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BACKGROUND/OBJECTIVES: The outcomes of patients with intraepithelial neoplasia at the pancreatic transection margin after pancreatic cancer surgery remain unclear. We evaluated the clinical impact of pancreatic transection margin status. METHODS: This retrospective observational study included 171 patients who underwent surgery for pancreatic ductal adenocarcinoma between January 2008 and December 2019. Patients were classified into three groups: negative pancreatic transection margin (group N), positive low-grade (group L), and positive high-grade (group H) intraepithelial neoplasia. The clinicopathological findings and prognoses were analyzed for each group. RESULTS: There were 140, 14, and 9 patients in groups N, L, and H, respectively. The median age was significantly higher in group H (p = 0.035). There were no significant differences in male ratio, preoperative chemotherapy administration rate, pretreatment tumor markers, operative procedure, operative time, or blood loss. Overall survival and recurrence-free survival were not significantly different; however, the cumulative risk of recurrence in the remnant pancreas was significantly higher in group H (p = 0.018). CONCLUSIONS: Intraepithelial neoplasia at the pancreatic transection margin did not affect overall/recurrence-free survival. As patients with high-grade intraepithelial neoplasia at the pancreatic transection margin have an increased risk of recurrence in the remnant pancreas, careful postoperative follow-up is required.
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Carcinoma in Situ , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Masculino , Carcinoma in Situ/patologia , Carcinoma Ductal Pancreático/patologia , Recidiva Local de Neoplasia/patologia , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , FemininoRESUMO
BACKGROUND AND AIM: Safe radical hepatectomy is important for patients with colorectal liver metastases complicated by sinusoidal obstruction syndrome (SOS) after oxaliplatin-based chemotherapy. This study aimed to investigate the impact of preoperative administration of cilostazol (CZ), an oral selective phosphodiesterase III inhibitor, on hepatectomy in rat SOS model. MATERIAL AND METHODS: Rats were divided into NL (normal liver), SOS (monocrotaline [MCT]-treated), and SOS + CZ (MCT + CZ-treated) groups. MCT or CZ was administered orally, and a 30% partial hepatectomy was performed 48 h after MCT administration. Postoperative survival rates were evaluated (n = 9, for each). Other rats were sacrificed on postoperative days (POD) 1 and 3 and evaluated histologically, immunohistochemically, biochemically, and using transmission electron microscopy (TEM), focusing particularly on SOS findings, liver damage, and liver sinusoidal endothelial cell (LSEC) injury. RESULTS: The cumulative 10-day postoperative survival rate was significantly higher in the SOS + CZ group than in the SOS group (88.9% vs 33.3%, P = 0.001). Total SOS scores were significantly lower in the SOS + CZ group than in the SOS group on both POD 1 and 3. Serum biochemistry and immunohistochemistry showed that CZ reduced liver damage after hepatectomy. TEM revealed that LSECs were significantly preserved morphologically in the SOS + CZ group than in the SOS group on POD 1 (86.1 ± 8.2% vs 63.8 ± 9.3%, P = 0.003). CONCLUSION: Preoperative CZ administration reduced liver injury by protecting LSECs and improved the prognosis after hepatectomy in rats with SOS.
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Cilostazol , Modelos Animais de Doenças , Hepatectomia , Hepatopatia Veno-Oclusiva , Inibidores da Fosfodiesterase 3 , Animais , Hepatopatia Veno-Oclusiva/prevenção & controle , Hepatopatia Veno-Oclusiva/etiologia , Hepatopatia Veno-Oclusiva/patologia , Cilostazol/farmacologia , Hepatectomia/efeitos adversos , Masculino , Inibidores da Fosfodiesterase 3/farmacologia , Inibidores da Fosfodiesterase 3/uso terapêutico , Prognóstico , Oxaliplatina/efeitos adversos , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/tratamento farmacológico , Taxa de Sobrevida , Ratos , Tetrazóis/administração & dosagem , Tetrazóis/farmacologia , Neoplasias Colorretais/patologia , Fígado/patologia , Ratos Sprague-DawleyRESUMO
We report 2 cases of portal vein stent placement for malignant portal stenosis due to recurrence of pancreatic cancer with symptoms of portal hypertension. Case 1: The patient was a 68-year-old female. Five years ago, a mass was found around the aorta on a computerized tomography(CT)scan taken after a residual pancreatectomy for pancreatic cancer. It was diagnosed as lymph node recurrence and S-1 therapy was started. As further tumor enlargement led to portal vein compression, venostasis around the ascending jejunum, anemia, and black stools, a portal vein stent was placed. The portal vein blood flow was improved, the collateral vessels disappeared, and the patient no longer experienced anemia or black stool. Case 2: A 75-year-old female patient underwent a subtotal gastric-sparing pancreaticoduodenectomy and combined resection of the portal vein for pancreas head cancer. On a postoperative CT scan taken 6 months later, a mass compressing the portal vein appeared, which was diagnosed as a local recurrence. As thrombocytopenia was observed, a portal vein stent was placed before starting chemotherapy. The portal vein blood flow and the platelet count improved. Portal vein stenting is an effective procedure for malignant portal stenosis, improving portal blood flow and clinical symptoms.
