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BACKGROUND: With recent dramatic developments in chemotherapy, attempts to incorporate surgery into the multidisciplinary treatment of unresectable pancreatic ductal adenocarcinoma with metastasis (UR-M PDAC) have emerged. Maintenance therapy with olaparib after chemotherapy including a platinum-based regimen, which inhibits the poly ADP-ribose polymerase (PARP) involved in DNA repair, was approved for UR-M PDAC with positive BRCA mutations. CASE PRESENTATION: A 47-year-old male patient with a high carbohydrate antigen 19-9 (CA19-9) level was diagnosed with PDAC in the pancreatic tail. Staging laparoscopy revealed occult liver metastasis. Because BRCA2 mutation was confirmed, triple combination chemotherapy with SOXIRI (S-1/oxaliplatin/irinotecan) was introduced and continued for 16 weeks, followed by 14 weeks of olaparib. After that, CA19-9 was normalized, and no obvious liver metastases of any size could be seen on imaging studies during chemotherapy. Since staging laparoscopy after chemotherapy proved that the liver metastasis had disappeared, laparoscopic distal pancreatectomy was performed, and curative resection was completed. After adjuvant chemotherapy with olaparib for 12 months, the patient is alive 36 months from his initial diagnosis and 27 months postoperatively without recurrence. CONCLUSION: We report a case of PDAC with liver metastasis and BRCA mutation-positivity who underwent conversion surgery and achieved long-term survival after irinotecan-based chemotherapy followed by maintenance therapy with olaparib.
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OBJECTIVES: This study aimed to evaluate the clinical impact of preoperative endoscopic ultrasound-guided tissue acquisition (EUS-TA) on the prognosis and incidence of positive peritoneal lavage cytology (PLC) during laparotomy or staging laparoscopy in patients with resectable (R) or borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC). METHODS: We retrospectively collected data from patients diagnosed with body and tail PDAC with/without EUS-TA at our hospital from January 2006 to December 2021. RESULTS: To examine the effect of EUS-TA on prognosis, 153 patients (122 in the EUS-TA group, 31 in the non-EUS-TA group) were analyzed. There was no significant difference in overall survival between the EUS-TA and non-EUS-TA groups after PDAC resection (P = 0.777). In univariate and multivariate analysis, preoperative EUS-TA was not identified as an independent factor related to overall survival after pancreatectomy [hazard ratio 0.96, 95 % confidence interval (CI) 0.54-1.70, P = 0.897]. Next, to examine the direct influence of EUS-TA on the results of PLC, 114 patients (83 in the EUS-TA group and 31 in the non-EUS-TA group) were analyzed. Preoperative EUS-TA was not statistically associated with positive PLC (odds ratio 0.73, 95 % CI 0.25-2.20, P = 0.583). After propensity score matching, overall survival and positive PLC were the same in both groups. CONCLUSIONS: EUS-TA had no negative impact on postoperative survival and PLC-positive rates in R/BR PDAC.
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Carcinoma Ductal Pancreático , Pancreatectomía , Neoplasias Pancreáticas , Lavado Peritoneal , Humanos , Masculino , Femenino , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/cirugía , Carcinoma Ductal Pancreático/diagnóstico por imagen , Anciano , Persona de Mediana Edad , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/diagnóstico por imagen , Estudios Retrospectivos , Pronóstico , Endosonografía , Anciano de 80 o más Años , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , CitologíaRESUMEN
Importance: Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking. Objective: To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy. Design, Setting, and Participants: This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months. Exposures: Preoperative chemotherapy (with or without radiotherapy) followed by resection. Main Outcomes and Measures: The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively. Results: Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89). Conclusions and Relevance: This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.
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Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/mortalidad , Masculino , Persona de Mediana Edad , Femenino , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/terapia , Adenocarcinoma/patología , Anciano , Terapia Neoadyuvante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resultado del Tratamiento , Estudios de Cohortes , Oxaliplatino/uso terapéutico , PancreatectomíaRESUMEN
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
PURPOSE: We investigated true indication of neoadjuvant therapy (NAT) in resectable pancreatic cancer and the optimal surgical timing in borderline resectable pancreatic cancer. METHODS: A total of 687 patients with resectable or borderline resectable pancreatic cancer were enrolled. Survival analysis was performed by intention-to-treat analysis and propensity score matching (PSM) was conducted. RESULTS: In resectable disease, the NAT group showed better overall survival (OS) compared with the upfront group. Multivariate analysis identified CA19-9 level (≥100 U/mL) and lymph node metastasis to be prognostic factors, and a tumor size of 25 mm was the optimal cut-off value to predict lymph node metastasis. There was no significant survival difference between patients with a tumor size ≤25 mm and CA19-9 < 100 U/mL and those in the NAT group. In borderline resectable disease, OS in the NAT group was significantly better than that in the upfront group. CEA (≥5 ng/mL) and CA19-9 (≥100 U/mL) were identified as prognostic factors; however, the OS of patients fulfilling these factors was worse than that of the NAT group. CONCLUSIONS: NAT could be unnecessary in patients with tumor size ≤25 mm and CA19-9 < 100 U/mL in resectable disease. In borderline resectable disease, surgery should be delayed until tumor marker levels are well controlled.
