Multiple liver metastases of pancreatic solid pseudopapillary tumor treated with resection following chemotherapy and transcatheter arterial embolization: A case report.

A 33-year-old female was diagnosed with a solid pseudopapillary tumor (SPT) of the pancreas and multiple liver metastases at the Department of Gastroenterological Surgery, Ishikawa Prefectural Central Hospital (Kanazawa, Japan). Distal pancreatectomy and postoperative systemic chemotherapy with gemcitabine (GEM) and S-1, an oral fluoropyrimidine derivative, was administered, however, liver metastases became enlarged and local recurrence occurred. Therefore, the patient was referred to the Department of Gastroenterologic Surgery at the Graduate School of Medicine (Kanazawa, Japan) for hepatic arterial infusion (HAI) chemotherapy. Oral S-1 (80 mg/m2) was administered as well as HAI chemotherapy with GEM (1,000 mg/standard liver volume). Following 18 cycles, tumor sizes were reduced and 18-fluorodeoxyglucose positron emission tomography (18FDG-PET) examination revealed obvious reduction of tumor FDG uptake. Transarterial tumor embolization (TAE) was performed for the previously unresectable right subphrenic liver tumor, and the other tumors were surgically resected. The resected tumors were diagnosed as liver metastases and a local recurrence of SPT in the postoperative pathological examination, which revealed that the resected tumors were composed of sheets of bland cells, which were positive for CD10, CD56, vimentin, neuron-specific enolase and α-antitrypsin. The postoperative course was uneventful, and the patient is currently under observation at an outpatient clinic; postoperative adjuvant chemotherapy with oral S-1 has continued, and additional TAE is planned. In the future, if the middle segment of the liver becomes enlarged, surgery for the residual right lobe tumor may be possible. This case demonstrates one method of SPT treatment: Preoperative HAI chemotherapy with GEM, plus oral S-1 and TAE. If complete resection can be achieved, the majority of patients with SPT have a favorable prognosis. In patients with unresectable metastases from SPT, it is crucial to conduct systematic multimodal treatment to maximize treatment success.

Case Report of an ABO-Incompatible Living-Donor Liver Transplant for a Familial Amyloid Polyneuropathy Patient.

Liver transplant is a treatment for familial amyloid polyneuropathy. Few cases of ABO-incompatible living-donor liver transplant for familial amyloid polyneuropathy exist. The outcome of an ABO-incompatible living-donor liver transplant has improved recently, using local infusion therapy and rituximab prophylaxis. Here, we describe a successful ABO-incompatible living-donor liver transplant in a patient with familial amyloid polyneuropathy in whom disease progression ceased at 2 years' follow-up. Additionally, no evidence of acute or chronic rejection, or adverse events of the immunosuppressive therapy, was seen. As a postoperative complication, fatty changes in the grafted liver because of malnutrition or adverse events of corticosteroids were confirmed by a liver biopsy taken early after transplant. The main cause of malnutrition was considered to be gastrointestinal dysfunction caused by familial amyloid polyneuropathy. Therefore, before deterioration of digestive function, liver transplants should be considered for familial amyloid polyneuropathy. This case suggests that an ABO-incompatible living-donor liver transplant may provide greater opportunities for familial amyloid polyneuropathy patients.

Evaluation of serum HER2-ECD levels in patients with gastric cancer.

BACKGROUND: Determination of the human epidermal growth factor receptor 2 (HER2) status of gastric cancer patients is indispensable in clinical practice. However, the clinical value of serum HER2-extracellular domain (ECD) in gastric cancer has not yet been defined. METHODS: The serum level of HER2-ECD was measured using the chemiluminescence immunoassay method, and its relationship with tissue HER2 status and clinicopathologic features was examined. Transition of serum HER2-ECD level was examined in patients during chemotherapy to clarify the correlation between changes in the level of HER2-ECD in serum and response to chemotherapy. RESULTS: A total of 150 gastric cancer patients were enrolled in this study; changes in HER2-ECD level were examined in 36 of these patients during chemotherapy. Serum levels of HER2-ECD ranged from 4.8 to 180.0 ng/ml (median 9.2 ng/ml) and were positive (cutoff value 15.2 ng/ml) in ten patients (6.7 %). There was a significant correlation between serum HER2-ECD level and tissue HER2 status (P < 0.001); however, no correlation with TNM stage was found. Change in serum HER2-ECD level during chemotherapy was significantly correlated with response to chemotherapy in patients with HER2-positive tumor tissue. CONCLUSIONS: Serum HER2-ECD is a potential biomarker of gastric cancer and could be used as a diagnostic marker with regard to tissue HER2 status, and also as a monitoring marker in relation to response to chemotherapy.

