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Background Posthepatectomy liver failure is a poor prognostic factor after hepatectomy. Various preventive treatments have been tried; however, there are no clinical trials that use posthepatectomy liver failure as the primary endpoint, and the clinical effects of posthepatectomy liver failure have not been fully verified. The aim of this study was to investigate whether administration of antithrombin III can prevent posthepatectomy liver failure in patients with coagulopathy after hepatectomy. This study also evaluated the safety of AT-III administration after hepatectomy. Methods The current study enrolled 141 patients diagnosed with coagulopathy after hepatectomy between October 2015 and September 2018 at 7 hospitals in Hiroshima, Japan (HiSCO group). Patients were randomized to undergo either administration of antithrombin III (n = 64) or non-administration (n = 77). The primary endpoint was the incidence of posthepatectomy liver failure. This randomized controlled trial was registered with the University Medical Information Network Clinical Trial Registry (UMIN000018852). Results Treatment for postoperative coagulopathy was performed safely without adverse events. The incidence of posthepatectomy liver failure was similar in both treatment groups (nonadministration of antithrombin III group, 28.5%, versus administration of antithrombin III group, 28.1%; P = .953) The rate of morbidity was higher in the administration group than the non-administrated group (17.2% vs 11.7%, P = .351). Following the multivariate analysis of the whole study group, body mass index ≥25, total bilirubin ≥1.5 mg/dL, and the disseminated intravascular coagulation score ≥5 postoperatively were the independent risk factors for posthepatectomy liver failure. Conclusion This study showed that the administration of antithrombin III resulted in no significant difference in preventing posthepatectomy liver failure, possibly through suppressing coagulopathy.

Background The permissible liver resection rate for preventing posthepatectomy liver failure (PHLF) remains unclear. We aimed to develop a novel PHLF-predicting model and to strategize hepatectomy for hepatocellular carcinoma (HCC). Methods This retrospective study included 335 HCC patients who underwent anatomical hepatectomy at eight institutions between 2013 and 2017. Risk factors, including volume-associated liver-estimating parameters, for PHLF grade B–C were analyzed in a training set (n = 122) via multivariate analysis, and a PHLF prediction model was developed. The utility of the model was evaluated in a validation set (n = 213). Results Our model was based on the three independent risk factors for PHLF identified in the training set: volume-associated indocyanine green retention rate at 15 min, platelet count, and prothrombin time index (the VIPP score). The areas under the receiver operating characteristic curve of the VIPP scores for severe PHLF in the training and validation sets were 0.864 and 0.794, respectively. In both sets, the VIPP score stratified patients at risk for severe PHLF, with a score of 3 (specificity, 0.92) indicating higher risk. Conclusion Our model facilitates the selection of the appropriate hepatectomy procedure by providing permissible liver resection rates based on VIPP scores., This research was supported by the Japan Agency for Medical Research and Development (AMED, grant number JP19fk0210051) and the Japanese Society for the Promotion of Science (JSPS KAKENHI, grant number JP18K08706)

Alpha-fetoprotein (AFP) has been widely used as a tumor marker for detecting hepatocellular carcinoma and yolk sac tumors. Recently, cases of gastrointestinal cancer with elevated serum AFP levels have been reported. However, AFP-producing colon cancer is considered rarer than other AFP-producing gastrointestinal cancers. In this study, we report on a case of a 47-year-old woman who was diagnosed with sigmoid colon cancer and underwent sigmoidectomy and lymph node dissection. Postoperative adjuvant chemotherapy (AC) was performed after the curative surgery. After the seventh course of AC, multiple liver masses and enlarged systemic lymph nodes were detected; these were later diagnosed as liver metastases from sigmoid colon cancer. Laboratory examination revealed high AFP levels (14,657.8 ng/mL). After confirming the recurrence, her condition worsened rapidly, and she eventually died 8 months after the operation. Autopsy and histopathological findings showed that the liver mass was positive for AFP staining, but the sigmoid colon cancer tissue was not. We then determined that liver metastases of the colon cancer were more likely than germ cell carcinoma according to the clinical course and pathological findings. We assumed that colon cancer cells can rapidly expand by dedifferentiation, and we diagnosed AFP-producing colon cancer with liver metastases. Despite curative surgery and AC for AFP-producing colon cancer, the patient died of liver and systemic lymph node metastases.

