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1.
J Anus Rectum Colon ; 8(3): 235-245, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39086872

RESUMEN

Objectives: The aim of this study was to identify the microbiota whose decrease in tumor area was associated with the metastatic process of distal colorectal cancer (CRC). Methods: Twenty-eight consecutive patients with distal CRC undergoing surgical resection in our hospital were enrolled. Microbiota in 28 specimens from surgically resected colorectal cancers were analyzed using 16S ribosomal ribonucleic acid gene amplicon sequencing and the relative abundance (RA) of microbiota was evaluated. The densities of tumor-infiltrating lymphocytes (TIL) and tumor associated macrophages (TAM) in the colorectal cancers were immunohistochemically evaluated. Results: Phocaeicola was the most abundant microbiota in normal mucosa. The RA of Phocaeicola in tumor tissues tended to be lower than that in normal mucosa although the difference was not significant (p=0.0732). The RA of Phocaeicola at tumor sites did not correlate either with depth of tumor invasion (pT-stage) or tumor size, however they were significantly reduced in patients with nodal metastases (p<0.05) and those with distant metastases (p<0.001). The RA of Phocaeicola at tumor sites showed positive correlation with the densities of CD3(+) or CD8(+) TIL. Since P. vulgatus was the most dominant species (47%) of the Phocaeicola, the RA of P. vulgatus and CRC metastasis and its association with TIL and TAM were also investigated. P. vulgatus showed a similar trend to genus Phocaeicola but was not statistically significant. Conclusions: A relative reduction of Phocaeicola attenuates the local anti-tumor immune response in distal CRC, which may facilitate metastatic spread.

2.
J Anus Rectum Colon ; 8(3): 259-264, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39086877

RESUMEN

Lateral lymph node (LLN) metastasis in T1 rectal cancer has an incidence of less than 1%. However, its clinical features are largely uncharted. We report a case of LLN metastasis in T1 rectal cancer and review the relevant literature. A 56-year-old female underwent rectal resection for lower rectal cancer 2 years previously (pT1bN0M0). During follow-up, an elevated tumor marker CA19-9 was documented. Enhanced CT and MRI showed a round shape nodule 2 cm in size on the left side of pelvic wall. PET-CT showed high accumulation of FDG in the same lesion, leading to a diagnosis of isolated LLN recurrence. Because no other site of recurrence was detected, surgical resection of the LLN was performed. Microscopic findings were consistent with metastatic lymph node originating from the recent rectal cancer. Adjuvant chemotherapy for six months was given, and patient remains free of recurrent disease seven months after LLN resection. Although LLN recurrence after surgery for T1 rectal cancer is rare, post-surgical follow-up should not be omitted. When LLN metastasis is suspected on CT, MRI and/or PET-CT will be recommended. Surgical resection of LLN metastasis in patients with T1 rectal cancer may lead to favorable outcomes, when recurrence in other areas is not observed.

3.
Cancers (Basel) ; 16(16)2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39199611

RESUMEN

Despite advances in systemic chemotherapy, patients with gastric cancer (GC) and peritoneal metastases (PMs) continue to have poor prognoses. Intraperitoneal (IP) administration of Paclitaxel (PTX) combined with systemic chemotherapy shows promise in treating PMs from GC. However, methods of drug administration need to be optimized to maximize efficacy. In this study, we utilized a mouse model with PMs derived from a human GC cell line, administering PTX either IP or intravenously (IV), and Carboplatin (CBDCA) IV 0, 1, and 4 days after PTX administration. The PMs were resected 30 min later, and concentrations of PTX and CBDCA in resected tumors were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results indicated that PTX concentrations were higher with IP administration than with IV administration, with significant differences observed on days 0 and 1. CBDCA concentrations 4 days post-IP PTX administration were higher than with simultaneous IV PTX administration. These findings suggest that IP PTX administration enhances CBDCA concentration in peritoneal tumors. Therefore, sequential IV administration of anti-cancer drugs appears more effective than simultaneous administration with IP PTX, a strategy that may improve prognoses for patients with PMs.

