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BACKGROUND: The natural history of branch-duct intraductal papillary mucinous cystic neoplasms (BD-IPMNs) in the pancreas remains unclear. This study aimed to answer this clinical question by focusing on the development of concomitant pancreatic ductal adenocarcinomas (cPDAC). METHODS: The Japan Pancreas Society conducted a prospective multicenter surveillance study of BD-IPMN every six months for five years. The primary endpoints were progression of BD-IPMN, progression to high-grade dysplasia/invasive carcinoma (HGD/IC), and cPDAC. Factors predicting the progression of BD-IPMN to HGD/IC and development of cPDAC were also assessed as secondary endpoints. RESULTS: Among the 2104 non-operated patients, 348 (16.5 %) showed progression of primary BD-IPMN. Cumulative incidences of BD-IPMN with HGD/IC and cPDAC during the 5.17-year surveillance period were 1.90 % and 2.11 %, respectively, and standard incidence ratios of BD-IPMN with HGD/IC and cPDAC were 5.28 and 5.73, respectively. Of 38 cPDACs diagnosed during surveillance, 25 (65.8 %) were resectable. The significant predictive characteristics of BD-IPMN for progression to HGD/IC were larger cyst size (p = 0.03), larger main pancreatic duct size (p < 0.01), and mural nodules (p = 0.02). Significant predictive characteristics for the development of cPDAC were male sex (p = 0.03) and older age (p = 0.02), while the size of IPMN was not significant. CONCLUSION: Careful attention should be given to "dual carcinogenesis" during BD-IPMN surveillance, indicating the progression of BD-IPMN to HGD/IC and development of cPDAC distinct from BD-IPMN, although the establishment of risk factors that predict cPDAC development remains a challenge (UMIN000007349).
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Here, we present a patient with hepatocellular carcinoma complicated by tumor thrombosis into the main portal trunk and perihepatic lymph node metastases who was treated with atezolizumab plus bevacizumab. Shrinkage of the main tumor, portal vein thrombosis, and lymph node metastases were achieved; therefore, hepatectomy with lymphadenectomy could be performed. Final pathology indicated a complete pathological response in the main tumor, portal vein thrombosis, and perihepatic lymph nodes. The patient is currently alive with no evidence of recurrence on radiological assessment at 3 months after surgery.
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BACKGROUND/AIM: The survival and prognostic factors in patients with advanced hepatocellular carcinoma (HCC) who underwent surgical intervention after lenvatinib treatment is not well-understood. PATIENTS AND METHODS: Seventy-six patients with advanced HCC who had lenvatinib treatment were retrospectively analyzed. RESULTS: Of 70 patients who were treated with lenvatinib, 14 patients underwent surgical intervention after lenvatinib treatment for 4-28 weeks. Progression-free survival (PFS) was significantly longer in patients who underwent surgical intervention than in patients with non-surgical treatment (median, 8.6 vs. 5.1 months, p=0.019). Non-significantly longer overall survival (OS) was also observed in patients with surgical intervention compared to patients with non-surgical treatment (median, unreached vs. 21.0 months, p=0.206). In patients who underwent surgical intervention, two patients had a partial response, and 12 had stable disease according to RECIST ver. 1.1 criteria. The serum alpha-fetoprotein (AFP) level was significantly lower after lenvatinib treatment than before lenvatinib treatment (median, 19.2 vs. 196.5 ng/ml, p=0.0081). Eleven patients underwent curative surgery with a 14% major postoperative complication (Clavien-Dindo ≥IIIa) rate. Patients who exhibited decreases in AFP levels or maintained AFP levels within the normal range during lenvatinib treatment had significantly longer PFS (median, 8.6 vs. 3.0 months, p=0.0009) and OS (median, unreached vs. 12.4 months, p=0.012) compared to those with persistently elevated AFP levels beyond the normal range. CONCLUSION: Surgical intervention after lenvatinib treatment for advanced HCC was associated with longer PFS. Patients exhibiting decreased AFP levels or maintaining AFP levels within the normal limit may be suitable candidates for surgical intervention after lenvatinib treatment for advanced HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Compuestos de Fenilurea , Quinolinas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/cirugía , Estudios Retrospectivos , alfa-Fetoproteínas , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugíaRESUMEN
