RESUMO
BACKGROUND: Cancer arising in the periampullary region can be anatomically classified in pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (dCCA), duodenal adenocarcinoma (DAC), and ampullary carcinoma. Based on histopathology, ampullary carcinoma is currently subdivided in intestinal (AmpIT), pancreatobiliary (AmpPB), and mixed subtypes. Despite close anatomical resemblance, it is unclear how ampullary subtypes relate to the remaining periampullary cancers in tumor characteristics and behavior. METHODS: This international cohort study included patients after curative intent resection for periampullary cancer retrieved from 44 centers (from Europe, United States, Asia, Australia, and Canada) between 2010 and 2021. Preoperative CA19-9, pathology outcomes and 8-year overall survival were compared between DAC, AmpIT, AmpPB, dCCA, and PDAC. RESULTS: Overall, 3809 patients were analyzed, including 348 DAC, 774 AmpIT, 848 AmpPB, 1,036 dCCA, and 803 PDAC. The highest 8-year overall survival was found in patients with AmpIT and DAC (49.8% and 47.9%), followed by AmpPB (34.9%, P < 0.001), dCCA (26.4%, P = 0.020), and finally PDAC (12.9%, P < 0.001). A better survival was correlated with lower CA19-9 levels but not with tumor size, as DAC lesions showed the largest size. CONCLUSIONS: Despite close anatomic relations of the five periampullary cancers, this study revealed differences in preoperative blood markers, pathology, and long-term survival. More tumor characteristics are shared between DAC and AmpIT and between AmpPB and dCCA than between the two ampullary subtypes. Instead of using collective definitions for "periampullary cancers" or anatomical classification, this study emphasizes the importance of individual evaluation of each histopathological subtype with the ampullary subtypes as individual entities in future studies.
Assuntos
Ampola Hepatopancreática , Carcinoma Ductal Pancreático , Colangiocarcinoma , Neoplasias do Ducto Colédoco , Neoplasias Duodenais , Neoplasias Pancreáticas , Humanos , Masculino , Feminino , Ampola Hepatopancreática/patologia , Ampola Hepatopancreática/cirurgia , Taxa de Sobrevida , Neoplasias Duodenais/patologia , Neoplasias Duodenais/cirurgia , Idoso , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Pessoa de Meia-Idade , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Neoplasias do Ducto Colédoco/patologia , Neoplasias do Ducto Colédoco/cirurgia , Neoplasias do Ducto Colédoco/mortalidade , Seguimentos , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Prognóstico , Estudos de Coortes , Estudos RetrospectivosRESUMO
BACKGROUND: Despite differences in tumour behaviour and characteristics between duodenal adenocarcinoma (DAC), the intestinal (AmpIT) and pancreatobiliary (AmpPB) subtype of ampullary adenocarcinoma and distal cholangiocarcinoma (dCCA), the effect of adjuvant chemotherapy (ACT) on these cancers, as well as the optimal ACT regimen, has not been comprehensively assessed. This study aims to assess the influence of tailored ACT on DAC, dCCA, AmpIT, and AmpPB. PATIENTS AND METHODS: Patients after pancreatoduodenectomy for non-pancreatic periampullary adenocarcinoma were identified and collected from 36 tertiary centres between 2010 - 2021. Per non-pancreatic periampullary tumour type, the effect of adjuvant chemotherapy and the main relevant regimens of adjuvant chemotherapy were compared. The primary outcome was overall survival (OS). RESULTS: The study included a total of 2866 patients with DAC (n = 330), AmpIT (n = 765), AmpPB (n = 819), and dCCA (n = 952). Among them, 1329 received ACT, and 1537 did not. ACT was associated with significant improvement in OS for AmpPB (P = 0.004) and dCCA (P < 0.001). Moreover, for patients with dCCA, capecitabine mono ACT provided the greatest OS benefit compared to gemcitabine (P = 0.004) and gemcitabine - cisplatin (P = 0.001). For patients with AmpPB, no superior ACT regime was found (P > 0.226). ACT was not associated with improved OS for DAC and AmpIT (P = 0.113 and P = 0.445, respectively). DISCUSSION: Patients with resected AmpPB and dCCA appear to benefit from ACT. While the optimal ACT for AmpPB remains undetermined, it appears that dCCA shows the most favourable response to capecitabine monotherapy. Tailored adjuvant treatments are essential for enhancing prognosis across all four non-pancreatic periampullary adenocarcinomas.
