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Extrahepatic portal vein obstruction (EHPVO) is a rare disease with myeloproliferative neoplasm (MPN) as the most common cause. We report that hypersplenic hematologic changes in EHPVO might be eliminated by MPN. Through experience with splenectomy for variceal control with EHPVO, we suspected that spleen might mask MPN-induced thrombocytosis, and that MPN might have a significant influence on excessive thrombocytosis after splenectomy. To clarify the influence of MPN and spleen on platelet trends, we conducted a retrospective hospital database analysis, evaluating 8 EHPVO patients with splenectomy (2 males, 6 females; from 17 years to 64 years, mean 38.3 years). Three (37.5%) of 8 were diagnosed as MPN by JAK2V617F mutation. The perioperative serum platelet counts in EHPVO without MPN were 10.5, 35.4, and 36.6 (x104/µL) preoperatively, after 1 week and 3 weeks, respectively. The platelet counts in EHPVO with MPN were 34.2, 86.4, and 137.0 (x104/µL), respectively. Splenectomy and MPN showed positive interaction on platelet increasing with statistical significance. We also examined the spleen volume index (SpVI: splenic volume (cm3) / body surface area (m2) and postoperative platelet elevations ratio (PER: 3-week postoperative platelet counts / preoperative platelet counts). However, both SpVI and PER showed no significant difference with or without MPN. Histological examination revealed splenic congestion in all 8 EHPVO cases, and splenic extramedullary hematopoiesis in 2 of 3 MPN. In EHPVO with MPN, hypersplenism causes feigned normalization of platelet count by masking MPN-induced thrombocytosis; however, splenectomy unveils postoperative thrombocytosis. Spleen in EHPVO with MPN also participates in extramedullary hematopoiesis.
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Extrahepatic portal vein obstruction (EHPVO) is a rare disease. Most EHPVO patients are usually referred to a gastroenterologist for intestinal bleeding and hypersplenic thrombocytopenia; however, hypercoagulative diseases may be occult in these patients and require anticoagulation. The purpose of this study was to elucidate the clinical characteristics of EHPVO. We conducted a retrospective analysis of the hospital database, evaluating the medical records of 15 patients (7 males, 8 females, mean age of onset 42.0 years, range 5-74 years). Thirteen of 15 EHPVO patients (86.7%) had intestinal varices. These included 10 esophageal (66.7%), 12 gastric (80.0%), and 6 ectopic varices (40.0%). Nine (60.0%) of 15 had a history of intestinal bleeding. Regarding comorbidities, 5 of 15 (33.3%) suffered from vascular diseases, including acute myocardial infarction, cerebral infarction, pulmonary embolism, Budd-Chiari syndrome, and mesenteric vein thrombosis. The former 3 vascular commodities manifested at less than 32 years of age. Four patients (26.7%) with JAK2V617F mutation were diagnosed as myeloproliferative neoplasm (MPN). 72.3% of EHPVO patients without MPN experienced thrombocytopenic state. No EHPVO patients with MPN experienced thrombo-leukocytopenia. The elevation of white blood cell and platelet counts, and decrease of protein S were seen in EHPVO with MPN, compared with EHPVO without MPN. EHPVO is frequently associated with underlying hypercoagulative factors, causing a dilemma between thrombotic complications and portal hypertensive bleeding. Most EHPVO patients experience an evident thrombocytopenic state due to severe hypersplenism; however, hypersplenic hematologic changes are eliminated in EHPVO with MPN. MPN should be suspected in EHPVO patients negative for thrombo-leukocytopenia.