Abnormal findings in the pancreatic duct without a mass may require serial pancreatic juice aspiration cytological examination. In cases of synchronous gastric cancer and stage 0 pancreatic cancer, spleen‐preserving pancreatectomy may have advantage.

Patient: Female, 84-year-old Final Diagnosis: Anal atresia Symptoms: Incomplete evacuation Medication:— Clinical Procedure: Surgery Specialty: Surgery Objective: Rare disease Background: Hartmann procedure can be necessary for the treatment of rectal cancer and colonic perforation. The distal diverted intestinal tract is usually disregarded, while the proximal colon is diverted with a stoma. Most of the reported complications related to a diverted intestinal tract following Hartmann procedure include inflammation and intestinal tumors; however, there are only a few reports about postoperative anal complications. Herein, we report a rare case of anal atresia following Hartmann procedure. Anal atresia is generally considered as a congenital malformation; therefore, this was an extremely rare case, as there are no previous reports about anal atresia following Hartmann procedure. Case Report: An 84-year-old woman presented to our hospital with a persistent feeling of incomplete evacuation. She had undergone Hartmann procedure for diverticular disease of the sigmoid colon, with perforation, 5 years ago and had no major complications after the surgery. She had no history of anal disorders such as hemorrhoids or anal fissures. On examination, her anus was found to be closed by a thin skin, and computed tomography revealed stool retention in the diverted rectum. The anus was surgically opened to remove the stool, after which the feeling of incomplete evacuation resolved with no subsequent recurrence. Conclusions: This is the first report of anal atresia in a patient following Hartmann procedure. The surgical intervention was effective in resolving the blockage and relieving the patient’s feeling of incomplete evacuation.

Patient: Female, 63-year-old Final Diagnosis: Cardiac metastasis Symptoms: Dyspnea Medication:— Clinical Procedure: Surgery Specialty: Oncology Objective: Unusual clinical course Background: Malignant tumors, such as lung and breast cancers, can metastasize to the heart. However, cardiac metastasis rarely occurs in colorectal cancer. Cardiac metastasis cases are typically asymptomatic and rarely cause cardiac tamponade. Heart failure due to systemic metastasis is a terminal symptom; therefore, cardiac metastasis is rarely diagnosed when a patient is alive. We report a case of stage II ascending colon cancer with cardiac tamponade due to pericardial metastasis. Case Report: The patient was a 63-year-old woman who underwent laparoscopic ileocecal resection for ascending colon cancer. The final pathological diagnosis was stage IIB cancer. At the time of surgery, computed tomography scans revealed no metastases to the regional lymph nodes, liver, lungs, and other organs. The patient was then referred for dyspnea 5 months after the surgery. Computed tomography revealed large quantities of pericardial effusion, and the patient was diagnosed with cardiac tamponade. The symptoms were alleviated after pericardiocentesis. Cytological examination of the pericardial fluid confirmed the diagnosis of adenocarcinoma, and by extension, cardiac metastasis of the ascending colon cancer. Anticancer agents were recommended, but the patient opted for palliative treatment. Conclusions: We report a rare case of ascending colon cancer with pericardial metastasis. The advancements in chemotherapy have made the prognosis of colorectal cancer more favorable. The prevalence of pericardial metastasis is expected to increase as well. As such, it is necessary to discuss similar case encounters and establish appropriate treatment.

