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BACKGROUND: Optimal preoperative biliary drainage for patients with pancreatic cancer before pancreatoduodenectomy remains unclear. This study aimed to investigate the comparison of efficacy and safety between a metallic stent (MS) and a plastic stent (PS). METHODS: Comparative studies on the use of MS and PS for pancreatic cancer before pancreatoduodenectomy were systematically searched using the MEDLINE and Web of Science databases. Pre- and postoperative data also were extracted. Random-effects meta-analyses were performed to compare post-endoscopic retrograde cholangiopancreatography (ERCP) complications as well as intra- and postoperative outcomes between the two arms of the study, and pooled odds ratios (ORs) or mean differences (MDs) were calculated with 95 percent confidence intervals (CIs). RESULTS: The study analyzed 12 studies involving 683 patients. Insertion of MS was associated with a lower incidence of re-intervention (OR, 0.06; 95% CI 0.03-0.15; P < 0.001), increased post-ERCP adverse events (OR, 2.22; 95% CI 1.13-4.36; P = 0.02), and similar operation time (MD, 18.0 min; 95% CI -29.1 to 65.6 min; P = 0.46), amount of blood loss (MD, 43.0 ml; 95% CI -207.1 to 288.2 ml; P = 0.73), and surgical complication rate (OR, 0.78; 95% CI 0.53-1.15; P = 0.21). The cumulative stent patency rate after 3 months was higher in the MS group than in the PS group (70-100 % vs 30.0-45.0 %). CONCLUSION: For biliary drainage in patients with pancreatic cancer during this era of multidisciplinary treatment, MS use might be the first choice because MS provides a more durable biliary drainage and a similar risk of postoperative outcomes compared with PS.
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Colestasis , Neoplasias Pancreáticas , Humanos , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Colestasis/etiología , Colestasis/cirugía , Drenaje/efectos adversos , Páncreas , Neoplasias Pancreáticas/terapia , Stents/efectos adversos , Resultado del TratamientoRESUMEN
Biliary complications after hepatectomy in living donors have yet to be eradicated. We hypothesized that a standardized upfront Glissonean approach and liver hanging maneuver (GH) would prevent mechanical and thermal injuries to the hilar plate of the remnant liver by determining the point of bile duct division and the final destination of hepatectomy preceding liver parenchymal transection (safety) and facilitate liver transection deep within the parenchyma and allow maximum length of hilar structures (rationality). GH was implemented in 2016 and its incidence of bile leakage was retrospectively compared against the conventional technique. GH comprises six steps: (1) development of the retrohepatic avascular plane between the right hepatic vein (RHV) and the middle hepatic vein (MHV) and isolation of the hepatic vein(s); (2) isolation of the right or left Glissonean pedicle with the corresponding Glissonean pedicles of the caudate lobe; (3) for right liver grafts and left liver grafts with the caudate lobe, passage of the tape for the liver hanging maneuver along the retrohepatic avascular plane and above the hilar plate, and for left liver grafts without the caudate lobe and for left lateral section grafts, passage of the tape from between the RHV and the MHV, along the Arantius ligament, and to the right of the umbilical portion; (4) liver transection; (5) isolation of hilar structures; and (6) graft procurement. Until 2020, 62 consecutive living donors underwent GH (success rate, 100%). The incidence of bile leakage from the hepatic hilum (0%) was significantly lower than that among 59 donors who underwent the conventional technique in 2011-2015 (9%; p = 0.01). In conclusion, GH is highly effective in reducing bile leakage from the hepatic hilum in living donors.
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Neoplasias Hepáticas , Trasplante de Hígado , Humanos , Donadores Vivos , Estudios Retrospectivos , Bilis , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Hígado/cirugía , Hígado/irrigación sanguínea , Hepatectomía/efectos adversos , Hepatectomía/métodos , Venas Hepáticas/cirugía , Neoplasias Hepáticas/cirugíaRESUMEN
Here, we describe a rare case of malignant lymphoma after liver transplantation for liver cirrhosis caused by human immunodeficiency virus (HIV) and hepatitis C virus (HCV) co-infection. A male patient was diagnosed with hemophilia A at 8 months of age. Since then, he had been receiving blood products, which led to HIV and HCV co-infection. His HIV viral load was suppressed with antiretroviral therapy, and a sustained virologic response was achieved for HCV using direct-acting antivirals. However, his decompensated liver cirrhosis progressed, and deceased donor liver transplantation was performed. A post-transplant lymphoproliferative disorder (PTLD) developed 105 days after liver transplantation, with enlarged para-aortic and hilar lymph nodes, a right renal mass, and masses in the small and large intestines. Histopathological examination confirmed monomorphic PTLD (diffuse large B-cell lymphoma). Against the treatment (reduction of immunosuppression, rituximab, and chemotherapy), the response was poor, and the patient died 94 days after the outbreak of PTLD. Both transplantation and HIV infection are risk factors for lymphoproliferative diseases. To the best of our knowledge, this is one of the very few reports of PTLD in a patient with HIV/HCV co-infection.