BACKGROUND: Minimally invasive distal pancreatectomy (MIDP), including laparoscopic and robotic distal pancreatectomy, has gained widespread acceptance over the last decade owing to its favorable short-term outcomes. However, evidence regarding its oncologic safety is insufficient. In March 2023, a randomized phase III study was launched in Japan to confirm the non-inferiority of overall survival in patients with resectable pancreatic cancer undergoing MIDP compared with that of patients undergoing open distal pancreatectomy (ODP). METHODS: This is a multi-institutional, randomized, phase III study. A total of 370 patients will be enrolled from 40 institutions within 4 years. The primary endpoint of this study is overall survival, and the secondary endpoints include relapse-free survival, proportion of patients undergoing radical resection, proportion of patients undergoing complete laparoscopic surgery, incidence of adverse surgical events, and length of postoperative hospital stay. Only a credentialed surgeon is eligible to perform both ODP and MIDP. All ODP and MIDP procedures will undergo centralized review using intraoperative photographs. The non-inferiority of MIDP to ODP in terms of overall survival will be statistically analyzed. Only if non-inferiority is confirmed will the analysis assess the superiority of MIDP over ODP. DISCUSSION: If our study demonstrates the non-inferiority of MIDP in terms of overall survival, it would validate its short-term advantages and establish its long-term clinical efficacy. TRIAL REGISTRATION: This trial is registered with the Japan Registry of Clinical Trials as jRCT 1,031,220,705 [ https://jrct.niph.go.jp/en-latest-detail/jRCT1031220705 ].
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Laparoscopía , Neoplasias Pancreáticas , Procedimientos Quirúrgicos Robotizados , Humanos , Pancreatectomía/efectos adversos , Pancreatectomía/métodos , Japón/epidemiología , Procedimientos Quirúrgicos Robotizados/efectos adversos , Procedimientos Quirúrgicos Robotizados/métodos , Recurrencia Local de Neoplasia/cirugía , Resultado del Tratamiento , Laparoscopía/efectos adversos , Laparoscopía/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios RetrospectivosRESUMEN
BACKGROUND: Subcutaneous emphysema (SCE) is a common complication in laparoscopic surgery. However, its precise incidence and impact on the clinical course are partially known. In this study, the incidence and risk factors of SCE were retrospectively analyzed. METHODS: Patients who underwent laparoscopic/robotic abdominal surgery (e.g., gastrointestinal, hepatobiliary, gynecologic, and urologic surgery) between October 2019 and September 2022 were retrospectively analyzed. The presence of SCE was confirmed by either conclusive findings obtained through chest/abdominal X-ray examination immediately after operation, or intraoperative palpation conducted by nurses. X-ray examination was performed in the operation room before extubation. RESULTS: A total of 2503 patients treated with laparoscopic/robotic abdominal surgery between October 2019 and September 2022 were identified and all of them were included in the analysis. SCE was confirmed in 23.1% of the patients (i.e., 577/2503). SCE was identified by X-ray examination in 97.6% of the patients. Extubation failure was observed in 10 patients; however, pneumothorax was not observed. Female sex (odds ratio [OR]: 2.09; 95% confidence interval [95%CI]: 1.69-2.57), age ≥ 80 years (OR 1.63; 95%CI 1.19-2.22), body mass index < 20 (OR 1.32; 95%CI 1.06-1.65), operation time > 360 min (OR 1.97; 95%CI 1.53-2.54), robotic surgery (OR 2.54; 95%CI 1.91-3.38), maximum intraabdominal pressure with CO2 > 15 mmHg (OR 1.79; 95%CI 1.02-3.16), and endo-tidal CO2 > 50 mmHg (OR 1.32; 95%CI 1.08-1.62)were identified as independent factors of SCE. Regarding the extubation failure due to SCE, age (OR 5.84; 95%CI 1.27-26.8) and maximum intraabdominal pressure with CO2 (OR 21.7; 95%CI 4.76-99.3) were identified as risk factors. CONCLUSION: Although the presence of SCE is associated with a low risk of severe complications, monitoring of the perioperative intraabdominal pressure is essential for performing safe laparoscopic/robotic surgery, particularly in elderly patients.
