RESUMEN
BACKGROUND: Excessive tension at the anastomosis contributes to anastomotic leakage (AL) in low anterior resection (LAR). However, the specific tension has not been measured. We assessed whether "Bridging," characterized by the proximal colon resembling a suspension bridge above the pelvic floor, is a significant risk factor for AL following LAR for rectal cancer. METHODS: This retrospective study reviewed the medical records and laparoscopic videos of 102 patients who underwent laparoscopic LAR using the double stapling technique at Yachiyo Hospital between January 2014 and December 2023. Patients were classified based on whether they had Bridging (tight or sagging) or were in a Resting state of the proximal colon, and the association between Bridging and AL was examined. RESULTS: AL occurred in 31.3% of the Tight Bridging group, 20% of the Sagging Bridging group, and 2.2% of the Resting group (P = 0.002). The incidence of AL was significantly higher in patients with Bridging than in those without (23.2% vs. 2.2%, P = 0.003). Multivariate analysis revealed that Bridging is an independent risk factor for AL (odds ratio = 6.97; 95% confidence interval: 1.45-33.6; P = 0.016). CONCLUSIONS: The presence of Bridging is a significant risk factor for AL following LAR for rectal cancer, suggesting the need for implementing preventive measures in patients with this condition.
RESUMEN
We investigated the effects of fermented rice bran (FRB) administration in two groups of C57BL/6J mice. The first group was fed with a high-fat diet, and the second group was fed with a high-fat diet supplemented with the FRB for 8 weeks. FRB supplementation suppressed the high-fat-induced weight gain and considerable alterations in the intestinal microbiota profile in the second group. Among 27 bacterial genera detected in the FRB, only Enterococcus, Lactobacillus, Bacteroides, Prevotella, and the unclassified family Peptostreptococcaceae were detected in mice feces. Their abundances were not particularly increased by FRB supplementation. The abundances of Enterococcus and the unclassified family Peptostreptococcaceae were even suppressed in the second group, suggesting that FRB supplementation didn't cause an addition of beneficial microbiome but inhibit the proliferation of specific bacteria. Fecal succinic acid concentration was significantly decreased in the second group and highly correlated with the relative abundances of Turicibacter, Enterococcus, and the unclassified family Peptostreptococcaceae. A significant increase in fumaric acid and a decrease in xylitol, sorbitol, uracil, glutamic acid, and malic acid levels were observed in the peripheral blood of the second group. FRB supplementation counteracted the high-fat-induced obesity in mice by modulating the gut microbiota and the host metabolism.
RESUMEN
Many clinical trials of peptide vaccines have been conducted. However, these vaccines have provided clinical benefits in only a small fraction of patients. The purpose of the present study was to explore microRNAs (miRNAs) as novel predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer. First, we carried out microarray analysis of pretreatment cancer tissues in a phase I study, in which peptide vaccines alone were given. Candidate miRNAs were selected by comparison of the better prognosis group with the poorer prognosis group. Next, we conducted microarray analysis of cancer tissues in a phase II study, in which peptide vaccines combined with chemotherapy were given. Candidate miRNAs were further selected by a similar comparison of prognosis. Subsequently, we carried out reverse-transcription PCR analysis of phase II cases, separating cancer tissues into cancer cells and stromal tissue using laser capture microdissection. Treatment effect in relation to overall survival (OS) and miRNA expression was analyzed. Three miRNA predictors were negatively associated with OS: miR-125b-1 in cancer cells (P = 0.040), and miR-378a in both cancer cells (P = 0.009) and stromal cells (P < 0.001). Multivariate analysis showed that expression of miR-378a in stromal cells was the best among the three predictors (HR, 2.730; 95% CI, 1.027-7.585; P = 0.044). In conclusion, miR-125b-1 and miR-378a expression might be considered as novel biomarkers to predict the efficacy of vaccine treatment against colorectal cancer.