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Terapia Neoadyuvante , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/patología , Masculino , Femenino , Anciano , Persona de Mediana Edad , Antígeno CA-19-9/sangre , Pronóstico , Análisis de Supervivencia , Metástasis Linfática , Puntaje de Propensión , Pancreatectomía , Adulto , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Central pancreatectomy (CP) is accepted as a function-preserving procedure for benign tumors. However, the indication of CP for pancreatic cancers is limited. This multicenter study aimed to clarify the indications of CP for clinical T1 pancreatic body cancer. METHODS: This multicenter study analyzed patients who underwent CP or distal pancreatectomy (DP) for clinical T1 pancreatic body cancer between 2013 and 2020 at three high-volume centers. RESULTS: A total of 50 patients were enrolled: nine patients, who underwent CP, were classified into the CP group, while 38 patients, who underwent DP, served as controls. Three patients converted CP to DP during operation were excluded. Five patients in the CP group and 15 patients in the control group underwent preoperative treatment. The 5-year survival rate was 100% in the CP group, and 42% (p = .040) in the control group. Recurrence was found in three patients in the CP group. Importantly, insulin was not required after surgery in patients in the CP group. CONCLUSION: The clinical outcomes of CP were comparable to or even better than that of conventional pancreatectomy. Our collaborative study suggests that CP may be an acceptable therapeutic option for selected patients with clinical T1 pancreatic body cancer.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Pancreatectomía/métodos , Resultado del Tratamiento , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/cirugía , Carcinoma Ductal Pancreático/patología , Páncreas/cirugía , Estudios Retrospectivos , Complicaciones Posoperatorias/cirugíaRESUMEN
INTRODUCTION: Lymph-nodal involvement (N+) represents an adverse prognostic factor after pancreatoduodenectomy (PD) for pancreatic adenocarcinoma (PDAC). Preoperative diagnostic and staging modalities lack sensitivity for identifying N+. This study aimed to investigate preoperative CA19.9 in predicting the N+ stage in resectable-PDAC (R-PDAC). METHODS: Patients included in a multi-institutional retrospective database of PDs performed for R-PDAC from January 2000 to June 2021 were analyzed. A preoperative laboratory value of CA19.9 >37 U/L was used in univariate and multivariate logistic regression analysis to determine a possible association with N+. Additionally, different cut-offs of CA19.9 related to the preoperative clinical T (cT) stage was assessed to evaluate the risk of N+. RESULTS: A total of 2034 PDs from thirteen centers were included in the study. CA19.9>37 U/L was significantly associated with higher N+ at univariate and multivariate analysis (P<0.001). CA19.9 levels >37 U/L were associated with N+ in 75.9%, 81.3%, and 85.7% of patients, respectively, in cT1, cT2, and cT3 tumors and with higher cut-off values for all cT stages. CONCLUSION: Lymph nodal involvement is strongly related to preoperative CA19.9 levels. Specially in patients staged as cT3 the CA 19.9 could represent a valid and easy tool to suspect nodal involvement. Due to these findings, R-PDAC patients with elevated CA19.9 values should be considered in a more biologically advanced stage.
