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OBJECTIVE/BACKGROUND: Various anastomotic and reconstruction techniques are used for minimally invasive total (miTG) and distal gastrectomy (miDG). Their effects on postoperative morbidity have not been extensively studied. METHODS: MiTG and miDG patients were selected from 9356 oncological gastrectomies performed 2017-2021 in 44 centers. Endpoints included anastomotic leakage (AL) rate and postoperative morbidity tested by multivariable analysis. RESULTS: Three major anastomotic techniques (circular stapled (CS); linear stapled (LS); hand sewn (HS)), and three major bowel reconstruction types (Roux (RX); Billroth I (BI); Billroth II (BII)) were identified in miTG (n=878) and miDG (n=3334). Postoperative complications including AL (5.2% vs. 1.1%), overall (28.7% vs. 16.3%) and major morbidity (15.7% vs. 8.2%), as well as 90-day mortality (1.6% vs. 0.5%) were higher after miTG compared with miDG. After miTG, AL rate was higher after CS (4.3%) and HS (7.9%) compared with LS (3.4%). Similarly, major complications (LS: 9.7%, CS: 16.2%, HS: 12.7%) were lowest after LS. Multivariate analysis confirmed anastomotic technique as predictive factor for AL, overall and major complications. In miDG, AL rate (BI: 1.4%, BII 0.8%, RX 1.2%), overall (BI: 14.5%, BII: 15.0%, RX: 18.7%,) and major morbidity (BI: 7.9%, BII: 9.1%, RX: 7.2%), and mortality (BI: 0%, BII: 0.1%, RY: 1.1%%) were not affected by bowel reconstruction. CONCLUSION: In oncologically suitable situations, miDG should be preferred to miTG, as postoperative morbidity is significantly lower. LS should be a preferred anastomotic technique for miTG in Western Centers. Conversely, bowel reconstruction in DG may be chosen according to surgeon's preference.
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OBJECTIVE: To analyse the impact of histological discordance of subtypes (subtypes or divergent differentiation [DD]) in specimens from transurethral resection (TUR) and radical cystectomy (RC) on the outcome of the patients with bladder cancer receiving RC. PATIENTS AND METHODS: We analysed data for 2570 patients from a Japanese nationwide cohort with bladder cancer treated with RC between January 2013 and December 2019 at 36 institutions. The non-urinary tract recurrence-free survival (NUTR-FS) and overall survival (OS) stratified by TUR or RC specimen histology were determined. We also elucidated the predictive factors for OS in patients with subtype/DD bladder cancer. RESULTS: At median follow-up of 36.9 months, 835 (32.4%) patients had NUTR, and 691 (26.9%) died. No statistically significant disparities in OS or NUTR-FS were observed when TUR specimens were classified as pure-urothelial carcinoma (UC), subtypes, DD, or non-UC. Among 2449 patients diagnosed with pure-UC or subtype/DD in their TUR specimens, there was discordance between the pathological diagnosis in TUR and RC specimens. Histological subtypes in RC specimens had a significant prognostic impact. When we focused on 345 patients with subtype/DD in TUR specimens, a multivariate Cox regression analysis identified pre-RC neutrophil-lymphocyte ratio and pathological stage as independent prognostic factors for OS (P = 0.016 and P = 0.001, respectively). The presence of sarcomatoid subtype in TUR specimens and lymphovascular invasion in RC specimens had a marginal effect (P = 0.069 and P = 0.056, respectively). CONCLUSION: This study demonstrated that the presence of subtype/DD in RC specimens but not in TUR specimens indicated a poor prognosis. In patients with subtype/DD in TUR specimens, pre-RC neutrophil-lymphocyte ratio and pathological stage were independent prognostic factors for OS.