Impact of histone deacetylase 1 and metastasis-associated gene 1 expression in esophageal carcinogenesis.

Animal models are important for the development of novel therapies for esophageal cancer. Histone deacetylase 1 (HDAC1)/metastasis-associated gene (MTA1) complexes inhibit p53 acetylation and thus, inhibit p53-induced apoptosis. The aim of the present study was to evaluate HDAC1 and MTA1 expression in esophageal carcinogenesis in rats. The rats underwent a total gastrectomy followed by esophagojejunostomy to induce chronic duodenal content reflux esophagitis. The rats were sacrificed sequentially at 20, 30, 40 and 50 weeks post-surgery and the esophagi were examined. Immunohistochemical analysis was conducted to assess the expression and localization of HDAC1 and MTA1. At 20 weeks post-surgery, squamous proliferative hyperplasia and Barrett's metaplasia (BM) were observed. While, adenocarcinoma-associated BM and squamous cell carcinoma were observed at 30-50 weeks post-surgery. The nuclear expression of HDAC1 and MTA1 was observed in all of the stages of squamous carcinogenesis and adenocarcinogenesis, although not in the normal esophageal epithelium. The expression of HDAC1 and MTA1 may be involved in duodenoesophageal reflux-induced neoplastic transformation of the esophageal mucosa into cancer cells with squamous and adeno differentiation.

Pancreatic body adenocarcinoma with neuroendocrine tumor characteristics: A case report.

A 61-year-old female with pancreatic body cancer underwent a distal pancreatectomy. The tumor was a moderately- to poorly-differentiated adenocarcinoma. Tumor growth filled the dilated main pancreatic duct (MPD) and infiltrated the surrounding area. Six months later, metastases to the left diaphragm and MPD of the remnant pancreatic head were detected. Chemoradiotherapy was administered, but the patient succumbed 22 months after surgery. An autopsy demonstrated that a moderately- to poorly-differentiated adenocarcinoma had arisen from the pancreatic head and infiltrated the duodenum and bile duct. Huge liver metastases and multiple peritoneal disseminations were also present. Microscopically, a portion of the tumor had a pseudo-rosette appearance in the adenocarcinoma component, while another section showed characteristics of a neuroendocrine tumor (NET) immunohistochemically. The original surgically-resected tumor also showed NET characteristics immunohistochemically. It is therefore necessary to search for NET components in pancreatic cancer with atypical growth and metastases, even when adenocarcinoma has been diagnosed histologically.

Comparative study of the antitumor activity of Nab-paclitaxel and intraperitoneal solvent-based paclitaxel regarding peritoneal metastasis in gastric cancer.

Intraperitoneal (i.p.) chemotherapy with paclitaxel (PTX) has been shown to be a promising treatment strategy for peritoneal metastasis. The present study focused on the comparative evaluation of the therapeutic efficacy of nanoparticle albumin-bound PTX (Nab-PTX) and i.p. administration of the conventional solvent-based PTX (Sb-PTX). We also investigated the difference in antitumor activity depending on the route of administration in the Nab-PTX treatment. Nab-PTX was administered i.p. or intravenously (i.v.) and Sb-PTX was administered i.p. at equitoxic and equal doses to nude mice bearing gastric cancer OCUM-2MD3 cell subcutaneous and peritoneal xenografts. Therapeutic efficacy of Sb-PTX and Nab-PTX was evaluated as inhibition of tumor growth using a peritoneal metastatic model with subcutaneous xenografts. The survival rate was also investigated using mouse peritoneal models. For assessment of subcutaneous tumors, the change in tumor volume was measured, and for assessment of peritoneal tumors, the weight of ascitic fluid and the total peritoneal tumor burden were measured for each individual mouse. At equitoxic doses, treatment with Nab-PTX resulted in a greater reduction in the size of subcutaneous tumors and the weight of ascites and peritoneal burden as compared with i.p. Sb-PTX (p<0.05). Treatment with i.p. and i.v. Nab-PTX also achieved greater survival benefit than i.p. Sb-PTX (p<0.05). In contrast, there was no significant difference in the degree of tumor reduction and the survival time between both drugs at equal doses. With regard to the route of administration, the antitumor efficacy of Nab-PTX after i.v. administration was equivalent to the efficacy after i.p. administration. These results suggest that i.v. Nab-PTX may be another encouraging treatment option that can target peritoneal dissemination in gastric cancer.