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Anemia , Neoplasias Pancreáticas , Feminino , Humanos , Idoso , Veia Porta/cirurgia , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/cirurgia , Pâncreas , MelenaRESUMO
Hyperglycemia associated with insulin resistance is common in surgical patients with and without diabetes and is associated with poor surgical outcomes. Several studies have recently shown that a closed-loop blood glucose monitoring system in the form of an artificial pancreas is safe and effective for surgical patients. In this study, we analyzed the risk factors for insulin resistance in patients using an artificial pancreas. We investigated 109 patients who underwent surgical management by an artificial pancreas for 24 hours from the start of surgery during either major hepatectomy (MH), defined as resection of more than two liver segments, or pancreaticoduodenectomy (PD). The target glucose range was from 80 to 110 mg/dL using an artificial pancreas. We analyzed the risk factors for and predictors of a high insulin dose, including sarcopenia markers, according to the median 24-hour total insulin infusion. The median total insulin dose and glycemic control rate (GCR), which is the rate of achieving the target blood glucose range, per 24 hours were 78.0 IU and 30.4% in the MH group and 82.6 IU and 23.5% in the PD group, respectively. The muscle volume was the only independent factor in the high-dose subgroup, and the GCR was significantly lower in the high-dose subgroup despite a high insulin dose in both the MH and PD groups. The results of this study suggest that preoperative sarcopenia is closely associated with insulin resistance in the perioperative period. Clinicians must effectively manage sarcopenia, which may result in improved perioperative glycemic control and reduced postoperative complications.
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Glicemia/metabolismo , Pâncreas Artificial , Assistência Perioperatória , Complicações Pós-Operatórias/sangue , Sarcopenia/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Hepatectomia , Humanos , Sistemas de Infusão de Insulina , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Pancreaticoduodenectomia , Estudos Prospectivos , Fatores de RiscoRESUMO
Most cancer patients receiving chemotherapy are accompanied by gut dysbiosis and intestinal mucosal barrier dysfunction to a greater or lesser degree. These disorders of the gut can easily cause bacterial translocation, resulting in the formation of immunothrombosis composed mainly of neutrophil extracellular traps and activated platelets in hepatic sinusoid in order to trap bacteria. At the same time, however, a lot of alarmin such as HMGB1, S100A8/S100A9 and VEGFâA which are released from immunothrombosis, promote to recruit many myeloidâderived suppressor cells(MDSCs)from bone marrow, leading to the strong immunosuppressive milieu in both liver and cancerous lesions. Therefore, intestinal care must be necessary for protection of intestinal barrier integrity during chemotherapy. Recently, we found that intestinal care using oral Lâglutamineâ enriched supplement and probiotics including Lactobacillus casei Shirota supplement(Yakult®)and Clostridium butyricum MIYAIRI 588 strain(MiyaâBM®)could induce a strong antiâtumor immune response through the induction of fully mature tertiary lymphoid structures in some pancreatic cancer patients who received 3 cycles of preoperative chemotherapy(gemcitabine 1,000 mg/m2 plus nabâpaclitaxel 125 mg/m2 on days 1, 8, and 15 of 28âday cycle). In this review article, we discussed the role of intestinal care in the induction of fully mature tertiary lymphoid structures in cancer patients receiving chemotherapy.