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PURPOSE: The postoperative mortality rate of distal pancreatectomy is lower than that of pancreaticoduodenectomy, although persistent complications may occur after distal pancreatectomy. Fluid collection (FC) is frequently observed after distal pancreatectomy; however, FC may occasionally progress to postoperative intra-abdominal abscess (PIAA), which requires conservative or progressive interventional treatment. This study aimed to compare the status between patients with or without PIAA, identify predictive factors for PIAA and clinically relevant postoperative pancreatic fistula, and investigate the clinical characteristics of patients with PIAA with interventional drainage. METHODS: We retrospectively reviewed data of patients who underwent distal pancreatectomy between January 2012 and December 2019 at two high-volume centers, where hepatobiliary-pancreatic surgeries were performed by expert specialist surgeons. Logistic regression analysis was performed to determine the predictive factors for PIAA. RESULTS: Overall, 242 patients were analyzed, among whom 49 (20.2%) had PIAA. The median postoperative period of PIAA formation was 9 (range: 3-49) days. Among the 49 patients with PIAA, 25 (51.0%) underwent percutaneous ultrasound, computed tomography, or endoscopic ultrasound-guided interventions for PIAA. In the univariate analysis, preoperative indices representing abdominal fat mass (i.e., body mass index, subcutaneous fat area, and visceral fat area) were identified as predictive factors for PIAA; in the multivariate analysis, C-reactive protein (CRP) level (continuous variable) on postoperative day (POD) 3 (odds ratio: 1.189, 95.0% confidence interval: 1.111 - 1.274; P < 0.001) was the only independent and significant predictive factor for PIAA. CONCLUSIONS: CRP level on POD 3 was an independent and significant predictive factor for PIAA after distal pancreatectomy.
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Absceso Abdominal , Pancreatectomía , Humanos , Pancreatectomía/efectos adversos , Estudios Retrospectivos , Pancreaticoduodenectomía/efectos adversos , Drenaje/efectos adversos , Fístula Pancreática/etiología , Complicaciones Posoperatorias/etiología , Absceso Abdominal/complicaciones , Factores de RiesgoRESUMEN
Environmental and genetic factors play a critical role in the pathogenesis of pancreatic cancer, which is likely to follow a multistep process that includes intraductal papillary mucinous neoplasm. The pathogenesis of familial pancreatic cancer has been reported; however, epidemiological characteristics and causative genes remain unclear. This study aimed to determine the relationship between the family history of pancreatic cancer and tumor malignancy and identify novel susceptible germline variants of pancreatic cancer. We performed an epidemiologic study at our institute on a cohort of 668 patients with intraductal papillary mucinous neoplasm and 242 with pancreatic cancer but without associated intraductal papillary mucinous neoplasm stratified by family history of pancreatic cancer. Whole-exome sequencing was conducted for 10 patients from seven families with familial pancreatic cancer and intraductal papillary mucinous neoplasm. We found that patients who had intraductal papillary mucinous neoplasm with positive family history of pancreatic cancer within first-degree relatives were more likely to develop malignancy in a shorter period than those without family history. Duplicate frameshift variants in TET2 c.3180dupG (p.Pro1061fs) and ASXL1 c.1934dupG (p.Gly646fs) in one family and POLN c.1194dupT (p.Glu399fs) in another were identified as pathogenic truncating germline variants which were previously recognised susceptibility genes. Moreover, PDIA2 c.1403C>T (p.Pro468Leu) and DPYSL4 c.926C>A (p.Pro309Gln) were shared in four and two patients, respectively. In particular, PDIA2 was identified as a novel candidate for one of the deleterious variants of familial pancreatic cancer.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Estudios Transversales , Genómica , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Neoplasias PancreáticasRESUMEN
BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare inherited disorder that causes the accumulation of protoporphyrin in the erythrocytes, skin, and liver. Severe protoporphyric hepatopathy results in liver failure, requiring both liver and bone marrow transplantation as a life-saving procedure and to correct the underlying enzymatic defect, respectively. CASE PRESENTATION: We report a 20-year-old man who underwent split liver transplantation using a right trisegment and caudate lobe graft for EPP-induced liver failure, but succumbed to a deadly combination of early relapse of EPP and subsequent, intractable, late-onset bile leakage from the cut surface of segment 4. EPP recurrence most likely created a high-risk situation for bile leakage from the non-communicating bile ducts of segment 4; therefore, this case shed light on the potential relationship between EPP recurrence and biliary complications. CONCLUSION: Physicians should recognize the potentially rapid and life-threatening progression of protoporphyric hepatopathy that leads to liver failure. For young patients with EPP, LT and sequential BMT should thoroughly be considered by a multidisciplinary team as soon as hepatic reserve deterioration becomes evident. Split liver transplantation should preferably be avoided and appropriate post-transplant management is critical before protoporphyrin depositions to the bile duct and hepatocyte causes irreversible damage to the liver graft.