4.
Transpl Int ; 37: 11336, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38962471

RESUMEN

Segmental grafts from living donors have advantages over grafts from deceased donors when used for small intestine transplantation. However, storage time for small intestine grafts can be extremely short and optimal graft preservation conditions for short-term storage remain undetermined. Secreted factors from mesenchymal stem cells (MSCs) that allow direct activation of preserved small intestine grafts. Freshly excised Luc-Tg LEW rat tissues were incubated in preservation solutions containing MSC-conditioned medium (MSC-CM). Preserved Luc-Tg rat-derived grafts were then transplanted to wild-type recipients, after which survival, injury score, and tight junction protein expression were examined. Luminance for each graft was determined using in vivo imaging. The findings indicated that 30-100 and 3-10 kDa fractions of MSC-CM have superior activating effects for small intestine preservation. Expression of the tight-junction proteins claudin-3, and zonula occludens-1 preserved for 24 h in University of Wisconsin (UW) solution containing MSC-CM with 50-100 kDa, as shown by immunostaining, also indicated effectiveness. Reflecting the improved graft preservation, MSC-CM preloading of grafts increased survival rate from 0% to 87%. This is the first report of successful transplantation of small intestine grafts preserved for more than 24 h using a rodent model to evaluate graft preservation conditions that mimic clinical conditions.


Asunto(s)
Intestino Delgado , Células Madre Mesenquimatosas , Preservación de Órganos , Ratas Endogámicas Lew , Animales , Intestino Delgado/trasplante , Ratas , Preservación de Órganos/métodos , Masculino , Soluciones Preservantes de Órganos , Supervivencia de Injerto , Medios de Cultivo Condicionados , Proteína de la Zonula Occludens-1/metabolismo , Claudina-3/metabolismo , Ratas Transgénicas , Glutatión , Rafinosa , Alopurinol , Insulina , Adenosina
5.
World J Surg ; 48(8): 1912-1920, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38923062

RESUMEN

BACKGROUND: Osteopenia reflects frailty and has been shown to be associated with outcomes in cancer patients. This study was undertaken to examine whether osteopenia is an independent prognostic factor in patients with esophageal cancer after resection. METHODS: A total of 214 patients who underwent surgery for esophageal cancer were analyzed retrospectively. Bone mineral density (BMD) of the 11th thoracic vertebra was measured by computed tomography scan, and patients classified into osteopenia and normal BMD groups with BMD <160 Hounsfield units as the cutoff. Clinicopathological data and prognosis were analyzed. RESULTS: The 5-year survival rate was 55.4% for the osteopenia group and 74.7% for the normal BMD group with a significantly worse prognosis in the osteopenia group (p = 0.0080). In multivariable analysis, osteopenia was a significant independent risk factor associated with overall survival (hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.27-3.34, and p = 0.0151) along with R1/2 resection (HR 3.02, 95% CI 1.71-5.18, and p = 0.0002). CONCLUSION: In patients with esophageal cancer undergoing resection, osteopenia may be a surrogate marker for frailty and an independent predictor of prognosis.


Asunto(s)
Enfermedades Óseas Metabólicas , Neoplasias Esofágicas , Esofagectomía , Humanos , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/complicaciones , Neoplasias Esofágicas/patología , Masculino , Femenino , Enfermedades Óseas Metabólicas/etiología , Enfermedades Óseas Metabólicas/diagnóstico , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Pronóstico , Densidad Ósea , Factores de Riesgo , Tasa de Supervivencia , Periodo Preoperatorio , Tomografía Computarizada por Rayos X , Anciano de 80 o más Años
6.
Cancers (Basel) ; 16(11)2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38893206