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Pancreatic ductal adenocarcinoma (PDAC) is a typical refractory malignancy, and many patients have distant organ metastases at diagnosis, such as liver metastasis and peritoneal dissemination. The standard treatment for unresectable PDAC with distant organ metastasis (UR-M) is chemotherapy, but the prognosis remained poor. However, with recent dramatic developments in chemotherapy, the prognosis has gradually improved, and some patients have experienced marked shrinkage or disappearance of their metastatic lesions. With this trend, attempts have been made to resect a small number of metastases (so-called oligometastases) in combination with the primary tumor or to resect the primary and metastatic tumor in patients with a favorable response to anti-cancer treatment after a certain period of time (so-called conversion surgery). An international consensus meeting on surgical treatment for UR-M PDAC was held during the Joint Congress of the 26th Meeting of the International Association of Pancreatology (IAP) and the 53rd Annual Meeting of the Japan Pancreas Society (JPS) in Kyoto in July 2022. The presenters showed their indications for and results of surgical treatment for UR-M PDAC and discussed their advantages and disadvantages with the experts. Although these reports were limited to a small number of patients, findings suggest that these surgical treatments for patients with UR-M PDAC who have had a significant response to chemotherapy may contribute to a prognosis of prolonged survival. We hope that this article summarizing the discussion and agreements at the meeting will serve as the basis for future trials and guidelines.
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Carcinoma Ductal Pancreático , Gastroenterología , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/patología , Japón , Páncreas/cirugía , Páncreas/patología , Neoplasias Pancreáticas/patología , Conferencias de Consenso como AsuntoRESUMEN
BACKGROUND: Based on the Japan Adjuvant Study Group of Pancreatic Cancer-01 results, S-1 adjuvant chemotherapy has been the standard in resected pancreatic ductal adenocarcinoma (PDAC) patients in Japan and elsewhere, initiated within 10 weeks after surgery. To assess the clinical impact of this timing, we conducted a secondary analysis of a nationwide survey by the Japan Pancreas Society. METHODS: A total of 3361 patients were divided into two groups: 2681 (79.8%) initiating the therapy within 10 weeks after surgery (standard) and 680 (20.2%) after 10 weeks (delayed). We compared recurrence-free survival (RFS) and overall survival (OS) using the log-rank test and Cox proportional hazards model with conditional landmark analysis between the groups. Results were verified by adjustment with inverse-probability-of-treatment weighting (IPTW) analysis. RESULTS: The median timing of S-1 adjuvant chemotherapy initiation was 50 days (interquartile range: 38-66). In the standard group, 5-year RFS and OS rates were 32.3-48.7%, respectively, compared with 25.0-38.7% in the delayed group. Hazard ratios (HRs) and 95% confidence intervals were 0.84 (0.76-0.93) for RFS (p < 0.001) and 0.77 (0.69-0.87) for OS (p < 0.001). The IPTW analysis yielded 5-year RFS rates of 32.1% and 25.3% in the standard versus delayed group, respectively [HR = 0.86 (0.77-0.96), p < 0.001] and 5-year OS rates of 48.3% and 39.8%, respectively [HR = 0.81 (0.71-0.92), p < 0.001]. CONCLUSIONS: Initiation of S-1 adjuvant chemotherapy in resected PDAC patients within 10 weeks after surgery may offer survival benefit over later initiation.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Japón , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Quimioterapia Adyuvante/métodos , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/cirugía , Páncreas/patología , Estudios Retrospectivos , Neoplasias PancreáticasRESUMEN
Locally advanced pancreatic cancer (LAPC), which progresses locally and surrounds major vessels, has historically been deemed unresectable. Surgery alone failed to provide curative resection and improve overall survival. With the advancements in treatment, reports have shown favorable results in LAPC after undergoing successful chemotherapy therapy or chemoradiation therapy followed by surgical resection, so-called "conversion surgery", at experienced high-volume centers. However, recognizing significant regional and institutional disparities in the management of LAPC, an international consensus meeting on conversion surgery for LAPC was held during the Joint Congress of the 26th Meeting of the International Association of Pancreatology (IAP) and the 53rd Annual Meeting of Japan Pancreas Society (JPS) in Kyoto in July 2022. During the meeting, presenters reported the current best multidisciplinary practices for LAPC, including preoperative modalities, best systemic treatment regimens and durations, procedures of conversion surgery with or without vascular resections, biomarkers, and genetic studies. It was unanimously agreed among the experts in this meeting that "cancer biology is surpassing locoregional anatomical resectability" in the era of effective multiagent treatment. The biology of pancreatic cancer has yet to be further elucidated, and we believe it is essential to improve the treatment outcomes of LAPC patients through continued efforts from each institution and more international collaboration. This article summarizes the agreement during the discussion amongst the experts in the meeting. We hope that this will serve as a foundation for future international collaboration and recommendations for future guidelines.
