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Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive cancer with striking fibrosis, and its mortality rate is ranked second across human cancers. Cancer-associated fibroblasts (CAFs) play a critical role in PDAC progression, and we reviewed the molecular understanding of PDAC CAFs and novel therapeutic potential at present. CAFs-associated genes (CAFGs) were tentatively classified into three categories by stroma specificity representing stroma/epithelia expression ratios (SE ratios). The recent classification using single cell transcriptome technology clarified that CAFs were composed of myofibroblasts (myCAFs), inflammatory CAFs (iCAFs), and other minor ones (e.g., POSTN-CAFs and antigen presenting CAFs, apCAFs). LRRC15 is a myCAFs marker, and myCAFs depletion by diphtheria toxin induces the rapid accumulation of cytotoxic T lymphocytes (CTLs) and therefore augment PDL1 antibody treatments. This finding proposes that myCAFs may be a critical regulator of tumor immunity in terms of PDAC progression. myCAFs are located in CAFs adjacent to tumor cells, while iCAFs marked by PDPN and/or COL14A1 are distant from tumor cells, where hypoxic and acidic environments being located in iCAFs putatively due to poor blood supply is consistent with HIF1A and GPR68 expressions. iCAFs may be shared with SASP (secretion-associated phenotypes) in senescent CAFs. myCAFs are classically characterized by CAFGs induced by TGFB1, while chemoresistant CAFs with SASP may dependent on IL6 expression and accompanied by STAT3 activation. Recently, it was found that the unique metabolism of CAFs can be targeted to prevent PDAC progression, where PDAC cells utilize glucose, whereas CAFs in turn utilize lactate, which may be epigenetically regulated, mediated by its target genes including CXCR4. In summary, CAFs have unique molecular characteristics, which have been rigorously clarified as novel therapeutic targets of PDAC progression.
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Fibroblastos Asociados al Cáncer , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/terapia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Regulación Neoplásica de la Expresión Génica , Microambiente Tumoral/genética , AnimalesRESUMEN
Comprehensive understanding prognostic relevance of distinct tumor microenvironment (TME) remained elusive in colon cancer. In this study, we performed in silico analysis of the stromal components of primary colon cancer, with a focus on the markers of cancer-associated fibroblasts (CAF) and tumor-associated endothelia (TAE), as well as immunological infiltrates like tumor-associated myeloid cells (TAMC) and cytotoxic T lymphocytes (CTL). The relevant CAF-associated genes (CAFG)(representing R index = 0.9 or beyond with SPARC) were selected based on stroma specificity (cancer stroma/epithelia, cS/E = 10 or beyond) and expression amounts, which were largely exhibited negative prognostic impacts. CAFG were partially shared with TAE-associated genes (TAEG)(PLAT, ANXA1, and PTRF) and TAMC-associated genes (TAMCG)(NNMT), but not with CTL-associated genes (CTLG). Intriguingly, CAFG were prognostically subclassified in order of fibrosis (representing COL5A2, COL5A1, and COL12A1) followed by exclusive TAEG and TAMCG. Prognosis was independently stratified by CD8A, a CTL marker, in the context of low expression of the strongest negative prognostic CAFG, COL8A1. CTLG were comprehensively identified as IFNG, B2M, and TLR4, in the group of low S/E, representing good prognosis. Our current in silico analysis of the micro-dissected stromal gene signatures with prognostic relevance clarified comprehensive understanding of clinical features of the TME and provides deep insights of the landscape.
