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BACKGROUND: Robotic pancreatoduodenectomy is increasingly being implemented worldwide, with good results reported from individual expert centers. However, it is unclear to what extent outcomes will continue to improve during the learning curve, as large international studies are lacking. METHODS: An international retrospective multicenter case series, including consecutive patients after robotic pancreatoduodenectomy from 18 centers in 8 countries in Europe, Asia, and South America until December 31, 2019, was conducted. A cumulative sum analysis was performed to determine the inflection points for the feasibility (operative time and blood loss) and proficiency (postoperative pancreatic fistula grade B/C and major morbidity) learning curves. Outcomes were compared in 3 groups on the basis of the learning curve inflection points. RESULTS: Overall, 2,186 patients after robotic pancreatoduodenectomy were included. The feasibility learning curve was reached after 30-45 robotic pancreatoduodenectomy procedures and the proficiency learning curve after 90 robotic pancreatoduodenectomy procedures. These inflection points created 3 phases, which were associated with major morbidity (24.7%, 23.4%, and 12.3%, P < .001) but not 30-day mortality (2.1%, 2.0%, and 1.5%, P = .670). Other outcomes mostly continued to improve, including median operative time 432, 390, and 300 minutes (P < .0001), conversion 6.0%, 4.7%, and 2.7% (P = .002), bile leakage 7.2%, 4.1%, and 2.4% (P < .001), postpancreatectomy hemorrhage 6.5%, 6.1%, and 1.8% (n = 21) but not R0 resection (pancreatic ductal adenocarcinoma only) 78.5%, 73.9%, and 82.8% (P = .35), and 90-day mortality rate 3.1%, 3.5%, and 2.1% (P = .191). Centers performing >20 robotic pancreatoduodenectomies annually had lower rates of conversion, reoperation, and shorter median operative time as compared with centers performing 10-20 robotic pancreatoduodenectomies annually. CONCLUSION: This international multicenter study demonstrates that most outcomes of robotic pancreatoduodenectomy continued to improve during 3 learning curve phases without a negative effect on 90-day mortality. Randomized studies are needed in high-volume centers that have surpassed the first learning curves, to compare these outcomes with the open approach.
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BACKGROUND: Surgical resection (SR) is the main treatment for small bowel adenocarcinoma (SBA), but it increases metabolic demand, systemic inflammation, and digestive dysfunction, resulting in major impacts on the postoperative outcomes of patients. This study, we aimed to investigate the role of the postoperative prognostic nutritional index (PNI), a surrogate marker of inflammation and nutrition, in patients with SBA after resection. METHODS: From June 2014 to March 2022, 44 consecutive patients who underwent SR for SBA in Taipei Veterans General Hospital were retrospectively reviewed. Factors associated with survival including PNI were analyzed. RESULTS: PNI decreased in patients after SR for SBA (median change: -1.82), particularly in those who underwent Whipple operation or developed postoperative pancreatic fistula. Postoperative PNI < 45.2 best predicted overall survival (OS) (AUROC: 0.826, p = 0.001). Patients with lower postoperative PNI had significantly worse OS compared to those higher postoperative values (median OS: 19.3 months vs. not reached, p < 0.001). Low postoperative PNI (hazard ratio [HR]: 11.404, p = 0.002), tumoral lymphovascular invasion (HR: 8.023, p = 0.012), and adjuvant chemotherapy (HR: 0.055, p = 0.002) were independent risk factors for OS. Postoperative PNI also significantly predicted recurrence-free survival independent of lymphovascular invasion and adjuvant chemotherapy (HR: 6.705, p = 0.001). CONCLUSION: PNI commonly decreases in patients with SBA who undergo Whipple surgery or develop postoperative pancreatic fistula. Postoperative PNI independently predicts survival and may serve as a clinical marker to optimize patient outcomes.