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Gastric cancer with peritoneal metastases is typically a devastating diagnosis. Ligamentum teres hepatis (LTH) metastasis is an extremely rare presentation with only four known cases. Herein, we report salvage surgery of successive metastases to the abdominal wall and LTH in a patient originally presenting with advanced gastric cancer with peritoneal metastasis, leading to long-term survival. A 72-year-old man with advanced gastric cancer underwent curative-intent distal gastrectomy with D2 lymph node dissection for gastric outlet obstruction. During this procedure, three small peritoneal metastases were detected in the lesser omentum, the small mesentery, and the mesocolon; however, intraoperative abdominal lavage cytology was negative. We added cytoreductive surgery for peritoneal metastasis. The pathological diagnosis of the gastric cancer was tubular adenocarcinoma with pT4aN1pM1(PER/P1b)CY0 stage IV (Japanese classification of gastric carcinoma/JCGC 15th), or T4N1M1b stage IV (UICC 7th). Post-operative adjuvant chemotherapy with S-1 (TS-1)+cisplatin (CDDP) was administered for 8 months followed by S-1 monotherapy for 4 months. At 28 months after the initial surgery, a follow-up computed tomography (CT) detected a small mass beneath the upper abdominal wall. The ass showed mild avidity on 18F-fluorodeoxyglucose positron-emission (FDG-PET) CT. Salvage resection was performed for diagnosis and treatment, and pathological findings were consistent with primary gastric cancer metastasis. At 49 months after the initial gastrectomy, a new lesion was detected in the LTH with a similar level of avidity on FDG-PET CT as the abdominal wall metastatic lesion. We performed a second salvage surgery for the LTH tumor, which also showed pathology of gastric cancer metastasis. There has been no recurrence up to 1 year after the LTH surgery. With multidisciplinary treatment the patient has survived almost 5 years after the initial gastrectomy. Curative-intent gastrectomy with cytoreductive surgery followed by adjuvant chemotherapy for advanced gastric cancer with localized peritoneal metastasis might have had a survival benefit in our patient. Successive salvage surgeries for oligometastatic lesions in the abdominal wall and the LTH also yielded favorable outcomes.
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Pared Abdominal , Neoplasias Peritoneales , Ligamento Redondo del Hígado , Neoplasias Gástricas , Masculino , Humanos , Anciano , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Peritoneales/cirugía , Neoplasias Peritoneales/tratamiento farmacológico , Fluorodesoxiglucosa F18 , Pared Abdominal/cirugía , Pared Abdominal/patología , Ligamento Redondo del Hígado/patología , Cisplatino/uso terapéutico , Gastrectomía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: It is unclear which body composition affects postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy. In the present study, we evaluated the relationship between nutritional factors, body composition, and POPF. METHODS: This was a prospective observational cohort study. Patients who underwent pancreaticoduodenectomy between March 2018 and July 2021 were included in this study. Preoperative body composition was measured using a bioelectrical impedance analyzer. In addition, the predictive factors for POPF were analyzed using logistic regression model. RESULTS: The study included 143 patients. Among these patients, 31 had POPF (POPF group) and 112 did not (non-POPF group) after pancreaticoduodenectomy. For body composition, the percent body fat was significantly higher in the POPF group (26.90 vs 23.48, P = 0.022). Multivariate analysis revealed that alcohol consumption (odds ratio 2.95, P = 0.03), pancreatic duct < 3 mm (odds ratio 3.89, P < 0.01), and percent body fat (odds ratio 1.08, P = 0.01) were significantly independent predictive factors for POPF. When the patients were divided into three groups based on their percent body fat (< 25, 25-35, and ≥ 35), POPF occurred more frequently in the group with ≥ 35 percent body fat (47.1%) than in the < 25 group (15.5%) (P = 0.008). CONCLUSION: Predictive factors for POPF related to nutritional status, such as percent body fat, should be considered before proceeding to pancreaticoduodenectomy (ClinicalTrials.gov trial registration no. NCT5257434).
