anti­EGFR treatments have no effect on KRAS­mutant CRC. Therefore, new therapeutic strategies targeting KRAS­mutant CRC are urgently needed. To clarify the direct effect of KRAS gene mutations, the present study transduced mutant forms of the KRAS gene (G12D, G12V and G13D) into CACO­2 cells. A drug­screening system (Mix Culture assay) was then applied, revealing that the cells were most sensitive to the MEK inhibitor trametinib among tested drugs, Cetuximab, Panitumumab, Regorafenib, Vemurafenib, BEZ­235 and Palbociclib. Trametinib suppressed phosphorylated ERK (p­ERK) expression and inhibited the proliferation of KRAS­mutant CACO­2 cells. However, low­dose treatment with trametinib also increased the expression of the anti­apoptotic protein Bcl­xL in a dose­dependent manner, leading to drug resistance. To overcome the resistance of KRAS­mutant CRC to apoptosis, the combination of trametinib and the Bcl­xL antagonist ABT263 was assessed by in vitro and in vivo experiments. Compared with the effects of low­dose trametinib monotherapy, combination treatment with ABT263 had a synergistic effect on apoptosis in mutant KRAS transductants in vitro. Furthermore, in vivo combination therapy using low­dose trametinib and ABT263 against a KRAS­mutant (G12V) xenograft synergistically suppressed growth, with an increase in apoptosis compared with the effects of trametinib monotherapy. These data suggest that a low dose of trametinib (10 nM), rather than the usual dose of 100 nM, in combination with ABT263 can overcome the resistance to apoptosis induced by Bcl­xL expression, which occurs concurrently with p­ERK suppression in KRAS­mutant cells. This strategy may represent a promising new approach for treating KRAS­mutant CRC.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Piridonas/administração & dosagem , Pirimidinonas/administração & dosagem , Proteína bcl-X/antagonistas & inibidores , Compostos de Anilina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Células CACO-2 , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Piridonas/farmacologia , Pirimidinonas/farmacologia , Sulfonamidas/farmacologia
17.
Traffic Inj Prev ; 21(7): 442-446, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32886011

RESUMO

OBJECTIVE: Intestinal injuries in seat belt syndrome are relatively uncommon but can be potentially lethal due to accompanying peritonitis and hemorrhaging. It can be difficult to identify the exact injury sites of the intestine as multiple areas are often damaged and massive intraperitoneal hemorrhaging may make it challenging to determine causal bleeding points of mesenteric injuries. This study aimed to clarify the incidence and distribution of intestinal injuries in seat belt syndrome. METHODS: We retrospectively reviewed the clinical records of 25 patients who underwent laparotomy for suspected intestinal injuries due to seat belt syndrome during a frontal impact. The incidence and distribution of the sites of intestinal injuries, as well as associated injuries, were investigated. Intestinal injuries were divided into bowel and mesenteric injuries. Additionally, bowel injuries were classified into two types: perforation and non-perforation (seromuscular tears/intramural hematomas). Regarding the injured sites, the small intestine was divided into the following three parts: (1) the ligament of Treitz (100-cm distal from the ligament [proximal jejunum]), (2) the ileocecal valve (100-cm proximal from the valve [distal ileum]), and (3) the intermediate area between those two regions (jejunoileal junction). RESULTS: In total, there were 64 major injuries among 25 patients requiring surgical intervention: 34 bowel injuries (20 perforations and 14 non-perforations) and 30 mesenteric injuries. Significantly more bowel perforations occurred in the small intestine (1 [interquartile range (IQR), 0-1]) than in the large intestine (0 [IQR, 0-0]) (p = 0.003). Similarly, significantly more mesenteric injuries occurred in the small intestine (1 [IQR, 0-1.25]) than in the large intestine (0 [IQR, 0-0]) (p < 0.001). Specific sites of the mesenteric injuries in the small intestine included the jejunoileal junction (0 [IQR, 0-1]) and distal ileum (0 [IQR, 0-1]); the jejunoileal junction was significantly more vulnerable than the proximal jejunum (0 [IQR, 0-0]) (p = 0.015). CONCLUSIONS: In patients with seat belt syndrome, the small intestine was more vulnerable to perforation and mesenteric injury than the large intestine. Additionally, for mesenteric injuries, the jejunoileal junction was more likely to be damaged than the proximal jejunum.


Assuntos
Traumatismos Abdominais/epidemiologia , Acidentes de Trânsito/estatística & dados numéricos , Cintos de Segurança/efeitos adversos , Adulto , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
18.
BMC Surg ; 20(1): 168, 2020 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-32711489