En bloc vascular resection for the treatment of borderline resectable pancreatic head carcinoma.

Borderline resectable (BR) pancreatic head carcinoma (PhC) is an advanced disease, presenting with infiltration of major vessels. Major vascular resection (VR), particularly arterial resection, to achieve microscopic no residual tumor (R0) is a controversial approach, due to the potential complications. In this study, we aimed to clarify the benefit of en bloc R0 resection with VR for PhC by retrospectively evaluating 78 PhC patients who underwent pancreatoduodenectomy at our institute. The patients were divided into 4 groups as follows: R, resectable (n=20); BR-V, BR involving the superior mesenteric vein or portal vein (PV) (n=28); BR-SMA, BR involving the superior mesenteric artery (n=21); and BR-HA, BR involving the hepatic artery (n=9). In total, 65 patients underwent VR, with 63, 21 and 9 patients undergoing PV, SMA and HA resection, respectively. The R0 rates were as follows: R group, 85%; BR-V, 82%; BR-SMA, 71%; and BR-HA, 33%. The median survival time and 5-year survival rate for R0 resection were 31 months and 25% in the R group, 22 months and 28% in the BR-V group, 17 months and 27% in the BR-SMA group and 10 months and 0% in the BR-HA group, respectively. The prognosis was comparable among the BR-V, BR-SMA and R groups, but was significantly poorer in the BR-HA group. In total, 5 patients (6.4%) died perioperatively (4 from postoperative hemorrhage and 1 from suffocation due to failure of expectoration, without pneumonia or asthma). Of the 4 patients who succumbed to hemorrhage, 3 had undergone arterial resection. Therefore, en bloc resection with major VR for R0 may be suitable for BR-V and BR-SMA PhC patients.

Currarino syndrome in an adult presenting with a presacral abscess: a case report.

INTRODUCTION: Currarino syndrome (Currarino triad) was described in 1981 as a triad syndrome with a common embryogenesis in infants and with three characteristics: anorectal stenosis, a defect in the sacral bone, and a presacral mass. We describe here an unusual case of Currarino syndrome in an adult presenting with a presacral abscess but no meningitis. CASE PRESENTATION: A 32-year-old Japanese man presented with fever, arthralgia and buttock pain. A digital rectal examination showed mild rectal stenosis with local warmth and tenderness in the posterior wall of his rectum. Computed tomography showed a scimitar-shaped deformity of his sacrum and an 8cm presacral mass, which continued to a pedicle of his deformed sacrum. This was diagnosed as Currarino syndrome with a presacral abscess. The abscess was drained by a perianal approach with our patient treated with antibiotics. His symptoms soon disappeared. After three months, an excision was performed through a posterior sagittal approach. His postoperative course was uneventful and he was discharged 10 days after surgery. A histopathological examination revealed an infected epidermoid cyst. He has been free from recurrence as of four years and six months after surgery. CONCLUSIONS: We report a case of Currarino syndrome in an adult who presented with a presacral abscess but no meningitis. Abscess drainage followed by radical surgery resulted in a successful outcome.

Perforated gastrointestinal stromal tumor (GIST) in a true jejunal diverticulum in adulthood: report of a case.

A 61-year-old man was referred to us for investigation of acute abdominal pain. Computed tomography showed a 5.9 × 5.3 × 5.0 cm lump of food residue in the jejunum, and a large amount of free air and ascites around the liver and right paracolic gutter. He underwent emergency laparotomy for suspected peritonitis from perforation by a foreign body in the small intestine. We identified purulent exudate in the abdominal cavity and perforation of a jejunal cystic mass, attached ~40 cm from Treitz's ligament at the anti-mesenteric side of the jejunum. Based on a diagnosis of jejunal duplication with perforation, we resected that part of the small intestine and performed intra-abdominal drainage. Pathological findings confirmed the diagnosis of a perforated gastrointestinal stromal tumor (GIST) in a true jejunal diverticulum. Histopathological evidence suggests that intestinal pressure and/or hemorrhage can cause perforation in the background of a true jejunal diverticulum. To our knowledge, this is the first case report of a perforated GIST in a true jejunal diverticulum.

