Regadenoson in Europe: first-year experience of regadenoson stress combined with submaximal exercise in patients undergoing myocardial perfusion scintigraphy.

PURPOSE: Regadenoson was approved for clinical use in Europe in 2011. Since then, it has become the default form of stress at our institution. We have assessed the side-effect profile and tolerability of regadenoson in patients undergoing clinically indicated myocardial perfusion scintigraphy between July 2011 and July 2012. METHODS: Clinical, stress and imaging data were recorded prospectively. Symptoms during stress were recorded and defined as mild, moderate or severe. An adverse event was defined as any symptom that persisted for more than 30 min or that required investigation or treatment. RESULTS: Of 1,764 consecutive patients, 1,581 (90%) received regadenoson combined with submaximal exercise unless contraindicated. Symptoms were common (63%) but transient and well-tolerated. The severity of symptoms was recorded in most patients as mild (84%). Dyspnoea (36%) and chest discomfort (12%) were the commonest side effects. Adverse events were reported in eight patients (0.5%), thought to be vasovagal in seven of these. All patients recovered fully without sequelae. There were no deaths, myocardial infarction or hospital admissions. Regadenoson stress was performed in 206 patients (12%) with asthma or chronic obstructive pulmonary disease (COPD) without bronchospasm or any other major side effect. CONCLUSION: We studied the symptom profile of regadenoson in the largest European cohort to date. Regadenoson combined with submaximal exercise was well tolerated, notably also in patients with asthma or COPD. The majority of regadenoson-related adverse events were vasovagal episodes without sequelae.

Metastatic gastric adenocarcinoma and synchronous carcinoid tumour mimicking appendicitis: A case report.

INTRODUCTION: Silent metastatic gastric adenocarcinoma presenting as appendicitis is very rare. Rare pathologies may be encountered during common operations such as appendicectomy and an awareness of possible alternative pathological entities would be helpful in a surgeon's wealth of knowledge. PRESENTATION OF CASE: A 63-year-old man presented with a three-day history of acute abdominal pain suggestive of appendicitis. Intra-operatively, a macroscopically inflamed and perforated appendix was found. There were however some atypical features, which included multiple inflamed ulcerated lesions throughout the small bowel mesentery and along the terminal ileum. Appendicectomy was performed and biopsies of these lesions were taken. Subsequent histopathology revealed that there were metastatic deposits of poorly differentiated adenocarcinoma in the appendix and mesenteric biopsies, as well as a neuroendocrine (carcinoid) tumour of the appendix. Upper endoscopy confirmed a gastric primary leading to peritoneal dissemination. The patient was scheduled to undergo a course of palliative chemotherapy. DISCUSSION: Metastatic gastric adenocarcinomas with peritoneal dissemination have a very poor prognosis and often the first choice of treatment is chemotherapy as a complete cure through surgery is often not feasible. As for classical carcinoid tumours smaller than 2 cm towards the tip of the appendix with low proliferative index and without angiolymphatic or mesoappendiceal extension, then appendicectomy alone is indicated. Synchronous neoplastic pathologies presenting as appendicitis is largely unknown. CONCLUSION: To our knowledge, this is the first report in the literature of synchronous carcinoid tumour and metastatic gastric cancer co-existing within an inflamed appendix.

De Garengeot hernia-Use of a novel surgical approach and literature review.

INTRODUCTION: De Garengeot hernia is a rare type of femoral hernia, defined as a sac containing a vermiform appendix. Due to its rare occurrence the information available on diagnosis and management is scarce. We report the use of a recently described technique for femoral hernia repair and appendicectomy. PRESENTATION OF CASE: A 67 year old female presented to the emergency department with features of incarcerated femoral hernia. CT imaging revealed an incarcerated appendix within a femoral hernia. The patient subsequently underwent surgery, where the femoral hernia was repaired and appendicectomy performed concurrently. DISCUSSION: Clinical diagnosis is difficult, and there have only been a few documented cases of pre-operative CT diagnoses in the literature. The usual risk factors for developing a hernia would apply to this pathology, and other anatomical and embryological considerations are explored. The King's College technique for femoral hernia repair involves an incision that allows repair of the hernia and also the ability to enter the peritoneal cavity using the same incision. This approach was used in this case, where the abdominal cavity had to be entered to perform the appendicectomy, before the femoral hernia could be repaired. CONCLUSION: Pre-operative diagnosis of De Garengeot hernia is difficult, as it may mimic an incarcerated femoral hernia containing other contents. The diagnosis becomes apparent intra-operatively. The clinical significance lies in that intra-abdominal access may be required to safely perform an appendicectomy before the repair of the hernia defect, and this article includes a description of a suitable technique for this particular pathology.