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Fístula Pancreática , Pancreaticoduodenectomía , Humanos , Pancreaticoduodenectomía/efectos adversos , Fístula Pancreática/diagnóstico , Fístula Pancreática/etiología , Impedancia Eléctrica , Estudios Prospectivos , Tejido Adiposo , Complicaciones Posoperatorias/diagnósticoRESUMEN
Survival remains poor even after resection of pancreatic cancer and the postoperative recurrence rate is extremely high. Thus, neoadjuvant treatment may improve outcomes for resectable pancreatic cancer (RPC). This study evaluated the efficacy of neoadjuvant therapy for radiologically judged RPC. A prospectively maintained institutional database was reviewed to identify patients who underwent potentially curative resection of radiologically judged RPC. Patient characteristics and intermediate-term outcomes were compared between groups that received neoadjuvant treatment or upfront surgery (UFS). We identified 353 eligible patients, including 55 patients who received neoadjuvant chemoradiotherapy (CRT group), 53 patients who received neoadjuvant gemcitabine plus nab-paclitaxel (GnP group), and 245 patients who underwent UFS (UFS group). The cumulative rates of pancreatic cancer recurrence at 2 years after pancreatic surgery were 49.5% in the UFS, 48.1% in the CRT group, and 52.7% in the GnP group. The recurrence rate tended to be improved after neoadjuvant treatment, although the difference was not significant at this follow-up point. While the clinical TNM classifications were noticeably different from the final pathological findings, the clinical and pathological TNM classifications were more similar in the groups that underwent neoadjuvant treatment. Neoadjuvant treatment can help identify good surgical candidates and avoid unnecessary laparotomy. Our results also suggest that neoadjuvant therapy might help improve the preoperative diagnostic accuracy for patients with RPC.
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BACKGROUND: It is unclear which patients with recurrence after a second hepatectomy will benefit from a third hepatectomy. METHODS: Patients who underwent hepatectomy for colorectal liver metastasis (CRLM) between April 2005 and July 2021 were included. Factors affecting recurrence after each hepatectomy were analyzed. RESULTS: Sixty-four of the 167 patients who had recurrence after the first hepatectomy underwent a second hepatectomy. Then, 46 patients had recurrence and 18 patients did not have recurrence after the second hepatectomy. Sixteen patients who underwent a third hepatectomy had better overall survival (OS) than those who did not (52 vs. 31 months, p = 0.043). However, the multivariate analysis demonstrated that only tumor size (>5 cm) during the second hepatectomy (p = 0.022) and carbohydrate antigen 19-9 (CA 19-9) level (>50 U/ml) (p = 0.041) at recurrence after the second hepatectomy were poor prognostic factors for OS. CONCLUSION: While a third hepatectomy can be performed if it is technically and oncologically appropriate, tumor size >5 cm and CA 19-9 >50 U/ml should be considered in terms of long-term outcomes before proceeding to surgery.
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Neoplasias Colorrectales , Neoplasias Hepáticas , Humanos , Hepatectomía , Neoplasias Colorrectales/patología , Recurrencia Local de Neoplasia/patología , Pronóstico , Neoplasias Hepáticas/secundario , Estudios RetrospectivosRESUMEN
BACKGROUND: The usefulness of neoadjuvant chemotherapy for patients with duodenal adenocarcinoma remains unclear. We report the case of a successfully resected duodenal adenocarcinoma managed by neoadjuvant chemotherapy using gemcitabine and S-1. CASE PRESENTATION: A 72-year-old female presented with a one-week history of abdominal bloating and vomiting after meals. Esophagogastroduodenoscopy revealed a circumferential epithelial lesion in the second portion of the duodenum. Abdominal computed tomography scan revealed thickened walls and narrowing of the duodenum. Further, an adenocarcinoma was noted on biopsy. Though she was diagnosed with duodenal adenocarcinoma, pancreatic cancer could not be completely ruled out. Therefore, she underwent neoadjuvant chemotherapy using gemcitabine and S-1 after bypass surgery. After six chemotherapy cycles, the tumor significantly reduced in size. Further, lymph nodes and distant metastases were not noted on abdominal computed tomography. The patient underwent pancreaticoduodenectomy. Pathological examination revealed a 0.5-mm lesion and surrounding fibrosis at the duodenum, distal from the ampulla of Vater and the pancreas. Her postoperative course was almost uneventful, and she was discharged on the 31st postoperative day. The patient was followed up and had no tumor recurrence at 24 months after surgery. CONCLUSION: Neoadjuvant chemotherapy with gemcitabine and S-1 was useful in reducing the size of a duodenal adenocarcinoma. This finding would aid physicians in managing patients that present with a similar presentation.