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Cistectomia , Neoplasias da Bexiga Urinária , Humanos , Cistectomia/métodos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/mortalidade , Masculino , Feminino , Prognóstico , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , Carcinoma de Células de Transição/mortalidade , Japão/epidemiologiaRESUMO
PURPOSE: To compare the diagnostic performance of photodynamic diagnosis (PDD) enhanced with oral 5-aminolaevulinic acid between the suspected upper tract urothelial carcinoma (UTUC) and bladder urothelial carcinoma (BUC) cases. METHODS: This retrospective study included 18 patients with suspected UTUC who underwent ureteroscopy (URS) with oral 5-ALA in the PDD-URS cohort between June 2018 and January 2019; and 110 patients with suspected BUC who underwent transurethral resection of bladder tumour (TURBT) in the PDD-TURBT cohort between January 2019 and March 2023. Sixty-three and 708 biopsy samples were collected during diagnostic URS and TURBT, respectively. The diagnostic accuracy of white light (WL) and PDD in the two cohorts was evaluated, and false PDD-positive samples were pathologically re-evaluated. RESULTS: The area under the receiver operating characteristic curve (AUC) of PDD was significantly superior to that of WL in both cohorts. The per biopsy sensitivity, specificity, and positive and negative predictive values of PDD in patients in the PDD-URS and PDD-TURBT cohorts were 91.2 vs. 71.4, 75.9 vs. 75.3, 81.6 vs. 66.3, and 88.0 vs. 79.4%, respectively. The PDD-URS cohort exhibited a higher AUC than did the PDD-TURBT cohort (0.84 vs. 0.73). Seven of four false PDD-positive samples (57.1%) in the PDD-URS cohort showed potential precancerous findings compared with eight of 101 (7.9%) in the PDD-TURBT cohort. CONCLUSION: The diagnostic performance of PDD in the PDD-URS cohort was at least equivalent to that in the PDD-TURBT cohort.
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Ácido Aminolevulínico , Carcinoma de Células de Transição , Fármacos Fotossensibilizantes , Neoplasias da Bexiga Urinária , Humanos , Estudos Retrospectivos , Ácido Aminolevulínico/administração & dosagem , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/diagnóstico , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/patologia , Fármacos Fotossensibilizantes/administração & dosagem , Administração Oral , Neoplasias Ureterais/patologia , Neoplasias Ureterais/diagnóstico , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Ureteroscopia , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: The relationship between preoperative prealbumin levels and long-term prognoses in patients with gastric cancer after gastrectomy has not been fully investigated. This study clarified the effect of preoperative prealbumin levels on the long-term prognosis of patients with gastric cancer after gastrectomy. METHODS: This retrospective cohort study included consecutive patients who underwent radical gastrectomy for primary pStage I-III gastric cancer and whose preoperative prealbumin levels were measured between May 2006 and March 2017. Participants were categorized according to their preoperative prealbumin levels into high (≥22 mg/dL), moderate (15-22 mg/dL), and low (<15 mg/dL) groups. The overall survival (OS) in the three groups was compared using the log-rank test, and prognostic factors were identified using Cox proportional hazards regression analysis. RESULTS: The median follow-up duration was 66 months. Of 4732 patients, 3649 (77.2%) were classified as high, 925 (19.6%) as moderate, and 158 (3.3%) as low. Lower prealbumin levels were associated with poorer prognoses (P < 0.001). Multivariate analysis showed that prealbumin levels of 15-22 mg/dL [hazard ratio (HR): 1.576, 95% confidence interval (CI): 1.353-1.835, P < 0.001] and <15 mg/dL (HR: 1.769, 95% CI: 1.376-2.276, P < 0.001) were independent poor prognostic factors for OS. When analyzed according to the cause of death, prealbumin levels were associated with other-cause survival, but not cancer-specific survival. CONCLUSIONS: Preoperative prealbumin levels correlated with OS in patients with gastric cancer after gastrectomy; the lower the prealbumin level, the worse is the prognosis. Prealbumin levels may be associated with other-cause survival.
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Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Pré-Albumina , Prognóstico , GastrectomiaRESUMO
BACKGROUND: Postoperative adjuvant chemotherapy with S-1 for 1 year (corresponding to eight courses) is the standard treatment for pathological stage II gastric cancer. The phase III trial (JCOG1104) investigating the non-inferiority of four courses of S-1 to eight courses was terminated due to futility at the first interim analysis. To confirm the primary results, we reported the results after a 5-years follow-up in JCOG1104. METHODS: Patients histologically diagnosed with stage II gastric cancer after radical gastrectomy were randomly assigned to receive S-1 for eight or four courses. In detail, 80 mg/m2/day S-1 was administered for 4 weeks followed by a 2-week rest as a single course. RESULTS: Between February 16, 2012, and March 19, 2017, 590 patients were enrolled and randomly assigned to 8-course (295 patients) and 4-course (295 patients) regimens. After a 5-years follow-up, the relapse-free survival at 3 years was 92.2% for the 8-course arm and 90.1% for the 4-course arm, and that at 5 years was 87.7% for the 8-course arm and 85.6% for the 4-course arm (hazard ratio 1.265, 95% CI 0.846-1.892). The overall survival at 3 years was 94.9% for the 8-course arm, 93.2% for the 4-course arm, and that at 5 years was 89.7% for the 8-course arm, and 88.6% for the 4-course arm (HR 1.121, 95% CI 0.719-1.749). CONCLUSIONS: The survival of the four-course arm was slightly but consistently inferior to that of the eight-course arm. Eight-course S-1 should thus remain the standard adjuvant chemotherapy for pathological stage II gastric cancer.