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Gastroenterología , Neoplasias Pancreáticas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Japón , Terapia Neoadyuvante/métodos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/cirugíaRESUMEN
Although nanoliposomal irinotecan combined with 5-fluorouracil and leucovorin (nal-IRI+5-FU/LV) has been used to treat first-line resistant unresectable pancreatic cancer, the efficacy and safety data among the elderly remain limited. We retrospectively analyzed clinical outcomes among elderly patients. Patients treated with nal-IRI+5-FU/LV were assigned to the elderly (≥75 years) and non-elderly (<75 years) groups. Herein, 85 patients received nal-IRI+5-FU/LV, with 32 assigned to the elderly group. Patient characteristics in the elderly and non-elderly groups were as follows: age: 78.5 (75-88)/71 (48-74), male: 17/32 (53%/60%), performance status (ECOG) 0:9/20 (28%/38%), nal-IRI+5-FU/LV in second line: 23/24 (72%/45%), respectively. A significantly high number of elderly patients exhibited aggravated kidney and hepatic functions. Median overall survival (OS) and progression-free survival (PFS) in the elderly group vs. non-elderly group were 9.4 months vs. 9.9 months (hazard ratio (HR) 1.51, 95% confidence interval (CI) 0.85-2.67, p = 0.16) and 3.4 months vs. 3.7 months (HR 1.41, 95% CI 0.86-2.32, p = 0.17). Both groups exhibited a similar incidence of efficacy and adverse events. There were no significant differences in OS and PFS between groups. We analyzed the C-reactive protein/albumin ratio (CAR) and neutrophil/lymphocyte ratio (NLR) as indicators that could determine eligibility for nal-IRI+5-FU/LV. The median CAR and NLR scores in the ineligible group were 1.17 and 4.23 (p < 0.001 and p = 0.018, respectively). Elderly patients with worse CAR and NLR score could be deemed ineligible for nal-IRI+5-FU/LV.
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PURPOSE: Since 2002, the Japan Surgical Society has established a board certification system for surgeons to be certified for a specialty. Surgery remains a male-dominated field in Japan. This study aimed to clarify if the Japanese surgical residency training system is equally suitable for female and male residents. METHODS: The Japan Surgical Society conducted the first questionnaire survey regarding the system of surgical training for the residents in 2016. The questionnaire included the degree of satisfaction with 7 aspects of the training system, including the number and variety of cases experienced and duration and quality of instruction, and the learning level for 31 procedures. The degree of satisfaction and level of learning were compared between female and male residents. RESULTS: The degree of satisfaction was similar for all items between female and male residents. Female residents chose breast surgery as their subspecialty more frequently than male residents and were more confident in breast surgery procedures than male residents. Conversely, fewer female residents chose gastrointestinal surgery and were less confident in gastrointestinal surgery procedures than male residents. CONCLUSION: Female residents were as satisfied with the current surgical training system as male residents. However, there may be room for improvement in the surgical system, considering that fewer applications for gastrointestinal surgery come from female residents than from males.
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Neoplasias de la Mama , Internado y Residencia , Humanos , Masculino , Femenino , Educación de Postgrado en Medicina/métodos , Japón , Encuestas y Cuestionarios , Satisfacción PersonalRESUMEN
Several previous case reports have shown that patients with immunoglobulin D (IgD) multiple myeloma (MM) can be withdrawn from hemodialysis, however, the characteristics that can predict withdrawal in these patients have not yet been elucidated. A 57-year-old Japanese woman required hemodialysis because of renal dysfunction due to IgD-λ and Bence Jones protein-λ MM. Bortezomib-based chemotherapy nine days after admission led to her withdrawal from hemodialysis on Day 50. In our case-based review, younger age and early initiation of bortezomib-based chemotherapy emerged as possible predictors of successful hemodialysis withdrawal.
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Mieloma Múltiple , Humanos , Femenino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Bortezomib/uso terapéutico , Inmunoglobulina D/uso terapéutico , Diálisis Renal , Cadenas lambda de InmunoglobulinaRESUMEN
BACKGROUND: /Objectives: Effects of chemotherapy on gut microbiota have been reported in various carcinomas. The current study aimed to evaluate the changes in the gut microbiota before and after neoadjuvant chemotherapy (NAC) in patients with resectable (R) and borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) and understand their clinical implications. METHODS: Twenty patients diagnosed with R/BR-PDAC were included in this study. Stool samples were collected at two points, before and after NAC, for microbiota analysis using 16S ribosomal RNA (16S rRNA) gene sequences. RESULTS: Of the 20 patients, 18 (90%) were treated with gemcitabine plus S-1 as NAC, and the remaining patients received gemcitabine plus nab-paclitaxel and a fluorouracil, leucovorin, irinotecan, and oxaliplatin combination. No significant differences were observed in the α- and ß-diversity before and after NAC. Bacterial diversity was not associated with Evans classification (histological grade of tumor destruction by NAC) or postoperative complications. The relative abundance of Actinobacteria phylum after NAC was significantly lower than that before NAC (P = 0.02). At the genus level, the relative abundance of Bifidobacterium before NAC in patients with Evans grade 2 disease was significantly higher than that in patients with Evans grade 1 disease (P = 0.03). Patients with Evans grade 2 lost significantly more Bifidobacterium than patients with Evans grade 1 (P = 0.01). CONCLUSIONS: The diversity of gut microbiota was neither decreased by NAC for R/BR-PDAC nor associated with postoperative complications. Lower incidence of Bifidobacterium genus before NAC may be associated with a lower pathological response to NAC.