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Background: Clinicopathological characteristics of intraductal papillary mucinous neoplasm derived from the ectopic pancreas have not been elucidated owing to its rarity. Methods: MEDLINE databases from 1985 to 2021 were searched. Data regarding patient characteristics, diagnostic modalities, treatment, and prognosis were extracted from the identified articles. Results: Comprehensive data on 13 patients (10 men and 3 women) with intraductal papillary mucinous neoplasm derived from ectopic pancreas were extracted. The median age was 69â¯years (range, 42-80â¯years). The tumors were located in the stomach in 6 patients, the duodenum in 1 patient, jejunum in 3 patients, ileum in 1 patient, and Meckel diverticulum in 2 patients. Histopathological examination revealed intraductal papillary mucinous neoplasm in 10 patients and intraductal papillary mucinous carcinoma in 3 patients. The median size of the tumor was not significantly different between the intraductal papillary mucinous carcinoma group and the intraductal papillary mucinous neoplasm group (Pâ¯=â¯.611). Conclusion: Accurate preoperative diagnosis and differential diagnosis between intraductal papillary mucinous neoplasm and intraductal papillary mucinous carcinoma remain difficult despite recent advances in imaging modalities.
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BACKGROUND: Owing to their rarity, pancreatic metastases from thyroid cancers have not been fully elucidated. METHODS: Observational studies written in English between 1990 and 2020 were included in this review. RESULTS: The median duration from thyroidectomy to the diagnosis of pancreatic metastases was 105 months. Twenty-five patients underwent surgery, including pancreatoduodenectomy in 10, distal pancreatectomy in 10, enucleation in 4, and total pancreatectomy in 1. The remaining 5 patients did not undergo surgery. Twenty-one patients survived and 9 died, with a median overall survival of 61 months. The overall 5-year survival rate after diagnosis was 58.7%. Of these patients, the overall 5-year survival rate was 63.4% in patients who underwent surgery (surgery group, n = 21), while 2 patients were censored during follow-up, and one patient died 20 months after diagnosis (non-operative group, n = 3) (p = 0.567). Of these patients, the overall 5-year survival rate was 85.7% in patients with curative resection and 53.6% in patients with noncurative resection. CONCLUSIONS: Patients with pancreatic metastases from thyroid cancer had good prognosis, if curative resection can be performed.
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Neoplasias Pancreáticas , Neoplasias de la Tiroides , Humanos , Estudios Observacionales como Asunto , Pancreatectomía , Pancreaticoduodenectomía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Angiosarcomas are rare malignant tumors that arise from the endothelium of blood vessels. They occur most commonly in the skin and soft tissue, and less commonly in the breast, liver, bone, and spleen. Gastrointestinal angiosarcomas are extremely rare. Herein, we present a case of duodenal epithelioid angiosarcoma that was treated with surgical resection. CASE PRESENTATION: A 68-year-old man presented with a 1-month history of fatigue and hypotension. He visited the outpatient clinic for a routine follow-up. Laboratory examination revealed anemia. Esophagogastroduodenoscopy revealed multiple duodenal lesions with central ulceration. A biopsy showed a sheet-like arrangement of large round and spindle-shaped tumor cells that were positive for CD31. Based on the histological and immunohistochemical staining findings, an epithelioid angiosarcoma was diagnosed. Computed tomography (CT) and positron emission tomography-CT revealed no lymph node metastasis or distant metastasis. Radical subtotal stomach-preserving pancreatoduodenectomy with lymphadenectomy was performed. After removing the specimen, reconstruction was performed using the Child procedure. Grossly, two dark-red polypoid tumors were found in the second portion of the duodenum. Histological evaluation revealed proliferation of malignant round and polygonal cells arranged in sheets and spindle-like cells arranged in bundles. Vasoformative structures were recognized as slit-like spaces containing red blood cells. Immunohistochemical staining demonstrated that the tumor cells were positive for CD31. These findings confirmed the diagnosis of epithelioid angiosarcoma in the duodenum. The patient's postoperative course was uneventful. The patient was discharged on postoperative day 19 without any complications. At a follow-up examination in the outpatient clinic at postoperative 4 months, no evidence of recurrence was detected. CONCLUSION: The present report describes a case of duodenal epithelioid angiosarcoma. Duodenal angiosarcomas may cause anemia and gastrointestinal bleeding. Because angiosarcomas sometimes show epithelioid cytomorphology, immunohistochemical analysis is useful for confirming the diagnosis.