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Neoplasias Gástricas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Seguimentos , Estadiamento de Neoplasias , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: Proximal gastrectomy (PG) is recommended for upper-third gastric cancer and esophagogastric junction (EGJ) cancer, preserving organ function while reducing postoperative symptoms. The double-flap technique (DFT) is one approach to minimize reflux after PG. However, laparoscopic PG with DFT (LPG-DFT) has drawbacks of increased complexity, such as hand sutures for anastomosis. Robotic surgery offers potential advantages for DFT reconstruction, but the safety of robotic DFT following PG (RPG-DFT) in the introductory phase is unknown. METHODS: This retrospective study compared the outcomes of RPG-DFT with LPG-DFT. Data from 402 patients (321 LPG-DFT, 81 RPG-DFT) between 2009 and 2023 were analyzed. Propensity score matching balanced patient demographics and tumor characteristics. Surgical parameters, complications, and long-term outcomes were assessed. RESULTS: The surgery time of LPG-DFT has stabilized in patients since 2016. Thus, LPG-DFT from 2016 was defined as a stable procedure. RPG-DFT was started in 2019, after minimally invasive DFT reconstruction had been mastered at our center. Therefore, we compared the surgical outcomes of introductory RPG-DFT with stable LPG-DFT. Matched analysis revealed that RPG-DFT in the introductory phase had significantly longer surgery times but less bleeding and shorter reconstruction times and hospital stays than stable LPG-DFT. Frequencies of short-term complications and reflux esophagitis were comparable in both groups. Although RPG-DFT in the introductory phase exhibited higher incidence of anastomotic stenosis than stable LPG-DFT, the incidence of anastomotic stenosis decreased over time. CONCLUSIONS: This study demonstrated the safety of RPG-DFT in the introductory phase for EGJ and upper-third stomach tumors, with outcomes comparable to stable LPG-DFT. RPG-DFT offers shorter reconstruction time and less blood loss compared with LPG-DFT. However, anastomotic stenosis is a complication to monitor in early robotic surgery.
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BACKGROUND: Intracorporeal mechanical gastrogastrostomy (IMG) techniques have recently been developed and their short-term safety was presented in their initial evaluation. However, whether they are comparable to extracorporeal hand-sewing gastrogastrostomy (EHG) remains unclear. The aim of the study is to establish the safety of IMG in totally laparoscopic pylorus-preserving gastrectomy (TLPPG) compared to EHG in laparoscopy-assisted pylorus-preserving gastrectomy (LAPPG). METHODS: We retrospectively analyzed the short-term outcomes of patients with middle-third early gastric cancer who underwent LAPPG or TLPPG between 2005 and 2022. The primary objective of this study was to evaluate the non-inferiority of IMG to EHG in terms of safety, with the primary endpoint being the risk difference in anastomosis-related complications (ARCs). The sample size required to achieve a statistical power of 80% for the non-inferiority test was 971 with a one-sided alpha level of 5% and non-inferiority of 5%. RESULTS: The analysis included a total of 1,021 patients who underwent LAPPG or TLPPG during the study period. Among them, 488 patients underwent EHG, while 533 underwent IMG. The incidences of ARCs were 11.3% and 11.4% in EHG and IMG, respectively. The observed difference in incidence was 0.0017 (90% confidence interval - 0.0313 to 0.0345), which statistically demonstrated the non-inferiority of IMG to EHG in the incidence of ARCs. Among other complications, the incidence of wound infection in IMG was lower than that in EHG. CONCLUSION: IMG is safe regarding ARCs compared with EHG. These results will encourage surgeons to introduce IMG for patients with early middle gastric cancer.