Duodenal gastrointestinal stromal tumors (dGISTs) are rare, and a lack of consensus exists regarding their treatment, particularly for recurrent disease. We herein report a rare case of liver metastasis 7 years after resection of a low-risk duodenal gastrointestinal stromal tumor. A 45-year-old woman revealed positive fecal occult blood. Upper gastrointestinal endoscopy revealed a submucosal duodenal tumor with ulceration and oozing on the apex. Endoscopic ultrasound showed a hypoechoic mass originating in the submucosa. Contrast-enhanced abdominal computed tomography (CT) revealed a 30-mm hyper-vascular tumor in the duodenal bulb. The patient underwent partial resection of the duodenal bulb with distal gastrectomy, followed by Roux-en-Y reconstruction. Histopathological evaluation revealed a tumor comprised of spindle-shaped cells including 5 mitotic figures per 50 high-power fields. Immunohistochemical evaluation indicated that the tumor cells were positive for c-Kit and CD34 expression. The tumor was diagnosed as low-risk dGIST. Postoperative follow-up was continued, and 7 years later, CT revealed a 39-mm enhanced tumor in liver segment 4. The tumor was diagnosed as a metastatic liver tumor, and the patient underwent S4 partial hepatectomy. As a result of histological and immunohistochemical analysis, the tumor was diagnosed as a liver metastasis from dGIST. The patient has been receiving oral imatinib 400 mg daily and remains free of disease 5 years after her last surgery. Low-risk dGIST can metastasize relatively long after surgery. However, an excellent long-term prognosis may be achieved by combining complete resection and imatinib therapy in patients with recurrent liver metastases.

Background Duodenal gastrointestinal stromal tumors are rare. If tumor growth is extraluminal and involves the head of the pancreas, the diagnosis of a duodenal gastrointestinal stromal tumor is difficult. Case presentation A 44-year-old Japanese woman was referred to our hospital with anemia. An enhanced computed tomography scan showed a hypervascular mass 30 mm in diameter, but the origin of the tumor, either the duodenum or the head of the pancreas, was unclear. Upper gastrointestinal endoscopy revealed bulging accompanied by erosion and redness in part of the duodenal bulb. Mucosal biopsy was not diagnostic. Endoscopic ultrasound fine-needle aspiration was difficult to perform because a pulsating blood vessel was present in the region to be punctured. These findings led to a diagnosis of pancreatic neuroendocrine tumor invasion to the duodenum. The patient underwent pancreaticoduodenectomy. Histologically, the tumor was made up of spindle-shaped cells immunohistochemically positive for c-Kit and CD34. The tumor was ultimately diagnosed as a duodenal gastrointestinal stromal tumor. Conclusion Extraluminal duodenal gastrointestinal stromal tumors are rare and mimic pancreatic neuroendocrine tumors. Endoscopic ultrasound fine-needle aspiration is useful for preoperative diagnosis, but it is not possible in some cases. Intraoperative diagnosis based on a completely resected specimen of the tumor may be useful for modifying the surgical technique.

Introduction To prevent port-site hernia, we established a simple and low-cost closure method that uses a venous catheter needle and suture, without any other special devices. Materials and surgical technique We used the inner needle of a 16-G venous catheter and a 2-0 absorbable bladed suture. To evaluate the efficacy of this technique, the procedure time was noted and compared among three operators (an experienced surgeon and two inexperienced surgeons). Discussion The median suturing time was 60.5 seconds (range, 26-130 seconds) per incision. Even an unexperienced surgeon can close the fascia safely and quickly after some experience with the procedure.

Highlights • Mixed adenoneuroendocrine carcinomas (MANECs) of the distal bile duct are extremely rare. • The treatment of MANECs of the bile duct remains controversial and the prognosis is poor. • Larger studies are required to establish standard treatment regimens of MANECs of the bile duct., Introduction Mixed adenoneuroendocrine carcinomas (MANECs) of the distal bile duct are extremely rare, and only a few cases have been reported in the English literature. Presentation of case An 82-year-old man was referred to our hospital for increasing biliary enzymes. Abdominal computed tomography (CT) showed enlargement of the intrahepatic bile ducts and stenosis of the distal bile duct. Endoscopic retrograde cholangiopancreatography showed stenosis of the distal bile duct and a high-density signal at the same site on diffusion weighted imaging. PET-CT showed increased FDG accumulation (SUVmax: 4.5) at the distal bile duct stenosis. Biopsy specimens obtained by endoscopic ultrasonography-guided fine-needle aspiration revealed adenocarcinoma. The patient was diagnosed with adenocarcinoma of the distal bile duct and underwent subtotal stomach-preserving pancreaticoduodenectomy with regional lymph node dissection. The resected distal bile duct tumor was 18 × 14 × 12 mm in diameter. Hematoxylin and eosin staining revealed a composite carcinoma with adenocarcinoma and non-adenocarcinoma elements. The non-adenocarcinoma component stained positive for synaptophysin and chromogranin A. The Ki-67 labeling index was 37%. The non-adenocarcinoma component was therefore diagnosed as a neuroendocrine carcinoma. The two composite carcinoma was diagnosed as MANEC of the distal bile duct. The patient was treated with surgery alone and he remained disease-free for 7 months after the surgery. Discussion The treatment of MANECs of the bile duct remains controversial and the prognosis is poor. Conclusions There is no standard treatment for MANECs of the bile duct. Larger studies are required to establish standard treatment regimens.