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BACKGROUND: Radioiodine (I-131) whole-body scintigraphy (WBS) is a useful modality for identifying functionally preserved thyroid tissue and metastases from differentiated thyroid cancer (DTC); however, the specificity of I-131 uptake is limited, and its accumulation in the pancreas has not been well described. CASE PRESENTATION: A 70-year-old male patient with DTC who had previously undergone total thyroidectomy (pT3N1bM0 Stage IV) received radioiodine treatment at our facility. After treatment, an I-131 WBS revealed abnormal I-131 uptake in the head of the pancreas. Computed tomography identified a round hypodense mass (10 × 20 mm) adjacent to the pancreas head that was impervious to fluorodeoxyglucose (18F-FDG) during subsequent 18F-FDG-positron emission tomography. A diagnosis of pancreatic metastasis from the DTC could not be excluded; therefore, local resection was performed for diagnostic certainty and treatment. Histopathology confirmed the mass to be an exophytic lymphoepithelial cyst (LEC) of the pancreas. The patient also had a transient pancreatic leak which spontaneously resolved after surgery, and he was discharged from the hospital on postoperative day 8. CONCLUSION: To the best of our knowledge, this is the first reported case of an exophytic pancreatic LEC producing a false-positive result during I-131 WBS. Knowledge of all potential I-131 false-positive findings may help improve the management of patients with DTC and circumvent misdiagnoses.
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BACKGROUND: Primary pancreatic cancer with synchronous primary tumors in other organs is a rare condition, and its treatment largely depends on the progression of pancreatic cancer. Here, we describe a rare case of double primary malignancies involving borderline resectable pancreatic body and extrahepatic bile duct cancers that were successfully resected after neoadjuvant chemotherapy (NAC), subsequently avoiding total pancreatectomy. CASE PRESENTATION: A 61-year-old Japanese male was referred to our hospital by his general practitioner after presenting with elevated liver enzymes during a routine check-up for type 2 diabetes mellitus. He was diagnosed with synchronous borderline resectable pancreatic cancer in the body of the pancreas and lower extrahepatic bile duct cancer with obstructive jaundice. Abdominal computed tomography (CT) confirmed a hypovascular mass in the pancreatic body with partial encasement of the common hepatic artery, left gastric artery, celiac artery, and splenic artery and invasion of the splenic vein. Endoscopic retrograde cholangiopancreatography and bile duct biopsy confirmed lower bile duct cancer. Following multidisciplinary discussion, endoscopic retrograde biliary drainage was performed, and neoadjuvant chemotherapy comprising gemcitabine plus nanoparticle albumin-bound paclitaxel (GEM + nab-PTX) was administered. After a total of seven cycles of chemotherapy, follow-up CT showed that the size of the pancreatic lesion reduced, following which the patient underwent pancreatoduodenectomy with splenic artery resection. The postoperative course was uneventful without any surgical complications or intensive hypoglycemic treatment. The pathological diagnosis was pancreatic ductal adenocarcinoma (ypT3N1aM0 ypStage IIB/UICC 8th) with synchronous extrahepatic cholangiocarcinoma (ypT2N1M0 ypStage IIB/UICC 8th). R0 pancreatic resection was performed with an Evans grade III response to neoadjuvant chemotherapy. The patient was followed up and had no tumor recurrence at 22 months after surgery with adjuvant S-1 chemotherapy, however, died after 32 months after surgery due to multiple liver metastasis and para-aortic lymph node metastasis despite salvage GEM + nab-PTX chemotherapy. CONCLUSION: In our case, neoadjuvant chemotherapy for borderline resectable pancreatic cancer and function-preserving pancreatoduodenectomy (R0 resection) for double primary malignancies achieved balanced patient survival and postoperative quality of life.