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Gastrectomia , Laparoscopia , Piloro , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Masculino , Laparoscopia/métodos , Gastrectomia/métodos , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Piloro/cirurgia , Idoso , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Técnicas de Sutura , Gastrostomia/métodos , Tratamentos com Preservação do Órgão/métodos , Estadiamento de NeoplasiasRESUMO
BACKGROUND: Recent studies have revealed that sarcopenia is associated with postoperative complications and poor prognosis. Although neoadjuvant chemotherapy is a promising treatment for gastric cancer, its toxicity may lead to the loss of skeletal muscle mass. This study investigates the changes in skeletal muscle mass during neoadjuvant chemotherapy and its clinical impact on patients with locally advanced gastric cancer. METHODS: Fifty patients who completed two courses of neoadjuvant chemotherapy followed by surgery were included. Skeletal muscle mass was measured using computed tomography images before and after chemotherapy. The proportion of skeletal muscle mass change (%SMC) during neoadjuvant chemotherapy and its cutoff value was explored using the receiver operating characteristic for the overall survival of patients undergoing R0 resection. Risk factors of skeletal muscle mass loss were also evaluated. RESULTS: Overall, 64% of patients had skeletal muscle mass loss during neoadjuvant chemotherapy (median %SMC -3.4%; range: -18.9% to 10.3%). Multivariable analysis identified older age (≥70 years) as an independent predictor of skeletal muscle mass loss (mean [95% confidence interval]: -4.70% [-8.83 to -0.58], p = 0.026). Among 43 patients undergoing R0 resection, %SMC <-6.9% was an independent poor prognostic factor for overall survival (hazard ratio, 11.53; 95% confidence interval, 2.78-47.80) and relapse-free survival (hazard ratio 4.54, 95% confidence interval 1.50-13.81). CONCLUSIONS: Skeletal muscle mass loss occurs frequently during neoadjuvant chemotherapy for locally advanced gastric cancer and could adversely affect survival outcomes.
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Músculo Esquelético , Terapia Neoadjuvante , Sarcopenia , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Terapia Neoadjuvante/métodos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Músculo Esquelético/diagnóstico por imagem , Gastrectomia , Tomografia Computadorizada por Raios X , Quimioterapia Adjuvante , Adulto , Prognóstico , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
BACKGROUND: It remains unclear which patients with biochemical recurrence after prostatectomy are most suitable for salvage radiotherapy. We evaluated the parameters related to outcomes. METHODS: We retrospectively evaluated patients who underwent salvage therapy for biochemical recurrence after prostatectomy between 2005 and 2019. This study aimed to evaluate biochemical recurrence-free survival (bRFS) after salvage radiotherapy and elucidate the parameters associated with bRFS. The bRFS rate was calculated using the Kaplan-Meier method, and the parameters associated with bRFS were evaluated using Cox regression analysis. RESULTS: This study included 67 patients treated with salvage radiotherapy with a median age of 67 years at salvage radiotherapy. The median follow-up period after salvage radiotherapy was 7.3 years. The 5-year bRFS rate following salvage radiotherapy was 47.1%. Univariate analysis showed that PSA doubling time < 6 months, positive surgical margin, and pathological Gleason score ≥ 8 were significantly associated with shorter bRFS (p < 0.001, p = 0.036, p = 0.047, respectively). Multivariable analysis showed that a PSA doubling time < 6 months and positive surgical margins were significantly associated with shorter bRFS (p = 0.001 and p = 0.018, respectively). No serious adverse events were observed. CONCLUSIONS: In our hospital, approximately half of the patients are under long-term control with salvage radiotherapy. A PSA doubling time of < 6 months and positive surgical margins were suggested to be associated with poor outcomes of salvage radiotherapy.
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Recidiva Local de Neoplasia , Antígeno Prostático Específico , Prostatectomia , Neoplasias da Próstata , Terapia de Salvação , Humanos , Masculino , Terapia de Salvação/métodos , Prostatectomia/métodos , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/sangue , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/radioterapia , Antígeno Prostático Específico/sangue , Gradação de Tumores , Intervalo Livre de Doença , Margens de ExcisãoRESUMO
BACKGROUND: Enfortumab vedotin is a novel antibody-drug conjugate used as a third-line therapy for the treatment of urothelial cancer. We aimed to elucidate the effect of enfortumab vedotin-related peripheral neuropathy on its efficacy and whether enfortumab vedotin-induced early electrophysiological changes could be associated with peripheral neuropathy onset. METHODS: Our prospective multicenter cohort study enrolled 34 patients with prior platinum-containing chemotherapy and programmed cell death protein 1/ligand 1 inhibitor-resistant advanced urothelial carcinoma and received enfortumab vedotin. The best overall response, progression-free survival, overall survival, and safety were assessed. Nerve conduction studies were also performed in 11 patients. RESULTS: The confirmed overall response rate and disease control rate were 52.9% and 73.5%, respectively. The median overall progression-free survival and overall survival were 6.9 and 13.5 months, respectively, during a median follow-up of 8.6 months. The patients with disease control had significantly longer treatment continuation and overall survival than did those with uncontrolled disease. Peripheral neuropathy occurred in 12.5% of the patients. The overall response and disease control rates were 83.3% and 100%, respectively: higher than those in patients without peripheral neuropathy (p = 0.028 and p = 0.029, respectively). Nerve conduction studies indicated that enfortumab vedotin reduced nerve conduction velocity more markedly in sensory nerves than in motor nerves and the lower limbs than in the upper limbs, with the sural nerve being the most affected in the patients who developed peripheral neuropathy (p = 0.011). CONCLUSION: Our results indicated the importance of focusing on enfortumab vedotin-induced neuropathy of the sural nerve to maximize efficacy and improve safety.