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Neoplasias Pancreáticas , Probióticos , Estruturas Linfoides Terciárias , Glutamina , Humanos , Imunidade , Mucosa Intestinal , Neoplasias Pancreáticas/terapiaRESUMO
BACKGROUND: Rhabdomyosarcoma (RMS), a malignant neoplasm that normally differentiates to form striated muscle, is the most common type of childhood soft tissue sarcoma. However, it infrequently occurs in adults and is uncommon in the liver. We herein report a case of RMS of the liver in an adult. CASE PRESENTATION: A 73-year-old woman was admitted to our institution for investigation of a hepatic mass. She had been followed for primary biliary cirrhosis for the past 20 years. A contrast-enhanced computed tomography scan of the abdomen showed a 12- × 10-cm heterogeneous low-density mass lesion containing cystic and solid components. A percutaneous liver biopsy was performed, and poorly differentiated cancer containing an RMS cell-like component was observed. The patient was diagnosed with RMS of the liver, and open surgery with right hepatic lobectomy was performed. Histopathological examination confirmed a diagnosis of pleomorphic RMS of the liver. The patient died of rapid progression of the tumor 6 months after the operation. CONCLUSIONS: The tumor site in the present case is rare. The details of this case add to the current evidence base regarding establishment of the standard diagnosis and treatment of this rare condition. We recommend consideration of RMS as a differential diagnosis for hepatic tumors.
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Neoplasias Hepáticas/diagnóstico , Rabdomiossarcoma/diagnóstico , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Hepáticas/cirurgia , Tomografia Computadorizada por Raios XAssuntos
Ampola Hepatopancreática , Carcinoma de Células Acinares , Neoplasias Pancreáticas , Humanos , Ampola Hepatopancreática/cirurgia , Carcinoma de Células Acinares/patologia , Pancreaticoduodenectomia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Neoplasias PancreáticasRESUMO
A 59-year-old man was admitted to our hospital for further investigation of abnormal uptake in the pancreatic body on positron emission tomography-computed tomography(PET-CT). He had chronic renal failure due to diabetic nephropathy, and had been on maintenance hemodialysis since he was 45-years-old. He was diagnosed with pancreatic body cancer(cT1c, cN0, cM0, cStageâ a)and was treated preoperatively with neoadjuvant chemotherapy(gemcitabine plus nab-paclitaxel). After 2 courses, we performed distal pancreatectomy. Histopathological examination revealed no viable tumor cells(pathological complete response). The postoperative course was uneventful, and he is alive without recurrence at 6 months after surgery, without adjuvant chemotherapy. Our findings suggest that gemcitabine plus nab-paclitaxel is a useful treatment for patients with pancreatic cancer on hemodialysis.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pancreáticas , Albuminas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Paclitaxel/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Diálise Renal , GencitabinaRESUMO
BACKGROUND: The clinical prognosis of gastric cancer with peritoneal dissemination is poor because of its chemoresistance and rich fibrosis. While several gastric cancer cell lines have been used to establish models of peritoneal dissemination by intraperitoneal injection, most peritoneal tumors that form adopt a medullary pattern in microscopic appearance. This histological finding for the model differs from that in the clinical situation. This study was performed to demonstrate the contribution of human peritoneal mesothelial cells (HPMCs) to fibrotic tumor formation and to establish a new xenograft model with high potential for peritoneal dissemination with organ invasion and extensive fibrosis. METHODS: We established four types of xenograft model: i) intraperitoneal injection of MKN45-P cells alone (control group), ii) injection of MKN45-P cells co-cultured with HPMCs (co-cultured group), iii) scratching the parietal peritoneum (parietal group), and iv) scratching the visceral peritoneum (visceral group) with a cotton swab before injection of co-cultured cells. Fibrosis, α-smooth muscle actin expression, and organ invasion by tumor cells were all assessed by immunohistochemical examination. RESULTS: All mice developed abdominal swelling with peritoneal tumors and bloody ascites. Tumors of the control and co-cultured groups were not invasive or fibrotic. Contrastingly, tumors of the scratch groups exhibited rich stromal fibrosis and possessed increased α-smooth muscle actin (α-SMA) expression. In particular, the visceral group showed edematous and spreading tumors invading the intestinal wall. CONCLUSION: We established a model of peritoneal dissemination with organ invasion and stromal fibrosis. Formation of peritoneal dissemination required a favorable environment for cell adhesion, invasion, and growth. This model may be useful for analyzing the pathogenesis and treatment of peritoneal dissemination of gastric cancer.