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Carcinoma Ductal Pancreático , Microbioma Gastrointestinal , Neoplasias Pancreáticas , Humanos , Terapia Neoadyuvante , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/cirugía , Desoxicitidina/uso terapéutico , ARN Ribosómico 16S , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/cirugía , Fluorouracilo/uso terapéutico , Leucovorina/uso terapéutico , Neoplasias PancreáticasRESUMEN
Due to the worldwide travel restrictions caused by the 2019 coronavirus disease pandemic, many universities and students lost opportunities to engage in international exchange over the past 2 years. Teleconferencing systems have thus been developed to compensate for severe travel restrictions. Kansai Medical University in Japan and Vilnius University in Lithuania have a collaborative research and academic relationship. The two universities have been conducting an online joint international surgery lecture series for the medical students of both universities. Fifteen lectures were given from October 2021 to May 2022. The lectures focused on gastrointestinal surgery, gastroenterology, radiology, pathology, genetics, laboratory medicine, and organ transplantation. A survey of the attendees indicated that they were generally interested in the content and satisfied with attending this lecture series. Our efforts were successful in providing Japanese and Lithuanian medical students with the opportunity to engage in international exchange through lectures held in each other's countries.
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Estudiantes de Medicina , Humanos , Encuestas y Cuestionarios , Universidades , JapónRESUMEN
Introduction: In patients with pancreatic ductal adenocarcinoma (PDAC) in the pancreatic body (Pb) and tail (Pt), the appropriate area for lymphadenectomy is controversial. This study aimed to reevaluate the extent of lymph node (LN) metastasis in Pb- and Pt-PDAC, and to define the optimal area of LN dissection. Patients and methods: This single-center retrospective study evaluated patients with Pb- and Pt-PDAC who underwent distal pancreatectomy with extended lymphadenectomy between 2006 and 2020. LN metastasis in >3.0% of patients were defined as new regional LN. Results: The study cohort included 135 patients with Pb-PDAC and 42 patients with Pt-PDAC. In patients with Pb-PDAC, LNs around the splenic artery (SPA) had the highest metastasis-positive rate (54.1%). LNs along the left gastric artery, common hepatic artery, celiac axis (CA), superior mesenteric artery (SMA), and splenic hilus were defined as new regional LNs. In patients with Pt-PDAC, LNs at the splenic hilum had the highest metastasis-positive rate (38.1%). The station and LN around the SPA were defined as new regional LNs in those with Pt-PDAC. Metastasis beyond the newly defined regional LNs was not associated with survival. The incidence of LN metastasis was lower in patients who received preoperative chemotherapy than in those who underwent upfront surgery in both Pb- and Pt-PDAC. Conclusion: Although it needs to be verified in future multicenter studies, LN of both the CA and SMA systems should be dissected in patients with Pb-PDAC. However, only those around the SPA and splenic hilus should be dissected routinely in those with Pt-PDAC.