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Anticorpos Monoclonais , Doenças do Sistema Nervoso Periférico , Humanos , Masculino , Feminino , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Idoso , Estudos Prospectivos , Pessoa de Meia-Idade , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Idoso de 80 Anos ou mais , Condução Nervosa/efeitos dos fármacos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/tratamento farmacológico , Intervalo Livre de Progressão , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/patologiaRESUMO
OBJECTIVES: The JAVELIN Bladder 100 phase 3 trial showed that avelumab first-line maintenance + best supportive care significantly prolonged overall survival and progression-free survival versus best supportive care alone in patients with advanced urothelial carcinoma who were progression-free following first-line platinum-based chemotherapy. We report findings from J-AVENUE (NCT05431777), a real-world study of avelumab first-line maintenance therapy in Japan. METHODS: Medical charts of patients with advanced urothelial carcinoma without disease progression following first-line platinum-based chemotherapy, who received avelumab maintenance between February and November 2021, were reviewed. Patients were followed until June 2022. The primary endpoint was patient characteristics; secondary endpoints included time to treatment failure and progression-free survival. RESULTS: In 79 patients analyzed, median age was 72 years (range, 44-86). Primary tumor site was upper tract in 45.6% and bladder in 54.4%. The most common first-line chemotherapy regimen was cisplatin + gemcitabine (63.3%). Median number of chemotherapy cycles received was four. Best response to chemotherapy was complete response in 10.1%, partial response in 58.2%, and stable disease in 31.6%. Median treatment-free interval before avelumab was 4.9 weeks. With avelumab first-line maintenance therapy, the disease control rate was 58.2%, median time to treatment failure was 4.6 months (95% CI, 3.3-6.4), and median progression-free survival was 6.1 months (95% CI, 3.6-9.7). CONCLUSIONS: Findings from J-AVENUE show the effectiveness of avelumab first-line maintenance in patients with advanced urothelial carcinoma in Japan in clinical practice, with similar progression-free survival to JAVELIN Bladder 100 and previous real-world studies, supporting its use as a standard of care.
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Anticorpos Monoclonais Humanizados , Carcinoma de Células de Transição , Quimioterapia de Manutenção , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Japão , Quimioterapia de Manutenção/métodos , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologiaRESUMO
OBJECTIVES: To determine the effects of prophylactic urethrectomy (PU) on oncological and perioperative outcomes in patients with bladder cancer (BC) undergoing radical cystectomy (RC). METHODS: This retrospective study analyzed data on 1976 evaluable patients with BC who underwent RC. Patients were drawn from 36 institutions within the Japanese Urological Oncology Group. Oncological outcomes were compared using restricted mean survival times (RMSTs) based on inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves for non-urinary tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS). Interaction terms within IPTW-adjusted Cox regression models were examined to assess the heterogeneity of treatment effect based on the risk of urethral recurrence (UR). The association between PU, estimated blood loss (EBL), and the incidence of severe postoperative surgical complications (SPSCs) (Clavien-Dindo grade 3 or higher) was analyzed. RESULTS: Of 1976 patients, 1448 (73.3%) received PU. IPTW adjustment was used to balance baseline characteristics between the treatment groups. Within the 107-month window of patient monitoring, PU showed no survival benefits (NUTRFS difference: 0.2 months [95% confidence interval: -6.8 to 7.3]; CSS, 1.2 [-4.9 to 7.3]; OS, 0 [-6.5 to 6.5]). No significant interactions were observed with factors associated with UR, and PU was associated with unfavorable perioperative outcomes (EBL, 1179 mL vs. 983 mL; SPSC, 14.6% vs. 7.0%). CONCLUSIONS: This study showed that (1) PU was not associated with survival in patients with BC undergoing RC, regardless of UR-associated factors, and (2) PU was associated with unfavorable perioperative outcomes.