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Neoplasias Peritoneais/secundário , Neoplasias Gástricas/patologia , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Fibrose/patologia , Xenoenxertos , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Peritônio/patologiaRESUMO
Cholangiolocarcinoma (CLC) is an extremely rare tumor classified as a subtype of small duct-type intrahepatic cholangiocarcinoma (iCCA). There are few detailed reports on CLC and the prognostic impact of tumor heterogeneity is not clear. Between April 2006 and June 2022, of the 774 primary liver cancer resection cases who presented at Kanazawa University Hospital, 14 patients were pathologically diagnosed with CLC through immunohistochemical analysis of their molecular and biological features. Clinicopathological features and prognoses were evaluated retrospectively. Additionally, tumor heterogeneity was assessed and tumors were classified into pure and partial types according to the CLC component proportion in a single tumor. Chronic liver disease was observed in nine patients (64.3%). All tumors were mass-forming, and pathological R0 resection was achieved in 11 patients (78.6%). Tumor heterogeneity was classified as pure in 11 (78.6%) and partial in three (21.4%) patients. The median follow-up was 59.5 months (12-114 months). There was no difference in the 5-year disease-specific survival rates between the pure and partial (90.0% vs. 100.0%; P=0.200) types, but rates were significantly higher in the R0 resection group compared with those in the R1 resection group (100.0% vs. 50.0%; P=0.025). In conclusion, these results suggest that it is important for CLC patients to achieve curative resection, and CLC may have a good prognosis regardless of the proportion of CLC components in a single tumor.
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BACKGROUND: The detailed mechanisms underlying the development of ischemia-type biliary lesions (ITBLs) in aged donor grafts remain unclear. In the present study we aimed to investigate the impact of aging on the response of the peribiliary gland (PBG) to ischemia-reperfusion injury (IRI) and its temporal changes. METHODS: Experiments were performed using a 90-min partial warm liver ischemia model in male Wistar rats of two age groups: young (7-8 weeks old) and old (52-60 weeks old). Liver tissues were obtained 24, 72, and 168 h after IRI. Histopathological and immunohistochemical assessments of the perihilar bile duct (PHBD), including the PBG, distal to the clip-clamped site were performed. RESULTS: Young rats showed little change in the bile duct tissues after IRI. However, old rats showed an increased PBG volume in the PHBD and marked PBG cell proliferation 24 h after IRI. Bile duct wall thickening with narrowing of the lumen peaked 72 h after IRI. Mucus production and oxidative stress in the PBG were significantly higher in old than in young rats after IRI. These findings showed a trend toward improvement 168 h after IRI. CONCLUSION: Age-dependent differences in the response of the PBG to IRI may be related to differences in ITBL frequency.
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OBJECTIVES: Although the dorsal pancreatic artery (DPA) is an important artery that supplies the pancreas, its morphology has not been sufficiently studied. We investigated the morphology of the DPA and the progression of pancreatic cancer along this vessel. MATERIALS AND METHODS: Overall, 142 patients with pancreatic cancer who underwent surgical resection at Kanazawa University Hospital between 2004 and 2015 were enrolled. We examined the morphology of the DPA using preoperative computed tomography and cancer progression along the DPA using resected specimens. We investigated the anatomical structures surrounding the DPA through cadaveric examination. RESULTS: The analysis of computed tomography images revealed the presence of the DPA in 141 patients. In typical cases, the DPA divides into a head and a body branch. Histopathological examination revealed cancer progression along the DPA in 32 patients. Cancer progression along the DPA was identified as a factor associated with a poor prognosis in pancreatic head or body cancer. Cadaveric examination showed the presence of abundant nerve and lymphatic tissues along the DPA. CONCLUSIONS: It is important to remove the soft tissue surrounding the DPA during surgery for pancreatic head or body cancer because it may serve as an important route for cancer progression.