RESUMEN

BACKGROUND: Osteopenia is a well-known risk factor for survival in patients with hepatocellular carcinoma; however, it is unclear whether osteopenia can apply to both genders and how osteopenia is associated with cancer progression. The aim of this study was to elucidate whether osteopenia predicts reduced survival in regression models in both genders and whether osteopenia is associated with the pathological factors associated with reduced survival. METHODS: This study included 188 consecutive patients who underwent hepatectomy. Bone mineral density was assessed using computed tomography (CT) scan images taken within 3 months before surgery. Non-contrast CT scan images at the level of the 11th thoracic vertebra were used. The cutoff value of osteopenia was calculated using a threshold value of 160 Hounsfield units. Overall survival (OS) curves and recurrence-free survival (RFS) were constructed using the Kaplan-Meier method, as was a log-rank test for survival. The hazard ratio and 95% confidence interval for overall survival were calculated using Cox's proportional hazard model. RESULTS: In the regression analysis, age predicted bone mineral density. The association in females was greater than that in males. The OS and RFS of osteopenia patients were shorter than those for non-osteopenia patients. According to univariate and multivariate analyses, osteopenia was an independent risk factor for OS and RFS. The sole pathological factor associated with osteopenia was microvascular portal vein invasion. CONCLUSION: Models suggest that osteopenia may predict decreased OS and RFS in patients undergoing resection of hepatocellular carcinoma due to the mechanisms mediated via microvascular portal vein invasion.

7.
Pediatr Transplant ; 28(4): e14599, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38713752

RESUMEN

BACKGROUND: The outcomes after liver transplantation have greatly improved, which has resulted in greater focus on improving non-hepatic outcomes of liver transplantation. The present study aimed to evaluate thoracic spine radio density in children and adolescents after liver transplantation. METHODS: A total of 116 patients who underwent living donor liver transplantation were retrospectively analyzed. The radio density at the eleventh thoracic vertebra was measured using computed tomography scan performed preoperatively then annually for 5 years postoperatively and subsequently every 2 or 3 years. RESULTS: The mean thoracic radio density of male recipients of male grafts had the lowest values during the study. The radio density of patients receiving a graft from a female donor was higher than in recipients with grafts from males. Total mean radio density decreased for first 5 years postoperatively and then increased. Changes in radio density were equally distributed in both steroid withdrawal and no steroid withdrawal groups for 5 years, after which patients with steroid withdrawal had a greater increase. Changes in radio density were equally distributed in both the steroid withdrawal and no steroid withdrawal groups up to age 20, after which patients in the steroid withdrawal group had a greater increase. CONCLUSIONS: Gender differences may affect the outcome of radio density changes after transplantation. Given the moderate association between thoracic radio density and bone mineral density in skeletally mature adults and further studies are needed to validate this relationship between thoracic radio density and bone mineral density changes in pediatric liver transplantation.


Asunto(s)
Densidad Ósea , Trasplante de Hígado , Donadores Vivos , Vértebras Torácicas , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Niño , Estudios Retrospectivos , Adolescente , Preescolar , Vértebras Torácicas/cirugía , Vértebras Torácicas/diagnóstico por imagen , Lactante , Adulto Joven , Resultado del Tratamiento , Factores Sexuales
8.
Sci Rep ; 14(1): 7832, 2024 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-38570542