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Hepatopatías , Fallo Hepático , Trasplante de Hígado , Protoporfiria Eritropoyética , Humanos , Hígado/cirugía , Hepatopatías/complicaciones , Fallo Hepático/complicaciones , Fallo Hepático/cirugía , Trasplante de Hígado/métodos , Masculino , Protoporfiria Eritropoyética/complicaciones , Protoporfiria Eritropoyética/cirugía , Protoporfirinas , Recurrencia , Adulto JovenRESUMEN
BACKGROUND: The incidence of pancreatic neuroendocrine neoplasm (PNEN) has been increasing. Resection is typically indicated for PNEN, regardless of its size; however, the indications for its resection are controversial. This study aimed to evaluate the treatment results of surgical resection of PNEN at our institute. METHODS: In this single-center, retrospective, case-control study, 87 patients who underwent PNEN resection and 17 patients with PNEN who did not undergo surgical resection between 1993 and 2020 were included in this study. Clinical characteristics and outcomes were reviewed and statistically compared. Survival was also estimated for the patients in each cohort. RESULTS: Seventeen patients who underwent resection (20%) had lymph node metastasis. Tumors measuring ≥ 2.0 cm and multiple lesions were identified as independent predictors for lymph node metastasis (odds ratio [OR] 17.3, 95% confidence interval [CI] 3.0-100.0, p = 0.001 and OR 8.7, 95% CI 1.5-52.0, p = 0.018, respectively). There was a significant difference in the survival curves depending on the presence or absence of lymph node metastasis (5-year overall survival 74.7% vs. 94.3%, p < 0.001; 5-year recurrence-free survival: 66.3% vs. 93.6%, p < 0.001). All 17 PNEN cases under observation with a median 8 mm (range 5-23) tumor size for a median of 34 (range 2.4-114) months showed slight morphological change with a median tumor growth rate of 0.15 mm (range 0-3.33) per year. CONCLUSION: Patients with tumors measuring ≥ 2.0 cm have a high probability of lymph node metastasis or recurrence, thereby requiring resection. PNEN measuring < 1.0 cm may be acceptable for observation.
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Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Tumores Neuroendocrinos/cirugía , Tumores Neuroendocrinos/patología , Metástasis Linfática , Neoplasias Pancreáticas/patología , Estudios Retrospectivos , Estudios de Casos y ControlesRESUMEN
BACKGROUND/OBJECTIVES: According to the revised international intraductal papillary mucinous neoplasm (IPMN) guidelines (2017), the indication for surgery is based on risk classification. However, some IPMNs with high-risk stigmata (HRS) can be observed for long periods without resection. Hence, we need to reconsider the risk stratification, and this study aimed to propose a novel risk stratification for HRS-IPMNs. METHODS: We enrolled 328 patients diagnosed with IPMN using endoscopic ultrasound between 2012 and 2019. We compared clinicopathological features between HRS and worrisome features (WF) and evaluated outcomes of HRS-IPMN. RESULTS: Fifty-three patients (HRS 38, WF 15) underwent resection at initial diagnosis and 275 patients were observed. Following observation for 30 months, 22 patients (17 HRS, 5 WF) underwent resection. Analysis of resected IPMNs (n = 75) revealed that HRS had dominantly pancreatobiliary mucin subtype. Pancreatobiliary-type IPMN had larger nodule sizes and lymphatic invasion and high recurrence with poor prognosis. Seventy-four patients were diagnosed with HRS, 55 underwent resection, and 19 continue to be observed. The resected group had larger nodule sizes (median 8 mm vs. 5 mm; P = 0.060), whereas the observed group had more main pancreatic duct (MPD) dilation (median 10 mm vs. 5 mm; P = 0.005). In the resected HRS group, only patients with MPD dilation ≥10 mm (n = 10) had no recurrence but had a favorable prognosis compared with those nodule size ≥5 mm (n = 45). CONCLUSIONS: Large nodule size may be associated with pancreatobiliary subtype and poor prognosis; however, patients with MPD dilation ≥10 mm with nodule size <5 mm did not require resection.