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BACKGROUND: In patients with hepatic artery variation (HAV), feasibility and justification of robotic pancreatoduodenectomy (RPD) for periampullary lesions have been not been well established. METHODS: A total of 600 patients with periampullary lesions receiving RPD or open pancreaticoduodenectomy (OPD) were identified from our prospectively collected computer database. Surgical outcomes, oncological radicality, and survival outcomes after RPD in HAV ( +) and (-) patients were compared. RESULTS: The incidence of HAV was 16%, including 12.7% in patients with RPD and 23.0% in those with OPD. In the HAV ( +) group, vascular injury rate had no statistical difference between the RPD (3.7%) and OPD (9.1%) patients, P = 0.404. Among the RPD patients, those with HAV ( +) had longer operation time (8.5 ± 2.5 vs. 7.7 ± 2.0 h, P = 0.013) and higher vascular injury (3.8% vs. 0.6%, P = 0.024) when compared with the HAV (-) patients. There was no significant difference between the HAV ( +) and (-) patients with RPD regarding blood loss, open conversion, vascular resection, and surgical mortality and morbidity. There was no survival difference between the HAV ( +) and (-) patients with pancreatic head adenocarcinoma after RPD. There was no survival difference between RPD and OPD in the HAV ( +) group. CONCLUSIONS: When compared with OPD, RPD is feasible and justifiable without increasing vascular injury rate for patients with HAV ( +). Hepatic artery variation has no negative impact on surgical, oncological, and survival outcomes following an RPD, if it is accurately identified pre-operatively and appropriately managed intraoperatively.
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Arteria Hepática , Neoplasias Pancreáticas , Pancreaticoduodenectomía , Procedimientos Quirúrgicos Robotizados , Humanos , Pancreaticoduodenectomía/métodos , Arteria Hepática/cirugía , Femenino , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Robotizados/métodos , Neoplasias Pancreáticas/cirugía , Anciano , Resultado del Tratamiento , Tempo Operativo , Estudios RetrospectivosRESUMEN
BACKGROUND: Duodenal adenocarcinoma is rare and its prognostic factors remain controversial. In our study, the role of cell-free deoxyribonucleic acid (cfDNA) as prognostic factor in duodenal adenocarcinoma was evaluated. METHODS: From June 2003 to July 2021, plasma samples were collected from 41 patients with duodenal adenocarcinoma. Plasma cfDNA was assessed in combination with clinicopathological and biochemical characteristics. Univariate and multivariate analyses were conducted to identify independent prognostic factors for overall survival with a Cox proportional hazards regression model. RESULTS: The 1- and 5-year survival rates of the patients with high plasma cfDNA level (>9288 copies/mL) group were 58.7% and 17.6%, respectively, which were much lower than patients with low cfDNA level (≤9288 copies/mL), with 95.2% and 64.6%. In univariate analysis, high cfDNA level, lymph node involvement, lymphovascular invasion, and tumor stage were associated with decreased survival. When subjected to multivariate analysis, only high cfDNA level showed significance in influencing the overall survival of duodenal cancer. CONCLUSION: cfDNA analysis is simple and noninvasive. High cfDNA level is a strong independent prognostic factor for decreased overall survival and it should be integrated into clinical care.
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Adenocarcinoma , Ácidos Nucleicos Libres de Células , Neoplasias Duodenales , Humanos , Adenocarcinoma/genética , Modelos de Riesgos Proporcionales , Biomarcadores de Tumor , PronósticoRESUMEN
Background: With the rapid development of robotic surgery, especially for the abdominal surgery, robotic pancreatic surgery (RPS) has been applied increasingly around the world. However, evidence-based guidelines regarding its application, safety, and efficacy are still lacking. To harvest robust evidence and comprehensive clinical practice, this study aims to develop international guidelines on the use of RPS. Methods: World Health Organization (WHO) Handbook for Guideline Development, GRADE Grid method, Delphi vote, and the AGREE-II instrument were used to establish the Guideline Steering Group, Guideline Development Group, and Guideline Secretary Group, formulate 19 clinical questions, develop the recommendations, and draft the guidelines. Three online meetings were held on 04/12/2020, 30/11/2021, and 25/01/2022 to vote on the recommendations and get advice and suggestions from all involved experts. All the experts focusing on minimally invasive surgery from America, Europe and Oceania made great contributions to this consensus guideline. Results: After a systematic literature review 176 studies were included, 19 questions were addressed and 14 recommendations were developed through the expert assessment and comprehensive judgment of the quality and credibility of the evidence. Conclusions: The international RPS guidelines can guide current practice for surgeons, patients, medical societies, hospital administrators, and related social communities. Further randomized trials are required to determine the added value of RPS as compared to open and laparoscopic surgery.