Clinicopathologic factors influencing the long-term prognosis following hepatic resection for large hepatocellular carcinoma more than 10 cm in diameter.

We resected 158 cases of hepatocellular carcinoma (HCC), including 20 (12.6%) cases of large HCC. These 20 cases were divided into group 1 (curative resection, n = 9) and group 2 (noncurative resection, n = 11). The clinicopathologic features and long-term survival of the cases were evaluated. In groups 1 and 2, portal vein invasion (Vp+) was noted in 44.4% and 63.3%, intrahepatic metastasis (IM+) in 77.8% and 100%, absence of a fibrous capsule (Fc-) in 55.6% and 63.6%, and stage III or IV in 77.8% and 100%, respectively. The DNA ploidy pattern was aneuploid in 44.4% of group 1 and 100% of group 2. In group 1, the 1-, 3-, and 5-year cumulative survival rates were 75%, 62.5%, and 62.5%, respectively (the longest survivor is alive after 11 years 1 month). Five cases survived more than 3 years in group 1, and all were Vp(-) and nonaneuploid. On the other hand, in group 2, the 1-year survival rate was only 33.3%; none survived more than 2 years. These results suggest that even patients with large HCC have a favorable long-term prognosis if their clinicopathologic factors are Vp(-) and nonaneuploid, and if curative resection can be performed.

Induction and involvement of endogenous IGF-I in pancreas regeneration after partial pancreatectomy in the dog.

To elucidate whether and how IGF-I is involved in the regeneration of the pancreas after partial pancreatectomy, IGF-I mRNA expression, IGF-I protein synthesis, ornithine decarboxylase (ODC) activity and DNA replication in the remnant pancreas were determined in the dog. After pancreatectomy, IGF-I mRNA expression was remarkably enhanced in the remnant pancreas, showing the maximal value at post-operative day (POD) 1. Subsequently, IGF-I synthesis in the tissue was significantly stimulated at POD 2, and its maximal concentration was observed at POD 3. Following IGF-I synthesis, ODC activity was induced and its maximal activity was also obtained at POD 3. Finally, DNA replication was induced in the remnant pancreas, and its maximal level was observed at POD 5. These responses in the remnant pancreatic tissue to partial pancreatectomy were greatly enhanced as the resection rate was increased up to 95%. Positive correlations were observed between IGF-I concentrations in the remnant pancreas and the activities of ODC and DNA synthesis in the tissue after 95% pancreatectomy. These results suggest that the gene expression of IGF-I is rapidly induced in the remnant pancreas after partial pancreatectomy, and subsequently synthesized endogenous IGF-I peptides may stimulate ODC and other cell growth-related activities in the tissue in paracrine and/or autocrine manners eventually to induce DNA replication and tissue regeneration.

Significance of multidisciplinary therapy for hepatocellular carcinoma.

The effect of multidisciplinary therapy for hepatocellular carcinoma (HCC) was evaluated in 121 resected cases. The 5-year survival was 100% for absolute curative resection (12 cases), 59.1% for relative curative resection (n = 37) and 10.9% for relative non-curative resection (n = 59). However, none of the patients survived for more than 3 years after absolute non-curative resection (n = 13). The non-recurrence in the preoperative TAE groups was different from that in non-TAE groups undergoing absolute and relative curative resection. The 1- and 3-year non-recurrence rates for relative non-curative resection were 92.3% and 53.8%, respectively, for the preoperative TAE group and 56.1% and 28.1%, respectively for the non-TAE group. These data show that preoperative TAE is effective in relative non-curative resection. Functional disturbances of the coagulation-fibrinolysis system in cirrhotic patients were improved after PSE. All patients undergoing hepatectomy after PSE had an uneventful postoperative course, including well-maintained function of the coagulation-fibrinolysis system and a decrease in splenic volume. At 1 year after hepatectomy, cirrhotic patients with critical liver function and poor coagulation-fibrinolysis showed appreciable hepatic regeneration. One patient died of hepatic failure 1 year after the operation. In recurrent HCC, the 1-, 2- and 3-year survival values after reresection were 100%, 75.0% and 25.0%, respectively. The respective values following TAE were 79.0%, 42.0% and 9.0%. Three cases of recurrent HCC were effectively treated, i.e., two patients achieved a partial response and one showed no change, by continuous intra-arterial infusion of 5-FU and lentinan with intermittent one-shot injections of epirubicin using a subcutaneous infusion pump. These three patients are alive at 1 year and 7 months, 1 year and 4 months and 6 months after the treatment, respectively.