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AIMS: The safety and efficacy of pancreaticoduodenectomy (PD) in patients over the age of 80 years remain controversial. We aimed to examine post-PD outcomes and to determine the age limit for PD. METHODS: Patients were divided into two subgroups: the younger (<80 years) group and octogenarian (≥80 years) group. We retrospectively evaluated the clinical benefit of PD for periampullary diseases in the younger and octogenarian groups, focusing on short- and long-term outcomes. RESULTS: From March 2005 to December 2018, 586 consecutive surgically curable patients with diagnosed periampullary diseases were studied, among whom 122 (20.8%) were ≥80 years old. The general preoperative physical condition (G8 screening, instrumental activities of daily living, and Charlson comorbidity index) and nutritional status were significantly worse in the octogenarian group. However, there were no significant differences between the younger and octogenarian groups in postoperative severe complication rates (34% vs 36%) or perioperative mortality rates (1.5% vs 0.0%). We observed significantly poorer 3-, 5-, and 10-year overall survivals in the octogenarian group than in the younger group (P = .007). In the younger group, the main cause of death (89.6%) was cancer recurrence. However, only 60% of patients in the octogenarian group developed and died from cancer recurrence. Increased neutrophilic/lymphocyte ratio and elevated Controlling Nutritional Status score were associated with worse outcomes. CONCLUSIONS: It is important to carefully determine the indication for PD in octogenarian patients with periampullary diseases, although patient age over 80 years should not be a contraindication for PD.
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BACKGROUND: Rituximab (RTx) desensitization protocol offered good outcome in ABO-incompatible (ABOi) living donor liver transplantation (LDLT). However, diffuse intrahepatic biliary stricture (DIHBS) is still inevitable hurdle. We selectively added postoperative high dose intravenous immunoglobulin (IVIG) and/or simultaneous splenectomy if ABO isoagglutinin titer just before liver transplantation after plasma exchange (PE) was higher than 1/16. Herein, we reported the excellent outcome of ABOi LDLT without DIHBS using tailored desensitization protocol and compared it with that of ABO-compatible (ABOc) LDLT. METHODS: Sixty-five cases (14.8%) of ABOi LDLTs were performed among 438 primary adult LDLTs in our center between March 2012 and June 2017. We performed 1-to-2 propensity score matching (PSM) to extract 60 cases of ABOi LDLTs and 120 cases of ABOc LDLTs. RESULTS: There were no significant differences in clinical characteristics between ABOi and ABOc recipients. There were no significant differences in complications and rejection. There was no DIHBS in both groups. The 1-, 3-, and 5-year overall survival rates were 98.3%, 86.7%, and 82.9% in ABOi group and 96.7%, 86.7%, and 85.4% in ABOc group, respectively (P=0.88). Most common cause of deaths of both groups was hepatocellular recurrence. The 1-, 3-, and 5-year biliary complication (anastomosis leakage or stricture) free survival rates were 81.4%, 69.5%, and 67.5% in ABOi group and 83.0%, 81.3%, and 80.0% in ABOc group, with no significant differences (P=0.11). CONCLUSIONS: RTx-based tailored (optional IVIG + splenectomy) desensitization protocol for ABOi LDLT was feasible and acceptable.
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PURPOSE: The safety and feasibility of preserving the remnant stomach during distal pancreatectomy (DP) in patients who have undergone distal gastrectomy (DG) remains unclear. METHODS: A retrospective review of a prospectively maintained database was performed to identify patients who underwent DP. A propensity score-matched analysis was performed to match post-DG patients with control patients. RESULTS: Among the 226 patients included in this study, 9 DP patients who had a history of DG were studied (4.0%). These nine patients in the DG group were matched to 45 patients in the control group. There were no significant differences in the incidence of postoperative morbidities, including postoperative pancreatic fistula rate or stomach-related complications. The hemoglobin A1C (HbA1c) levels in the DG group after surgery decreased to the normal range. CONCLUSION: Our study suggested that the remnant stomach may be safely preserved when performing DP in patients with a history of DG with respect to short-term morbidities. However, there are some concerns about the long-term nutritional status in patients with a history of DG.