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Adenocarcinoma Mucinoso , Carcinoma Ductal Pancreático , Neoplasias Intraductales Pancreáticas , Neoplasias Pancreáticas , Adenocarcinoma Mucinoso/cirugía , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/cirugía , Humanos , Neoplasias Intraductales Pancreáticas/diagnóstico por imagen , Neoplasias Intraductales Pancreáticas/cirugía , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND: Despite the increasing number of laparoscopic liver resection (LLR) procedures, postoperative bile leakage (POBL) remains a major complication. We occasionally experienced intraoperative bile leakage (IOBL) during LLR and managed it within the restrictions of laparoscopic surgery. However, there have been no reports about IOBL in LLR. We therefore investigated the impact of IOBL on postoperative outcomes and its predictive factors. METHODS: We reviewed 137 patients who underwent LLR from April 2016 to March 2019 at our institute and assigned them to IOBL-positive or IOBL-negative groups. We compared clinicopathological characteristics and perioperative outcomes. Patients were further divided into four groups according to IOBL pattern, and the frequency of POBL in each was calculated. Predictors of IOBL were identified using multivariate logistic regression analysis. RESULTS: There were 30 and 107 patients in the IOBL-positive and IOBL-negative groups, respectively. In the IOBL-positive group, operative time and postoperative hospital stays were significantly longer (P < 0.001). The frequency of POBL was significantly higher in the IOBL-positive group (P = 0.006). The IOBL-positive group was divided into two subgroups: IOBL from the transected parenchyma (IOBL-TP, n = 18) and from the main Glissonean pedicle (IOBL-mGP, n = 12). The IOBL-negative group was divided into two subgroups: bile staining in the mGP (BS-mGP, n = 9) and no change (NC, n = 98). POBL occurred in 11% (n = 2/18) of patients with IOBL-TP, 25% (n = 3/12) of those with IOBL-mGP, 11% (n = 1/9) of those with BS-mGP, and 1% (n = 1/98) of those with NC. Age, diabetes mellitus, indocyanine green retention rate, and Glissonean approach were predictors of IOBL (P < 0.05). CONCLUSIONS: IOBL was relatively common during LLR and resulted in a higher incidence of POBL. Depending on the predictive factors, IOBL must be promptly identified and appropriately managed.
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Laparoscopía , Neoplasias Hepáticas , Bilis , Hepatectomía/efectos adversos , Humanos , Laparoscopía/efectos adversos , Neoplasias Hepáticas/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios RetrospectivosRESUMEN
BACKGROUND: Pancreatic fistulas remain a significant concern after pancreatectomy owing to the associated high risk of mortality and high costs. It is not possible to perform preoperative risk stratification for all patients. This study aimed to evaluate the usefulness of the measurement of portal vein (PV) distance as a predictive indicator of pancreatic fistula development after pancreatoduodenectomy and compare it with the usefulness of other indicators such as body mass index (BMI), and abdominal fat area. METHODS: Patient characteristics, preoperative laboratory data, radiographic findings, and their association with pancreatic fistula development after pancreatoduodenectomy were analyzed for 157 patients who underwent resection during 2011-2017. Clinically relevant postoperative pancreatic fistulas (CR-POPF) were defined as Grade B or C fistulas based on the International Study Group of Pancreatic Surgery (ISGPS) 2016 consensus. RESULTS: CR-POPF developed in 38 patients (24.2%). Multivariate logistic regression indicated that PV distance and BMI were potential candidates for predictive models for pancreatic fistula development, and small pancreatic duct diameter, diabetes mellitus development, and pathology of non-pancreatic cancers were independent factors for CR-POPF. When comparing the two risk models (PV distance- and BMI-based models), the PV distance-derived risk model was compatible to the BMI-based stratification models (area under the curve 0.831 vs. 0.830). CONCLUSIONS: PV distance was confirmed to be a useful risk predictor for CR-POPF. This research highlighted the efficacy of abdominal thickness measurement, which is simple and easily applicable in the clinical setting.