RESUMEN

The vagus nerve is the only pathway for transmitting parasympathetic signals between the brain and thoracoabdominal organs, thereby exhibiting anti-inflammatory functions through the cholinergic anti-inflammatory pathway. Despite often being resected during lymph node dissection in upper gastrointestinal cancer surgery, the impact of vagotomy on postoperative outcomes in gastric cancer patients remains unclear. Sub-diaphragmatic vagotomy was performed on C57BL/6 mice. Three weeks later, syngeneic murine gastric cancer cell line YTN16P was injected into the peritoneal cavity, and the number of peritoneal metastases (PM) on the mesentery and omentum compared with control mice. The phenotypes of immune cells in peritoneal lavage and omental milky spots one day after tumor inoculation were analyzed using flow cytometry and immunohistochemistry. Intraperitoneal transfer of 3 × 105 YTN16P significantly increased the number of metastatic nodules on the mesentery in the vagotomy group compared to the control group. The omental metastasis grade was also significantly higher in the vagotomy group. Phenotypic analysis of immune cells in peritoneal lavage did not reveal significant differences after vagotomy. However, vagotomized mice exhibited a notable increase in milky spot area, with a higher presence of cytokeratin(+) tumor cells, F4/80(+) macrophages, and CD3(+) T cells. Vagus nerve signaling appears to regulate the immune response dynamics within milky spots against disseminated tumor cells and inhibits the development of PM. Preserving the vagus nerve may offer advantages in advanced gastric cancer surgery to reduce peritoneal recurrence.


Asunto(s)
Neoplasias Peritoneales , Neoplasias Gástricas , Humanos , Ratones , Animales , Neoplasias Peritoneales/secundario , Neoplasias Gástricas/patología , Ratones Endogámicos C57BL , Epiplón/patología , Nervio Vago/cirugía , Nervio Vago/patología
9.
J Breast Cancer ; 27(2): 121-129, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38529589

RESUMEN

This study investigated the clinical effect of metformin on breast cancer patients with preexisting type 2 diabetes mellitus (T2DM). We analyzed 177 patients with T2DM who underwent breast cancer surgery and assessed tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs) in patients who underwent tumor resection with or without metformin treatment using multiplex immunohistochemistry (IHC). Patients who received metformin either pre- or postoperatively exhibited reduced distant organ recurrence and improved postoperative recurrence-free survival compared to those of patients who did not. Additionally, in a subgroup of 40 patients receiving preoperative systemic therapy, metformin treatment was associated with increased rates of pathological complete response. IHC analysis revealed significantly lower levels of cluster of differentiation (CD) 68(+) CD163(+) M2-type TAMs (p < 0.01) but higher CD3(+) and CD8(+) TIL densities in the metformin-treated group compared with the same parameters in those without metformin treatment, with a significant difference in the CD8(+)/CD3(+) TIL ratio (p < 0.01). Despite the constraints posed by our small sample size, our findings suggest a potential role for metformin in modulating the immunological microenvironment, which may contribute to improved outcomes in diabetes patients with breast cancer.

10.
Sci Rep ; 14(1): 4496, 2024 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-38402307

RESUMEN

The spleen is a key source of circulating and tumor-infiltrating immune cells. However, the effect of splenectomy on tumor growth remains unclear. At 3 weeks after splenectomy, we subcutaneously injected LuM1 cells into BALB/c mice and evaluated the growth of primary tumors and lung metastases at 4 weeks after tumor inoculation. In addition, we examined the phenotypes of immune cells in peripheral blood by using flow cytometry and in tumor tissue by using multiplex immunohistochemistry. The growth of primary tumors was reduced in splenectomized mice compared with the sham-operated group. Conversely, splenectomized mice had more lung metastases. Splenectomized mice had fewer CD11b+cells, especially monocytic MDSCs (CD11b+Gr-1neg-lowLy6chigh), and NK cells (CD49b+CD335+). The proportion of NK cells was inversely correlated with the number of lung metastases. In splenectomized mice, the density of CD3+ and granzyme B+ CD8+ T cells was increased, with fewer M2-type macrophages in primary tumors, but NK cells were decreased markedly in lung. Splenectomy concurrently enhances T cell-mediated acquired immunity by reducing the number of monocytic MDSCs and suppresses innate immunity by decreasing the number of NK cells. Splenectomy has opposite effects on primary and metastatic lesions through differential regulation on these two immune systems.