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Pâncreas , Neoplasias Pancreáticas , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/diagnóstico por imagem , Masculino , Feminino , Idoso , Pâncreas/patologia , Pâncreas/irrigação sanguínea , Pâncreas/diagnóstico por imagem , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Artérias/patologia , Artérias/diagnóstico por imagem , Progressão da Doença , Adulto , Prognóstico , CadáverRESUMO
BACKGROUND: Although postoperative portal vein thrombosis (PVT) is a frequent complication of splenectomy, few studies have examined PVT after simultaneous hepatectomy and splenectomy (HS). The aim of this study was to clarify the risk factors for and characteristics of PVT after HS. METHODS: This retrospective observational study included 102 patients, including 76 with liver cirrhosis (LC) and 26 without, who underwent HS between April 2004 and April 2021. The incidence and location of postoperative PVT detected on contrast-enhanced CT 1 week after surgery were analyzed. In addition, pre- and intraoperative parameters were compared between patients with postoperative PVT and those without in order to determine risk factors for PVT after HS. RESULTS: Among the 102 patients, 29 (28.4 %), including 32.9 % with LC and 15.4 % without LC, developed PVT after surgery. Among the 29 patients with PVT, 21 (72.4 %), 4 (13.8 %), and 4 (13.8 %) developed thrombus in the intrahepatic portal vein only, extrahepatic portal vein only, and both the extra- and intrahepatic portal veins, respectively. Multivariable analysis showed that preoperative splenic vein dilatation was an independent risk factor for PVT after HS (odds ratio: 1.53, 95 % confidence interval: 1.156-2.026, P = 0.003). CONCLUSION: Our results suggest that splenic vein dilatation is an independent risk factor for PVT after simultaneous HS, and that PVT after HS occurs more frequently in the intrahepatic portal vein. After HS for cases with dilated splenic veins, we should pay particular attention to the PVT development in the intrahepatic portal vein regardless of the type of liver resection.
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BACKGROUND: Synovial sarcoma is a malignant tumor that constitutes up to 10% of all soft-tissue sarcomas. The most frequent metastatic sites of synovial sarcoma are the lungs, lymph nodes, and bone, whereas pancreatic metastasis is extremely rare. Here, we report a case of pancreatic metastasis of synovial sarcoma. CASE PRESENTATION: Nine years before presentation, a 31-year-old woman underwent extensive resection of the primary tumor after chemotherapy for left upper extremity synovial sarcoma. Six months before presentation, interscapulothoracic amputation was performed for an enlarged mass in the left upper extremity; the patient was treated with pazopanib. Three months before presentation, chest computed tomography showed multiple lung metastases; during subsequent follow-up, abdominal computed tomography revealed a pancreatic metastasis of synovial sarcoma. The doubling time of the pancreatic tumor was 14 days, and it grew rapidly. Furthermore, treatment-resistant pancreatitis symptoms were detected; thus, we performed distal pancreatectomy and administered one course of a 70% dose of trabectedin. However, the patient died of rapid progression of lung metastasis and respiratory failure within 2 months after surgery. CONCLUSIONS: Pancreatectomy may be carefully performed in cases of isolated pancreatic metastasis. However, the presence of other distant extrapancreatic metastases (e.g., uncontrolled lung metastases) may rule out pancreatectomy treatment.
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BACKGROUND: High-flow continuous hemodiafiltration (HF-CHDF) combines diffusive and convective solute removal and is employed for artificial liver adjuvant therapy. However, there is no report on dosage planning of vancomycin (VCM) in patients with acute liver failure under HF-CHDF. CASE PRESENTATION: A 20-year-old woman (154 cm tall, weighing 50 kg) was transferred to the intensive care unit (ICU) with acute liver failure associated with autoimmune liver disease. On the following day, HF-CHDF was started due to elevated plasma ammonia concentration. On ICU day 8, VCM was started for suspected pneumonia and meningitis (30 mg/kg loading dose, then 20 mg/kg every 12 hrs). However, on ICU day 10, VCM blood concentration was under the limit of detection (< 3.0 µg/mL) and the patient developed anuria. The VCM dose was increased to 20 mg/kg every 6 hrs. Calculation with a one-compartment model using the HF-CHDF blood flow rate as a surrogate for VCM clearance, together with hematocrit and protein binding ratio, predicted a trough VCM blood concentration of 15 µg/mL. The observed concentration was about 12 µg/mL. The difference may represent non-HF-CHDF clearance. Finally, living donor liver transplantation was performed. CONCLUSION: We report an acute liver failure patient with anuria under HF-CHDF in whom VCM administration failed to produce an effective blood concentration, likely due to HF-CHDF-enhanced clearance. VCM dosage adjustment proved successful, and was confirmed by calculation using a one-compartment model.