Assuntos
Adenocarcinoma , Neoplasias Duodenais , Humanos , Masculino , Feminino , Quimioterapia Adjuvante , Pessoa de Meia-Idade , Idoso , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Neoplasias Duodenais/tratamento farmacológico , Neoplasias Duodenais/patologia , Neoplasias Duodenais/cirurgia , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ampola Hepatopancreática/patologia , Pancreaticoduodenectomia , Estudos de Coortes , Neoplasias do Ducto Colédoco/tratamento farmacológico , Neoplasias do Ducto Colédoco/cirurgia , Neoplasias do Ducto Colédoco/patologia , Neoplasias do Ducto Colédoco/mortalidade , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Estudos Retrospectivos , Capecitabina/uso terapêutico , Capecitabina/administração & dosagemRESUMO
BACKGROUND: Standard lymphadenectomy for pancreatoduodenectomy is defined for pancreatic ductal adenocarcinoma and adopted for patients with non-pancreatic periampullary cancer (NPPC), ampullary adenocarcinoma (AAC), distal cholangiocarcinoma (dCCA), or duodenal adenocarcinoma (DAC). This study aimed to compare the patterns of lymph node metastases among the different NPPCs in a large series and in a systematic review to guide the discussion on surgical lymphadenectomy and pathology assessment. METHODS: This retrospective cohort study included patients after pancreatoduodenectomy for NPPC with at least one lymph node metastasis (2010-2021) from 24 centers in nine countries. The primary outcome was identification of lymph node stations affected in case of a lymph node metastasis per NPPC. A separate systematic review included studies on lymph node metastases patterns of AAC, dCCA, and DAC. RESULTS: The study included 2367 patients, of whom 1535 had AAC, 616 had dCCA, and 216 had DAC. More patients with pancreatobiliary type AAC had one or more lymph node metastasis (67.2% vs 44.8%; P < 0.001) compared with intestinal-type, but no differences in metastasis pattern were observed. Stations 13 and 17 were most frequently involved (95%, 94%, and 90%). Whereas dCCA metastasized more frequently to station 12 (13.0% vs 6.4% and 7.0%, P = 0.005), DAC metastasized more frequently to stations 6 (5.0% vs 0% and 2.7%; P < 0.001) and 14 (17.0% vs 8.4% and 11.7%, P = 0.015). CONCLUSION: This study is the first to comprehensively demonstrate the differences and similarities in lymph node metastases spread among NPPCs, to identify the existing research gaps, and to underscore the importance of standardized lymphadenectomy and pathologic assessment for AAC, dCCA, and DAC.