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Fístula Pancreática , Pancreaticoduodenectomía , Humanos , Fístula Pancreática/diagnóstico por imagen , Fístula Pancreática/etiología , Pancreaticoduodenectomía/efectos adversos , Vena Porta/diagnóstico por imagen , Complicaciones Posoperatorias/diagnóstico por imagen , Estudios Retrospectivos , Factores de Riesgo , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Pheochromocytoma is a catecholamine-secreting tumour that leads to various symptoms. Haemoptysis is rarely caused by a pheochromocytoma occurring outside the bronchus or thoracic cavity. Here, we report the case of an extra-adrenal abdominal pheochromocytoma initially manifesting as haemoptysis/dyspnoea during exercise without classic symptoms. CASE PRESENTATION: A 22-year-old man with a history of severe dyspnoea experienced difficulties in breathing following a marathon owing to haemoptysis that required ventilator management 1 year before presentation. His father had undergone surgery for ectopic pheochromocytoma. Computed tomography (CT) revealed a 30-mm tumour between the inferior vena cava and pancreatic head while urinalysis revealed abnormally high noradrenaline levels. He was clinically diagnosed with an extra-adrenal abdominal ectopic pheochromocytoma. After controlling blood pressure, surgery was performed, and the tumour was successfully removed. Histopathology revealed chromogranin A (+), synaptophysin (+), S100 protein (+), and MIB-1 index of 1%. Therefore, the patient was finally diagnosed with extra-adrenal abdominal ectopic pheochromocytoma. CONCLUSIONS: Haemoptysis is a rare manifestation of abdominal ectopic paraganglioma. Prompt consideration of pheochromocytoma/paraganglioma when patients experience haemoptysis without any other possible aetiology may prevent inappropriate diagnosis and treatment and ultimately fatalities.
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Neoplasias de las Glándulas Suprarrenales , Hemoptisis , Feocromocitoma , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Neoplasias de las Glándulas Suprarrenales/cirugía , Adulto , Hemoptisis/etiología , Humanos , Masculino , Recurrencia Local de Neoplasia , Feocromocitoma/diagnóstico , Feocromocitoma/cirugía , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
The expression of classical human leukocyte antigen class I antigens (HLA-I) on the surfaces of cancer cells allows cytotoxic T cells to recognize and eliminate these cells. Reduction or loss of HLA-I is a mechanism of escape from antitumor immunity. The present study aimed to investigate the clinicopathological impacts of HLA-I and non-classical HLA-I antigens expressed on pancreatic ductal adenocarcinoma (PDAC) cells. We performed immunohistochemistry to detect expression of HLA-I antigens in PDAC using 243 PDAC cases and examined their clinicopathological influences. We also investigated the expression of immune-related genes to characterize PDAC tumor microenvironments. Lower expression of HLA-I, found in 33% of PDAC cases, was significantly associated with longer overall survival. Higher expression of both HLA-E and HLA-G was significantly associated with shorter survival. Multivariate analyses revealed that higher expression of these three HLA-I antigens was significantly correlated with shorter survival. Higher HLA-I expression on PDAC cells was significantly correlated with higher expression of IFNG, which also correlated with PD1, PD-L1 and PD-L2 expression. In vitro assay revealed that interferon gamma (IFNγ) stimulation increased surface expression of HLA-I in three PDAC cell lines. It also upregulated surface expression of HLA-E, HLA-G and immune checkpoint molecules, including PD-L1 and PD-L2. These results suggest that the higher expression of HLA-I, HLA-E and HLA-G on PDAC cells is an unfavorable prognosticator. It is possible that IFNγ promotes a tolerant microenvironment by inducing immune checkpoint molecules in PDAC tissues with higher HLA-I expression on PDAC cells.
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Carcinoma Ductal Pancreático/mortalidad , Antígenos HLA-G/metabolismo , Antígenos de Histocompatibilidad Clase I/metabolismo , Neoplasias Pancreáticas/mortalidad , Escape del Tumor , Anciano , Antígeno B7-H1/metabolismo , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/cirugía , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica/inmunología , Antígenos HLA-G/análisis , Antígenos HLA-G/inmunología , Antígenos de Histocompatibilidad Clase I/análisis , Antígenos de Histocompatibilidad Clase I/inmunología , Humanos , Inmunohistoquímica , Interferón gamma/metabolismo , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Páncreas/patología , Páncreas/cirugía , Pancreatectomía , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Pronóstico , Proteína 2 Ligando de Muerte Celular Programada 1/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Microambiente Tumoral/inmunología , Antígenos HLA-ERESUMEN
Formalin-fixed paraffin-embedded (FFPE) tissues used for routine pathological diagnosis are valuable for cancer genomic analysis; however, the association between mutation status derived from these specimens and prognosis in pancreatic ductal adenocarcinoma (PDAC) remains unclear. We analyzed 50 cancer-related gene mutations including driver genes in PDAC, using next-generation sequencing (NGS) to clarify the association between gene mutations and prognosis. DNA was extracted from FFPE tissues obtained from 74 patients with untreated resectable PDAC who underwent surgery at our institution between 2013 and 2018. Fifty of the 74 patients with DNA extracts from FFPE samples suitable for NGS were analyzed. The prevalence of driver gene mutations was as follows: 84% for KRAS, 62% for TP53, 32% for SMAD4, and 18% for CDKN2A. There were no cases of single SMAD4 mutations; its rate of coincidence with KRAS or TP53 mutations was 30% and 2%, respectively. The combination of KRAS and SMAD4 mutations resulted in significantly shorter relapse-free survival (RFS; median survival time [MST], 12.3 vs. 28.9 months, P = .014) and overall survival (OS; MST, 22.3 months vs. not reached, P = .048). On multivariate analysis, the combination of KRAS and SMAD4 mutations was an independent prognostic factor for RFS (hazard ratio [HR] 4.218; 95% confidence interval [CI], 1.77-10.08; P = .001) and OS (HR 6.730; 95% CI, 1.93-23.43; P = .003). The combination of KRAS and SMAD4 mutations in DNA obtained from FFPE tissues is an independent poor prognostic factor in PDAC.