Highlights • Few cases of splenic hamartomas associated with thrombocytopenia have been reported. • Imaging findings in splenic hamartomas are non-specific, variable, and making definitive preoperative diagnosis difficult. • Surgery is necessary for diagnosis when malignancy cannot be ruled out. • Surgery may also improve symptoms of hypersplenism, including thrombocytopenia., Introduction Hamartomas are rare, benign tumors of the spleen. Few cases of splenic hamartomas associated with thrombocytopenia have been reported. Presentation of case An asymptomatic 64-year-old man with myelodysplastic syndrome was found to have a splenic tumor. Laboratory tests were significant for thrombocytopenia, with a platelet count of 7.8 × 104/μL. Ultrasonography showed splenomegaly (10.8 × 6.6 cm), and a hypoechoic splenic mass (8.0 × 7.0 cm). Color doppler ultrasound revealed blood flow within the mass, and the mass density was homogeneous on abdominal computed tomography (CT). Contrast-enhanced CT showed heterogeneous enhancement of the splenic mass during the arterial phase. Positron emission tomography (PET)-CT showed no significant fludeoxyglucose (FDG) accumulation within the mass. The differential diagnosis included splenic hamartoma, splenic hemangioma, splenomegaly associated with extramedullary hematopoiesis, and malignant tumor, including solitary splenic metastasis. A laparoscopic splenectomy was performed due to the possibility of malignancy, the presence of thrombocytopenia, and the risk of splenic rupture. The resected specimen showed a localized, well-demarcated, 8.0 × 7.0 cm splenic mass. Histological examination revealed abnormal red pulp proliferation and the absence of normal splenic structures. The patient’s post-operative course was uneventful. His platelet count improved on post-operative day 1 and he was discharged on post-operative day 9. He remained in good health with a normal platelet count one month after surgery. Discussion Making definitive preoperative diagnosis is difficult in splenic hamartomas. Surgery is necessary for diagnosis when malignancy cannot be ruled out. Conclusions Surgery may also improve symptoms of hypersplenism, including thrombocytopenia.

Background Mucinous nonneoplastic cyst of the pancreas is a rare disease defined as a cystic lesion lined with mucinous epithelium, supported by hypocellular stroma and not communicating with the pancreatic ducts. Mucinous nonneoplastic cyst of the pancreas has no malignant potential and does not require surgical resection or surveillance. However, its preoperative differentiation from other cystic lesions of the pancreas is difficult because of several overlapping clinical, radiological, and biochemical features. We report a rare case of large mucinous nonneoplastic cyst of the pancreas in which surgery was required due to infection and the possibility of malignancy. Case presentation A 75-year-old Japanese man was found to have a pancreatic cyst in 2006 while undergoing postoperative evaluation for colon cancer. In 2015, the cyst ruptured, and it was treated conservatively. In 2017, he fell down on a road with a fever of 40 °C and was transported emergently to a nearby hospital. Enhanced computed tomography revealed a cystic lesion in the body of the pancreas measuring 119 mm × 100 mm and an adjacent left renal cyst measuring 63 mm in diameter. The wall of the pancreatic cyst was thickened. Magnetic resonance imaging demonstrated a liquid surface in the pancreatic cyst. Pancreatic cyst infection was diagnosed as the source of infection. However, identification of the organism was difficult. Furthermore, due to the increase in the size and wall thickness of the cyst, it was unclear whether the cystic mass was neoplastic with malignant potential. For these reasons, the patient underwent distal pancreatectomy and splenectomy with deroofing of the left renal cyst. Intraoperatively, the pancreatic cyst adhered to the descending colon, and partial resection of the colon was added. Pathologic analysis of the resected cyst demonstrated a simple cyst lined by mucinous epithelium. There was no underlying stromal condensation or epithelial dysplasia, and communication with the native pancreatic ducts was not observed. Based on the operative and histological findings, a final diagnosis of mucinous nonneoplastic cyst of the pancreas with colonic communication was made. The colonic fistula was presumed to be the source of infection. Conclusion Mucinous nonneoplastic cyst of the pancreas is generally benign and requires little follow-up, but large cysts may penetrate other organs and cause severe complications.