Surgical treatment of hepatocellular carcinoma.

The effect of surgical treatment for hepatocellular carcinoma (HCC) was evaluated in 149 resected cases, 83.2% of which were associated with liver cirrhosis. The 3- and 5-year survival rates were 60.1% and 39.4%, respectively. The mortality rate was 4.1%. In patients aged over 70 years, liver cirrhosis was found in 53.3% of cases and the mortality rate was 6.7%. The 3- and 5-year survival rates were 50.8% and 33.9%, respectively. Factors that significantly affected survival for more than 5 years were a tumor size of less than 3 cm, Stage I disease, vp(-), IMo, and diploid type. The 5-year survival rate for patients with a single tumor of 3 cm or less was 54.2%, regardless of the surgical procedure. All 15 patients with a solitary tumor of 2 cm or less (Stage I, small liver tumor) were alive with a 5-year survival rate of 100%. The problem is the treatment of patients with a tumor measuring 3-5 cm in diameter and associated liver cirrhosis, because their prognosis after surgery is the worst. HrS (subsegmentectomy) is the minimal procedure of limited hepatectomy for these cases with postoperative multidisciplinary therapy.

Pathophysiological effect of hepatic ischemia and reperfusion after hepatectomy in dogs with obstructive jaundice, focusing on the effect of coenzyme Q10 and styrene-co-maleic acid superoxide dismutase.

The purpose of the present study was to elucidate the effect of hepatic reflow following ischemia on the remnant liver after hepatectomy with occluded hepatic blood inflow in dogs with obstructive jaundice. When 40% hepatectomy was performed with 10-min occlusion of hepatic blood inflow in dogs with obstructive jaundice, the lipid peroxide content in the remnant liver increased significantly, together with a reduction in superoxide dismutase (SOD)-like activity. The levels of endotoxin and beta-N-acetyl hexosaminase (NAH) in peripheral blood also increased. The phagocytic index increased transiently after 30 min, followed by a marked decrease after 3h. Histologically, degeneration and necrosis of the hepatic parenchymal cells were demonstrated, and survival rate at 7 days was only 23.1%. With the administration of coenzyme Q10 (CoQ10) or styrene-co-maleic acid SOD (SM-SOD), these phenomena were significantly inhibited, and the survival rate improved. After hepatectomy, Kupffer cells in the remnant liver were activated by increased endotoxin levels in the portal vein, inducing the production of free radicals, which, in turn, damaged the Kupffer cells by reducing endotoxin clearance. Finally, the impaired functional reserve in the remnant liver provoked liver failure. The administration of CoQ10 or SM-SOD prevented the occurrence of these phenomena triggered by the free radicals generated by Kupffer cells, stimulated by endotoxin in the portal vein.

Hepatocellular carcinoma associated with anabolic steroid therapy: report of a case and review of the Japanese literature.

We report herein the case of a 35-year-old woman with aplastic anemia who developed hepatocellular carcinoma after long-term therapy with oxymetholone. She was treated with 60 mg/day of oxymetholone for 3 years (total dose 64.8 g). Alpha-fetoprotein, hepatitis B surface antigen, and hepatitis C antibody were all negative, but serum titers of carcinoembryonic antigen and carbohydrate antigen were elevated. Lateral segmentectomy of the liver was performed. The histopathological findings were compatible with those of multiple hepatocellular carcinoma without liver cirrhosis. Three years since the operation, the patient is doing well and no signs of tumor recurrence have been detected. According to our review of Japanese cases of hepatocellular carcinoma associated with anabolic steroid therapy, in all instances the tumors developed after long-term administration of anabolic steroids for hematologic diseases. In patients under long-term anabolic steroid therapy, routine screening of the liver by ultrasonography and computed tomography should be performed to detect liver tumors in the early stages.

Triple carcinomas of the biliary tract associated with congenital choledochal dilatation and pancreaticobiliary maljunction.