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BACKGROUND: The intratumor heterogeneity (ITH) of cancer cells plays an important role in breast cancer resistance and recurrence. To develop better therapeutic strategies, it is necessary to understand the molecular mechanisms underlying ITH and their functional significance. Patient-derived organoids (PDOs) have recently been utilized in cancer research. They can also be used to study ITH as cancer cell diversity is thought to be maintained within the organoid line. However, no reports investigated intratumor transcriptomic heterogeneity in organoids derived from patients with breast cancer. This study aimed to investigate transcriptomic ITH in breast cancer PDOs. METHODS: We established PDO lines from ten patients with breast cancer and performed single-cell transcriptomic analysis. First, we clustered cancer cells for each PDO using the Seurat package. Then, we defined and compared the cluster-specific gene signature (ClustGS) corresponding to each cell cluster in each PDO. RESULTS: Cancer cells were clustered into 3-6 cell populations with distinct cellular states in each PDO line. We identified 38 clusters with ClustGS in 10 PDO lines and used Jaccard similarity index to compare the similarity of these signatures. We found that 29 signatures could be categorized into 7 shared meta-ClustGSs, such as those related to the cell cycle or epithelial-mesenchymal transition, and 9 signatures were unique to single PDO lines. These unique cell populations appeared to represent the characteristics of the original tumors derived from patients. CONCLUSIONS: We confirmed the existence of transcriptomic ITH in breast cancer PDOs. Some cellular states were commonly observed in multiple PDOs, whereas others were specific to single PDO lines. The combination of these shared and unique cellular states formed the ITH of each PDO.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/metabolismo , Transcriptoma , Mama , Perfilação da Expressão Gênica , Organoides/metabolismoRESUMO
BACKGROUND: Laparoscopic pylorus-preserving gastrectomy (LPPG) is performed for cT1N0 gastric cancer as a function-preserving surgery, but reflux esophagitis can develop as a mid- to long-term complication postoperatively. We aimed to clarify the incidence rate of this complication and the factors correlated with it. METHODS: Patients with gastric cancer who underwent LPPG between 2005 and 2017 were analyzed. Postoperative reflux esophagitis was evaluated with esophagogastroduodenoscopy; patients were diagnosed as having reflux esophagitis with erosive esophagitis using the modified Los Angeles classification. The incidence rate of postoperative reflux esophagitis was estimated; factors correlated with postoperative reflux esophagitis were analyzed using the logistic regression model. RESULTS: During the study period, 813 patients underwent LPPG for gastric cancer, and 127 (15.6%) of them developed grade B or more severe postoperative reflux esophagitis. The factors correlated with postoperative reflux esophagitis were male sex (odds ratio, 2.68; 95% confidence interval, 1.77-4.05; P < 0.001), preoperative grade A reflux esophagitis (odds ratio, 3.05; 95% confidence interval, 1.28-7.27; P = 0.012), body mass index of ≥ 23 kg/m2 at 1 year postoperatively (odds ratio, 2.18; 95% confidence interval, 1.34-3.53; P = 0.002), postoperative hiatal hernia (odds ratio, 4.35; 95% confidence interval, 2.35-8.04; P < 0.001), and long-term stasis (odds ratio, 1.58; 95% confidence interval, 1.01-2.47; P = 0.044). CONCLUSIONS: Careful attention should be paid in performing LPPG and in postoperative management after LPPG for gastric cancer patients with those risk factors.
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Esofagite Péptica , Laparoscopia , Neoplasias Gástricas , Humanos , Masculino , Feminino , Piloro/cirurgia , Neoplasias Gástricas/complicações , Esofagite Péptica/etiologia , Esofagite Péptica/diagnóstico , Esofagite Péptica/cirurgia , Gastrectomia/efeitos adversos , Laparoscopia/efeitos adversosRESUMO
BACKGROUND: To obtain a pathologically negative proximal margin (PM) for gastric cancer with gross esophageal invasion (EI) or esophagogastric junction (EGJ) cancer, we should transect the esophagus beyond the proximal boundary of gross EI with a safety margin because of a discrepancy between the gross and pathological boundaries of cancer. However, recommendations regarding the esophageal resection length for these cancers have not been established. METHODS: Patients who underwent proximal or total gastrectomy for gastric cancer with gross EI or EGJ cancer were enrolled. A parameter ΔPM, which corresponded to the length of a discrepancy between the gross and pathological proximal boundary of the tumor, was evaluated. The maximum ΔPM, which corresponded to the minimum length ensuring a pathologically negative PM, was first determined in all patients. Then subgroup analyses according to factors associated with ΔPM ≥ 10 mm were performed to identify alternative maximum ΔPMs. RESULTS: A total of 289 patients with gastric cancer with gross EI or EGJ cancer were eligible and analyzed in this study. The maximum ΔPM was 25 mm. Clinical tumor (cTumor) size and growth and pathological types were independently associated with ΔPM ≥ 10 mm. In subgroup analyses, the maximum ΔPM was 15 mm for cTumor size ≤ 40 mm and superficial growth type. Furthermore, the maximum ΔPM was 20 mm in the expansive growth type. CONCLUSIONS: Required esophageal resection lengths to ensure a pathologically negative PM for gastric cancer with gross EI or EGJ cancer are proposed.