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Fibroblastos Asociados al Cáncer , Neoplasias del Colon , Humanos , Fibroblastos Asociados al Cáncer/metabolismo , Pronóstico , Neoplasias del Colon/patología , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND & AIMS: Despite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases of nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs. METHODS: In this Japanese multicenter study, data were retrospectively collected from patients who underwent pancreatectomy between January 1996 and December 2019, were pathologically diagnosed with pNEN, and were treated according to the World Health Organization 2019 classification. Overall, 1490 patients met the eligibility criteria, and 1014 were included in the analysis cohort. RESULTS: In the analysis cohort, 606 patients (59.8%) had NF-spNENs, with 82% classified as grade 1 (NET-G1) and 18% as grade 2 (NET-G2) or higher. The incidence of lymph node metastasis (N1) by grade was significantly higher in NET-G2 (G1: 3.1% vs G2: 15.0%). Independent factors contributing to N1 were NET-G2 or higher and tumor diameter ≥15 mm. The predictive ability of tumor size for N1 was high. Independent factors contributing to recurrence included multiple lesions, NET-G2 or higher, tumor diameter ≥15 mm, and N1. However, the independent factor contributing to survival was tumor grade (NET-G2 or higher). The appropriate timing for surgical resection of NET-G1 and NET-G2 or higher was when tumors were >20 and >10 mm, respectively. For neoplasms with unknown preoperative grades, tumor size >15 mm was considered appropriate. CONCLUSIONS: NF-spNENs are heterogeneous with varying levels of malignancy. Therefore, treatment strategies based on tumor size alone can be unreliable; personalized treatment strategies that consider tumor grading are preferable.
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Pancreatectomía , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/mortalidad , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Japón/epidemiología , Adulto , Tumores Neuroendocrinos/cirugía , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/terapia , Tumores Neuroendocrinos/diagnóstico , Anciano de 80 o más Años , Metástasis Linfática , Clasificación del Tumor , Carga TumoralRESUMEN
BACKGROUND: Previously, we reported SMR (skeletal muscle radiodensity) as a potential prognostic marker for colorectal cancer. However, there have been limited studies on the association between SMR and the continuation of adjuvant chemotherapy in colorectal cancer. METHODS: In this retrospective study, 143 colorectal cancer patients underwent curative surgery and adjuvant chemotherapy using the CAPOX regimen. Patients' SMRs were measured from preoperative CT images and divided into low (bottom quarter) and high (top three quarters) SMR groups. We compared chemotherapy cycles, capecitabine and oxaliplatin doses, and adverse effects in each group. RESULTS: The low SMR group had significantly fewer patients completing adjuvant chemotherapy compared to the high SMR group (44% vs. 68%, P < 0.01). Capecitabine and oxaliplatin doses were also lower in the low SMR group. Incidences of Grade 2 or Grade 3 adverse effects did not differ between groups, but treatment discontinuation due to adverse effects was significantly higher in the low SMR group. Logistic regression analysis revealed Stage III disease (odds ratio 18.09, 95% CI 1.41-231.55) and low SMR (odds ratio 3.26, 95% CI 1.11-9.56) as factors associated with unsuccessful treatment completion. Additionally, a higher proportion of low SMR patients received fewer than 2 cycles of chemotherapy (50% vs. 12%). CONCLUSION: The low SMR group showed higher treatment incompletion rates and received lower drug doses during adjuvant chemotherapy. Low SMR independently contributed to treatment non-completion in colorectal cancer patients.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorrectales , Humanos , Capecitabina/efectos adversos , Oxaliplatino/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Quimioterapia Adyuvante/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Colorrectales/patología , Fluorouracilo/efectos adversos , Estadificación de NeoplasiasRESUMEN
BACKGROUND/PURPOSE: The aim of this study was to clarify the clinical characteristics of acute cholangitis (AC) after bilioenteric anastomosis and stent-related AC in a multi-institutional retrospective study, and validate the TG18 diagnostic performance for various type of cholangitis. METHODS: We retrospectively reviewed 1079 AC patients during 2020, at 16 Tokyo Guidelines 18 (TG 18) Core Meeting institutions. Of these, the post-biliary reconstruction associated AC (PBR-AC), stent-associated AC (S-AC) and common AC (C-AC) were 228, 307, and 544, respectively. The characteristics of each AC were compared, and the TG18 diagnostic performance of each was evaluated. RESULTS: The PBR-AC group showed significantly milder biliary stasis compared to the C-AC group. Using TG18 criteria, definitive diagnosis rate in the PBR-AC group was significantly lower than that in the C-AC group (59.6% vs. 79.6%, p < .001) because of significantly lower prevalence of TG 18 imaging findings and milder bile stasis. In the S-AC group, the bile stasis was also milder, but definitive-diagnostic rate was significantly higher (95.1%) compared to the C-AC group. The incidence of transient hepatic attenuation difference (THAD) and pneumobilia were more frequent in PBR-AC than that in C-AC. The definitive-diagnostic rate of PBR-AC (59.6%-78.1%) and total cohort (79.6%-85.3%) were significantly improved when newly adding these items to TG18 diagnostic imaging findings. CONCLUSIONS: The diagnostic rate of PBR-AC using TG18 is low, but adding THAD and pneumobilia to TG imaging criteria may improve TG diagnostic performance.