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Laparoscopía , Procedimientos Quirúrgicos Robotizados , Enfisema Subcutáneo , Humanos , Femenino , Anciano , Anciano de 80 o más Años , Procedimientos Quirúrgicos Robotizados/efectos adversos , Estudios Retrospectivos , Dióxido de Carbono , Laparoscopía/efectos adversos , Enfisema Subcutáneo/epidemiología , Enfisema Subcutáneo/etiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiologíaRESUMEN
BACKGROUND: We compared the results of preoperative pancreatic juice cytology (PJC) and final pathological diagnosis after resection in patients who underwent resection of intraductal papillary mucinous neoplasm (IPMN) of the pancreas to determine whether preoperative PJC can help determine therapeutic strategies. METHODS: Of 1130 patients who underwent surgical resection IPMN at 11 Japanese tertiary institutions, the study included 852 patients who underwent preoperative PJC guided by endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: The accuracy of preoperative PJC for differentiation between cancerous and noncancerous lesions were 55% for IPMN overall; 59% for the branch duct type; 49% for the main pancreatic duct type; 53% for the mixed type, respectively. On classifying IPMN according to the diameters of the mural nodule (MN) and main pancreatic duct (MPD), the corresponding values for diagnostic performance were 40% for type 1 (MN ≥5 mm and MPD ≥ 10 mm); 46% for type 2 (MN ≥5 mm and MPD < 10 mm); 61% for type 3 (MN < 5 mm and MPD ≥ 10 mm); 72% for type 4 (MN < 5 mm and MPD < 10 mm), respectively. CONCLUSIONS: PJC in IPMN is not a recommended examination because of its low overall sensitivity and no significant difference in diagnostic performance by type, location, or subclassification. Although the sensitivity is low, the positive predictive value is high, so we suggest that pancreatic juice cytology be performed only in cases where the patient is not sure about surgery.
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Carcinoma Ductal Pancreático , Neoplasias Intraductales Pancreáticas , Neoplasias Pancreáticas , Humanos , Jugo Pancreático , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/cirugía , Carcinoma Ductal Pancreático/patología , Neoplasias Intraductales Pancreáticas/patología , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Conductos Pancreáticos/cirugía , Estudios RetrospectivosRESUMEN
Background: Nab-paclitaxel plus gemcitabine is a standard treatment for metastatic/locally advanced pancreatic cancer. The effectiveness of neoadjuvant therapy with nab-paclitaxel plus gemcitabine (GnP-NAT) in patients with borderline resectable pancreatic cancer (BRPC) remains unclear. Patients and Methods: This single-arm phase II trial included 61 patients with BRPC that were treated with two cycles of GnP-NAT, (nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2), on days 1, 8, and 15 over a 4-week period, which comprised one cycle. The primary endpoint was overall survival time. In the absence of disease progression, patients underwent planned pancreatectomy. Results: Median overall survival, the primary endpoint, was 25.2 months, and the median recurrence-free survival was 12.3 months. The overall rate of grade 3/4 events was 73.8%. One patient, who had a history of radiation therapy for past esophageal cancer, died from exacerbation via pneumonia. The overall resection rate was 73.8% (n = 45), and the R0 resection rate was 63.9% (n = 39). Overall, postoperative complications were found in 19 patients (42%) with 24 events, and nine patients (20%) with nine events ≥ grade IIIa, based on Dindo's classification. Conclusions: This protocol treatment is thought to be a feasible, safe, and promising treatment regimen, but we caution against its use in patients with a history of interstitial lung disease and/or prior pulmonary irradiation. The survival data from this study suggest the need for further investigations of GnP-NAT efficacy in patients with BRPC, as well as prospective evaluation of adverse events. Clinical Trial Registration: UMIN Clinical Trials Registry, UMIN000024154 and ClinicalTrials.gov, NCT02926183.