BACKGROUND Because recombinant human granulocyte colony-stimulating factor (rhG-CSF) is known to modulate function of antigen-presenting cells, we examined effects of pretransplant host treatment with rhG-CSF on allograft survival. METHODS In DA-to-Lewis rat heart transplantation, hosts were given pretransplant injections of rhG-CSF (250 microg/kg/day subcutaneously from day -5-0) and/or posttransplant injections of tacrolimus (2 mg/kg/day intramuscularly from day 0-3). Cytokine mRNA levels in grafts were measured by real-time reverse-transcription polymerase chain reaction. RESULTS rhG-CSF pretreatment was effective in prolonging allograft survival only in tacrolimus-treated hosts (P

We examined the effects of granulocyte colony-stimulating factor (G-CSF)-mobilized donor leukocyte infusion (G-DLI) on facilitation of allograft survival using heart transplantation from DA to Lewis rats that were transiently treated with tacrolimus (2 mg/kg i.m. on day 0). Other DA rats were given G-CSF (250 microg/kg/day s.c. from days -5 to 0), and isolated leukocytes were infused into Lewis recipients after surgery. Cytokine mRNA levels were quantified by reverse transcription and real-time polymerase chain reaction. After G-CSF treatment, leukocytes in circulation increased by 7.6 times and secreted in-vitro 6.0-times-higher levels of IL-10 after lipopolysaccharide stimulation than did untreated leukocytes. G-DLI facilitated graft survival dose-dependently. Significant IL-10 mRNA upregulation was detected in grafts 24 h after surgery but not in the recipient's heart, spleen, or liver. On day 6, IFN-gamma and IL-2 mRNA levels were approximately half those of the control levels. Allograft-restricted IL-10 upregulation followed by type-1 cytokine downregulation can be achieved by the use of G-DLI.

The Anorectic Behavior Observation Scale (ABOS) is a questionnaire developed to obtain information from relatives about behaviors and attitudes of patients with eating disorders. The original report of the ABOS revealed three factors. This is the first study to confirm the factor structure by use of confirmatory analyses. Relatives of 102 patients with eating disorders completed the ABOS, and exploratory factor analyses were performed. Confirmatory factor analyses were performed for this Japanese sample, and the fitness of the factor structure was compared between that in the original report proposed by Vandereycken and that used in the present study. A three-factor structure was revealed by the data of Japanese patients, including factor I (eating behavior meeting the criteria of anorexia; concern with weight, foods, and denial), factor II (bulimia; including bingeing, disposing, furtive eating and purging, and talk about thinness and dieting), and factor III (hyperactivity, eating slowly, and chopping food into very small pieces). Confirmatory analyses supported the improvement of fitness in this modified three-factor structure in comparison with the original three-factor model. This Japanese ABOS study revealed three dimensions, which differed from the original subscales in Belgium. Cross-cultural differences were observed, though the ABOS may be useful in Japan as an instrument for assessing eating disorders.

A 78-year-old female underwent an abdomino-perineal resection for lower rectal cancer with para-aortic, right iliac artery and left inguinal lymph node metastasis. Two weeks later, an enlargement of para-aortic and right iliac artery lymph node metastasis was detected by CT. S-1 (100 mg/day for 2 weeks followed by a 1-week rest period) + CPT-11 (120 mg/m2, day 1)treatment was initially administered. However, the patient developed grade 2 anorexia so this treatment regimen was terminated. After complete recovery from the adverse reaction, the regimen was converted to S-1 administration at 100mg/day S-1 for 2 weeks followed by a 1-week rest period. Eventually, this schedule was modified to 100mg/day for 1 week followed by a 1-week rest period. A year after the operation, CT revealed the lymph node metastasis to have disappeared, and no relapse occurred for 32 months. This was a successful case in which S-1 yielded an extended complete response for advanced rectal cancer. Treatment with S-1 is an effective choice for patients who for various reasons can not tolerate the standard treatment for unresectable advanced colorectal cancer. Moreover, randomized controlled trials have to be started to evaluate the efficacy of S-1 treatment for advanced rectal cancer as soon as possible.