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Colangitis , Colestasis , Humanos , Estudios Retrospectivos , Tokio , Colangitis/diagnóstico por imagen , Colangitis/etiología , Colangitis/cirugía , Anastomosis Quirúrgica/efectos adversos , StentsRESUMEN
BACKGROUND: It has been reported that weight loss or lean body mass (LBM) loss after gastrectomy for gastric cancer is associated with prognosis and nutritional support alone is insufficient to prevent LBM loss. Branched-chain amino acids (BCAA) play an important role in muscle catabolism, however their clinical effects on suppression of LBM loss in gastric cancer patients undergoing gastrectomy remains elusive. In this current study, we investigated the effect of our original PPN regimen including BCAA (designated to BCAA-regimen) on LBM loss. METHODS: We conducted a randomized controlled trial (RCT) at a single institution where patients undergoing gastrectomy were assigned to either receive a five-day early postoperative course of the BCAA-regimen (BCAA group) or conventional nutrition. The primary endpoint was the % reduction in LBM at postoperative day 7. The secondary endpoints included the % reduction in LBM at 1 and 3 months postsurgery. RESULTS: At postoperative day 7, LBM loss in the BCAA group tended to be lower than in the control group (0.16% vs. 1.7%, respectively; P = 0.21), while at 1 month postsurgery, LBM loss in the BCAA group was significantly different to that of the control group (- 0.3% vs. 4.5%, respectively; P = 0.04). At 3 months postgastrectomy, however, LBM loss was similar between the BCAA and the control groups. CONCLUSION: Our RCT clinical trial clarified that early administration of the postoperative BCAA regimen improved LBM loss at 1 month after surgery in gastric cancer patients undergoing gastrectomy.
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Aminoácidos de Cadena Ramificada , Gastrectomía , Complicaciones Posoperatorias , Neoplasias Gástricas , Pérdida de Peso , Humanos , Aminoácidos de Cadena Ramificada/administración & dosificación , Gastrectomía/efectos adversos , Estado Nutricional , Neoplasias Gástricas/cirugía , Pérdida de Peso/efectos de los fármacos , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & controlRESUMEN
BACKGROUND: CD44 and CD133 are stem cell markers in colorectal cancer (CRC). CD44 has distinctive isoforms with different oncological properties like total CD44 (CD44T) and variant CD44 (CD44V). Clinical significance of such markers remains elusive. METHODS: Sixty colon cancer were examined for CD44T/CD44V and CD133 at mRNA level in a quantitative PCR, and clarified for their association with clinicopathological factors. RESULTS: (1) Both CD44T and CD44V showed higher expression in primary colon tumors than in non-cancerous mucosas (p<0.0001), while CD133 was expressed even in non-cancerous mucosa and rather decreased in the tumors (p = 0.048). (2) CD44V expression was significantly associated with CD44T expression (R = 0.62, p<0.0001), while they were not correlated to CD133 at all in the primary tumors. (3) CD44V/CD44T expressions were significantly higher in right colon cancer than in left colon cancer (p = 0.035/p = 0.012, respectively), while CD133 expression were not (p = 0.20). (4) In primary tumors, unexpectedly, CD44V/CD44T/CD133 mRNA expressions were not correlated with aggressive phenotypes, but CD44V/CD44T rather significantly with less aggressive lymph node metastasis/distant metastasis (p = 0.040/p = 0.039, respectively). Moreover, both CD44V and CD133 expressions were significantly decreased in liver metastasis as compared to primary tumors (p = 0.0005 and p = 0.0006, respectively). CONCLUSION: Our transcript expression analysis of cancer stem cell markers did not conclude that their expression could represent aggressive phenotypes of primary and metastatic tumors, and rather represented less demand on stem cell marker-positive cancer cells.