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Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Adenocarcinoma/patologia , Junção Esofagogástrica/cirurgia , Junção Esofagogástrica/patologia , Margens de Excisão , Gastrectomia , Estudos RetrospectivosRESUMO
In older patients with cT1N0M0 gastric cancer in the middle third of the stomach, LPPG has advantages over LDGB1 in maintaining skeletal muscle mass. BACKGROUND: Laparoscopic pylorus-preserving gastrectomy (LPPG) for early gastric cancer in the middle third of the stomach is expected to be an alternative procedure to laparoscopic distal gastrectomy (LDG). However, whether LPPG is safe and more useful than LDG in older patients is unclear because of their comorbidities and organ dysfunctions. METHODS: We retrospectively analyzed the data of consecutive patients aged 75 or over who underwent LDG with Billroth I reconstruction (LDGB1) or LPPG for cT1N0M0 gastric cancer in the middle third of the stomach between 2005 and 2019. After propensity score matching was used to improve the comparability between the LDGB1 and LPPG groups, we compared surgical and postoperative nutritional outcomes, including the postoperative trends of bodyweight (%BW) and skeletal muscle index (%SMI). RESULTS: A total of 132 patients who underwent LDGB1 (n = 88) and LPPG (n = 44) were collected for this study. No significant difference in postoperative complications was observed. The total protein levels after LPPG were significantly higher than those after LDGB1 for 4 postoperative years. Both %BW and %SMI after LPPG were significantly maintained compared with those after LDGB1 during the first year after surgery. For the subsequent years, %BW after LPPG became similar to that after LDGB1, while %SMI after LPPG was significantly larger than LDGB1 continuously. CONCLUSIONS: LPPG has a great advantage in maintaining the postoperative skeletal muscle mass as well as the nutritional parameters of older patients. LPPG is expected to be an alternative to LDG in older patients.
Assuntos
Laparoscopia , Neoplasias Gástricas , Humanos , Idoso , Piloro/cirurgia , Neoplasias Gástricas/cirurgia , Estudos Retrospectivos , Gastrectomia/métodos , Laparoscopia/métodos , Músculo Esquelético/cirurgia , Complicações Pós-Operatórias/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: As there is no consensus on the impact of antithrombotic drugs on post-gastrectomy outcomes in gastric cancer patients, this study aimed to investigate the impact of antithrombotic drugs on postoperative outcomes in these patients after gastrectomy. METHODS: Patients with Stage I-III primary gastric cancer who underwent radical gastrectomy between April 2005 and May 2022 were included. We performed propensity score matching to adjust for patient background and compared bleeding complications. Multivariate analysis with logistic regression analysis was performed to identify risk factors associated with bleeding complications. RESULTS: Of the 6798 patients, 310 (4.6%) were in the antithrombotic group and 6488 (95.4%) were in the non-antithrombotic group. Twenty-six patients (0.38%) experienced bleeding complications. After matching, the number of patients in each group was 300, with insignificant differences in any factor. A comparison of postoperative outcomes showed no difference in bleeding complications (P = 0.249). In the antithrombotic group, 39 (12.6%) continued drugs, and 271 (87.4%) discontinued them before surgery. After matching, there were 30 and 60 patients, respectively, with no differences in patient background. A comparison of postoperative outcomes showed no differences in bleeding complications (P = 0.551). In multivariate analysis, antithrombotic drug use and continuation of antiplatelet agents were not risk factors for bleeding complications. CONCLUSION: Antithrombotic drugs and its continuation may not worsen bleeding complications in patients with gastric cancer after radical gastrectomy. Bleeding complications were rare, and further studies are needed on risk factors for bleeding complications in larger databases.
Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/complicações , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/induzido quimicamente , Estudos Retrospectivos , Inibidores da Agregação Plaquetária/efeitos adversos , Gastrectomia/efeitos adversos , Pontuação de Propensão , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgiaRESUMO
BACKGROUND: Gastric cancer often exhibits discrepancies between the gross and pathological tumor boundaries, and the degree of discrepancy may be a tumor characteristic. However, whether these discrepancies influence oncological outcomes remains unclear. METHODS: The data of patients who underwent total gastrectomy for gastric cancer from 2005 to 2018 were collected. A new parameter, ΔPM, which corresponds to the length of the discrepancy between the gross and pathological proximal boundaries, was calculated and the patients were divided into two groups: patients with long ΔPM and those with short ΔPM. Oncological outcomes were compared between the two groups. RESULTS: A length of 8 mm was determined as the cutoff value for long or short ΔPM. Tumor size, growth pattern, pathological type, depth, and esophageal invasion were associated with ΔPM > 8 mm. Overall survival of the ΔPM > 8 mm group was significantly worse than that of the ΔPM ≤ 8 mm group (5-year overall survival: 58% vs 78%; p < 0.0001). Multivariate analysis revealed that ΔPM > 8 mm was an independent risk factor for poor survival and peritoneal metastasis. The likelihood ratio test revealed a significant interaction between pT status and ΔPM (p = 0.0007). Circumferential involvement and gross esophageal invasion were poorer survival factors in the ΔPM > 8 mm group. CONCLUSIONS: ΔPM > 8 mm is related to several clinicopathological characteristics and is an independent risk factor for poorer survival and peritoneal metastasis but not local recurrence. ΔPM > 8 mm combined with circumferential involvement or esophageal invasion is associated with relatively poor survival outcomes.