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BACKGROUND/OBJECTIVE: Robotic pancreaticoduodenectomy in ampullary cancer has never been studied. This study aimed to clarify the feasibility and justification of robotic pancreaticoduodenectomy in ampullary cancer in terms of surgical risks, and oncologic and survival outcomes. METHODS: A propensity score-matching comparison of robotic and open pancreaticoduodenectomy based on seven factors commonly used to predict the survival outcomes in ampullary cancer patients. RESULTS: A total of 147 patients were enrolled, of which 101 and 46 underwent robotic and open pancreaticoduodenectomies, respectively. After propensity score-matching with a 2:1 ratio, 88 and 44 patients in the robotic and open pancreaticoduodenectomy groups were included. The operation time was of no significant difference after matching. The median intraoperative blood loss was much less in those who underwent robotic pancreaticoduodenectomy, both before (median, 120 vs. 320 c.c. P < 0.001) and after (100 vs. 335 mL P < 0.001) score-matching. There were no significant differences in terms of surgical risks, including surgical mortality, surgical morbidity, Clavien-Dindo severity classification, postoperative pancreatic fistula, delayed gastric emptying, post-pancreatectomy hemorrhage, chyle leak, bile leak, and wound infection, both before or after score-matching. The survival outcomes were also similar between the two groups, regardless of matching. CONCLUSIONS: Robotic pancreaticoduodenectomy for ampullary cancer is not only technically feasible and safe without increasing surgical risks, but also oncologically justifiable without compromising surgical radicality and survival outcomes.
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Ampolla Hepatopancreática , Neoplasias del Conducto Colédoco , Laparoscopía , Neoplasias Pancreáticas , Procedimientos Quirúrgicos Robotizados , Humanos , Pancreaticoduodenectomía/efectos adversos , Ampolla Hepatopancreática/cirugía , Puntaje de Propensión , Neoplasias del Conducto Colédoco/cirugía , Complicaciones Posoperatorias/etiología , Resultado del Tratamiento , Estudios Retrospectivos , Neoplasias Pancreáticas/cirugíaRESUMEN
BACKGROUND: The role of the robotic approach for pancreaticoduodenectomy has not been well established with robust data. This study aimed to reappraise feasibility and justification of robotic pancreaticoduodenectomy (RPD) over time. METHODS: A total of 500 patients undergoing RPD were enrolled and divided into early (first 250 patients) and late (last 250 patients) groups for a comparative study. RESULTS: The conversion rate was 8.8% overall and was significantly lower in the late group (5.6% vs. 12.0%; p = .012). The overall median intraoperative blood loss was 130 mL. Radicality of resection was similar between early and late groups. The overall surgical mortality after RPD was 1.3%. The overall surgical morbidity and major complication was 44.1% and 13.2%, respectively, and similar between early and late groups. Chyle leakage was the most common complication after RPD (25.0%), followed by postoperative pancreatic fistula (POPF). The POPF rate was 8.6% overall, with 5.9% in the early group and 11.0% in the late group, p = .051. The overall delayed gastric emptying rate was 3.5%. The late group had better survival outcomes than those of the early group after RPD for ampullary adenocarcinoma (p = .027) but not for pancreatic head adenocarcinoma. CONCLUSIONS: Reappraisal of this study has confirmed that RPD is not only technically feasible without increasing surgical risks but also oncologically justified without compromising survival outcomes for both pancreatic head and other periampullary cancers over time. Moreover, RPD is associated with the benefits of low surgical mortality, blood loss, and delayed gastric emptying.