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Neoplasias del Colon , Neoplasias Hepáticas , Humanos , Receptores de Hialuranos/genética , Receptores de Hialuranos/metabolismo , Neoplasias del Colon/patología , Isoformas de Proteínas/genética , Células Madre Neoplásicas/metabolismo , Neoplasias Hepáticas/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Antígeno AC133/genética , Antígeno AC133/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismoRESUMEN
The benefits of robot-assisted laparoscopic surgery (RALS) for rectal cancer remain controversial. Only a few studies have evaluated the safety and feasibility of RALS following neoadjuvant chemoradiotherapy (NCRT). This study aimed to compare the short-term outcomes of RALS versus conventional laparoscopic surgery (CLS) after NCRT for rectal cancer. Propensity score matching of 111 consecutive patients who underwent RALS or CLS after NCRT for rectal adenocarcinoma between February 2014 and February 2022 was performed. Among them, 60 matched patients were enrolled and their short-term outcomes were compared. Although operative time, conversion rate to open laparotomy and blood loss were comparable, the incidence of postoperative complications, including anastomotic leakage, was significantly lower, urinary retention tended to be lower, and the days to soft diet intake and postoperative hospital stay were significantly shorter in the RALS than the CLS group. No postoperative mortality was observed in either group, and there were no significant differences in terms of resection margins and number of lymph nodes dissected. RALS after NCRT for rectal cancer is safe and technically feasible, and has acceptable short-term outcomes. Further studies are required for validation of the long-term oncological outcomes.
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Laparoscopía , Neoplasias del Recto , Procedimientos Quirúrgicos Robotizados , Robótica , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Terapia Neoadyuvante , Resultado del Tratamiento , Puntaje de Propensión , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Estudios Retrospectivos , QuimioradioterapiaRESUMEN
OBJECTIVE: The aim of this study was to investigate the safety and survival benefits of portal vein and/or superior mesenteric vein (PV/SMV) resection with jejunal vein resection (JVR) for pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA: Few studies have shown the surgical outcome and survival of pancreatic resection with JVR, and treatment strategies for patients with PDAC suspected of jejunal vein (JV) infiltration remain unclear. METHODS: In total, 1260 patients who underwent pancreatectomy with PV/ SMV resection between 2013 and 2016 at 50 facilities were included; treatment outcomes were compared between the PV/SMV group (PV/ SMV resection without JVR; n = 824), PV/SMV-J1 V group (PV/SMV resection with first jejunal vein resection; n = 394), and PV/SMV-J2,3 V group (PV/SMV resection with second jejunal vein or later branch resection; n = 42). RESULTS: Postoperative complications and mortality did not differ between the three groups. The postoperative complication rate associated with PV/ SMV reconstruction was 11.9% in PV/SMV group, 8.6% in PV/SMV-J1 V group, and 7.1% in PV/SMV-J2,3V group; there were no significant differences among the three groups. Overall survival did not differ between PV/SMV and PV/SMV-J1 V groups (median survival; 29.2 vs 30.9 months, P = 0.60). Although PV/SMV-J2,3 V group had significantly shorter survival than PV/SMV group who underwent upfront surgery ( P = 0.05), no significant differences in overall survival of patients who received preoperative therapy. Multivariate survival analysis revealed that adjuvant therapy and R0 resection were independent prognostic factors in all groups. CONCLUSION: PV/SMV resection with JVR can be safely performed and may provide satisfactory overall survival with the pre-and postoperative adjuvant therapy.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Pancreatectomía , Vena Porta/cirugía , Vena Porta/patología , Venas Mesentéricas/cirugía , Pancreaticoduodenectomía , Resultado del Tratamiento , Complicaciones Posoperatorias/cirugía , Estudios Retrospectivos , Neoplasias PancreáticasRESUMEN