[A case report of hepatic arterial infusion chemotherapy and RFA for liver metastasis from pancreatic cancer].

A 71-year-old female patient was administered 2 courses of neoadjuvant chemotherapy (GS therapy) for pancreatic body cancer, and underwent pancreatic body and tail resection. She was diagnosed as having T3N0M0, Stage III disease, and adjuvant chemotherapy with gemcitabine was started. However, a solitary 9 mm liver metastasis was found using CT imaging 3 months after the operation. We started hepatic arterial infusion chemotherapy (GEM+5-FU), with additional treatment using RFA after 5 courses, and a CR was achieved. The HAI regimens were changed to GEM+S-1 and a further 18 courses were administered. After HAI, adjuvant chemotherapy (S-1) was continued, but 2 further liver metastases were found. The patient was still alive 4 years after surgery and continued to undergo radiation chemotherapy.

Duodenal ulcer penetration into the liver at the previous left hemihepatectomy site.

INTRODUCTION: Duodenal ulcer penetration into the liver is a rare, but serious complication. Its frequency was thought to have decreased owing to advances in therapies for peptic ulcers. However, we encountered a case in which the duodenal ulcer had penetrated into a previous hemihepatectomy site. PRESENTATION OF CASE: A 69-year-old man with a history of left hemihepatectomy 20 months previously presented to the emergency room with sudden-onset abdominal pain and nausea. An upper gastrointestinal examination with a fiberscope revealed a giant ulcer in the duodenal bulb. In addition, a foreign body was detected at the ulcer floor and was strongly suspected of being a ligature from previous hemihepatectomy. DISCUSSION: The presence of a gas-filled liver mass and bowel wall thickening with inflammatory changes are important imaging findings for prompt diagnosis of such a condition, but in this case, none of these were reported. Further, no definite abscess was found. Thus, the patient was treated conservatively with a proton pump inhibitor. CONCLUSION: This case demonstrates the importance of using absorbable suture materials, adequate lavage in the postoperative peritoneal space and gastroduodenal mucosal protection postoperatively.

Internal hernia in a liver transplant recipien: a case report.

Biliary complications have great importance for liver transplant recipients because of affecting long-term prognosis. In rare situations, an internal hernia of the Roux-en-Y loop cause graft injury. A 42-year-old woman with a history of living donor liver transplantation 6 years ago presented with prolonged graft injury during the past 6 months. She suddenly developed ileus of the small bowel with internal hernia through the defect of the mesentery around the Roux-en-Y limb of the hepaticojejunostomy. Emergent surgery was performed to reduce the hernia and volvulus; also the mesenteric rent was closed with interrupted suture of silk. Internal hernia of the small bowel after liver transplantation is rare but causes graft injury due to associated biliary complications and rapid deterioration of patient's condition.

Topical nitrate drip infusion using cystic duct tube for retained bile duct stone: A six patients case series.

A retained bile duct stone after operation for cholelithiasis still occurs and causes symptoms such as biliary colic and obstructive jaundice. An endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy (EST), followed by stone extraction, are usually an effective treatment for this condition. However, these procedures are associated with severe complications including pancreatitis, bleeding, and duodenal perforation. Nitrates such as glyceryl trinitrate (GTN) and isosorbide dinitrate (ISDN) are known to relax the sphincter of Oddi. In 6 cases in which a retained stone was detected following cholecystectomy, topical nitrate drip infusion via cystic duct tube (C-tube) was carried out. Retained stones of 2-3 mm diameter and no dilated common bile duct in 3 patients were removed by drip infusion of 50 mg GTN or 10 mg ISDN, which was the regular dose of intravenous injection. Three other cases failed, and EST in 2 cases and endoscopic biliary balloon dilatation in 1 case were performed. One patient developed an adverse event of nausea. Severe complications were not observed. We consider the topical nitrate drip infusion via C-tube to be old but safe, easy, and inexpensive procedure for retained bile duct stone following cholecystectomy, inasmuch as removal rate was about 50% in our cases.

[Gemcitabine augments major histocompatibility complex class I-related chain A expression in pancreatic cancer].