Large-cell neuroendocrine carcinoma (LCNEC) in the distal bile duct is very rare and different from common distal bile duct adenocarcinoma. A 77-year-old man was admitted with obstructive jaundice. Severe stenosis of the distal bile duct was revealed by percutaneous transhepatic cholangiography. Subtotal stomach-preserving pancreaticoduodenectomy was performed. A tumor measuring 1.8 cm in diameter was located in the distal bile duct. Both histopathological and immunohistochemical examination of the resected specimen revealed features of LCNEC of the bile duct. The patient developed multiple liver metastases, lung metastases, and local recurrence and died of disease 3 months after the operation. The clinical behavior of LCNEC in the distal bile duct appears to be highly aggressive with early metastases and a fatal outcome.

Since recombinant human granulocyte colony-stimulating factor (rhG-CSF)-treated donor leukocyte infusion (G-DLI) has been shown to downregulate type-1 immunity in a heart transplant model, we examined influences of G-DLI on tumor growth in immunosuppressed hosts. F344 rats were treated with tacrolimus (8 mg/kg i.m.) and syngeneic colon adenocarcinoma RCN-9 cells (3 × 10 6 ) were inoculated subcutaneously. For G-DLI, allogeneic DA rats were pretreated with rhG-CSF (250 μg/kg, days −5 to 0) and isolated leukocytes or sorted CD8 + cells were injected intravenously to the hosts on day 0. Tumors in tacrolimus-treated hosts continuously grew over 5 weeks. G-DLI of 100 × 10 6 leukocytes attenuated tumor growth rate while direct host pretreatment with rhG-CSF did not. Notably, G-DLI of 10 × 10 6 CD8 + cells blocked tumor expansion after day 14. Tacrolimus-induced inhibition of lymphocyte infiltration into tumors was recovered by the G-DLIs. Flow cytometry showed no detectable donor-type T cells in the tumor and circulation. Quantification of intratumor transcription levels using reverse transcription–real-time polymerase chain reaction showed recovery from tacrolimus-induced downregulation of interleukin-4 but not interferon-γ levels. In vivo rhG-CSF-treated CD8 + allogeneic cells demonstrate potent anti-tumor effects by restoring type-2 immunity of immunosuppressed hosts.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is an immunoregulatory drug whose effects include modulation of antigen-presentation. We investigated the potential ameliorative effect of pretreatment with rhG-CSF in a hapten-induced colitis animal model. Sprague-Dawley rats were given rhG-CSF (125 microg/kg subcutaneously twice a day for 5 days) before a colonic instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) in 50% ethanol. Consequent colonic damage was evaluated pathologically, and cytokine mRNA expression levels in macroscopically inflamed sites were measured by real-time quantitative reverse transcription-polymerase chain reaction. Pretreatment with rhG-CSF remarkably attenuated both the loss of body weight and colonic wall thickening due to progressive transmural inflammation. In the control, treatment with TNBS led to a statistically significant (p < 0.05) upregulation of IFN-gamma mRNA expression in the inflammatory sites measured at post-treatment day 7. In the experimental group, pretreatment with rhG-CSF abrogated transcription of IFN-gamma (p < 0.05), but was not, however, associated with an upregulation of IL-4 or the regulatory cytokines TGF-beta and IL-10. Furthermore, transcription of IL-12p35 (a rate-limiting factor for the production of IL-12) was significantly (p < 0.05) downregulated by rhG-CSF at 24h post-TNBS instillation, whereas IL-12p40 was not affected. Pretreatment with rhG-CSF drastically attenuated the degree of TNBS-induced colitis through selective downregulation of Th1-associated cytokines.