Asunto(s)
Neoplasias del Colon , Neoplasias Pulmonares , Ratones , Animales , Esplenectomía , Linfocitos T CD8-positivos , Células Asesinas Naturales , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Neoplasias del Colon/patología
11.
Sci Rep ; 14(1): 4605, 2024 02 26.
Artículo en Inglés | MEDLINE | ID: mdl-38409241

RESUMEN

Intestinal adaptation does not necessarily recover absorptive capacity in short bowel syndrome (SBS), sometimes resulting in intestinal failure-associated liver disease (IFALD). Additionally, its therapeutic options remain limited. Polyamines (spermidine and spermine) are known as one of the autophagy inducers and play important roles in promoting the weaning process; however, their impact on intestinal adaptation is unknown. The aim of this study was to investigate the impact of polyamines ingestion on adaptation and hepatic lipid metabolism in SBS. We performed resection of two-thirds of the small intestine in male Lewis rats as an SBS model. They were allocated into three groups and fed different polyamine content diets (0%, 0.01%, 0.1%) for 30 days. Polyamines were confirmed to distribute to remnant intestine, whole blood, and liver. Villous height and number of Ki-67-positive cells in the crypt area increased with the high polyamine diet. Polyamines increased secretory IgA and mucin content in feces, and enhanced tissue Claudin-3 expression. In contrast, polyamines augmented albumin synthesis, mitochondrial DNA copy number, and ATP storage in the liver. Moreover, polyamines promoted autophagy flux and activated AMP-activated protein kinase with suppression of lipogenic gene expression. Polyamines ingestion may provide a new therapeutic option for SBS with IFALD.


Asunto(s)
Síndrome del Intestino Corto , Ratas , Animales , Masculino , Síndrome del Intestino Corto/metabolismo , Poliaminas/metabolismo , Ratas Sprague-Dawley , Ratas Endogámicas Lew , Intestino Delgado/metabolismo , Dieta , Modelos Teóricos , Mucosa Intestinal/metabolismo
12.
J Thorac Dis ; 16(1): 391-400, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38410613

RESUMEN

Background: Adjuvant nivolumab therapy has become the standard therapy for patients with localized advanced esophageal cancer with non-pathological complete response after neoadjuvant chemoradiotherapy followed by curative surgery. However, the necessity of this therapy for patients after neoadjuvant chemotherapy (NAC) with docetaxel, cisplatin, and 5-fluorouracil (DCF) regimen followed by surgery is unclear, and the prognosis of grouping based on the presence or absence of pathological tumor and lymph node findings has not been analyzed. Therefore, our study aimed to address these questions. Methods: This retrospective cohort study included patients with cT1N1-3M0 and cT2-3N0-3M0 esophageal cancer according to the Japanese Classification of Esophageal Cancer, 11th edition, who received NAC with DCF followed by curative surgery between 2008 and 2020 at Jichi Medical University Hospital. We divided patients with ypT0-3N0-3M0 into four histological groups, namely ypT0N0, ypT+N0, ypT0N+, and ypT+N+, and we evaluated overall survival as the primary outcome and the prognostic relationship of lymph node metastasis as the secondary outcome. Results: A total of 101 patients were included in this study. Kaplan-Meier analysis showed that the curves of the ypT0N0 and ypT+N0 groups were almost identical, while they differed from the other two groups. The hazard ratio of ypN+ was 4.44 (95% confidence interval: 2.03-9.71; P<0.001). Conclusions: The prognosis of the ypT+N0 group after NAC with DCF followed by surgery was similar to that of pathological complete remission. Grouping patients according to pathological lymph node status is a reasonable predictor of prognosis.