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Adenocarcinoma , Gastroparesia , Neoplasias Pancreáticas , Procedimientos Quirúrgicos Robotizados , Humanos , Pancreaticoduodenectomía/efectos adversos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Gastroparesia/complicaciones , Gastroparesia/cirugía , Páncreas/cirugía , Fístula Pancreática/etiología , Complicaciones Posoperatorias/cirugía , Adenocarcinoma/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND: Central pancreatectomy (CP) is an ideal parenchyma-sparing procedure. The experience of r robotic central pancreatectomy (RCP) is very limited. MATERIALS AND METHODS: Patients undergoing CP were included. Comparisons were made between RCP and open central pancreatectomy (OCP) groups. RESULTS: The most common lesion in patients undergoing CP was serous cystadenoma (35.5%). The median operation time was 4.2 h for RCP versus 5.5 h for OCP. The median blood loss was significantly lower in RCP, 20 c.c. versus 170 c.c., p = 0.001. Postoperative pancreatic fistula occurred in 19.4% of all patients, with 22.1% in RCP and 15.4% in OCP. There was no significant difference regarding other surgical complications between the RCP and OCP groups. Only one patient in the OCP group developed de novo diabetes mellitus (DM), and no steatorrhoea/diarrhoea occurred after either RCP or OCP. CONCLUSIONS: RCP is feasible and safe without compromising surgical outcomes and pancreatic functions.
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Aim: Whether to execute pancreaticoduodenectomy or not for older people could pose a dilemma. This study clarifies the safety and justification of robotic pancreaticoduodenectomy (RPD) for older individuals over 80. Methods: A total of 500 patients undergoing RPD were divided into group O (≥ 80 y/o) and group Y (< 80 y/o) for comparison. Results: There were 62 (12.4%) patients in group O. Surgical mortality was 1.6% for overall patients and higher in group O, 6.5% vs 0.9%; p = 0.001. The surgical complication was comparable between groups O and Y. Delayed gastric emptying and bile leakage were higher in group O, 9.7% vs 2.5%; p = 0.004, and 6.5% vs 0.9%; p = 0.001, respectively. Length of stay was also longer in group O, with a median of 26 vs 19 days; p = 0.001. Survival outcome after RPD was poorer in group O for overall periampullary adenocarcinomas, with a 5-year survival of 48.1% vs 51.2%; p = 0.025 and also for the subgroup of pancreatic head adenocarcinoma, with a 3-year survival of 27.4% vs 42.5%; p = 0.030. Conclusion: RPD is safe and justified for the selected octogenarians and even nonagenarians, whoever is fit for a major operation. Nevertheless, pancreatic head cancer and higher mortality risk for the aged over 80 with advanced ASA score ≥ 3 should be informed as part of counselling in offering RPD.
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Neoplasias Pancreáticas , Procedimientos Quirúrgicos Robotizados , Anciano de 80 o más Años , Humanos , Anciano , Pancreaticoduodenectomía/efectos adversos , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Neoplasias Pancreáticas/cirugía , Neoplasias PancreáticasRESUMEN
BACKGROUND: Cell-free DNA (cfDNA) as an oncological biomarker has drawn much attention in recent years, but very limited effort has been made to investigate the prognostic values of cfDNA in distal common bile duct (CBD) cancer. METHODS: Plasma cfDNA was measured in 67 patients with resectable distal CBD cancer. Survival outcomes and the correlation of cfDNA with other conventional prognostic factors were determined. RESULTS: cfDNA levels were significantly higher in female patients, and those with poor tumor differentiation, abnormal serum carcinoembryonic antigen (CEA) level, and stage III cancer. The significant prognostic factors included a high cfDNA level (>8955 copies/mL), abnormal serum CEA level, stage III cancer, and positive resection margins. Compared with patients with high cfDNA level, those with lower cfDNA level (≤8955 copies/mL) had significantly better overall survival outcomes (74.4% vs 100% and 19.2% vs 52.6%, for 1- and 5-year survival rates, respectively, p = 0.001). The cfDNA level, perineural invasion, CEA level, and radicality were identified as independent prognostic factors for distal CBD cancer after multivariate analysis. CONCLUSION: Circulating cfDNA levels play a significant role in predicting the prognosis and survival outcome for resectable distal CBD cancer. Furthermore, acting as a promising liquid biopsy, cfDNA could serve as a prognostic and predictive biomarker in combination with current conventional markers to improve diagnostic and prognostic efficacy.