Major histocompatibility complex(MHC)class I related chain A( MICA) expressed on the cell surface of tumor cells functions as a ligand for natural killer group 2, member D (NKG2D), an important immunoreceptor expressed on natural killer ( NK ), CD8, and γδT cells. The interaction of MICA and NKG2D stimulates NK cell-mediated cytotoxicity. Gemcitabine (GEM), a key drug for pancreatic cancer treatment, stimulates the expression of cell surface MICA in tumor cells to enhance the cytotoxicity of NK cells. The combination of GEM and S-1 is used as a neoadjuvant chemotherapy (NAC) drug for pancreatic cancer in our department. We investigated the effect of GEM on pancreatic cancer. On immunohistochemistry, MICA expression was positive in 11 of 13 (85%) pancreatic ductal adenocarcinomas in the NAC group, and in 4 of 11 (36%) in the placebo control group. There was a greater proportion of NKG2D-positive cells in 5 random samples taken from both the NAC groups( 10 of 13, 77%) than in equivalent samples taken from the placebo control group( 3 of 11, 27%). In addition, CD16-positive cells were more prevalent among NK, CD8, and γδT cells in the NAC group( 9 of 13, 69%) than in the placebo control group( 3 of 11, 27%). Therefore, GEM may induce MICA expression on the surface of pancreatic cells and thus cause the accumulation of NKG2D and CD16-positive cells around tumors.

[Hepatic arterial infusion chemotherapy with gemcitabine for patients with postoperative liver metastases from pancreatic cancer].

Herein, we describe hepatic arterial infusion (HAI) chemotherapy with gemcitabine (GEM) for the treatment of patients with postoperative liver metastases from pancreatic cancer. Seven patients received HAI with GEM plus 5-fluorouracil (5- FU) or oral S-1 from 2008 to 2010 at the Kanazawa University Hospital. Of the 7 patients, partial response (PR) and stable disease( SD) were observed in 6 patients according to the Response Evaluation Criteria In Solid Tumors( RECIST) evaluation criteria (response rate, 85.7%). The median survival time was 14 months; however, all 7 patients ultimately died of another metastatic lesion. Importantly, there were no life-threatening toxicities. However, 6 patients developed catheter- related complications, and the HAI catheter and the subcutaneous implantable port system had to be removed. Peripheral blood concentrations of GEM after HAI were analyzed in 7 other patients. At a dose level of 400 to 800 mg/standard liver volume( SLV),the GEM concentrations were less than one-tenth that of the intravenously administered 1,000 mg/m2. However, at a dose level of 1,000 mg/SLV, the GEM concentration in the peripheral blood was almost the same as that administered intravenously. In conclusion, HAI chemotherapy is safe and effective for the treatment of patients with liver metastases from pancreatic cancer. Our results suggest that a dose level of 800 mg/SLV could be considered optimal for local therapy.

Valproic acid, a histone deacetylase inhibitor, enhances radiosensitivity in esophageal squamous cell carcinoma.

Histone deacetylase (HDAC) inhibitors have been shown to enhance radiation response in various cancer cell lines. Valproic acid (VPA) has been used in clinical practice for the treatment of epilepsy and other seizure disorders and is also one of the most represented HDAC inhibitors. The aim of this study was to evaluate the radiosensitizing ability of VPA and its mechanisms in four esophageal squamous cell carcinoma (ESCC) cell lines (TE9, TE10, TE11 and TE14). VPA inhibited the viability of all ESCC cells in a dose-dependent manner. The 50% inhibitory concentration (IC50) value of VPA in each cell line was between 1.02-2.15 mM, which is higher than clinically used safe concentrations. VPA induced the hyperacetylation of histones H3 and H4, as well as apoptosis and had a radiosensitizing effect on all four ESCC cell lines at a concentration of 0.5 mM which is equivalent to the therapeutic plasma concentration of anti-epilepsy therapy in humans. The radiosensitization was accompanied by an increase in γH2AX levels, indicating the presence of double-strand breaks (DSBs), and decrease in Rad51 expression, a DSB repair protein. These results suggest that a clinically safe dose of VPA can enhance radiation-induced cytotoxicity in human ESCC cells by chromatin decondensation with histone hyperacetylation and downregulation of Rad51. In conclusion, VPA appears to be a safe and promising radiosensitizer for esophageal cancer radiotherapy.