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Hemophagocytic lymphohistiocytosis (HLH) is a rare but lethal complication of liver transplantation (LT). HLH is characterized by pathologic macrophage activation with hypercytokinemia, excessive inflammation, and tissue destruction, resulting in progressive organ dysfunction. HLH is also known as macrophage activation syndrome (MAS) when complicated by rheumatic or autoinflammatory diseases. Measuring several serum cytokines could be helpful in diagnosing HLH and MAS. Cytokines related to macrophage activation: neopterin, interleukin-18 (IL-18), and soluble tumor necrosis factor receptors (sTNF-R) I and II have not been assessed in patients with HLH complicated by LT. In this case, these cytokines were evaluated in the perioperative period of LT. The patient was a 24-year-old woman who underwent living-donor LT for acute worsening of autoimmune hepatitis. On postoperative day 12, the patient was diagnosed with HLH on the basis of the criteria. Plasma exchange, steroid pulse therapy, intravenous immunoglobulin and granulocyte-colony stimulating factor effectively inhibited progression to lethal HLH. When HLH occurred after LT, cytokine analysis showed that neopterin, IL-18, sTNFR-I, and II were elevated: cytokine storm. Of note, cytokine analysis on hospital admission also revealed elevated cytokine levels. Particularly, IL-18 levels were markedly elevated, suggesting that activation of the innate immune system was involved. These results revealed that a cytokine storm and macrophage activation developed before LT. Based on these findings, cytokine analysis related to macrophage activation may be useful for diagnosing and predicting HLH and MAS in patients with LT.
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Hepatite Autoimune , Transplante de Fígado , Linfo-Histiocitose Hemofagocítica , Síndrome de Ativação Macrofágica , Feminino , Humanos , Adulto Jovem , Adulto , Citocinas , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/etiologia , Interleucina-18 , Transplante de Fígado/efeitos adversos , Hepatite Autoimune/complicações , Hepatite Autoimune/diagnóstico , Ativação de Macrófagos , Síndrome da Liberação de Citocina , Neopterina , Síndrome de Ativação Macrofágica/diagnóstico , Síndrome de Ativação Macrofágica/etiologia , Síndrome de Ativação Macrofágica/terapiaRESUMO
Sinusoidal obstruction syndrome (SOS) is a type of fatal hepatic injury, which predominantly occurs following exposure to drugs, such as oxaliplatin, or bone marrow transplantation. Extravasated platelet aggregation (EPA) plays an important role in the development of SOS in rat and mouse models. Furthermore, platelets invading the space of Disse adhere to hepatocytes and are phagocytized in patients with SOS. Aging platelets and platelets in patients with sepsis are phagocytized by hepatocytes through AshwellMorell receptors, and thrombopoietin (TPO) is produced by the JAK2STAT3 signaling pathway. The purpose of the present study was to examine the significance of TPO as a biomarker of SOS. SOS was induced in Crl:CD1(ICR) female mice by intraperitoneal administration of monocrotaline (MCT). TPO levels were measured in the serum and liver tissue. Pathological and immunohistochemical studies of the liver were performed to analyze the expression levels of TPO. TPO mRNA expression levels were measured using reverse transcriptionquantitative PCR. In the SOS model, the platelet counts in peripheral blood samples were significantly decreased at 24 and 48 h after MCT treatment as compared with that at 0 h. In addition, a pathological change in hepatic zone 3 was observed in the SOS model group. Furthermore, the protein levels of TPO in liver tissue were significantly increased in the SOS model group compared with those in the control group, which was confirmed by immunohistochemistry. By contrast, serum TPO protein levels were significantly decreased in the SOS model group compared with those in the control group. These results indicated that EPA may induce sinusoidal endothelial fenestration in a mouse model of SOS, preventing TPO from translocating into the blood. In conclusion, serum TPO levels may be reduced in a mouse model of SOS owing to the accumulation in hepatocytes, suggesting that TPO could be a useful biomarker of SOS.
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Hepatopatia Veno-Oclusiva , Animais , Biomarcadores , Modelos Animais de Doenças , Feminino , Hepatopatia Veno-Oclusiva/induzido quimicamente , Hepatócitos/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos ICR , Monocrotalina/toxicidade , Ratos , Trombopoetina/genética , Trombopoetina/metabolismoRESUMO
We report a rare case of intrahepatic cholangiocarcinoma (iCCA) that arose from a simple hepatic cyst. A 72-year-old man was transferred to our hospital for treatment of a liver tumor. Dynamic contrast-enhanced computed tomography (CT) detected a small tumor surrounding a hepatic cyst in segment 8 that showed low attenuation on a pre-contrast CT, rim-like enhancement in the arterial dominant phase, and delayed enhancement in the delayed phase. On gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced dynamic magnetic resonance imaging (MRI), the hepatic tumor had hypointensity on T1-weighted images, hyperintensity on T2-weighted images, hyperintensity on diffusion-weighted images, and hypointensity on the hepatobiliary phase. The tumor increased in size after 6 months, and partial hepatectomy was performed. Histopathologically, the tumor was consistent with moderately to poorly differentiated adenocarcinoma with the microscopic lymphatic, portal, and hepatic venous invasion. The epithelium of the cystic region largely comprised carcinoma in situ, with dysplastic biliary epithelial cells and a small portion of normal biliary epithelial cells. The transition from carcinoma in situ to invasive carcinoma was confirmed, and the patient was diagnosed with iCCA arising from a hepatic cyst via dysplasia and carcinomatous transformation.