The patient was a male in his 60s who presented with obstructive jaundice and was diagnosed with pancreatic head cancer. He was referred to the Department of Surgery 2 months later due to prolonged jaundice and immediately underwent pylorus-preserving pancreatoduodenectomy with the diagnosis of resectable pancreatic cancer. Pathology showed pN1b (14/37), but 16b1 interaorticocaval was 0/1. The patient was then diagnosed with Stage â ¡B, R0. After completion of adjuvant chemotherapy with S-1, 1 year after surgery, CA19-9 was reelevated and PET/CT-positive enlarged lateroaortic lymph nodes and multiple nodules in both lungs were observed. The lymph nodes were also seen on preoperative CT, and the preoperative diagnosis was Stage â £. After insertion of an implantable central venous port, mFOLFIRINOX therapy was initiated. The patient had an anaphylactic reaction after 7 courses of L-OHP, and the treatment was continued without L-OHP. After 40 courses of mFOLFIRINOX therapy, the aortic lymph nodes reduced in size, PET results were negative, and the pulmonary nodules partially resolved. We report a case of a patient with Stage â £ pancreatic head cancer who maintained PR for more than 1 year and 7 months after the initiation of mFOLFIRINOX therapy and survived for more than 2 years and 10 months since the initial diagnosis.
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Neoplasias Pancreáticas , Tomografía Computarizada por Tomografía de Emisión de Positrones , Antígeno CA-19-9 , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos , Metástasis Linfática , Masculino , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/cirugía , Neoplasias PancreáticasRESUMEN
Whether albumin and bilirubin levels, platelet counts, ALBI, and ALPlat scores could be useful for the assessment of permanent liver functional deterioration after repeat liver resection was examined, and the deterioration after laparoscopic procedure was evaluated. For 657 patients with liver resection of segment or less in whom results of plasma albumin and bilirubin levels and platelet counts before and 3 months after surgery could be retrieved, liver functional indicators were compared before and after surgery. There were 268 patients who underwent open repeat after previous open liver resection, and 224 patients who underwent laparoscopic repeat after laparoscopic liver resection. The background factors, liver functional indicators before and after surgery and their changes were compared between both groups. Plasma levels of albumin (p = 0.006) and total bilirubin (p = 0.01) were decreased, and ALBI score (p = 0.001) indicated worse liver function after surgery. Laparoscopic group had poorer preoperative performance status and liver function. Changes of liver functional values before and after surgery and overall survivals were similar between laparoscopic and open groups. Plasma levels of albumin and bilirubin and ALBI score could be the indicators for permanent liver functional deterioration after liver resection. Laparoscopic group with poorer conditions showed the similar deterioration of liver function and overall survivals to open group.
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INTRODUCTION: Whether rectal cancer surgery by robotic-assisted laparoscopic surgery provides beneficial advantages remains controversial. Although favorable outcomes in terms of the safety and technical feasibility of robotic-assisted laparoscopic surgery have been demonstrated for rectal cancer, long-term oncological outcomes for robotic-assisted laparoscopic surgery have only been examined in a few studies. This retrospective study of subjects who underwent robotic-assisted laparoscopic surgery evaluated short- and long-term outcomes of consecutive rectal cancer patients. METHODS: Between November 2016 and January 2020, we analyzed the records of 62 consecutive patients who underwent robotic-assisted laparoscopic surgery for rectal adenocarcinoma without distant metastasis to evaluate short- and long-term outcomes. RESULTS: Tumors were located in the lower or mid-rectum (88.7%) in most patients. The median operative time was 357 min. No patient received transfusions, and the median blood loss was 10.5 ml. Open laparotomy was not required in any patient. A Clavien-Dindo classification of all grades was observed in 12 patients (19.4%). Positive radial margin was not observed in any patient. Duration of median follow-up was 40.5 mo, while 3-y overall survival and 3-y relapse-free survival rates were 96.8% and 85.0%, respectively. The local recurrence rate was 3.4%. CONCLUSION: Favorable short- and long-term outcomes demonstrated robotic-assisted laparoscopic surgery was safe and technically feasible for rectal cancer.