14.
Ann Surg Oncol ; 31(2): 735-743, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37952018

RESUMEN

BACKGROUND: Intraperitoneal chemotherapy is promising for gastric cancer with peritoneal metastasis. Although a phase III study failed to show a statistically significant superiority of intraperitoneal paclitaxel combined with S-1 and intravenous paclitaxel, the sensitivity analysis suggested clinical efficacy. Thus, attempts to combine intraperitoneal paclitaxel with other systemic therapies with higher efficacy have been warranted. We sought to explore the efficacy of intraperitoneal paclitaxel with S-1 and cisplatin. PATIENTS AND METHODS: Gastric cancer patients with peritoneal metastasis were enrolled in the phase II trial. In addition to the established S-1 and cisplatin regimen every 5 weeks, intraperitoneal paclitaxel was administered on days 1, 8, and 22 at a dose of 20 mg/m2. The primary endpoint was overall survival rate at 1 year after treatment initiation. Secondary endpoints were progression-free survival and toxicity. RESULTS: Fifty-three patients were enrolled and fully evaluated for efficacy and toxicity. The 1-year overall survival rate was 73.6% (95% confidence interval 59.5-83.4%), and the primary endpoint was met. The median survival time was 19.4 months (95% confidence interval, 16.1-24.6 months). The 1-year progression-free survival rate was 49.6% (95% confidence interval, 34.6-62.9%). The incidences of grade 3/4 hematological and non-hematological toxicities were 43% and 47%, respectively. The frequent grade 3/4 toxicities included neutropenia (25%), anemia (30%), diarrhea (13%), and anorexia (17%). Intraperitoneal catheter and implanted port-related complications were observed in four patients. There was one treatment-related death. CONCLUSIONS: Intraperitoneal paclitaxel combined with S-1 and cisplatin is well tolerated and active in gastric cancer patients with peritoneal metastasis.


Asunto(s)
Neoplasias Peritoneales , Neoplasias Gástricas , Humanos , Cisplatino , Neoplasias Gástricas/patología , Paclitaxel , Neoplasias Peritoneales/secundario , Protocolos de Quimioterapia Combinada Antineoplásica
15.
Intern Med ; 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38044154

RESUMEN

The prognosis of patients with peritoneal metastases from pancreatic cancer is poor, largely due to massive ascites, which precludes systemic treatment. Two patients with a poor performance status and malignant ascites were treated with cell-free and concentrated ascites reinfusion therapy followed by combined chemotherapy with intraperitoneal paclitaxel, intravenous gemcitabine, and nab-paclitaxel. These patients achieved a survival of 19 and 36 weeks with a relatively good quality of life. Combined intraperitoneal paclitaxel and systemic chemotherapy may provide effective palliative management for some patients with peritoneal metastases from pancreatic cancer.

16.
Sci Rep ; 13(1): 15637, 2023 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-37731041

RESUMEN

It is important to assess the prognosis and intervene before and after surgery in patients with hepatocellular carcinoma. This study aims to elucidate the association of outcomes and residual liver function after hepatectomy. A total of 176 patients who underwent the initial resection for hepatocellular carcinoma between January 2011 and March 2021 at Jichi Medical University were included. Hepatic clearance of the remnant liver was measured using 99mTc-galactosyl serum albumin scintigraphy. The log-rank test was used to analyze survival using the Kaplan-Meier method. Hazard ratios (HR) and 95% confidence intervals (CI) for overall survival were calculated using Cox's proportional hazard model. In multivariate analysis, microvascular invasion, intraoperative blood loss, and hepatic clearance of the remnant liver were independently associated with overall survival. Hepatic clearance of the remnant liver was independently associated with recurrence free survival. This is the first report to show that lower residual liver function is associated with shorter survival in patients with hepatocellular carcinoma undergoing hepatectomy. Preoperative determination of remnant liver function may allow assessment of prognosis in patients planned to undergo resection of hepatocellular carcinoma. Preservation of liver functional reserve may be crucial for improved long-term outcomes after hepatectomy.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Hepatectomía , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/cirugía , Pérdida de Sangre Quirúrgica
17.
Pharmaceutics ; 15(6)2023 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-37376112