Pretransplant treatment of recipients with recombinant human granulocyte colony-stimulating factor (rhG-CSF, 250 μg/kg/day s.c. for 5 days) facilitates heart allograft acceptance in tacrolimus-treated rat recipients. We examined effectiveness of transfusion of in vivo rhG-CSF-treated blood since rhG-CSF induces immunoregulatory cells in human blood. DA heart grafts were transplanted into tacrolimus (2 mg/kg i.m. on day 0)-treated Lewis recipients. Although graft survival prolongation by blood transfusion on day 0 from rhG-CSF-treated syngeneic Lewis was comparable to that in directly rhG-CSF-pretreated recipients ( p =0.22), transfusion of rhG-CSF-treated allogeneic DA blood was much more effective ( p =0.0016). Intragraft cytokine mRNA levels were measured by reverse transcription and real-time polymerase chain reaction at 24 h after transplantation. IL-12p35 expression was downregulated by both treatments. Notably, IL-12p40 was upregulated by rhG-CSF-treated DA blood transfusion but downregulated by transfusion of rhG-CSF-treated isogeneic blood. Differential expression of IL-12 subunits was associated with facilitation of graft acceptance by rhG-CSF-treated donor blood transfusion.

Because recombinant human granulocyte colony-stimulating factor (rhG-CSF) is known to modulate function of antigen-presenting cells, we examined effects of pretransplant host treatment with rhG-CSF on allograft survival.In DA-to-Lewis rat heart transplantation, hosts were given pretransplant injections of rhG-CSF (250 microg/kg/day subcutaneously from day -5-0) and/or posttransplant injections of tacrolimus (2 mg/kg/day intramuscularly from day 0-3). Cytokine mRNA levels in grafts were measured by real-time reverse-transcription polymerase chain reaction.rhG-CSF pretreatment was effective in prolonging allograft survival only in tacrolimus-treated hosts (P0.001). Intragraft mRNA expression of interleukin (IL)-12 subunits (p35, p40) at 24 hours after transplantation was significantly (P0.05) down-regulated by the addition of rhG-CSF and was associated with suppression of interferon-gamma levels on day 6, although other proinflammatory cytokines (tumor necrosis factor -alpha, IL-1beta, IL-6, IL-18) and anti-inflammatory cytokines (IL-10, transforming growth factor-beta) were not.rhG-CSF pretreatment down-regulates intragraft expression of the type-1 T-helper cell (Th1)-driving cytokine IL-12 and facilitates tacrolimus-induced graft acceptance.

Since recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been reported to induce immune deviation, we examined the effects of pretransplant treatment of recipients with rhG-CSF on heart allograft survival. Before heterotopic heart transplantation from DA to Lewis rats, recipients were given rhG-CSF (125microg/kg s.c. twice a day from day -5 to 0) and/or tacrolimus (2mg/kg i.m. on day 0). Combined treatment with both rhG-CSF and tacrolimus prolonged graft survival significantly (P0.05), while rhG-CSF or tacrolimus alone did not. At 24h after transplantation, cytokine mRNA levels in the grafts were measured by reverse transcription and real-time polymerase chain reaction. IL-12 p35 expression was highly inhibited by rhG-CSF treatment, but tacrolimus did not change the levels. Conversely, rhG-CSF treatment did not affect IL-2 levels, while tacrolimus completely blocked its expression. Combined pretreatment was effective for suppressing acute rejection reaction by downregulating these two key type-1 cytokines, IL-12 and IL-2, with unchanged levels of IL-10.

Aims: Recent studies have demonstrated that administration of recombinant IL-12 induces cytotoxicity against regenerating hepatocytes. We measured transcription levels of IL-12 in the remnant liver in a model of partial hepatectomy (PHx) to elucidate the mechanism of already reported facilitation of liver regeneration by recombinant human G-CSF (rhG-CSF). Methods: After PHx of F344 rats, total RNA of the remnant liver was extracted and mRNA levels of IL-12p35 and G-CSF were quantified by RT-real time PCR. Results: G-CSF mRNA levels increased and IL12p35 mRNA levels decreased at 6 and 20 hours after PHx (P