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Biomarcadores de Tumor/genética , Carcinoma Ductal Pancreático/genética , Neoplasias Pancreáticas/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteína Smad4/genética , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/mortalidad , Análisis Mutacional de ADN/métodos , Femenino , Formaldehído , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Masculino , Persona de Mediana Edad , Mutación , Neoplasias Pancreáticas/mortalidad , Adhesión en Parafina , Pronóstico , Fijación del TejidoRESUMEN
BACKGROUND: Although surgery is the definitive curative treatment for biliary tract cancer (BTC), outcomes after surgery alone have not been satisfactory. Adjuvant therapy with S-1 may improve survival in patients with BTC. This study examined the safety and efficacy of 1 year adjuvant S-1 therapy for BTC in a multi-institutional trial. METHODS: The inclusion criteria were as follows: histologically proven BTC, Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, R0 or R1 surgery performed, cancer classified as Stage IB to III. Within 10 weeks post-surgery, a 42-day cycle of treatment with S-1 (80 mg/m2/day orally twice daily on days 1-28 of each cycle) was initiated and continued up to 1 year post surgery. The primary endpoint was adjuvant therapy completion rate. The secondary endpoints were toxicities, disease-free survival (DFS), and overall survival (OS). RESULTS: Forty-six patients met the inclusion criteria of whom 19 had extrahepatic cholangiocarcinoma, 10 had gallbladder carcinoma, 9 had ampullary carcinoma, and 8 had intrahepatic cholangiocarcinoma. Overall, 25 patients completed adjuvant chemotherapy, with a 54.3% completion rate while the completion rate without recurrence during the 1 year administration was 62.5%. Seven patients (15%) experienced adverse events (grade 3/4). The median number of courses administered was 7.5. Thirteen patients needed dose reduction or temporary therapy withdrawal. OS and DFS rates at 1/2 years were 91.2/80.0% and 84.3/77.2%, respectively. Among patients who were administered more than 3 courses of S-1, only one patient discontinued because of adverse events. CONCLUSIONS: One-year administration of adjuvant S-1 therapy for resected BTC was feasible and may be a promising treatment for those with resected BTC. Now, a randomized trial to determine the optimal duration of S-1 is ongoing. TRIAL REGISTRATION: UMIN-CTR, UMIN000009029. Registered 5 October 2012-Retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009347.
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Neoplasias de los Conductos Biliares/tratamiento farmacológico , Ácido Oxónico/administración & dosificación , Tegafur/administración & dosificación , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Ampolla Hepatopancreática , Neoplasias de los Conductos Biliares/cirugía , Carcinoma/tratamiento farmacológico , Carcinoma/cirugía , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/cirugía , Supervivencia sin Enfermedad , Esquema de Medicación , Combinación de Medicamentos , Estudios de Factibilidad , Femenino , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Neoplasias de la Vesícula Biliar/cirugía , Humanos , Masculino , Persona de Mediana Edad , Ácido Oxónico/efectos adversos , Estudios Prospectivos , Tegafur/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Synovial sarcoma is a soft tissue malignancy that frequently affects the extremities, adjacent to the large joints. Synovial sarcoma has a high rate of distant metastasis; however, pancreatic metastasis is extremely rare, and to our knowledge, there has been no report of bleeding due to spontaneous tumor rupture. This study reports the case of a patient with synovial sarcoma pancreatic metastasis causing tumor rupture and bleeding, which was successfully managed with emergent distal pancreatectomy. CASE PRESENTATION: A 27-year-old woman underwent extensive resection of the primary tumor and partial lung resection after chemotherapy for left femoral synovial sarcoma and multiple lung metastases 4 years prior. During the follow-up, a 35-mm tumor was noted in the pancreatic tail on abdominal computed tomography (CT), and no other distant metastases were detected via positron emission tomography CT. Laparoscopic distal pancreatectomy was scheduled for pancreatic metastasis of synovial sarcoma. However, before the scheduled pancreatectomy could be conducted, the patient visited the emergency department because of abdominal pain that occurred after consuming a small amount of alcohol, and CT showed ascites with high CT values and leakage of contrast media. She was diagnosed with intra-abdominal hemorrhage due to a ruptured metastatic pancreatic tumor, and an emergency operation was performed. In total, 1500 mL of blood was evacuated from the abdomen, and the bleeding pancreatic tail tumor was resected. Histopathological findings revealed synovial sarcoma metastasis and a ruptured tumor capsule, and tumor cells were observed in the hematoma. After discharge on postoperative day 18, the patient was carefully monitored and confirmed to be in relapse-free survival, without chemotherapy, at 6 months post-surgery. CONCLUSIONS: While the rate of tumor growth varies depending on the grade of the tumor, the possibility of rupture should be considered even in metastatic pancreatic tumors. In the case of pancreatic tumor rupture with stable circulation, radiological evaluation for oncology is necessary, and primary resection may be compatible with resectable cases.