Asunto(s)
Vacunas contra el Cáncer/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , MicroARNs/genética , Animales , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/prevención & control , Femenino , Humanos , Captura por Microdisección con Láser , Masculino , Ratones , Análisis por Micromatrices , Pronóstico , Vacunas de Subunidad/administración & dosificaciónRESUMEN
We previously conducted a phase I clinical trial combining the HLA-A*2402-restricted KIF20A-derived peptide vaccine with gemcitabine for advanced pancreatic cancer (PC) and confirmed its safety and immunogenicity in cancer patients. In this study, we conducted a multicenter, single-armed, phase II trial using two antiangiogenic cancer vaccines targeting VEGFR1 and VEGFR2 in addition to the KIF20A peptide. We attempted to evaluate the clinical benefit of the cancer vaccination in combination with gemcitabine. Chemotherapy naïve PC patients were enrolled to evaluate primarily the 1-year survival rate, and secondarily overall survival (OS), progression free survival (PFS), response rate (RR), disease control rate (DCR) and the peptide-specific immune responses. All enrolled patients received therapy without the HLA-A information, and the HLA genotypes were used for classification of the patients. Between June 2012 and May 2013, a total of 68 patients were enrolled. No severe systemic adverse effects of Grade 3 or higher related to these three peptides were observed. The 1-year survival rates between the HLA-A*2402-matched and -unmatched groups were not significantly different. In the HLA-A*2402 matched group, patients showing peptide-specific CTL induction for KIF20A or VEGFR1 showed a better prognosis compared to those without such induction (P = 0.023, P = 0.009, respectively). In the HLA-A*2402-matched group, the patients who showed a strong injection site reaction had a better survival rate (P = 0.017) compared to those with a weak or no injection site reaction. This phase II study demonstrated that this therapeutic peptide cocktail might be effective in patients who demonstrate peptide-specific immune reactions although predictive biomarkers are needed for patient selection in its further clinical application.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Vacunas contra el Cáncer/uso terapéutico , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamiento farmacológico , Péptidos/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Vacunas contra el Cáncer/administración & dosificación , Vacunas contra el Cáncer/efectos adversos , Vacunas contra el Cáncer/inmunología , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Antígeno HLA-A24/genética , Antígeno HLA-A24/inmunología , Humanos , Cinesinas/inmunología , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/inmunología , Péptidos/administración & dosificación , Péptidos/efectos adversos , Péptidos/inmunología , Pronóstico , Linfocitos T Citotóxicos/inmunología , Factores de Tiempo , Resultado del Tratamiento , Receptor 1 de Factores de Crecimiento Endotelial Vascular/inmunología , Receptor 2 de Factores de Crecimiento Endotelial Vascular/inmunología , GemcitabinaRESUMEN
BACKGROUND: Lentinan (LNT) is a purified ß-1, 3-glucan that augments immune responses. The present study was conducted to assess the efficacy of LNT in combination with S-1 as a first-line treatment for unresectable or recurrent gastric cancer. PATIENTS AND METHODS: Eligible patients were randomly assigned to receive S-1 alone or S-1 plus LNT. The primary end-point was overall survival (OS). Secondary end-points were time-to-treatment failure (TTF), overall response rate (ORR), safety, quality of life (QOL), and biomarker. The percentages of LNT-binding monocytes in peripheral blood prior to treatment were analysed for the biomarker assessment. RESULTS: One hundred and fifty-four and 155 patients were randomly assigned to receive S-1 alone or S-1 plus LNT, respectively. The median OS was 13.8 and 9.9 months (P = 0.208), the median TTF was 4.3 and 2.6 months (P < 0.001), the ORR was 22.3% and 18.7% for the S-1 and S-1 plus LNT groups, respectively. The incidences of haematologic and non-haematologic adverse events were similar, and no significant changes in QOL scores were observed during the treatment in both groups. In a subpopulation of patients with LNT-binding monocytes ≥2%, patients who received more than two cycles of chemotherapy showed a longer survival time in the S-1 plus LNT group. CONCLUSIONS: OS did not improve and TTF was significantly worse in the S-1 plus LNT group as compared with the S-1-only group. This study showed no efficacy of LNT when combined with S-1 treatment in patients with unresectable or recurrent gastric cancer. CLINICAL TRIAL REGISTRATION ID NUMBER: UMIN 000000574.