RESUMO

BACKGROUND: Adhesive small bowel obstruction (ASBO) is one of the most common causes of postoperative morbidity. According to Boyle's law, decreased barometric pressure expands the volume of intestinal gas. We aimed to elucidate the relationship between barometric pressure and ASBO. METHODS: We divided 215 admissions of 120 patients with ASBO into three groups: the fasting group, which responded to fasting (n = 51); the decompression group, which was successfully treated with gastrointestinal decompression (n = 104); and the surgery group which required emergency or elective surgery to treat ASBO (n = 60). We compared and examined clinical backgrounds, findings on admission, and barometric pressure during the peri-onset period (29 days: from 14 days before to 14 days after the onset of ASBO). RESULTS: There were significant differences among the three groups regarding gender, history of ASBO, hospital length of stay, and barometric pressure on the onset day of ASBO. Barometric pressure on the onset day was significantly higher in the fasting group than in the decompression group (p = 0.005). During pre-onset day 5 to post-onset day 2, fluctuations in the barometric pressure in the fasting and decompression groups showed reciprocal changes with a symmetrical axis overlapping the median barometric pressure in Matsumoto City; the fluctuations tapered over time after onset. In the fasting group, the barometric pressure on the onset day was significantly higher than that on pre-onset days 14, 11, 7, 4, 3, and 2; post-onset days 3 and 10; and the median pressure in Matsumoto City. Conversely, in the decompression group, the barometric pressure on the onset day was lower than that on pre-onset days 14, 5-2; post-onset days 1, 2, 7, 8, 11, 13, and 14; and the median pressure in Matsumoto City. In the surgery group, the barometric pressure on the onset day was equivalent to those on the other days. CONCLUSIONS: ASBO with response to conservative treatment is vulnerable to barometric pressure. Additionally, ASBO that is successfully treated with fasting and decompression is associated with a different barometric pressure on the onset day and reciprocal fluctuations in the barometric pressure during the peri-onset period.


Assuntos
Pressão Atmosférica , Obstrução Intestinal , Intestino Delgado/fisiopatologia , Aderências Teciduais/complicações , Idoso , Idoso de 80 Anos ou mais , Jejum/fisiologia , Feminino , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/fisiopatologia , Obstrução Intestinal/cirurgia , Obstrução Intestinal/terapia , Intestino Delgado/patologia , Intestino Delgado/cirurgia , Intubação Gastrointestinal , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Aderências Teciduais/cirurgia , Resultado do Tratamento
19.
Case Rep Oncol ; 13(1): 145-152, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32231536

RESUMO

Disseminated carcinomatosis of the bone marrow (DCBM) in colorectal cancer is an extremely rare complication with a poor prognosis. Here, we report a case of DCBM due to rectal cancer successfully treated with a combination of FOLFOX and an anti-epidermal growth factor receptor (EGFR) agent. The patient was a 38-year-old man diagnosed with rectal cancer with multiple bone and para-aortic lymph node metastases complicated by disseminated intravascular coagulation (DIC). He first recovered from DIC following cotreatment with FOLOX plus cetuximab; subsequently, the second attack was successfully treated with FOLFOX plus panitumumab. His initial condition was extremely poor, but he survived with two FOLFOX plus anti-EGFR regimens and died 333 days after introduction of chemotherapy.

20.
Anat Rec (Hoboken) ; 301(5): 796-805, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29232767

RESUMO

To better understand the cellular origins and differentiation of anal canal epithelial neoplasms, the immunohistochemical profiles of the anal canal epithelium in humans and swine were evaluated. Formalin-fixed tissue sections were immunostained for mucin (MUC: MUC2, MUC5AC, MUC5B), desmoglein 3 (DGS3), p63, CDX2, SOX2, and α-smooth muscle actin (α-SMA). The anal transitional zone (ATZ) epithelium covered the anal sinus and consisted of a stratified epithelium with mucous cells interspersed within the surface lining. Anal glands opened into the anal sinus. Ducts and acini of intraepithelial or periepithelial mucous type were the main structures of human anal glands, whereas those of swine were compound tubuloacinar mixed glands. Distal to the ATZ epithelium, non-keratinized stratified squamous epithelium merged with the keratinized stratified squamous epithelium of the perianal skin. MUC5AC expression predominated over MUC5B expression in the ATZ epithelium, while MUC5B expression was higher in the anal glands. SOX2 was positive in the ATZ epithelium, anal glands, and squamous epithelium except in the perianal skin. In humans, DGS3 was expressed in the ATZ epithelium, anal gland ducts, and squamous epithelium. p63 was detected in the ATZ epithelium, anal glands, and squamous epithelium. Myoepithelial cells positive for α-SMA and p63 were present in the anal glands of swine. Colorectal columnar cells were MUC5B+ /MUC2+ /CDX2+ /MUC5AC- /SOX2- . The ATZ epithelium seems to be a distinctive epithelium, with morphological and functional features allowing smooth defecation. The MUC5AC+ /SOX2+ /MUC2- /CDX2- profile of the ATZ epithelium and anal glands is a useful feature for diagnosing adenocarcinoma arising from these regions. Anat Rec, 301:796-805, 2018. © 2017 Wiley Periodicals, Inc.


Assuntos
Canal Anal/metabolismo , Células Epiteliais/metabolismo , Mucosa Intestinal/metabolismo , Mucinas/metabolismo , Actinas/metabolismo , Animais , Fator de Transcrição CDX2/metabolismo , Desmogleína 3/metabolismo , Humanos , Imuno-Histoquímica , Fatores de Transcrição SOXB1/metabolismo , Suínos
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