Assuntos
Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Peritoneais/patologia , Estudos Retrospectivos , Fatores de Risco , Gastrectomia , Prognóstico , Estadiamento de NeoplasiasRESUMO
PURPOSE: A phase III trial comparing S-1 and docetaxel with S-1 alone as postoperative chemotherapy for pathologically Stage III gastric cancer was conducted and clarified the superiority of the doublet in terms of 3-year relapse-free survival as the primary endpoint (67.7% versus 57.4%, hazard ratio [HR] 0.715, 95% confidence interval [CI] 0.587-0.871; p = 0.0008). This final report analyzed 5-year survival outcomes along with the incidence and pattern of late recurrences. PATIENTS AND METHODS: Patients with histologically confirmed Stage III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were randomly assigned to receive adjuvant chemotherapy with either S-1 plus docetaxel or S-1 alone. The same 912 patients who were evaluated for 3-year survival outcomes in the previous report were analyzed. RESULTS: Five-year overall survival rate of the S-1 plus docetaxel group (67.91%) was significantly superior to that in the S-1 group (60.27%; HR 0.752, 95% CI 0.613-0.922; p = 0.0059). The incidence of late recurrence at > 3 years after randomization was similar in both groups (7.3% versus 7.2%). Peritoneal dissemination was the most common pattern of late recurrence. Addition of docetaxel significantly suppressed relapse through the lymphatic (6.8% [95% CI 4.52-9.17] versus 15% [95% CI 11.76-18.30]; p < 0.0001) and hematogenous (10.2% [95% CI 7.37-12.94] versus 15.7% [95% CI 12.36-19.01]; p < 0.0137) pathways throughout the 5 years of follow-up. CONCLUSION: The survival benefit of postoperative chemotherapy with S-1 and docetaxel in terms of 5-year overall survival rate was confirmed for patients with pathologically Stage III gastric cancer, although late recurrences were not prevented.
Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Docetaxel/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Modelos de Riscos Proporcionais , Estadiamento de Neoplasias , Gastrectomia/métodosRESUMO
BACKGROUND: The Cancer-VTE Registry was a large-scale, multicenter, prospective registry designed to investigate real-world data on venous thromboembolism (VTE) incidence and risk factors in adult Japanese patients with solid tumors. This pre-specified subgroup analysis aimed to estimate the incidence of VTE, including VTE types other than symptomatic VTE, and identify risk factors of VTE in stomach cancer from the Cancer-VTE Registry. METHODS: Stage II-IV stomach cancer patients who planned to initiate cancer therapy and underwent VTE screening within 2 months before registration were enrolled. RESULTS: Of 1,896 patients enrolled, 131 (6.9%) had VTE at baseline, but 96.2% were asymptomatic. Female sex, age ≥ 65 years, VTE history, and D-dimer > 1.2 µg/mL were independent risk factors of VTE at baseline. Notably, patients with D-dimer > 1.2 µg/mL at the time of cancer diagnosis had an approximately 20-fold risk of VTE. During follow-up, event incidences were symptomatic VTE, 0.3%; incidental VTE requiring treatment, 1.1%; composite VTE, 1.4%; bleeding, 1.6%; cerebral infarction/transient ischemic attack/systemic embolic events, 0.7%; and all-cause death, 15.0%. The incidence of all-cause death was higher in patients with VTE vs without VTE at baseline (adjusted hazard ratio 1.67; 95% confidence interval 1.21-2.32; p = 0.002). CONCLUSIONS: VTE prevalence at the time of cancer diagnosis was not negligible and was extremely high when the patients had high D-dimer. VTE screening by D-dimer before starting cancer treatment is advisable, even for asymptomatic patients, regardless of whether the patient is undergoing surgery or chemotherapy. TRIAL REGISTRATION: UMIN000024942.