Assuntos
Adenocarcinoma , Ampola Hepatopancreática , Neoplasias do Ducto Colédoco , Neoplasias Duodenais , Excisão de Linfonodo , Metástase Linfática , Neoplasias Pancreáticas , Pancreaticoduodenectomia , Humanos , Estudos Retrospectivos , Ampola Hepatopancreática/patologia , Ampola Hepatopancreática/cirurgia , Neoplasias do Ducto Colédoco/patologia , Neoplasias do Ducto Colédoco/cirurgia , Neoplasias Duodenais/patologia , Neoplasias Duodenais/cirurgia , Masculino , Feminino , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Colangiocarcinoma/cirurgia , Colangiocarcinoma/patologia , Idoso , Pessoa de Meia-Idade , Prognóstico , Seguimentos , Linfonodos/patologia , Linfonodos/cirurgia , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/secundárioRESUMO
This international multicenter cohort study included 30 centers. Patients with duodenal adenocarcinoma (DAC), intestinal-type (AmpIT) and pancreatobiliary-type (AmpPB) ampullary adenocarcinoma, distal cholangiocarcinoma (dCCA), and pancreatic ductal adenocarcinoma (PDAC) were included. The primary outcome was 30-day or in-hospital mortality, and secondary outcomes were major morbidity (Clavien-Dindo 3b≥), clinically relevant post-operative pancreatic fistula (CR-POPF), and length of hospital stay (LOS). Results: Overall, 3622 patients were included in the study (370 DAC, 811 AmpIT, 895 AmpPB, 1083 dCCA, and 463 PDAC). Mortality rates were comparable between DAC, AmpIT, AmpPB, and dCCA (ranging from 3.7% to 5.9%), while lower for PDAC (1.5%, p = 0.013). Major morbidity rate was the lowest in PDAC (4.4%) and the highest for DAC (19.9%, p < 0.001). The highest rates of CR-POPF were observed in DAC (27.3%), AmpIT (25.5%), and dCCA (27.6%), which were significantly higher compared to AmpPB (18.5%, p = 0.001) and PDAC (8.3%, p < 0.001). The shortest LOS was found in PDAC (11 d vs. 14-15 d, p < 0.001). Discussion: In conclusion, this study shows significant variations in perioperative mortality, post-operative complications, and hospital stay among different periampullary cancers, and between the ampullary subtypes. Further research should assess the biological characteristics and tissue reactions associated with each type of periampullary cancer, including subtypes, in order to improve patient management and personalized treatment.
RESUMO
BACKGROUND: Most studies on minimally invasive pancreatoduodenectomy (MIPD) combine patients with pancreatic and periampullary cancers even though there is substantial heterogeneity between these tumors. Therefore, this study aimed to evaluate the role of MIPD compared to open pancreatoduodenectomy (OPD) in patients with non-pancreatic periampullary cancer (NPPC). METHODS: A systematic review of Pubmed, Embase, and Cochrane databases was performed by two independent reviewers to identify studies comparing MIPD and OPD for NPPC (ampullary, distal cholangio, and duodenal adenocarcinoma) (01/2015-12/2021). Individual patient data were required from all identified studies. Primary outcomes were (90-day) mortality, and major morbidity (Clavien-Dindo 3a-5). Secondary outcomes were postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), blood-loss, length of hospital stay (LOS), and overall survival (OS). RESULTS: Overall, 16 studies with 1949 patients were included, combining 928 patients with ampullary, 526 with distal cholangio, and 461 with duodenal cancer. In total, 902 (46.3%) patients underwent MIPD, and 1047 (53.7%) patients underwent OPD. The rates of 90-day mortality, major morbidity, POPF, DGE, PPH, blood-loss, and length of hospital stay did not differ between MIPD and OPD. Operation time was 67 min longer in the MIPD group (P = 0.009). A decrease in DFS for ampullary (HR 2.27, P = 0.019) and distal cholangio (HR 1.84, P = 0.025) cancer, as well as a decrease in OS for distal cholangio (HR 1.71, P = 0.045) and duodenal cancer (HR 4.59, P < 0.001) was found in the MIPD group. CONCLUSIONS: This individual patient data meta-analysis of MIPD versus OPD in patients with NPPC suggests that MIPD is not inferior in terms of short-term morbidity and mortality. Several major limitations in long-term data highlight a research gap that should be studied in prospective maintained international registries or randomized studies for ampullary, distal cholangio, and duodenum cancer separately. PROTOCOL REGISTRATION: PROSPERO (CRD42021277495) on the 25th of October 2021.