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BACKGROUND: Although the standard therapy for advanced-stage hepatocellular carcinoma (HCC) is systemic chemotherapy, the combination of atezolizumab and bevacizumab (atezo + bev) with a high objective response rate may lead to conversion to resection in patients with initially unresectable HCC. This study aims to evaluate the efficacy of atezo + bev in achieving conversion surgery and prolonged progression-free survival (PFS) for initially unresectable HCC. METHODS: The RACB study is a prospective, single-arm, multicenter, phase II trial evaluating the efficacy of combination therapy with atezo + bev for conversion surgery in patients with technically and/or oncologically unresectable HCC. The main eligibility criteria are as follows: (1) unresectable HCC without a history of systemic chemotherapy, (2) at least one target lesion based on RECIST ver. 1.1, and (3) a ChildâPugh score of 5-6. The definition of unresectable tumors in this study includes macroscopic vascular invasion and/or extrahepatic metastasis and massive distribution of intrahepatic tumors. Patients will be treated with atezolizumab (1200 mg/body weight) and bevacizumab (15 mg/kg) every 3 weeks. If the patient is considered resectable on radiological assessment 12 weeks after initial chemotherapy, the patient will be treated with atezolizumab monotherapy 3 weeks after combination chemotherapy followed by surgery 3 weeks after atezolizumab monotherapy. If the patient is considered unresectable, the patient will continue with atezo + bev and undergo a radiological assessment every 9 weeks until resectable or until disease progression. The primary endpoint is PFS, and the secondary endpoints are the overall response rate, overall survival, resection rate, curative resection rate, on-protocol resection rate, and ICG retention rate at 15 min after atezo + bev therapy. The assessments of safety and quality of life during the treatment course will also be evaluated. The number of patients has been set at 50 based on the threshold and the expected PFS rate at 6 months after enrollment of 40% and 60%, respectively, with a one-sided alpha error of 0.05 and power of 0.80. The enrollment and follow-up periods will be 2 and 1.5 years, respectively. DISCUSSION: This study will elucidate the efficacy of conversion surgery with atezo + bev for initially unresectable HCC. In addition, the conversion rate, safety and quality of life during the treatment course will also be demonstrated. TRIAL REGISTRATION: This study is registered in the Japan Registry of Clinical Trials (jRCTs051210148, January 7, 2022).
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Bevacizumab/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/cirugía , Estudios Prospectivos , Calidad de Vida , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Estudios Multicéntricos como AsuntoRESUMEN
BACKGROUND/AIMS: Pancreatic cancer has the poorest survival rate among all cancer types. Therefore, it is essential to develop an effective treatment strategy for this cancer. METHODS: We performed carbon ion radiotherapy (CIRT) in human pancreatic cancer cell lines and analyzed their survival, apoptosis, necrosis, and autophagy. To investigate the role of CIRT-induced autophagy, autophagy inhibitors were added to cells prior to CIRT. To evaluate tumor formation, we inoculated CIRT-treated murine pancreatic cancer cells on the flank of syngeneic mice and measured tumor weight. We immunohistochemically measured autophagy levels in surgical sections from patients with pancreatic cancer who received neoadjuvant chemotherapy (NAC) plus CIRT or NAC alone. RESULTS: CIRT reduced the survival fraction of pancreatic cancer cells and induced apoptotic and necrotic alterations, along with autophagy. Preincubation with an autophagy inhibitor accelerated cell death. Mice inoculated with control pancreatic cancer cells developed tumors, while those inoculated with CIRT/autophagy inhibitor-treated cells showed significant evasion. Surgical specimens of NAC-treated patients expressed autophagy comparable to control patients, while those in the NAC plus CIRT group expressed little autophagy and nuclear staining. CONCLUSION: CIRT effectively killed the pancreatic cancer cells by inhibiting their autophagy-inducing abilities.
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Radioterapia de Iones Pesados , Neoplasias Pancreáticas , Humanos , Animales , Ratones , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/metabolismo , Autofagia , Resultado del Tratamiento , Neoplasias PancreáticasRESUMEN
We report a 58-year-old male with a histopathologically proven grade 2 (G2) pancreatic neuroendocrine neoplasm and multiple abdominal node metastases by use of a laparoscopic pancreatic body and tail resection procedure, plus abdominal lymph node dissection. A primary pancreatic tail neuroendocrine tumor sized 20 × 25 mm was detected by contrast-enhanced computed tomography, somatostatin receptor scintigraphy (SRS), and fluorodeoxyglucose positron emission tomography (FDG-PET) examinations and pathologically diagnosed as a pancreatic neuroendocrine tumor (PNET, G2) based on positive immunostaining for somatostatin receptor (SSTR) type 2. Of three metastatic histopathological lymph nodes, two measured 18 × 21 and 10 × 12 mm, respectively, with whole strong SSTR immunostaining showing moderate uptake in SRS findings, whereas the other node, sized 8 × 10 mm, had strong SSTR immunostaining only in a small 6 × 6-mm-sized portion and showed no uptake in SRS findings, likely because of the limited spatial resolution of scintigraphy. On the other hand, only the largest node (18 × 21 mm) was visualized by FDG-PET. SRS may be useful for metastatic lymph node diagnosis based on SSTR immunostaining, though a disadvantage is the spatial resolution limitation.