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Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Lentinano/uso terapéutico , Ácido Oxónico/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Tegafur/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monocitos/metabolismo , Calidad de VidaRESUMEN
An 86-year-old woman underwent a cholecystectomy for gallbladder cancer. Seven months later, an abdominal CT scan showed multiple liver and lymph node metastases. Treatment with S-1 was started at a dose of 100 mg/day, but was changed to alternate-day administration because of diarrhea. Metastatic lesions showed a complete response after 7 months of chemotherapy. S-1 alternate-day therapy could be maintained without any severe adverse events. This method can be managed safely and with certainty in an elderly patient and it has demonstrated efficacy in the treatment of recurrent gallbladder cancer.
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Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Ácido Oxónico/uso terapéutico , Tegafur/uso terapéutico , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/administración & dosificación , Combinación de Medicamentos , Femenino , Neoplasias de la Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/cirugía , Humanos , Neoplasias Hepáticas/secundario , Metástasis Linfática , Ácido Oxónico/administración & dosificación , Recurrencia , Tegafur/administración & dosificación , Resultado del TratamientoRESUMEN
BACKGROUND: We previously conducted a phase I trial for advanced colorectal cancer (CRC) using five HLA-A*2402-restricted peptides, three derived from oncoantigens and two from vascular endothelial growth factor (VEGF) receptors, and confirmed safety and immunological responses. To evaluate clinical benefits of cancer vaccination treatment, we conducted a phase II trial using the same peptides in combination with oxaliplatin-based chemotherapy as a first-line therapy. METHODS: The primary objective of the study was the response rates (RR). Progression free survival (PFS), overall survival (OS), and immunological parameters were evaluated as secondary objective. The planned sample size was more than 40 patients for both HLA2402-matched and -unmatched groups. All patients received a cocktail of five peptides (3 mg each) mixed with 1.5 ml of IFA which was subcutaneously administered weekly for the first 12 weeks followed by biweekly administration. Presence or absence of the HLA-A*2402 genotype were used for classification of patients into two groups. RESULTS: Between February 2009 and November 2012, ninety-six chemotherapy naïve CRC patients were enrolled under the masking of their HLA-A status. Ninety-three patients received mFOLFOX6 and three received XELOX. Bevacizumab was added in five patients. RR was 62.0% and 60.9% in the HLA-A*2402-matched and -unmatched groups, respectively (p=0.910). The median OS was 20.7 months in the HLA-A*2402-matched group and 24.0 months in the unmatched group (log-rank, p=0.489). In subgroup with a neutrophil/lymphocyte ratio (NLR) of <3.0, patients in the HLA-matched group did not survive significantly longer than those in the unmatched group (log-rank, p=0.289) but showed a delayed response. CONCLUSIONS: Although no significance was observed for planned statistical efficacy endpoints, a delayed response was observed in subgroup with a NLR of <3.0. Biomarkers such as NLR might be useful for selecting patients with a better treatment outcome by the vaccination. TRIAL REGISTRATION: Trial registration: UMIN000001791.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Femenino , Antígenos HLA/análisis , Humanos , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Péptidos/administración & dosificación , Análisis de SupervivenciaRESUMEN
AIM: We performed a phase II study of irinotecan with 5'-deoxy-5-fluorouridine (5'-DFUR) for metastatic colorectal cancer based on UDP-glucuronosyltransferase (UGT) 1A1 polymorphism. PATIENTS AND METHODS: A total of 28 patients were enrolled. The dose of irinotecan was 150 mg/m(2) for patients with the *1/*1 wild-type genotype, and 70 mg/m(2) for those with the *1/*28 mutated genotype. The primary end-point was the response rate (RR); secondary end-points were safety, time to treatment failure (TTF), and overall survival (OS). RESULTS: In 28 patients total, genotype was wild-type in 22 and mutated in six. The RR was *1/*1 (22.7%; wild-type) vs. *1/*28 (16.7%; mutated); the median TTF was 5 months vs. 4.5 months, and the median OS was 13 months vs. 17.5 months, respectively. None of these differences were significant. Toxicities of grade 3 or higher were neutropenia (9.0% vs. 0%, respectively) and diarrhea (13.6% vs. 0%, respectively). CONCLUSION: This genotype-oriented therapy was effective and safe, and thus appears useful for patients who have complications or advanced age.