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Laparoscopía , Neoplasias del Recto , Procedimientos Quirúrgicos Robotizados , Humanos , Laparoscopía/efectos adversos , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/cirugía , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Resultado del TratamientoRESUMEN
INTRODUCTION: The advantages of robotic-assisted laparoscopic surgery (RALS) for rectal cancer remain controversial. This study clarified and compared the short-term outcomes of RALS for rectal cancer with those of conventional laparoscopic surgery (CLS). METHODS: The records of 303 consecutive patients who underwent RALS or CLS for rectal adenocarcinoma between November 2016 and November 2021 were analyzed using propensity score-matched analysis. After matching, 188 patients were enrolled in our study to compare short-term outcomes, such as operative results, postoperative complications, and pathological findings, in each group. RESULTS: After matching, baseline characteristics were comparable between groups. Although operative time in the RALS group was significantly longer than in the CLS group (p < 0.0001), the conversion rate to open laparotomy and the postoperative complication rate in the RALS group were significantly lower than in the CLS group (p = 0.0240 and p = 0.0109, respectively). Blood loss was comparable between groups. In the RALS group, postoperative hospital stay and days to soft diet were significantly shorter than those in the CLS group (p = 0.0464 and p < 0.0001, respectively). No postoperative mortality was observed in either group and significant differences were observed in resection margins and number of lymph nodes harvested. CONCLUSION: Robotic-assisted laparoscopic surgery for rectal cancer was safe, technically feasible, and had acceptable short-term outcomes. Further studies are required to validate long-term oncological outcomes.
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Laparoscopía , Neoplasias del Recto , Procedimientos Quirúrgicos Robotizados , Humanos , Laparoscopía/métodos , Complicaciones Posoperatorias/etiología , Puntaje de Propensión , Neoplasias del Recto/patología , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/métodos , Resultado del TratamientoRESUMEN
Background: Myopenia and myosteatosis are reported to be long-term prognostic factors in patients with colorectal cancer (CRC). However, the established parameters are unsuitable for the Japanese population because their body composition is different from that of the Western population. Objective: We aimed to elucidate the effect of skeletal muscle changes among Japanese adults, measured using preoperative computed tomography (CT) as a prognostic factor in patients with stage III CRC. Patients: We retrospectively analyzed 341 patients diagnosed with stage III CRC. The cross-sectional area (skeletal muscle index: SMI) and mean radiodensity of skeletal muscle (skeletal muscle radiodensity: SMR) were measured using preoperative CT. The optimal sex-specific cutoff value, which was used to divide the patients according to the risk of recurrence, was set for SMI and SMR. Univariate and multivariate analysis were performed to determine the prognostic factors for recurrence-free survival (RFS). Results: The cutoff values of SMI for men and women were set as 48.5 and 41.4, respectively, and those of SMR were 35.0 and 21.7, respectively. Univariate analysis identified low SMI and SMR in men and low SMR in women as the worst prognostic factors for RFS. Multivariate analysis identified low SMI in men and low SMR in women as independent poor prognostic factors for RFS (hazard ratio [HR] = 1.87, 95% confidence interval [CI], 1.08-3.47, P = .03 and HR = 2.49, CI, 1.21-4.95, P = .01). Conclusion: Low SMI in men and low SMR in women were the independent prognostic factors for patients with stage III CRC.
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The purpose of this study was to investigate the population pharmacokinetics of prophylactic flomoxef based on serum and liver tissue concentrations and to demonstrate a pharmacodynamic target concentration in the serum and liver tissue exceeding the MIC in order to design an effective dosing regimen. Serum samples (n = 210) and liver tissue samples (n = 29) from 43 individuals were analyzed using a nonlinear mixed-effects model. The pharmacodynamics index target value was regarded as the probability of maintaining flomoxef serum trough and liver tissue concentrations exceeding the MIC90 values, 0.5 mg/L and 1.0 mg/L, for Escherichia coli and methicillin-susceptible Staphylococcus aureus, respectively. The final population pharmacokinetic model was a two-compartment model with linear elimination. Creatinine clearance (CLCR) was identified as a significant covariate influencing total clearance when CLCR was less than 60 mL/min. The probability of achieving concentrations in the serum and liver tissue exceeding the MIC90 for E. coli or methicillin-susceptible S. aureus for a 1 g bolus dose was above 90% at 2 h after the initial dose. Our findings suggest that population pharmacokinetic parameters are helpful for evaluating flomoxef pharmacokinetics and determining intraoperative flomoxef redosing intervals.