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BACKGROUND: Characteristics and prognoses of patients with occult metastases (OM) of pancreatic ductal adenocarcinoma (PDAC) compared with radiologically defined metastases (RM) have been rarely reported. OBJECTIVE: We aimed to clarify the prognosis of OM compared with RM and to establish a treatment strategy for PDAC patients with OM. METHODS: This single-institution, retrospective study evaluated patients with unresectable PDAC between 2008 and 2018. OM was defined as abdominal metastasis that was detected by staging laparoscopy or open laparotomy but not in the initial assessment of radiological images. RESULTS: OM and RM were identified in 135 and 112 patients, respectively. Eastern Cooperative Oncology Group Performance Status (ECOG PS), neutrophil to lymphocyte ratio (NLR), tumor diameter, and rate of local unresectability were significantly lower in the OM group. Median overall survival (OS) of OM was significantly better than that of RM (13.0 vs 8.9 months, p < 0.001). In multivariate analysis of OS, ECOG PS ≥ 1 (HR 1.64, p = 0.009), NLR ≥5 (HR 1.97, p = 0.004), carbohydrate antigen (CA) 19-9 ≥1000 (HR 1.68, p = 0.001), tumor diameter ≥40 mm (HR 1.40, p = 0.027), conversion surgery (HR 0.12, p < 0.001), and multiple lines of chemotherapy (HR 0.38, p < 0.001) were independent predictors. However, type of metastasis (OM vs RM) not an independent predictor (HR 1.10, p = 0.590). CONCLUSION: The prognosis of PDAC with OM was relatively better than that with RM, but general and nutritional statuses, primary tumor size and CA19-9, conversion surgery and multiple lines of chemotherapy were independent predictors but not tumor burden.
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Carcinoma Ductal Pancreático , Neoplasias Hepáticas , Neoplasias Pancreáticas , Humanos , Estudios Retrospectivos , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/terapia , Pronóstico , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Neoplasias PancreáticasRESUMEN
Visible particles (VPs) formation in liquid monoclonal antibody formulations is a critical quality issue. Formulations that include poloxamer 188 (PX188) as a surfactant are prone to the formation of VPs comprising aggregated complexes of protein and polydimethylsiloxane (PDMS; silicone oil) derived from primary containers. However, the mechanisms through which these VPs form are complicated and remain to be fully elucidated. This study demonstrates for the first time the dominant spot and pathway of protein-PDMS VP formation in a particular liquid vial formulation. Specifically, when a vial sealed with a PDMS-coated stopper is stored in an upright position under conditions whereby the antibody solution has become well-adhered to the stopper and an air phase exists in the vicinity, protein-PDMS aggregates form on the stopper and are then desorbed into the drug solution to be detected as VPs. Here, we evaluated the effects of several factors on VP formation: adhesion of the drug solution to the stopper, storage orientation, silicone coating on the stopper, vial material, and hydrophobicity of PX188. Remarkably, we found that changing any one of the factors could significantly affect VP formation. Our findings are instructive for better understanding the mechanisms of VP formation in vial products and can provide strategies for VP mitigation in biotherapeutics.
Asunto(s)
Anticuerpos Monoclonales , Embalaje de Medicamentos , Aceites de SiliconaRESUMEN
Background: Surgical resection for liver-only synchronous metastases of pancreatic ductal adenocarcinoma remains controversial. We investigated the role of conversion surgery in patients with a favorable response to systemic chemotherapy. Methods: Patients (n=49) were diagnosed liver-only synchronous metastases using staging laparoscopy or open laparotomy between 2007 and 2022. Clinical outcomes were retrospectively compared among patients who underwent conversion surgery (n=10), upfront surgery with or without short-term neoadjuvant chemotherapy (UpS/short NAC) for oligometastases and occult metastases limited to the liver (n=8), and chemotherapy only for resectable or borderline resectable disease with occult liver-only metastases (n=31). The surgical indication of conversion surgery was fixed as the ABC criteria, namely, Anatomical objective response of disappearance of liver metastases on imaging studies, Biological response of CA19-9 level decrease to ≤150 U/mL, and Conditional response of surgical fitness. In addition to the above ABC criteria, tumor disappearance at the liver was repeatedly confirmed using staging laparoscopy (laparoscopic response; L), and metabolic complete responses were confirmed using positron emission tomography-computed tomography (CT) (metabolic response; M). Results: Median survival time from initial treatment was 9.9 months [95% confidence interval (CI): 8.3-10.9] in the chemotherapy group, 10.4 months (95% CI: 6.6-17.8) in the UpS/short NAC group, and 36.7 months (95% CI: 19.0-84.8) in the conversion surgery group (conversion surgery vs. UpS/short NAC, P=0.002; conversion surgery vs. chemotherapy, P<0.001; UpS/short NAC vs. chemotherapy, P=0.554). One patient in the UpS/short NAC group and three in the conversion surgery group achieved 5-year survival. Among them, two patients with initially multiple liver metastases (≥10) in the conversion surgery group survived beyond 5 years. Only conversion surgery was a significant independent prognostic factor in a total cohort (hazard ratio; 0.173, P=0.002). Conclusions: Conversion surgery, but not UpS/short NAC, may enhance survival in patients with synchronous liver metastases and favorably anatomical, biological and conditional responses to systemic chemotherapy.