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/análogos & derivados , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Floxuridina/análogos & derivados , Glucuronosiltransferasa/genética , Polimorfismo Genético , Anciano , Antineoplásicos/uso terapéutico , Camptotecina/efectos adversos , Camptotecina/uso terapéutico , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/patología , Femenino , Floxuridina/efectos adversos , Floxuridina/uso terapéutico , Humanos , Irinotecán , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Análisis de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Paclitaxel and 5'-deoxy-5-fluorouridine (5'-DFUR) have single-agent activity in gastric cancer and have distinct mechanisms of action and no overlap of key toxicities. To evaluate the efficacy and safety of their combination, we conducted a combination phase II study of paclitaxel and 5'-DFUR in patients with unresectable or recurrent gastric cancer who had received up to one prior chemotherapy. PATIENTS AND METHODS: Treatment included paclitaxel at 70 mg/m(2) i.v. on days 1, 8 and 15 every four weeks, and 5'-DFUR at 600 mg p.o. every day. The primary end-point was the response rate (RR) and secondary end-points were overall survival (OS), progression-free survival (PFS), time-to-treatment failure (TTF) and rate of adverse events. RESULTS: In 42 eligible patients, the RR was 40.5%. OS, PFS and TTF were 371 days, 170 days, and 147 days, respectively. Adverse events were relatively mild. Commonly observed grade 3/4 adverse events were neutropenia (26.2%), anorexia (4.8%), neuropathy (4.8%) and fatigue (4.8%). CONCLUSION: The combination of weekly paclitaxel and 5'-DFUR chemotherapy is active and well-tolerated.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Floxuridina/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Paclitaxel/administración & dosificación , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Antimetabolitos Antineoplásicos/uso terapéutico , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Floxuridina/efectos adversos , Floxuridina/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Paclitaxel/efectos adversos , Paclitaxel/uso terapéutico , Tasa de SupervivenciaRESUMEN
Although individuals carrying the UGT1A1 allele *28 have an increased risk of severe toxicities associated with irinotecan, no phase I study has been conducted based on the polymorphism. This report presents the recommended doses of irinotecan for patients with the respective genotypes. Twenty-seven patients with advanced colorectal cancer were enrolled in this study, and the UGT1A1*28 polymorphism was genotyped before chemotherapy. One course of chemotherapy consisted of irinotecan infused once every 2 weeks at 70, 100, 120, and 150 mg/m(2) at dose levels 1, 2, 3, and 4, respectively, and doxifluridine was administered orally. This treatment continued for at least 12 weeks. The dose-limiting toxicity was determined as grade 3 hematological and non-hematological toxicities for the TA(6)/TA(6) (6/6) and TA(6)/TA(7) (6/7) genotypes. The pharmacokinetics of irinotecan, SN-38, and SN-38 glucuronide, was assessed at dose level 2. Eighteen and nine patients had the 6/6 and 6/7 genotypes, respectively. The maximum tolerated dose (MTD) was not observed up to dose level 4 in patients with the 6/6 genotype. In contrast, MTD was observed at dose level 2 (100 mg/m(2)) in patients with the 6/7 genotype. Patients with the 6/7 genotype had a significantly higher area under the plasma time-concentration curve (0-infinity) SN-38 (P = 0.022) and biliary index (P = 0.030) than those with 6/6. The recommended starting doses of biweekly irinotecan for phase II/III were 150 mg/m(2) for patients with the UGT1A1 6/6 genotype and 70 mg/m(2) for those with the 6/7 genotype, respectively. The gene polymorphism should be considered when determining the precise recommended doses to be administered in phase I studies.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Glucuronosiltransferasa/genética , Polimorfismo Genético , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Femenino , Floxuridina/administración & dosificación , Humanos , Irinotecán , Masculino , Persona de Mediana Edad , Metástasis de la NeoplasiaRESUMEN