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BACKGROUND: The prognostic impact of radiographic duodenal invasion (rDI) of pancreatic ductal adenocarcinoma (PDAC) has yet to be fully elucidated. This retrospective study aimed to investigate the prognostic and clinicopathological significance of rDI in patients with PDAC after pancreatoduodenectomy (PD). MATERIALS AND METHODS: We retrospectively analyzed 223 consecutive patients with resectable (R) and borderline resectable (BR)-PDAC that underwent up-front PD between 2002 and 2018. rDI was assessed by preoperative multi-detector row computed tomography. RESULTS: Ninety-three (42%) patients with PDAC had rDI, and all of them had pathological DI (pDI). The rDI(+) group had larger tumor size, BR-PDAC was more common, there was higher serum CA19-9 level, and microscopic lymphovascular invasion was more common than in the rDI(-) group. rDI was associated with significant reduction in overall survival (OS) (P < 0.001) and recurrence-free survival (RFS) (P < 0.001). In multivariate analysis, rDI was an independent prognostic factor in OS [hazard ratio (HR) = 0.52; 95% confidence interval (CI) 0.38-0.73, P < 0.001] and RFS [HR = 0.56; 95% CI 0.40-0.78, P = 0.001]. rDI was also an independent risk factor for early recurrence within 12 months [odds ratio (OR) = 0.36; 95% CI 0.18-0.73, P = 0.005]. rDI had positive correlation with liver recurrence (P = 0.024). CONCLUSION: Biological aggressiveness of PDAC with rDI implies short OS and early recurrence with frequent liver metastasis. Aggressive perioperative chemotherapy is recommended to improve prognosis, especially for R-PDAC patients with rDI.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Estudios Retrospectivos , Recurrencia Local de Neoplasia/patología , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/tratamiento farmacológico , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/cirugía , Carcinoma Ductal Pancreático/tratamiento farmacológico , Pronóstico , Neoplasias PancreáticasRESUMEN
BACKGROUND/OBJECTIVES: The detection of malignancy is a major concern in the management of intraductal papillary mucinous neoplasm (IPMN). The height of the mural nodule (MN), estimated using endoscopic ultrasound (EUS) and computed tomography (CT), has been considered crucial for predicting malignant IPMN. Currently, whether surveillance using CT or EUS alone is sufficient for detecting MNs remains unclear. This study aimed to compare the ability of CT and EUS to detect MNs in IPMN. METHODS: This multicenter, retrospective observational study was conducted in 11 Japanese tertiary institutions. Patients who underwent surgical resection of IPMN with MN after CT and EUS examinations were eligible to participate. The MN detection rates between CT and EUS were examined. RESULTS: Two-hundred-and-forty patients who underwent preoperative EUS and CT had pathologically confirmed MNs. The MN detection rates of EUS and CT were 83% and 53%, respectively (p < 0.001). Additionally, the MN detection rate of EUS was significantly higher than that of CT regardless of morphological type (76% vs. 47% in branch-duct-type IPMN; 90% vs. 54% in mixed IPMN; 98% vs. 56% in main-duct-type IPMN; p < 0.001). Further, pathologically confirmed MNs ≥5 mm were more frequently observed on EUS than on CT (95% vs. 76%, p < 0.001). CONCLUSIONS: EUS was superior to CT for the detection of MN in IPMN. EUS surveillance is essential for the detection of MNs.