Assuntos
Neoplasias Duodenais , Laparoscopia , Neoplasias Pancreáticas , Humanos , Pancreaticoduodenectomia/métodos , Neoplasias Duodenais/cirurgia , Estudos Prospectivos , Pâncreas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Neoplasias Pancreáticas/cirurgia , Estudos RetrospectivosRESUMO
OBJECTIVE: Assessment of minimally invasive pancreatoduodenectomy (MIPD) in patients with pancreatic ductal adenocarcinoma (PDAC) is scarce and limited to non-randomized studies. This study aimed to compare oncological and surgical outcomes after MIPD compared to open pancreatoduodenectomy (OPD) for patients after resectable PDAC from published randomized controlled trials (RCTs). METHODS: A systematic review was performed to identify RCTs comparing MIPD and OPD including PDAC (Jan 2015-July 2021). Individual data of patients with PDAC were requested. Primary outcomes were R0 rate and lymph node yield. Secondary outcomes were blood-loss, operation time, major complications, hospital stay and 90-day mortality. RESULTS: Overall, 4 RCTs (all addressed laparoscopic MIPD) with 275 patients with PDAC were included. In total, 128 patients underwent laparoscopic MIPD and 147 patients underwent OPD. The R0 rate (risk difference(RD) -1%, P = 0.740) and lymph node yield (mean difference(MD) +1.55, P = 0.305) were comparable between laparoscopic MIPD and OPD. Laparoscopic MIPD was associated with less perioperative blood-loss (MD -91ml, P = 0.026), shorter length of hospital stay (MD -3.8 days, P = 0.044), while operation time was longer (MD +98.5 min, P = 0.003). Major complications (RD -11%, P = 0.302) and 90-day mortality (RD -2%, P = 0.328) were comparable between laparoscopic MIPD and OPD. CONCLUSIONS: This individual patient data meta-analysis of MIPD versus OPD in patients with resectable PDAC suggests that laparoscopic MIPD is non-inferior regarding radicality, lymph node yield, major complications and 90-day mortality and is associated with less blood loss, shorter hospital stay, and longer operation time. The impact on long-term survival and recurrence should be studied in RCTs including robotic MIPD.
Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Laparoscopia , Neoplasias Pancreáticas , Humanos , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Pancreáticas/cirurgia , Carcinoma Ductal Pancreático/cirurgia , Laparoscopia/efeitos adversos , Adenocarcinoma/cirurgia , Estudos Retrospectivos , Neoplasias PancreáticasRESUMO
OBJECTIVE: This study aimed to compare surgical and oncological outcomes after minimally invasive pancreatoduodenectomy (MIPD) versus open pancreatoduodenectomy (OPD) for distal cholangiocarcinoma (dCCA). BACKGROUND: A dCCA might be a good indication for MIPD, as it is often diagnosed as primary resectable disease. However, multicenter series on MIPD for dCCA are lacking. METHODS: This is an international multicenter propensity score-matched cohort study including patients after MIPD or OPD for dCCA in 8 centers from 5 countries (2010-2021). Primary outcomes included overall survival (OS) and disease-free interval (DFI). Secondary outcomes included perioperative and postoperative complications and predictors for OS or DFI. Subgroup analyses included robotic pancreatoduodenectomy (RPD) and laparoscopic pancreatoduodenectomy (LPD). RESULTS: Overall, 478 patients after pancreatoduodenectomy for dCCA were included of which 97 after MIPD (37 RPD, 60 LPD) and 381 after OPD. MIPD was associated with less blood loss (300 vs 420 mL, P =0.025), longer operation time (453 vs 340 min; P <0.001), and less surgical site infections (7.8% vs 19.3%; P =0.042) compared with OPD. The median OS (30 vs 25 mo) and DFI (29 vs 18) for MIPD did not differ significantly between MIPD and OPD. Tumor stage (Hazard ratio: 2.939, P <0.001) and administration of adjuvant chemotherapy (Hazard ratio: 0.640, P =0.033) were individual predictors for OS. RPD was associated with a higher lymph node yield (18.0 vs 13.5; P =0.008) and less major morbidity (Clavien-Dindo 3b-5; 8.1% vs 32.1%; P =0.005) compared with LPD. DISCUSSION: Both surgical and oncological outcomes of MIPD for dCCA are acceptable as compared with OPD. Surgical outcomes seem to favor RPD as compared with LPD but more data are needed. Randomized controlled trials should be performed to confirm these findings.