A 47-year-old male presented to our Hospital in February 2005 with acute colonic obstruction due to transverse colon cancer. The patient had undergone emergency transverse colectomy with loop colostomy. After stabilization of patient's general condition, a further investigation revealed multiple liver metastases. The patient had a further multidisciplinary management with surgical lateral hepatectomy 10 weeks after the first presentation. Furthermore, radiofrequency ablation (RFA) used for other liver metastases, and likewise chemotherapy with S-1. This patient also had 7 sessions of RFA within 3 years for different liver metastases. In May 2008, CT abdomen revealed metastases surrounding superior mesenteric artery lymph nodes and more of liver metastases. Chemotherapy started in May 2008 till February 2009 with mFOLFOX6+bevacizumab (a total of 16 sessions). In November 2008, liver metastases vanished and lymph nodes had shrunken. In February 2009, we performed stereotactic radiotherapy on the lymph nodes metastases and one more session of mFOLFOX6, He showed no visible abdominal metastases on CT scan. The patient is currently in good health with no residual symptoms. The loco-regional cancer treatment with chemo, radiotherapy, RFA as well as surgery improved patient's survival with advanced colonic cancer and added to a quality of life.
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Colon Transverso , Neoplasias del Colon/patología , Neoplasias Hepáticas/secundario , Metástasis Linfática/patología , Colectomía , Neoplasias del Colon/cirugía , Terapia Combinada , Humanos , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana EdadRESUMEN
We encountered a resected case of advanced gastric cancer after successful chemotherapy. The patient remained alive in good condition without any signs of recurrence at 2 years and 8 months after surgery. The 40-year-old woman initially complained of low abdominal pain, which was diagnosed as gastric cancer with metastasis of ovaries and carcinomatous ascites. We administered TS-1 (100 mg/body/day) for 3 weeks followed by 2-week rest and CDDP (60 mg/body) on the 8th day of one cycle. After 3 cycles of treatment, carcinomatous ascites disappeared and the ovarian lesion was reduced. The patient underwent total gastrectomy, ileocecal resection, cholecystectomy and radical hysterectomy. The antitumor efficacy of the treatment was histologically Grade 2. We administered 17 cycles of TS-1 treatment, and the patient is alive in good condition at this writing. This shows that TS-1 and CDDP may have potent therapeutic efficacy in advanced gastric cancer patients. For the future, the safety and efficacious administration of TS-1 and CDDP should be examined further.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ascitis/etiología , Neoplasias Ováricas/secundario , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Adulto , Ascitis/tratamiento farmacológico , Colecistectomía , Cisplatino/administración & dosificación , Terapia Combinada , Esquema de Medicación , Combinación de Medicamentos , Femenino , Gastrectomía , Humanos , Histerectomía , Íleon/cirugía , Neoplasias Ováricas/cirugía , Ácido Oxónico/administración & dosificación , Inducción de Remisión , Neoplasias Gástricas/cirugía , Tegafur/administración & dosificaciónRESUMEN
A 10-year-old girl with a patent ductus venosus associated with multiple autoimmune disorders presented with hypoxia, cyanosis of her lips, and exertional dyspnea. Ultrasonography and abdominal computed tomography of the liver showed a communication between the portal vein and the inferior vena cava through a patent ductus venosus. Portography showed flow from the portal vein directly into the inferior vena cava via the portosystemic shunt. The portosystemic venous shunt ratio was estimated to be 71.8% by scintigraphy using 123I-IMP. Intraoperatively, the authors diagnosed this portosystemic shunt as patent ductus venosus because of the absence of the ductus venosus on real anatomic position. The portal venous pressure was 8.2 cm H2O, which increased to 17.7 cm H2O when the ductus venosus was temporarily occluded. After surgical ligation of the ductus venosus, the color of liver improved, indicating restored liver circulation. The postoperative course was uneventful, and the patient has been asymptomatic for 6 months.