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Adenocarcinoma Mucinoso , Carcinoma Ductal Pancreático , Neoplasias Intraductales Pancreáticas , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/patología , Japón , Adenocarcinoma Mucinoso/diagnóstico por imagen , Adenocarcinoma Mucinoso/cirugía , Adenocarcinoma Mucinoso/patología , Neoplasias Pancreáticas/patología , Tomografía Computarizada por Rayos X , Estudios RetrospectivosRESUMEN
BACKGROUND: The histological features and radiological shape of extrahepatic cholangiocarcinoma (eCCA) have not been widely studied in relation to prognosis. Multi-detector computed tomography (MDCT) is thought to be useful in diagnosis of progress and tumor distribution; it can also show morphological differences (round, triangular, and square forms) at the tumoral obstruction sites. Histological types of eCCA may be revealed, with potential association with tumor growth and survival. METHODS: We examined the distribution of tumor radiological shape subtypes on MDCT. The surgical outcomes of consecutive patients with eCCA who underwent macroscopic curative resection were reviewed. RESULTS: CT subtypes in 109 patients were 62 triangular, 35 square, and 12 round. There were clear prognostic differences in long-term survival rates (P < 0.001); 5-year survival rates were 100% in round, 64% in triangular, and 19% in square types. There was no recurrence in any cases of round-type tumor at the site of obstruction. Depth of tumor invasion and rates of nodal involvement were significantly higher in triangular and square-type tumors than in round-type tumors. In papillary adenocarcinoma, radiological obstructions were round type in seven patients (78%) and triangular type in two patients (22%). In tubular adenocarcinoma, all round-type tumors were well differentiated, the ratio of square-type tumors increasing as the degree of differentiation decreased from "well" to "moderate," and "poor" respectively (23%, 39%, 57%; P = 0.033). CONCLUSIONS: Tumor radiological shape predicts tumor progression, histological type, and survival in eCCA. This information may be helpful in preoperative radiological staging on MDCT.
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Adenocarcinoma , Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Neoplasias de los Conductos Biliares/cirugía , Colangiocarcinoma/diagnóstico por imagen , Colangiocarcinoma/cirugía , Pronóstico , Adenocarcinoma/patología , Conductos Biliares Intrahepáticos/diagnóstico por imagen , Conductos Biliares Intrahepáticos/patología , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: This study aimed to clarify the risk factors of clinically relevant pancreatic fistula after early drain removal with higher drain fluid amylase after pancreaticoduodenectomy. Clinical evaluation of early drain removal with a higher drain fluid amylase after pancreaticoduodenectomy has been controversial. The safety and effectiveness have not been sufficiently examined. METHODS: Between 2015 and 2020, prophylactic surgical drains were prospectively removed on postoperative day 4 regardless of drain fluid amylase level in 364 study-eligible patients who underwent pancreaticoduodenectomy. Patients were classified according to drain fluid amylase on postoperative day 1: 281 patients with drain fluid amylase <4,000 U/L, and 83 patients with drain fluid amylase ≥4,000 U/L. RESULTS: Clinically relevant pancreatic fistula occurred in 40 of 364 enrolled patients (11.0%). In the entire cohort, male, positive postoperative day 1 drain fluid culture, and postoperative day 1 drain fluid amylase ≥4,000 U/L were independent risk factors for clinically relevant pancreatic fistula after early drain removal. When stratifying by 4,000 U/L of postoperative day 1 drain fluid amylase, the rate of clinically relevant pancreatic fistula in postoperative day 1 drain fluid amylase <4,000 U/L was significantly lower than that in postoperative day 1 drain fluid amylase ≥4,000 U/L (4% vs 35%, P < .001) after early drain removal. Moreover, in postoperative day 1 drain fluid amylase <4,000 U/L, positive postoperative day 1 drain fluid culture did not develop clinically relevant pancreatic fistula after early drain removal. However, in postoperative day 1 drain fluid amylase ≥4,000 U/L, multivariate analysis clarified that positive postoperative day 1 drain fluid culture was the only independent risk factor of clinically relevant pancreatic fistula after early drain removal (odds ratio 26.27, 95% confidence interval 5.59-123.56, P = .001). CONCLUSION: Positive drain fluid culture on postoperative day 1 might predict clinically relevant pancreatic fistula in early drain removal with a higher drain fluid amylase.