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Ácidos Nucleicos Libres de Células , Neoplasias , Humanos , Femenino , Pronóstico , Antígeno Carcinoembrionario , Biomarcadores de Tumor , Conducto ColédocoRESUMEN
BACKGROUND: Although we previously proposed a nomogram to predict malignancy in intraductal papillary mucinous neoplasms (IPMN) and validated it in an external cohort, its application is challenging without data on tumor markers. Moreover, existing nomograms have not been compared. This study aimed to develop a nomogram based on radiologic findings and to compare its performance with previously proposed American and Korean/Japanese nomograms. METHODS: We recruited 3708 patients who underwent surgical resection at 31 tertiary institutions in eight countries, and patients with main pancreatic duct >10 mm were excluded. To construct the nomogram, 2606 patients were randomly allocated 1:1 into training and internal validation sets, and area under the receiver operating characteristics curve (AUC) was calculated using 10-fold cross validation by exhaustive search. This nomogram was then validated and compared to the American and Korean/Japanese nomograms using 1102 patients. RESULTS: Among the 2606 patients, 90 had main-duct type, 900 had branch-duct type, and 1616 had mixed-type IPMN. Pathologic results revealed 1628 low-grade dysplasia, 476 high-grade dysplasia, and 502 invasive carcinoma. Location, cyst size, duct dilatation, and mural nodule were selected to construct the nomogram. AUC of this nomogram was higher than the American nomogram (0.691 vs 0.664, P = .014) and comparable with the Korean/Japanese nomogram (0.659 vs 0.653, P = .255). CONCLUSIONS: A novel nomogram based on radiologic findings of IPMN is competitive for predicting risk of malignancy. This nomogram would be clinically helpful in circumstances where tumor markers are not available. The nomogram is freely available at http://statgen.snu.ac.kr/software/nomogramIPMN.
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Adenocarcinoma Mucinoso , Carcinoma Ductal Pancreático , Carcinoma Papilar , Neoplasias Intraductales Pancreáticas , Neoplasias Pancreáticas , Humanos , Nomogramas , Neoplasias Intraductales Pancreáticas/diagnóstico por imagen , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/cirugía , Carcinoma Ductal Pancreático/patología , Adenocarcinoma Mucinoso/diagnóstico por imagen , Adenocarcinoma Mucinoso/cirugía , Adenocarcinoma Mucinoso/patología , Carcinoma Papilar/patología , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Biomarcadores de Tumor , Hiperplasia , Estudios RetrospectivosRESUMEN
The study of robotic pancreaticouodenectomy (RPD) focusing on delayed gastric emptying (DGE) is seldom reported. This study explored the incidence of DGE in RPD with extracorporeal hand-sewn gastrojejunostomy involving downward positioning of the stomach. Patients with periampullary lesions undergoing RPD or open pancreaticouodenectomy (OPD) were included for comparison. A variety of clinical factors were evaluated for the risk of developing DGE. There were 409 (68.2%) RPD and 191 (31.8%) OPD in this study. DGE occurred in 7.7% of patients after pancreaticoduodenectomy, with 4.4% in RPD and 14.7% in OPD, p < 0.001. Nausea/vomiting (12.6% vs. 6.3%) and jaundice (9.9% vs. 5.2%) were significant preoperative risk factors for DGE, while malignancy (8.7% vs. 2.2%) and lymph node involvement (9.8% vs. 5.6%) were significant pathological risk factors. Intraoperative blood loss > 200 c.c. was the other factor related to DGE (11.2% vs. 4.4% in those with blood loss ≤ 200 c.c.). None of the postoperative complications was significantly associated with DGE. Hospital stay was significantly longer in the group with DGE (median, 37 vs. 20 days in the group without DGE). After multivariate analysis by binary logistic regression, compared with OPD, RPD was the only independent factor associated with a lower incidence of DGE. RPD with extracorporeal hand-sewn antecolic, antiperistaltic, and inframesocolic gastrojejunostomy via a small umbilical wound involving careful downward positioning of the stomach was associated with a low incidence of DGE and presented as the most powerful independent predictor of this condition.