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Gastrectomía/métodos , Muñón Gástrico , Tratamientos Conservadores del Órgano/métodos , Pancreatectomía/métodos , Enfermedades Pancreáticas/cirugía , Anciano , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fístula Pancreática/epidemiología , Complicaciones Posoperatorias/epidemiología , Puntaje de Propensión , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: The development of treatment strategies to protect against ischemia-reperfusion injury (IRI) to livers is important not only for liver surgeries but also in regard to increasing the utilization of livers from marginal donors. In this study, we examined whether inhalational carbon monoxide (CO) therapy reduced IRI after a 45-min (min) warm ischemia (WI) in a miniature swine model. MATERIALS AND METHODS: Six CLAWN miniature swine underwent a 45-min hepatic WI induced by clamping the portal vein and proper hepatic artery. Three animals were subjected to control conditions while the remaining three were treated with CO inhalation for a total of 345-min, including 120-min after reperfusion to maintain a concentration of CO-Hb under 15% (CO-treated group). IRI of the livers was evaluated by liver function tests, serum pro-inflammatory cytokines, and liver biopsies. RESULTS: All controls had statistically significant increased levels of liver enzymes compared to the CO-treated group (p < 0.05). In controls, liver biopsies at 2 h after reperfusion showed marked histological changes including diffuse hemorrhage, congestion, necrosis, vacuolization, and neutrophil infiltration with apoptosis. In contrast, the CO-treated group showed less obvious or only minimal histological changes. Furthermore, increases in high-mobility group box 1, TNF-α, and IL-6 in sera that were induced by IRI in controls were markedly inhibited by the CO treatment. CONCLUSION: We demonstrated that low-dose CO inhalation reduces hepatic warm IRI, potentially through downregulation of pro-inflammatory mediators and activation of anti-apoptotic pathways. To our knowledge, this is the first report demonstrating CO inhalation attenuated hepatic IRI following WI in a large animal model.
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Proteína HMGB1 , Daño por Reperfusión , Animales , Monóxido de Carbono , Hígado , Daño por Reperfusión/prevención & control , Porcinos , Porcinos EnanosRESUMEN
BACKGROUND: We have achieved greater than a 6-month survival of a life-supporting kidney co-transplanted with a vascularized thymic graft into non-human primates (NHPs). Although we have achieved pig-specific unresponsiveness in vitro, immunosuppression was not able to be fully weaned. Studies in mice and humanized mice suggest that a hybrid pig thymus (Hyb-thy)-containing host thymic epithelial cells (TECs) can optimize intra-thymic selection, achieving xenograft tolerance with improved reconstitution of T-cell function. METHODS: We have tested the feasibility of the preparation of a Hyb-thy that contains NHP TECs in the donor thymic grafts. We first prepared the Hyb-thy in the donor pigs 2-3 weeks before xeno-Tx. We performed six cases of Hyb-thy preparation in six juvenile miniature swine. Two pigs received non-manipulated cynomolgus monkey thymic cells that were isolated from an excised atrophic thymus via injection into their thymic lobes (Group 1). The remaining four received thymic cells that were isolated from non-atrophic thymic glands (Groups 2 and 3). Pigs in Group 2 received unmanipulated thymic cells in one thymic lobe, as well as CD2-positive cell-depleted TEC-enriched cells in the contralateral lobe. Pigs in Group 3 received TEC-enriched cells alone. RESULTS: All thymus-injected pigs received tacrolimus and rapamycin until endpoint (POD16). We detected cynomolgus monkey TEC networks in pig thymus from Groups 1 and 3, while pigs in Group 2 rejected the thymic cells. We demonstrated the preparation of Hyb-thy in pigs using tacrolimus plus rapamycin therapy. CONCLUSIONS: Our results suggest that the enrichment of TEC from the excised NHP thymus facilitated NHP TEC engraftment in pig thymus.