RESUMEN

Despite remarkable recent progress in developing anti-cancer agents, outcomes of patients with solid tumors remain unsatisfactory. In general, anti-cancer drugs are systemically administered through peripheral veins and delivered throughout the body. The major problem with systemic chemotherapy is insufficient uptake of intravenous (IV) drugs by targeted tumor tissue. Although dose escalation and treatment intensification have been attempted in order to increase regional concentrations of anti-tumor drugs, these approaches have produced only marginal benefits in terms of patient outcomes, while often damaging healthy organs. To overcome this problem, local administration of anti-cancer agents can yield markedly higher drug concentrations in tumor tissue with less systemic toxicity. This strategy is most commonly used for liver and brain tumors, as well as pleural or peritoneal malignancies. Although the concept is theoretically reasonable, survival benefits are still limited. This review summarizes clinical results and problems and discusses future directions of regional cancer therapy with local administration of chemotherapeutants.

18.
Int J Colorectal Dis ; 38(1): 173, 2023 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-37340243

RESUMEN

BACKGROUND: The safety of intraperitoneally administrated paclitaxel (op PTX) was demonstrated in the phase I trial of ip PTX combined with conventional systemic chemotherapy for colorectal cancer with peritoneal carcinomatosis. Moreover, the median survival time was 29.3 months, which was longer than that observed in previous studies. Here, we planned the phase II trial of ip PTX: the iPac-02 trial. METHODS: This multicenter, open-label, single assignment interventional clinical study includes patients with colorectal cancer with unresectable peritoneal carcinomatosis. FOLFOX-bevacizumab or CAPOX-bevacizumab is administered concomitantly as systemic chemotherapy. PTX 20 mg/m2 is administered weekly through the peritoneal access port in addition to these conventional systemic chemotherapies. The response rate is the primary endpoint. Progression-free survival, overall survival, peritoneal cancer index improvement rate, rate of negative peritoneal lavage cytology, safety, and response rate to peritoneal metastases are the secondary endpoints. A total of 38 patients are included in the study. In the interim analysis, the study will continue to the second stage if at least 4 of the first 14 patients respond to the study treatment. The study has been registered at the Japan Registry of Clinical Trials (jRCT2031220110). RESULTS: We previously conducted phase I trial of ip PTX combined with conventional systemic chemotherapy for colorectal cancer with peritoneal carcinomatosis [1]. In the study, three patients underwent mFOLFOX, bevacizumab, and weekly ip PTX, and the other three patients underwent CAPOX, bevacizumab, and weekly ip PTX treatment. The dose of PTX was 20 mg/m [2]. The primary endpoint was the safety of the chemotherapy, and secondary endpoints were response rate, peritoneal cancer index improvement rate, rate of negative peritoneal lavage cytology, progression-free survival, and overall survival. Dose limiting toxicity was not observed, and the adverse events of ip PTX combined with oxaliplatin-based systemic chemotherapy were similar to those described in previous studies using systemic chemotherapy alone [3, 4]. The response rate was 25%, peritoneal cancer index improvement rate was 50%, and cytology in peritoneal lavage turned negative in all the cases. The progression-free survival was 8.8 months (range, 6.8-12 months), and median survival time was 29.3 months [5], which was longer than that observed in previous studies. CONCLUSION: Here, we planned the phase II trial of ip paclitaxel combined with conventional chemotherapy for colorectal cancer with peritoneal carcinomatosis: the iPac-02 trial.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Peritoneales , Humanos , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/secundario , Bevacizumab/uso terapéutico , Paclitaxel/uso terapéutico , Neoplasias Colorrectales/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase II como Asunto
19.
Breast Cancer ; 30(4): 531-540, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37058224