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Derivación Gástrica , Gastroparesia , Humanos , Pancreaticoduodenectomía/efectos adversos , Gastroparesia/epidemiología , Gastroparesia/etiología , Estudios Retrospectivos , Derivación Gástrica/efectos adversos , Factores de Riesgo , Vaciamiento Gástrico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiologíaRESUMEN
Background and Aims: There is no consensus on the superiority of robotic distal pancreatectomy (RDP) over laparoscopic distal pancreatectomy (LDP). Methods: Data of patients undergoing RDP and LDP were prospectively collected and compared. Results: There were 65 RDP and 112 LDP. RDP took a shorter operation time than LDP. Overall, DP with splenectomy took a longer operation time than that with spleen preservation. This difference was only significant in LDP group. In both RDP and LDP groups, splenectomy was associated with increased blood loss, as compared with spleen preservation. No significant differences were observed in surgical morbidity between RDP and LDP. The hospital cost in RDP was almost double that of LDP, with a median of 13,404 versus 7765 USD. Conclusion: LDP is comparable to RDP in regard to surgical outcomes. LDP with spleen preservation is highly recommended whenever possible and feasible for benign or low malignant lesions in terms of lower costs and less blood loss.
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BACKGROUND: This study aimed to clarify the feasibility and justification of pancreatic head sparing (PHS) enucleation for patients with agenesis of the dorsal pancreas (ADP) associated with a solid pseudopapillary tumor (SPT). METHODS: Data of the SPT patients with and without ADP, including clinical presentations, surgical options, and surgical and survival outcomes, were recruited for comparison. RESULTS: A total of 31 patients with SPTs were included, three of whom displayed ADP and underwent PHS enucleation. Surgical complications were comparable between the groups. Overall, the 5- and 10-year disease-free survival rates were 100% and 90%, respectively. The 20- and 25-year overall survival rates were 100% and 66.7%, respectively. Only one patient (3.2%) developed tumor recurrence 7.3 years after pancreatectomy for an SPT with lymph node involvement, and the patient survived 24.5 years after the initial operation. No tumor recurrence occurred in any patient with ADP after PHS enucleation. CONCLUSION: PHS enucleation seems to be feasible and justifiable for SPT patients with ADP in terms of surgical and survival outcomes, and this approach could be recommended to avoid pancreatic insufficiency.
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Neoplasias Glandulares y Epiteliales , Neoplasias Pancreáticas , Humanos , Anomalías Congénitas , Recurrencia Local de Neoplasia , Páncreas/anomalías , Neoplasias Pancreáticas/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND/OBJECTIVE: Pancreatic neuroendocrine tumors (P-NETs) are highly heterogeneous with wide spectrum of biological behaviors and growth patterns. Here, we aimed to assess the impact of tumor grading on P-NETs prognosis and survival outcomes. METHODS: Patients with P-NET were recruited to determine correlations between grades and clinicopathological factors, survival outcomes and prognostic factors. RESULT: A total of 152 patients with P-NETs were enrolled. G1 P-NET were associated with significantly lower rates of perineural invasion, lymphovascular invasion, lymph node involvement and distant metastasis. The pancreatic head was the most common location of P-NETs. The 1-year, 5-year and 10-year overall survival rates of the patients were 94.4%, 89.1% and 78.8%, respectively. Majority of pancreatic neuroendocrine carcinoma (P-NEC) were unresectable (90.9%), and P-NECs patients had poor survival rates (1-year, 20% and no 5-year). Male sex, tumor size ≥2.5 cm, perineural invasion, lymph node invasion, metastasis, and advanced stage were significantly associated with poorer survival outcomes. Tumor grade and sex were independent survival predictors. Moreover, tumor grade was the most powerful prognostic factor. CONCLUSIONS: Tumor grade, sex, perineural invasion, tumor size, lymph node involvement, metastasis, and stage are survival predictors for patients with P-NETs. Tumor grade is the most powerful independent prognostic factor.