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Neoplasias dos Ductos Biliares , Carcinoma in Situ , Carcinoma Hepatocelular , Colangiocarcinoma , Cistos , Neoplasias Hepáticas , Idoso , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos/patologia , Carcinoma Hepatocelular/patologia , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/cirurgia , Meios de Contraste , Cistos/complicações , Cistos/diagnóstico por imagem , Cistos/cirurgia , Gadolínio DTPA , Humanos , Hepatopatias , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética/métodos , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVES: Resectability status is considered an important indicator for progression of pancreatic cancer. We verified the superior mesenteric artery (SMA) factors of resectability status by radiological and pathological analysis in patients who underwent pancreatoduodenectomy with combined resection of the SMA. METHODS: We enrolled 22 patients who underwent pancreatoduodenectomy with combined resection of the SMA. Patients were divided into 3 groups according to the contact angle between the tumor and the SMA in preoperative computed tomography images (no contact, R-sma; contact within 180 degrees, BR-sma; contact more than 180 degrees, UR-sma). We pathologically evaluated cancer progression toward the SMA. RESULTS: There were 3 patients with R-sma, 12 with BR-sma, and 7 with UR-sma. The median distance (mm) between the cancer and the SMA was 7.0 with R-sma, 1.0 with BR-sma, and 0 with UR-sma (P = 0.0003). Invasion to the superior mesenteric nerve plexus was positive in none with R-sma, 11 with BR-sma, and 7 with UR-sma (P < 0.0001). Invasion to the SMA was positive in none with R-sma and BR-sma, and 7 with UR-sma (P < 0.0001). CONCLUSIONS: Superior mesenteric artery factors of resectability status are reliable indicator for cancer progression toward the SMA.
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Artéria Mesentérica Superior/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Tomografia Computadorizada por Raios X , Progressão da Doença , HumanosRESUMO
Neoadjuvant chemotherapy (NAC) has become a standard treatment for borderline resectable pancreatic ductal adenocarcinoma (PDAC). The present study examined the maximum tolerated dose of NAC with gemcitabine plus nab-paclitaxel (GnP) in patients with resectable PDAC. Between 2015 and 2019, 39 patients with resectable PDAC were enrolled in the present study. GnP was administered for two 28-day cycles on days 1, 8 and 15. The planned doses for levels 1, 2 and 3 were 75, 100 and 125 mg/m2, respectively, for nab-paclitaxel and 600, 800 and 1,000 mg/m2, respectively, for gemcitabine. Dose-limiting toxicity (neutropenia, anemia, thrombocytopenia and/or liver injury) was observed in 44.4% of patients treated at dose level 1 (21 patients) and 60.0% of those treated at dose level 2 (18 patients). Therefore, the maximum tolerated dose was set as level 1. Six patients withdrew from protocol treatment because of non-hematologic adverse events (skin rash, pancreatitis and biliary tract infection). Among the 31 patients with pathologically confirmed PDAC, partial response, stable disease and disease progression were recorded in 4 (12.9%), 24 (77.4%) and 3 (9.7%) patients, respectively. NAC significantly reduced tumor size according to computed tomography, and CA19-9 levels and the 18F-fluorodeoxyglucose maximum standardized uptake value were decreased in positron emission tomography. No postoperative complications attributable to NAC were recognized. Among the 27 patients with PDAC who underwent resection, the pathological treatment effect was judged as grades Ia, Ib and II in 21 (77.8%), 4 (14.8%) and 2 (7.4%) patients, respectively. R0 resection was performed in 24 out of 27 patients (88.9%). Adjuvant chemotherapy with oral S-1 was administered to 21 out of 27 patients (77.8%). In conclusion, NAC with GnP was safe and feasible for resectable PDAC at dose level 1. In the future, verification of the long-term results of the present study will be necessary, and a phase II clinical trial is anticipated.