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Escherichia coli , Staphylococcus aureus , Antibacterianos/uso terapéutico , Cefalosporinas , Humanos , Hígado/cirugía , Meticilina , Pruebas de Sensibilidad MicrobianaRESUMEN
Pancreatic hamartoma is a rare tumor-like malformation and could mimic other pancreatic tumors including malignant neoplasm. Due to its rarity, magnetic resonance (MR) imaging findings including those diffusion-weighted (DW) imaging have not been clarified. We present a curious case of pancreatic hamartoma presenting high apparent diffusion coefficient (ADC) value with histopathological correlation. A 49-year-old woman with a pancreatic mass found incidentally on ultrasonography for medical checkup was referred to our institution for further examination and treatment because it slightly enlarged in the follow-up examination. Contrast-enhanced computed tomography (CT) and gadoxetic acid disodium-enhanced MR imaging revealed a well-demarcated solid mass of 13 mm in diameter in the pancreas body, which was gradually and homogeneously enhanced in the delayed/transient phase. It showed hyper intensity on T2-weight and DW images, and the mean ADC value was high (1.86 × 10-3mm2/s). Laparoscopic distal pancreatectomy was conducted with suspicious preoperative diagnosis of pancreatic hypovascular neuroendocrine neoplasm (NEN). Histologically, the mass consisted of many disarranged small ducts without atypia embedded in abundant fibrous stroma and contained scant fatty tissue in the periphery, which was not identified on CT and MR images. There were no islets and peripheral nerves throughout the mass. Finally, it was pathologically diagnosed as a solid-type pancreatic hamartoma. Based on radiological-pathological correlation, it was considered that the abundant fibrous stroma and both the widely distributed myxomatous periductal stroma and scattered edematous stroma corresponded with delayed homogenous enhancement on CT/MR images and high ADC value, respectively. Although it is difficult to distinguish solid-type pancreatic hamartoma from other solid pancreatic neoplasms including hypovascular NEN on the basis of usual radiological findings, the high ADC value reflecting the specific pathology may be helpful for the differential diagnosis.
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Hamartoma , Neoplasias Pancreáticas , Imagen de Difusión por Resonancia Magnética/métodos , Femenino , Hamartoma/diagnóstico por imagen , Hamartoma/cirugía , Humanos , Persona de Mediana Edad , Páncreas/diagnóstico por imagen , Páncreas/patología , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/cirugía , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Pancreas-related complications after laparoscopic gastrectomy (LG) for gastric cancer can be fatal. We developed a gastrectomy procedure with no pancreas contact to prevent such complications and herein report the surgical outcomes. METHODS: We retrospectively reviewed 182 consecutive patients with gastric cancer who underwent LG at Kitasato University Hospital from January 2017 to January 2020. These patients were divided into a pancreas-contact group (C group) and pancreas-contactless group (CL group) for comparison of postoperative complications, and inflammatory parameters such as body temperature (BT) and C-reactive protein (CRP). RESULTS: Postoperative complications of CDc grade ⧠IIIa were significantly fewer in the CL group than in the C group [0/76 (0%) vs. 6/106 (5.7%), P = 0.035]. The median drain amylase (drain-AMY) on postoperative day 1 (POD1) was significantly lower in the CL group than in the C group (641 vs. 1162 IU/L, P = 0.02), as was BT at POD1 (37.4 °C vs. 37.7 °C, P = 0.04), the patient group with a BT above 37.5 °C at POD3 [5/76 (6.5%) vs. 18/106 (17%), P = 0.037], and those showing a CRP above 20.0 mg/dL at POD3 [5/76 (6.5%) vs. 20/106 (19%), P = 0.018]. CONCLUSIONS: Our technique to prevent pancreas contact during supra-pancreatic lymph node dissection during LG could minimize the inflammatory response and prevent further postoperative complications. Further large-scale, prospective studies are now required.