RESUMEN

Various surgical energy devices are used for axillary lymph-node dissection. However, those that reduce seroma during axillary lymph-node dissection are unknown. We aimed to determine the best surgical energy device for reducing seroma by performing a network meta-analysis to synthesize the current evidence on the effectiveness of surgical energy devices for axillary node dissection for breast cancer patients. We searched MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and World Health Organization International Clinical Trials Platform Search Portal. Two reviewers independently selected randomized controlled trials (RCTs) comparing electrosurgical bipolar vessel sealing (EBVS), ultrasonic coagulation shears (UCS), and conventional techniques for axillary node dissection. Primary outcomes were seroma, drained fluid volume (mL), and drainage duration (days). We analyzed random-effects and Bayesian network meta-analyses. We evaluated the confidence of each outcome using the CINeMA tool. We registered with PROSPERO (CRD42022335434). We included 34 RCTs with 2916 participants. Compared to the conventional techniques, UCS likely reduces seroma (risk ratio [RR], 0.61; 95% credible interval [CrI], 0.49-0.73), the drained fluid volume (mean difference [MD], - 313 mL; 95% CrI - 496 to - 130), and drainage duration (MD - 1.79 days; 95% CrI - 2.91 to - 0.66). EBVS might have little effect on seroma, the drained fluid volume, and drainage duration compared to conventional techniques. UCS likely reduce seroma (RR 0.44; 95% CrI 0.28-0.69) compared to EBVS. Confidence levels were low to moderate. In conclusion, UCS are likely the best surgical energy device for seroma reduction during axillary node dissection for breast cancer patients.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Metaanálisis en Red , Neoplasias de la Mama/cirugía , Seroma/etiología , Seroma/prevención & control , Seroma/cirugía , Escisión del Ganglio Linfático/efectos adversos , Escisión del Ganglio Linfático/métodos , Drenaje/métodos , Axila
20.
Cancer Sci ; 114(7): 2939-2950, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36939028

RESUMEN

Small extracellular vesicles (sEV) contain various microRNAs (miRNAs) and play crucial roles in the tumor metastatic process. Although miR-29b levels in peritoneal exosomes were markedly reduced in patients with peritoneal metastases (PM), their role has not been fully clarified. In this study, we asked whether the replacement of miR-29b can affect the development of PM in a murine model. UE6E7T-12, human bone marrow-derived mesenchymal stem cells (BMSCs), were transfected with miR-29b-integrating recombinant lentiviral vector and sEV were isolated from culture supernatants using ultracentrifugation. The sEV contained markedly increased amounts of miR-29b compared with negative controls. Treatment with transforming growth factor-ß1 decreased the expression of E-cadherin and calretinin with increased expression of vimentin and fibronectin on human omental tissue-derived mesothelial cells (HPMCs). However, the effects were totally abrogated by adding miR-29b-rich sEV. The sEV inhibited proliferation and migration of HPMCs by 15% (p < 0.005, n = 6) and 70% (p < 0.005, n = 6), respectively, and inhibited adhesion of NUGC-4 and MKN45 to HPMCs by 90% (p < 0.0001, n = 5) and 77% (p < 0.0001, n = 5), respectively. MicroRNA-29b-rich murine sEV were similarly obtained using mouse BMSCs and examined for in vivo effects with a syngeneic murine model using YTN16P, a highly metastatic clone of gastric cancer cell. Intraperitoneal (IP) transfer of the sEV every 3 days markedly reduced the number of PM from YTN16P in the mesentery (p < 0.05, n = 6) and the omentum (p < 0.05, n = 6). Bone marrow mesenchymal stem cell-derived sEV are a useful carrier for IP administration of miR-29b, which can suppress the development of PM of gastric cancer.


Asunto(s)
Exosomas , Vesículas Extracelulares , MicroARNs , Neoplasias Peritoneales , Neoplasias Gástricas , Animales , Humanos , Ratones , Modelos Animales de Enfermedad , Exosomas/metabolismo , Vesículas Extracelulares/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Peritoneales/genética , Neoplasias Peritoneales/metabolismo , Neoplasias Gástricas/patología
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