We report a rare case of triple carcinomas of the biliary tract associated with congenital choledochal dilatation (CCD) and pancreaticobiliary maljunction (PBM). The patient was a 58-year-old Japanese man who complained of epigastralgia. Ultrasonography and computed tomography revealed an elevated lesion inside the markedly dilated extrahepatic bile duct, thickening of the gallbladder wall, and small polypoid lesions in the gallbladder. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography showed CCD and PBM. With a diagnosis of carcinoma of the bile duct and cholesterol polyps in the gallbladder, pylorus-preserving pancreaticoduodenectomy was performed. The resected specimen showed two elevated lesions in the dilated bile duct, cholesterol polyps, and an area of irregular mucosa in the gallbladder. Histopathological examination showed two carcinomas in the bile duct, an adenosquamous cell carcinoma, and a moderately differentiated tubular adenocarcinoma, and a well differentiated tubular adenocarcinoma of the gallbladder. Two years and 6 months after the operation, a solitary metastatic liver tumor was detected. Left hepatic lobectomy was performed. At present, 7 months after the second operation, the patient is doing well with no signs of recurrence. Multiple carcinomas in the biliary tract associated with CCD and PBM, including the details in the present patient, were reviewed.

Primary adenosquamous carcinoma of liver resected by right trisegmentectomy: report of a case and review of the literature.

A case of primary adenosquamous carcinoma of the liver in a patient with an elevated level of serum squamous cell carcinoma-related antigen is reported. A 68-year-old man was admitted to our hospital with a 10-day history of fever and jaundice. From the results of laboratory and imaging studies before surgery, a diagnosis of cholangiocellular carcinoma was made, and the patient underwent right trisegmentectomy with regional lymph node dissection. Histopathological examination of the resected specimen revealed adenocarcinoma, squamous cell carcinoma, and a transitional area containing both types of cancer cells. The number of argyrophilic nucleolar organizer regions and the labeling index of proliferating cell nuclear antigen were markedly elevated and the deoxyribonucleic acid ploidy pattern was aneuploid in the squamous component. The patient died due to liver metastases 3 months after the operation. We reviewed the 31 cases of adenosquamous carcinoma of the liver reported in the Japanese and English language literature, including the present case.

Cholangiocellular carcinoma of the liver.

Of the 118 patients with primary liver cancer treated in our clinic during a 6 year 7 month period, 11 patients had cholangiocellular carcinoma of the liver. Ten (90.9 percent) of the 11 patients underwent surgery, and 9 (90 percent) had major hepatic resection with no operative deaths. Seven were still alive at the time of the study 2 months to 4 years 1 month after surgery. Three patients died from recurrence 9 months, 11 months, and 1 year 4 months after surgery. The 1 and 3 year actuarial survival rates after hepatic resection were excellent (85.7 and 61.2 percent, respectively) compared with the 1 and 3 year rates of 58.8 and 0 percent in the Japanese series. Even though the cholangiocellular carcinomas in our 11 patients were in the advanced stages, good results were obtained by hepatic resection. If they were detected at a much earlier time, an even more remarkable survival rate could be expected.

Surgical treatment of giant hemangioma of the liver.

During a 5 year period, we treated 5 patients with giant hemangioma of the liver. There were 4 women and 1 man who ranged in age from 34 to 51 years with an average age of 43.8 years. The symptoms were an abdominal mass with Kasabach-Merritt syndrome in 2 patients, an uncomfortable sensation in the upper abdomen in two patients, and pain in the right upper quadrant in one patient. All five patients underwent surgical treatment with a successful outcome. Three of the patients underwent hepatic lobectomy, one patient underwent left lateral segmentectomy with ligation of the right hepatic artery, and one patient had ligation of the left hepatic artery with radiation. In two of the patients, Kasabach-Merritt syndrome was cured promptly after hepatic lobectomy. We believe that a symptomatic giant hemangioma within one lobe should be treated by hepatectomy, but if it involves both lobes, ligation of the hepatic artery, with or without radiation, should be considered.

Changes after major resection of experimental cirrhotic liver.

Liver cirrhosis was induced experimentally in dogs--hemodynamically, by constriction of the hepatic vein and pharmacologically, by administration of dimethylinitrosamine (DMNA)--after which approximately 45 per cent of the liver was resected. Results indicate that death after major resection of a cirrhotic liver was caused not only by too extensive a resection but also by the rapid progression of cirrhotic changes in the remnant liver during the postoperative course.

Changes in carbohydrate metabolism and endocrine function of remnant pancreas after major pancreatic resection.

Changes of glucose tolerance after partial pancreatectomy were divided into three types depending on the extent of resection. When 88 per cent or more of the pancreas was resected, hyperglycemia developed immediately, and when 70 to 88 per cent of the pancreas was resected, diabetes occurred after six weeks or more, but diabetes did not develop at all when less than 70 per cent of the pancreas was removed. The secretion of glucagon was maintained well, but that of insulin was easily impaired after resection of 70 per cent or more of the entire pancreas.

Resectability and functional reserve of the liver with obstructive jaundice in dogs.