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Laparoscopía , Neoplasias Gástricas , Proteína C-Reactiva , Gastrectomía/efectos adversos , Gastrectomía/métodos , Humanos , Inflamación/etiología , Inflamación/prevención & control , Laparoscopía/métodos , Escisión del Ganglio Linfático/métodos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/cirugía , Estudios Prospectivos , Estudios Retrospectivos , Neoplasias Gástricas/patologíaRESUMEN
We herein report a rare case of torsion of a wandering spleen in a patient with myeloproliferative disease. A 66-year-old Japanese woman presented to our hospital with abdominal pain and a fever. She had a medical history of polycythemia and secondary myelofibrosis. Abdominal enhanced computed tomography showed an enlarged spleen without enhancement in the lower pelvic region. The clinical diagnosis was severe torsion of a wandering spleen in a patient with myeloproliferative disease, necessitating surgical intervention. Splenectomy was performed after de-rotating to revascularize the spleen. After the operation, the platelet count gradually increased, and aspirin was administered to prevent thrombosis.
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Trastornos Mieloproliferativos , Ectopía del Bazo , Dolor Abdominal/etiología , Anciano , Femenino , Humanos , Trastornos Mieloproliferativos/complicaciones , Esplenectomía/métodos , Anomalía Torsional/complicaciones , Anomalía Torsional/diagnóstico por imagen , Ectopía del Bazo/complicaciones , Ectopía del Bazo/diagnóstico por imagen , Ectopía del Bazo/cirugíaRESUMEN
BACKGROUND: Prevention of bile duct injury and vasculo-biliary injury while performing laparoscopic cholecystectomy (LC) is an unsolved problem. Clarifying the surgical difficulty using intraoperative findings can greatly contribute to the pursuit of best practices for acute cholecystitis. In this study, multiple evaluators assessed surgical difficulty items in unedited videos and then constructed a proposed surgical difficulty grading. METHODS: We previously assembled a library of typical video clips of the intraoperative findings for all LC surgical difficulty items in acute cholecystitis. Fifty-one experts on LC assessed unedited surgical videos. Inter-rater agreement was assessed by Fleiss's κ and Gwet's agreement coefficient (AC). RESULTS: Except for one item ("edematous change"), κ or AC exceeded 0.5, so the typical videos were judged to be applicable. The conceivable surgical difficulty gradings were analyzed. According to the assessment of difficulty factors, we created a surgical difficulty grading system (agreement probability = 0.923, κ = 0.712, 90% CI: 0.587-0.837; AC2 = 0.870, 90% CI: 0.768-0.972). CONCLUSION: The previously published video clip library and our novel surgical difficulty grading system should serve as a universal objective tool to assess surgical difficulty in LC.
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Colecistectomía Laparoscópica , Colecistitis Aguda , Colecistectomía Laparoscópica/efectos adversos , Colecistitis Aguda/cirugía , HumanosRESUMEN
BACKGROUND: Socratic method, which is an educational method to promote critical thinking through a dialogue, has never been practiced in a large number of people at the academic societies. METHODS: Modified Socratic method was performed for the first time as an educational seminar using an example case of moderate acute cholecystitis based on the evidence described in Tokyo Guidelines 2018. We adopted a method that Takada had been modifying for many years: the instructor first knows the degree of recognition of the audience, then the instructor gives a lecture in an easy-to-understand manner and receives questions from the audience, followed by repeated questions and answers toward a common recognition. RESULTS: Using slides, video, and an answer pad, 281 participants including the audience, instructors and moderators came together to repeatedly ask and answer questions in the five sessions related to the case scenario. The recognition rate of the topic of Critical View of Safety increased significantly before vs after this method (53.0% vs 90.3%). The seminar had been successfully performed by receiving a lot of praise from the participants. CONCLUSION: This educational method is considered to be adopted by many academic societies in the future as an effective educational method.