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Fístula Pancreática , Pancreaticoduodenectomía , Humanos , Masculino , Amilasas/análisis , Drenaje/efectos adversos , Fístula Pancreática/diagnóstico , Fístula Pancreática/epidemiología , Fístula Pancreática/etiología , Pancreaticoduodenectomía/efectos adversos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Factores de RiesgoRESUMEN
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
BACKGROUND: Improvement of the completion rate of postoperative adjuvant chemotherapy is a key to obtaining favorable prognosis in patients who undergo macroscopically curative pancreatectomy for pancreatic ductal adenocarcinoma. STUDY DESIGN: This study is a prospective single-center phase II trial that aimed to examine whether a supervised exercise therapy for pancreatic ductal adenocarcinoma improved the completion rate of S-1 adjuvant chemotherapy in the development of a tolerable and effective exercise plan for patients undergoing adjuvant therapy. RESULTS: Forty-three patients were included in the study. The completion rate of S-1 therapy, the primary endpoint, was 93%, which exceeded the threshold completion rate of 53% (p < 0.001). As secondary endpoints, the relative dose intensity of S-1 was 100.0 [95.9 to 100.0] (median [interquartile range]), the median recurrence-free survival was 20.4 months, and the median overall survival was not reached, confirming the safety of the protocol treatment. Regarding frailty status, there was significant decrease in the Kihon checklist score (p = 0.002) and significant increase in G8 questionnaire score (p < 0.001), indicating that exercise therapy reduced frailty. There were no incidences of serious adverse events except for 1 case of grade 3 febrile neutropenia. The differences between before/after therapy (between 6 months/baseline) of mean muscle mass, mean body fat mass, mean body fat percentage, and mean controlling nutrition status score were 1.52 (p < 0.001), -1.18 (p = 0.007), -2.47 (p < 0.001), and -0.59 (p = 0.006), respectively. CONCLUSIONS: Adjuvant chemotherapy combined with supervised exercise therapy for pancreatic ductal adenocarcinoma was confirmed to improve the completion rate of S-1 adjuvant chemotherapy.
Asunto(s)
Carcinoma Ductal Pancreático , Fragilidad , Neoplasias Pancreáticas , Humanos , Estudio Históricamente Controlado , Estudios Prospectivos , Neoplasias Pancreáticas/patología , Quimioterapia Adyuvante/métodos , Carcinoma Ductal Pancreático/patología , Terapia por Ejercicio , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias PancreáticasRESUMEN
The neuroendocrine carcinoma of the gastrointestinal system (GIS-NEC) is a rare but highly malignant neoplasm. We analyzed 115 cases using whole-genome/exome sequencing, transcriptome sequencing, DNA methylation assays, and/or ATAC-seq and found GIS-NECs to be genetically distinct from neuroendocrine tumors (GIS-NET) in the same location. Clear genomic differences were also evident between pancreatic NECs (Panc-NEC) and nonpancreatic GIS-NECs (Nonpanc-NEC). Panc-NECs could be classified into two subgroups (i.e., "ductal-type" and "acinar-type") based on genomic features. Alterations in TP53 and RB1 proved common in GIS-NECs, and most Nonpanc-NECs with intact RB1 demonstrated mutually exclusive amplification of CCNE1 or MYC. Alterations of the Notch gene family were characteristic of Nonpanc-NECs. Transcription factors for neuroendocrine differentiation, especially the SOX2 gene, appeared overexpressed in most GIS-NECs due to hypermethylation of the promoter region. This first comprehensive study of genomic alterations in GIS-NECs uncovered several key biological processes underlying genesis of this very lethal form of cancer. SIGNIFICANCE: GIS-NECs are genetically distinct from GIS-NETs. GIS-NECs arising in different organs show similar histopathologic features and share some genomic features, but considerable differences exist between Panc-NECs and Nonpanc-NECs. In addition, Panc-NECs could be classified into two subgroups (i.e., "ductal-type" and "acinar-type") based on genomic and epigenomic features. This article is highlighted in the In This Issue feature, p. 587.
Asunto(s)
Carcinoma Neuroendocrino , Tumores Neuroendocrinos , Carcinoma Neuroendocrino/genética , Exoma , Humanos , Recién Nacido , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/patología , Páncreas/patología , Secuenciación del ExomaRESUMEN
BACKGROUND/AIM: The potential benefits of pancreatectomy with major arterial resection have been studied in the past, but findings remain controversial. Pancreatic neck/body cancer (PNBC) involving arteries frequently requires combined resection of the pancreas, artery and portal vein. PATIENTS AND METHODS: Nine prospectively-registered consecutive patients with PNBC were enrolled, all underwent pancreatoduodenectomy with common hepatic artery en-bloc resection (PD-CHAR). We investigated the safety of PD-CHAR by blood flow evaluation with intraoperative indocyanine green fluorescence imaging in reconstructed vessels/organs. RESULTS: Among patients who underwent PD-CHAR, there was no severe morbidity. Artery/portal vein combined resection and reconstruction was performed in all patients. Four (44%) patients had pathological positivity for cancer cell invasion into the nerve plexus of artery at the site of radiographic artery involvement, although one (11%) was diagnosed with pathological artery involvement. CONCLUSION: PD-CHAR following neoadjuvant therapy might be feasible for PNBC without severe postoperative complications. Survival benefits in PNBC should be confirmed in further studies.