Fifty-five dogs were used to evaluate the resectability of the liver with obstructive jaundice. Cholecystectomy and ligation of the distal common bile duct were used to produce obstructive jaundice. It was found that 40 per cent of the liver with obstructive jaundice was resectable with biliary decompression 2 weeks after ligation. At 1 week after induction of obstructive jaundice, 70 per cent hepatectomy with biliary decompression may be tolerated with careful postoperative management. From serum chemical studies it was found that if the serum albumin level was below 2.0 g/dl, 60 per cent of the dogs died after 40 per cent hepatectomy and all died after 70 per cent hepatectomy. From the standpoint of hepatic functional reserve 40 per cent hepatectomy is successful if the maximal removal rate of indocyanine green is above 0.14 mg/kg/min. Hepatic functional reserve is reliable for predicting the risk of hepatectomy, and it correlates well with the rate of hepatic regeneration after hepatectomy.

Carbohydrate metabolism and endocrine function in the pancreas remnant after major pancreatic resection.

Changes in glucose tolerance, in secretion of pancreatic hormones and in the islets of the pancreas were investigated after major resection of the pancreas in dogs to elucidate the pathophysiologic features of carbohydrate metabolism and the difference in the amount of insulin required in diabetes after total and partial pancreatectomy. In diabetes after 90 percent or more pancreatectomy, both insulin secretion and the function of the anti-insulin system decreased, associated with degeneration of the islet B, A, and D cells. The required insulin amount was similar to that needed after total pancreatectomy. Diabetes developed more than 6 weeks after 70 to 90 percent pancreatectomy, and insulin secretion decreased but the function of the anti-insulin system was accentuated with an increase in plasma glucagon levels, associated with degeneration in B cells but not in A and D cells. The amount of insulin required was 3 to 4 times greater than that needed after total pancreatectomy.

Diagnosis and treatment of cholangiocellular carcinoma of the liver.

Of the 239 patients with primary liver cancer treated in our department over the last 13 years, 27 had cholangiocellular carcinoma, and 4 cystic adenocarcinoma of the liver. In this paper, the diagnosis and treatment of cholangiocellular carcinoma was reviewed and discussed. Twenty-four (88.9%) of the 27 patients with cholangiocellular carcinoma underwent surgery and 16 (66.7%) had hepatic resection. There were no operative deaths. None with hilar type cancer survived more than 2 years but in the case of the peripheral type the one-year cumulative survival rate after hepatectomy was 63.6%, the 3- and 5-year rates were both 33.9%. Two cases survived more than 5 years. One was a 69-year-old female who died of tumor recurrence 5 years and 6 months after hepatectomy; the other a 61-year-old female who is still alive and well, without recurrence, 10 years and 5 months after right trisegmentectomy. Although the cholangiocellular carcinoma in our series were in the advanced stages, good results were obtained by hepatic resection with multimodal treatment.

Preoperative estimation of surgical risk of hepatectomy in cirrhotic patients.

In order to improve the results of hepatectomy in cirrhotic patients, functional resectability of the liver was evaluated before surgery, in 119 cases of hepatectomy, including 85 cases with cirrhosis, over the last 10 years. Our total risk, measured by multivariate analysis of hepatic function tests, was very useful in selecting the suitable operative method. Functional reserve of the remnant liver and that of per unit volume of the liver evaluated by ICGRmax, were also good indicators for estimating long-term prognosis and liver regeneration following hepatectomy. Furthermore, from our experience with 4 cirrhotic patients who developed disseminated intravascular coagulopathy after hepatectomy, the preoperative evaluation of function in the coagulation-fibrinolysis system was also important for estimating the operative risk of hepatectomy in cirrhotic patients.

Definition and diagnosis of early cancer of the biliary tract.

From the study on correlation between the depth of cancer invasion and the results of surgery, early cancer of the biliary tract may be defined as cancer cell invasion limited to the mucosal or muscularis propria in the case of carcinoma of the gallbladder, and to the mucosal or fibro-muscular layer in the case of carcinoma of the bile duct. With few exceptions, these tumors had no lymph node metastasis, venous invasion, perineural infiltration or involvement of the lymphatic vessels. Since the cumulative 5-year survival rate was 100% after resection of early cancer, the choice of surgical procedures was considered to be extended cholecystectomy for early cancer of the gallbladder, and the standard radical resective operation for early cancer of the bile duct. An accurate diagnosis was not made preoperatively in most cases of early cancer of the biliary tract. The diagnostic approach is discussed, including the recently developed imaging modalities, such as endoscopic ultrasonography and percutaneous transhepatic cholecystoscopy or cholangioscopy.