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Células Epiteliales/inmunología , Rechazo de Injerto/inmunología , Supervivencia de Injerto/inmunología , Timo/inmunología , Animales , Tolerancia Inmunológica/inmunología , Terapia de Inmunosupresión/métodos , Macaca fascicularis , Primates , Porcinos , Porcinos Enanos , Trasplante Heterólogo/métodosRESUMEN
MSUD is a hereditary metabolic disorder that is characterized by impaired activity of the BCKADC. Liver transplantation has been approved as a treatment for some MSUD cases in which the control of BCAAs is insufficient. Although there have been several reports about DDLT for MSUD, few LDLT cases have been reported. Because either of parents who are heterozygote of this disease usually applies to be a candidate of donor in LDLT, the impairment of BCKADC activity of graft liver should be concerned. We performed LDLT for 10 month-old girl with a left lateral segment graft from her father. BCKADC activities of the patient and her parents were measured using lysates of lymphocytes isolated from peripheral blood specimen before the transplant. As a consequence, the activity of BCKADC of father was not inferior to a normal range. The patient tolerated the operation well. Postoperative course was uneventful and mixed milk was started at 8th POD. The serum BCAAs levels have remained within normal range. It should be necessary to follow the physical growth and mental development of the recipient in the future.
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Trasplante de Hígado/métodos , Enfermedad de la Orina de Jarabe de Arce/genética , Enfermedad de la Orina de Jarabe de Arce/cirugía , Aminoácidos de Cadena Ramificada/metabolismo , Padre , Femenino , Heterocigoto , Humanos , Lactante , Donadores Vivos , Masculino , Periodo Posoperatorio , Resultado del TratamientoRESUMEN
The indications for duct-to-duct (DD) biliary reconstruction in living donor liver transplantation (LDLT) for small children are still controversial. In this study, the feasibility of DD biliary reconstruction versus Roux-en-Y (RY) biliary reconstruction was investigated in terms of long-term outcomes. Fifty-six children who consecutively underwent LDLT with a weight less than or equal to 10.0 kg were enrolled. Biliary reconstruction was performed in a DD fashion for 20 patients and in an RY fashion for 36 patients. During a minimum follow-up of 2 years, the incidence of biliary strictures was 5.0% in the DD group and 11.1% in the RY group. Cholangitis during the posttransplant period was observed in the RY group only. There were no deaths related to biliary problems. This study shows that DD reconstruction in LDLT for small children (weighing 10.0 kg or less) is a feasible option for biliary reconstruction.
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Anastomosis en-Y de Roux/métodos , Trasplante de Hígado , Donadores Vivos , Anastomosis en-Y de Roux/efectos adversos , Conductos Biliares/cirugía , Peso Corporal , Preescolar , Colangiografía/métodos , Colangitis/etiología , Colestasis/etiología , Enfermedad Hepática en Estado Terminal/cirugía , Enfermedad Hepática en Estado Terminal/terapia , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: In some small infants who are transplanted with a large-for-size graft by living donor liver transplantation, an incisional hernia is intentionally made to decrease the tension on the graft. The procedure and timing for repair of this type of hernia were retrospectively evaluated. PATIENTS AND METHODS: Repair was carried out in 3 patients at 4 to 11 years after living donor liver transplantation. The preoperative, perioperative, and postoperative statuses were analyzed in each patient. RESULT: Fascial closure was possible in all 3 patients. In 2 patients, separation of a component of the rectus sheath or a lower part of the major pectoral muscle was required for approximation of the fascia. One recipient had transient bile leakage that was treated successfully. CONCLUSION: An intentionally made hernia should be as small as possible to facilitate easy primary closure at a later date. A procedure resembling the "clam-shell opening" method, which used a partly separated and extended sheet of the fascia, was feasible to avoid the requirement for an artificial mesh. Preschool ages may be suitable for easier approximation of the fascia.