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Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Masculino , Recién Nacido , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/patología , Estudios Retrospectivos , Pronóstico , Clasificación del TumorRESUMEN
INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive and has poor prognosis. There are few biomarkers to inform treatment decisions, and collecting tumour samples for testing is challenging. METHODS: Circulating tumour cells (CTCs) from patients with PDAC liquid biopsies were expanded ex vivo to form CTC-derived organoid cultures, using a laboratory-developed biomimetic cell culture system. CTC-derived organoids were tested for sensitivity to a PDAC panel of nine drugs, with tests conducted in triplicate, and a weighted cytotoxicity score (CTS) was calculated from the results. Clinical response to treatment in patients was evaluated using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 criteria at the time of blood sampling and 3 months later. The correlation between CTS and clinical response was then assessed. RESULTS: A total of 41 liquid biopsies (87.8% from patients with Stage 4 disease) were collected from 31 patients. The CTC-derived organoid expansion was achieved in 3 weeks, with 87.8% culture efficiency. CTC-derived organoid cultures were positive for EpCAM staining and negative for CD45 staining in the surface marker analysis. All patients had received a median of two lines of treatment prior to enrolment and prospective utility analysis indicated significant correlation of CTS with clinical treatment response. Two representative case studies are also presented to illustrate the relevant clinical contexts. CONCLUSIONS: CTCs were expanded from patients with PDAC liquid biopsies with a high success rate. Drug sensitivity profiles from CTC-derived organoid cultures correlated meaningfully with treatment response. Further studies are warranted to validate the predictive potential for this approach.
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Carcinoma Ductal Pancreático , Células Neoplásicas Circulantes , Neoplasias Pancreáticas , Biomarcadores de Tumor/metabolismo , Carcinoma Ductal Pancreático/patología , Humanos , Células Neoplásicas Circulantes/patología , Organoides/metabolismo , Neoplasias Pancreáticas/patología , Estudios Prospectivos , Neoplasias PancreáticasRESUMEN
BACKGROUND: Whether epidural anesthesia and analgesia (EA) improves long-term outcomes after pancreatic cancer surgery remains controversial. We conducted this retrospective cohort study to investigate the influence of EA on cancer recurrence and overall survival after surgery for pancreatic cancer. METHODS: We conducted an electronic medical chart review of patients with pancreatic cancer who underwent curative resection at our hospital from 2008 to 2017 and were followed up until December 2019. Patient demographics, anesthetic and surgical characteristics, and pathologic features were also collected. The effects of EA on postoperative cancer recurrence and overall survival were evaluated using proportional hazards regression models with inverse probability of treatment weighting (IPTW) based on propensity scores to balance unequal distributions of observed covariates. For sensitivity analysis, multivariable regression modeling and quintile-stratified propensity adjustments were also used. RESULTS: Among the 252 included patients, the median follow-up period was 15.9 months (interquartile range 6.8-28.2 months), and 88 (35%) received EA after pancreatic cancer surgery. EA was not associated with greater cancer recurrence (IPTW adjusted HR: 0.98; 95% CI, 0.78%-1.24%; p = 0.87) or all-cause mortality (IPTW adjusted HR: 1.02; 95% CI, 0.82%-1.27%; p = 0.85) after pancreatic cancer resection. In sensitivity analysis, both the multivariable and stratified Cox regression analyses failed to demonstrate significant effects of EA on cancer recurrence and survival after surgery. CONCLUSION: There were no significant associations between EA and cancer recurrence and overall survival after curative surgery for pancreatic cancer. Prospective studies should be considered to elucidate the relationship between EA and cancer outcomes after pancreatic cancer surgery.
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Analgesia Epidural , Recurrencia Local de Neoplasia , Evaluación de Resultado en la Atención de Salud , Neoplasias Pancreáticas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor Postoperatorio/prevención & control , TaiwánRESUMEN
BACKGROUND: This study is to clarify the feasibility of and justification for robotic pancreaticoduodenectomy (RPD) in patients with pancreatic adenocarcinoma. METHODS: A 1-to-1 propensity score-matched comparison of RPD and open pancreaticoduodenectomy (OPD) was performed based on six covariates commonly used to predict the survival outcome for pancreatic adenocarcinoma. RESULTS: A total of 130 patients were enrolled, with 65 in each study group after propensity score matching. The median operating time was longer for RPD (8.3 h vs. 7.0 h, P = 0.002). However, RPD was associated with less blood loss, lower overall surgical complication rate, and lower incidence of delayed gastric emptying. The resection radicality was oncologically similar between these two groups, but the median lymph node yield was higher for RPD (18 vs. 16, P = 0.038). Before propensity score matching, the 5-year survival was better in RPD (27.0% vs. 17.6%, P = 0.006). After matching, there was still a trend towards improved overall survival in the RPD group; however, the difference in 5-year survival between RPD and OPD was not significant (24.5% vs. 19.7%, P = 0.088). CONCLUSION: RPD is not only technically feasible with no increase in surgical risk but also oncologically justifiable without compromising survival outcome. However, unlike randomized control trials, the limitations in this propensity score-matched analysis only accounted for 6 observed covariates commonly used to predict the survival outcome in patients with pancreatic adenocarcinoma, and confounders not included in this study could also affect our results.