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Hemorragia/etiología , Pancreatectomía , Neoplasias Pancreáticas/cirugía , Sarcoma Sinovial , Adulto , Femenino , Humanos , Recurrencia Local de Neoplasia , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/secundario , Rotura Espontánea , Sarcoma Sinovial/patologíaRESUMEN
BACKGROUND: Oesophageal cancer has a high metastatic potential and poor prognosis, with a significant risk of recurrence after radical resection. However, resected pancreatic metastasis from oesophageal cancer is rare. CASE PRESENTATION: Eleven years prior, a seventy-year-old woman had been treated with transthoracic radical oesophagectomy for oesophageal squamous cell carcinoma. Four years prior, she had undergone chemotherapy for lymph node recurrence at the splenic hilum and achieved a partial response. She had also received chemoradiotherapy for lymph node recurrence at the splenic hilum 3 years prior; a complete response was achieved. However, routine follow-up with abdominal computed tomography recently revealed a tumour at the pancreatic tail and swollen lymph nodes. The patient underwent distal pancreatectomy on the basis of a pre-operative diagnosis of primary pancreatic cancer, although a histological examination of the surgical specimen revealed metastatic squamous cell carcinoma that was compatible with metachronous pancreatic metastasis from oesophageal squamous cell carcinoma. The patient has been undergoing clinical follow-up without adjuvant therapy and has been disease-free for 24 months after resection of the pancreatic metastasis. CONCLUSIONS: Resection of pancreatic metastasis may improve prognosis and should be considered when treating patients with solitary metastasis from oesophageal squamous cell carcinoma.
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Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/terapia , Recurrencia Local de Neoplasia/terapia , Neoplasias Pancreáticas/terapia , Anciano de 80 o más Años , Quimioradioterapia Adyuvante , Endosonografía , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago/diagnóstico por imagen , Carcinoma de Células Escamosas de Esófago/secundario , Esofagectomía , Femenino , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/patología , Páncreas/diagnóstico por imagen , Páncreas/patología , Páncreas/cirugía , Pancreatectomía , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/secundario , Esplenectomía , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
BACKGROUND: Bloodstream infection (BSI) is a life-threatening complication after living donor liver transplantation (LDLT). We aimed to explore the incidence and predisposing factors of BSI at our institution. METHODS: We conducted a retrospective cohort analysis on all consecutive adults with BSI within 6 months after LDLT performed between 2005 and 2016. For antimicrobial prophylaxis, ampicillin/sulbactam, cefotaxime, and micafungin were administered. From 2011, methicillin-resistant Staphylococcus aureus (MRSA) carriers were decolonized using mupirocin ointment and chlorhexidine gluconate soap. Risk factors for BSI were identified by uni- and multivariate logistic regression. RESULTS: Of a total of 106 LDLTs, 42 recipients (40%) suffered BSI. The BSI group demonstrated significantly higher in-hospital mortality rates compared with the non-BSI group (24% vs. 7%, P = .01). We identified MRSA carrier (odds ratio [OR], 19.1; P < .001), ABO incompatibility (OR, 2.9; P = .03), and estimated glomerular filtration rate <30 mL/min/1.73m2 (OR, 15.8; P = .02) as independent risk factors for BSI. Decolonization treatment for MRSA carriers did not reduce the incidence of all-cause BSI but reduced the frequency of BSI caused by MRSA. CONCLUSION: To our knowledge, for the first time, MRSA carriers were revealed to be highly vulnerable to BSI after LDLT.
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Bacteriemia/epidemiología , Portador Sano/epidemiología , Infección Hospitalaria/epidemiología , Trasplante de Hígado/efectos adversos , Donadores Vivos/estadística & datos numéricos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Infecciones Estafilocócicas/epidemiología , Anciano , Bacteriemia/microbiología , Portador Sano/microbiología , Infección Hospitalaria/microbiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Japón/epidemiología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Infecciones Estafilocócicas/microbiologíaRESUMEN
BACKGROUND: We aimed to evaluate the efficacy and safety of 5-fluorouracil-based neoadjuvant chemoradiotherapy (NACRT) in patients with resectable/borderline resectable pancreatic ductal adenocarcinoma (PDAC). METHODS: This retrospective study investigated the clinicopathological features and > 5-year survival of patients with T3/T4 PDAC who underwent NACRT at our institute between 2003 and 2012. RESULTS: Seventeen resectable and eight borderline resectable patients were included. The protocol treatment completion and resection rates were 92.0% and 68.0%, respectively. Two patients failed to complete chemotherapy owing to cholangitis or anorexia. Common grade 3 toxicities included anorexia (12%), neutropenia (4%), thrombocytopenia (4%), anemia (4%), and leukopenia (12%). Pathologically negative margins were achieved in 94.1% of patients who underwent pancreatectomy. Pathological response according to Evans' classification was grade IIA in 10 patients (58.8%), IIB in 5 patients (29.4%), and IV in 2 patients (11.8%). Postoperative pancreatic fistulas were observed in four patients (23.5%), delayed gastric emptying in one patient (5.9%), and other operative morbidities in four patients (23.5%). The 1-, 2-, 5-, and 10-year overall survival rates were 73.9%, 60.9%, 60.9%, and 39.1%, respectively (median follow-up period, 80.3 months). CONCLUSIONS: NACRT is tolerable and beneficial for resectable/borderline resectable PDAC, even in the long-term.
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Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Ductal Pancreático/terapia , Quimioradioterapia/mortalidad , Pancreatectomía/mortalidad , Neoplasias Pancreáticas/terapia , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/patología , Cisplatino/administración & dosificación , Terapia Combinada , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Mitomicina/administración & dosificación , Neoplasias Pancreáticas/patología , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
The efficacy of next-generation sequencing (NGS) of tumor-derived DNA from intraoperative peritoneal washing fluid (IPWF) of patients with pancreatic ductal adenocarcinoma (PDAC) who intend to undergo curative resection remains unclear. The aim of the present study was to evaluate whether genomic mutations in tumor-derived DNA from IPWF samples of patients with PDAC who intend to undergo curative resection could be detected using NGS. A total of 12 such patients were included in this study. Cytology of IPWF (CY) was assessed and NGS of genomic tumor-derived DNA from the IPWF was performed to determine whether genomic mutations could be detected in these patient samples. A total of 2 patients (16.7%) had a CY(+) status and 1 patient (8.3%) showed intraoperative macro-peritoneal dissemination; 11 patients underwent radical surgery. Actionable gene alterations were detected in 8 (80.0%) out of the 10 patients with CY(-) status based on NGS of IPWF samples, and 3 (37.5%) patients among those with actionable gene mutations identified from IPWF samples underwent peritoneal dissemination after surgery within ~12 months. The most common genomic mutation was in KRAS (9 patients, 75.0%), followed by TP53 (3 patients, 25.0%), SMAD4 (1 patient, 8.3%) and CDKN2A (1 patient, 8.3%). These findings indicated that the genomic mutations identified in tumor-derived DNA from IPWF samples of patients with PDAC with a CY(-) status who intend to undergo curative resection are potential biomarkers for predicting the recurrence of early peritoneal dissemination.
RESUMEN
Hepatocyte transplantation (HCT) is a potential bridging therapy or an alternative to liver transplantation. Conventionally, single-cell hepatocytes are injected via the portal vein. This strategy, however, has yet to overcome poor cell engraftment and function. Therefore, we developed an orthotopic HCT method using a liver-derived extracellular matrix (L-ECM) gel. PXB cells (flesh mature human hepatocytes) were dispersed into the hydrogel solution in vitro, and the gel solution was immediately gelated in 37°C incubators to investigate the affinity between mature human hepatocyte and the L-ECM gel. During the 3-day cultivation in hepatocyte medium, PXB cells formed cell aggregates via cell-cell interactions. Quantitative analysis revealed human albumin production in culture supernatants. For the in vivo assay, PXB cells were encapsulated in the L-ECM gel and transplanted between the liver lobes of normal rats. Pathologically, the L-ECM gel was localized at the transplant site and retained PXB cells. Cell survival and hepatic function marker expression were verified in another rat model wherein thioacetamide was administered to induce liver fibrosis. Moreover, cell-cell interactions and angiogenesis were enhanced in the L-ECM gel compared with that in the collagen gel. Our results indicate that L-ECM gels can help engraft transplanted hepatocytes and express hepatic function as a scaffold for cell transplantation.