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Adenocarcinoma , Neoplasias Pancreáticas , Procedimientos Quirúrgicos Robotizados , Adenocarcinoma/cirugía , Estudios de Factibilidad , Humanos , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Puntaje de Propensión , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/métodosRESUMEN
BACKGROUND/OBJECTIVE: This study is to assess immunological and graft survival outcomes after pancreas transplant at a single institute in Asia. METHODS: Patients undergoing pancreas transplant with enteric drainage were included. Clinical data and outcomes were evaluated and compared between each subgroup. RESULTS: There were 165 cases of pancreas transplant, including 38 (23 %) simultaneous pancreas-kidney transplant (SPK), 24 (15 %) pancreas after kidney transplant (PAK), 75 (46 %) pancreas transplant alone (PTA), and 28 (17 %) pancreas before kidney transplant (PBK). The overall surgical complication rate was 46.1 %, with highest (62.5 %) in PAK and lowest (32.0 %) in PTA, P = 0.008. The late complications included 32.7 % infection and 3.6 % malignancy. Overall rejection of pancreas graft was 24.8 % including 18.2 % acute and 9.7 % chronic rejection. Rejection was highest in PTA group (36.0 %) and lowest in PBK (3.6 %). There were 56 cases (33.9 %) with graft loss in total, with highest graft loss rate in PTA (38.7 %). The 1-year, 5-year and 10-year pancreas graft survivals for total patients were 98.0 %, 87.7 % and 70.9 % respectively. CONCLUSIONS: Enteric drainage in pancreas transplant could be applied safely not only in SPK but also in other subgroups. Enteric drainage itself would not compromise the immunological and graft survival outcomes.
Asunto(s)
Trasplante de Páncreas , Drenaje , Rechazo de Injerto/epidemiología , Supervivencia de Injerto , Humanos , Páncreas , Tasa de SupervivenciaRESUMEN
Theoretically, pancreas transplant alone in uremic (PTAU) patients could also be one of the options for those waiting for both pancreas and kidney grafts, but it has never been reported. There were 160 cases of pancreas transplant in this study, including 16% PTAU. The 5-year patient survival was 66.2% after PTAU, 94.5% after SPK, 95.8% after PAK, and 95.4% after PTA. Rejection of pancreas graft was significantly lower in PTAU group (3.8%), followed by 16.7% in pancreas after kidney transplant (PAK), 29.8% in simultaneous pancreas and kidney transplant (SPK) and 37.0% in pancreas transplant alone (PTA). Fasting blood sugar and serum HbA1c levels after PTAU were not significantly different from those by other subgroups. The 5-year death-censored pancreas graft survival was 100% after PTAU and PAK, and 97.0% after SPK and 77.9% after PTA. However, the 5-year death-uncensored pancreas graft survival was 67.0% after PTAU, 100% after PAK, 91.3% after SPK, and 74.0% after PTA. The superior graft survival in the PTAU group was achieved only if deaths with a functioning graft were censored. In conclusion, given the inferior patient survival outcome, PTAU is still not recommended unless SPK and PAK is not available. Although PTAU could be a treatment option for patients with diabetes complicated by end-stage renal disease (ESRD) in terms of surgical risks, endocrine function, and immunological and graft survival outcomes, modification of the organ allocation policies to prioritize SPK transplant in eligible patients should be the prime goal.