Fibroblast activation protein and its prognostic significance in correlation with vascular endothelial growth factor in pancreatic adenocarcinoma.

Fibroblast activation protein (FAP), a selective protein for tumor stromal fibroblasts, is expressed in >90% of human epithelial carcinomas. A characteristic feature of pancreatic cancer is an extensive fibrotic or desmoplastic reaction surrounding the primary tumor. The present study aimed to evaluate the expression levels of FAP and vascular endothelial growth factor (VEGF) and determine their correlation in pancreatic adenocarcinoma. Confocal laser scanning microscopy and conventional immunohistochemical analysis were used to quantify FAP and VEGF expression levels in formalin­fixed and paraffin­embedded tissue biopsies from 46 patients (male, 26; female, 20; mean age, 66 years; age range, 53­80 years) with pancreatic adenocarcinoma stage IIA or IIB. The expression levels of FAP in the neoplastic and adjacent normal tissue were significantly higher in stage IIB patients, compared with stage IIA patients. FAP expression was correlated with positive lymph nodes, resulting in poor prognosis for stage IIB patients. The partial correlation coefficient between FAP and VEGF expression levels was 0.39 (P=0.007), and the two factors had an effect on patient survival. Multivariate analysis demonstrated the prognostic superiority of FAP over VEGF, which is considered to be the most consistently reproducible molecular marker with prognostic value in resected pancreatic adenocarcinoma. Due to the limited beneficial effect of current systemic therapies for pancreatic adenocarcinoma, targeting FAP may be a potential therapeutic strategy and requires further investigation.

Carcinoid tumors of the duodenum and the ampulla of Vater: current diagnostic and therapeutic approach in a series of 8 patients. Case series.

AIM: To describe the specific characteristics of duodenal/perivaterian carcinoids and to analyze the diagnostic/therapeutic approach. MATERIAL AND METHODS: Eight patients were included in our study. Symptoms on admission included dyspepsia, upper gastrointestinal (GI) bleeding and anemia. All patients underwent upper GI endoscopy and gastrointestinal peptides (gastrin) and neuroendocrine markers (Chromogranin-A, CgA) measurement. Imaging studies were performed in all patients, including OCTREOSCAN, while in patients with ACs MRCP or ERCP was also performed, when necessary. Definite diagnosis was confirmed by histopathologic examination. RESULTS: Polypoid masses (carcinoids) were revealed at duodenal bulb and ampulla of Vater, in 5 and 3 patients, respectively. Serum gastrin was moderately increased in 4 patients, while in one patient it was more than 1000 pg/ml. Serum CgA was moderately increased in one patient, in whom OCTREOSCAN detected a solitary hepatic metastasis. Two patients with DC, of less than 1 cm of diameter, were treated by endoscopic polypectomy, while all the other patients underwent surgery. The patient with hepatic metastasis and positive OCTREOSCAN received also Octreotide LAR, resulting in stabilization of disease. No recurrence or metastases were observed during follow-up (range : 1.5-9.6 years). CONCLUSIONS: In DC tumors <1 cm endoscopic excision with close follow-up is an adequate treatment, while in tumors >1 cm and in AC, surgical resection is the treatment of choice. In metastatic tumors, resection of the primary lesion with administration of somatostatin analogues may stabilize the disease and improve patient's quality of life.

Stapled cholecystojejunostomy for palliative treatment of the malignant jaundice; an effective and feasible alternative to hand-sewn method.

Unresectable periampullary cancer is commonly characterized by painless jaundice and has a rapid evolution with dismal prognosis. Biliary drainage can be achieved by various techniques and approaches, with the endoscopic drainage being the preferred method. However, when open surgery is performed with the intent to resect a tumor which is finally found to be unresectable, open drainage of the biliary tree is indicated. We present a new technique of cholecystojejunostomy using a circular mechanical stapler, which could be used in patients with intact gallbladder and widely patent the cystic duct. The described cholecystoenterostomy with the use of a circular mechanical stapler is the first reported in the literature. The procedure has been successfully used in 6 patients with excellent results. No early recurrence of biliary obstruction, cholangitis or post-operative anastomotic complications were observed. The relative simplicity of the procedure, the shorter operative time and the effective relief of jaundice, are the main advantages of the proposed technique. We believe that this method needs further investigation and can be proved effective in reducing hospitalization and anastomotic complications, compared to hand-sewn techniques.

Hypothyroidism and the aorta. evidence of increased oxidative DNA damage to the aorta of hypothyroid rats.

BACKGROUND: Although it has been suggested that the hypometabolic state is associated with a decrease in oxidative stress, literature data are controversial, revealing an individuality of oxidant status in relation to tissue properties and responsiveness. Hypothyroidism has profound direct and indirect actions on the vascular system, inducing characteristic hemodynamic changes while the aorta represents an important determinant of vascular performance. This study aims to examine the oxidant status on the aorta in chronic experimental hypothyroidism. MATERIALS AND METHODS: Chronic hypothyroidism was successfully induced in 20 male Wistar rats by administration of 0.05% 6-n-propyl 2-thiouracil in their drinking water for 8 weeks. Age-matched euthyroid rats were used as controls. Lipid peroxidation in the serum was determined by the end-product malondialdehyde (MDA). Oxidative damage to genomic DNA of aortic tissue and serum was investigated by measuring 8-oxo-dG, one of the base modifications produced in DNA by the reaction of reactive oxygen species. Serum lipids measurement was performed. RESULTS: A hypothyroid state was confirmed by levels of serum thyroid hormones, lipidemic profile, clinical examination, pathological findings and cardiovascular hemodynamics parameters. Hypothyroidism was associated with a significant increase in lipid peroxidation. (MDA 1.44 +/-0.93 vs 0.64 +/- 0.53 nmol/l, p < 0 .01). Levels of 8-oxo-dG on the aortic ring, expressing the oxidant damage on genomic DNA and in the serum, were observed to be significantly raised in the hypothyroid group compared to controls (8-oxodG(serum) 29.22 +/- 17.78 vs. 17.56 +/- 4.44 ng/ml, p < 0.01; 8-oxo-dG(aorta)11.58 +/- 2.70 vs. 4.09 +/- 1.27 ng/ml, p < 0. 001). A statistical correlation between measurements of 8-oxo-dG in the aorta and serum was found (correlation coefficient = 0.36, p < 0.05). A hyperlipidemic profile in hypothyroid animals was revealed. CONCLUSION: Vascular oxidative stress seems to play a pivotal role in the evolution of vascular pathology. Hypothyroidism was associated with increased DNA oxidative damage to the aorta. Hypercholesterolemia and an increase in mean arterial pressure associated with hypothyroidism may have a contributive role in the accumulation of damage in nuclear DNA of the vascular wall. 8-Oxo-dG is one of the mutagenic base modifications produced in DNA. Although clinical studies in other tissues have indicated a direct correlation between in vivo 8-oxo-dG formation and pathological processes, its role on the vascular wall needs further investigation.

Hepatitis C. An update.

Hepatitis C is a long-term viral infection affecting the liver caused by the hepatitis C virus HCV. Hepatitis C can be silent for years before symptoms appear, and liver damage occurs. The hepatitis C virus is extremely infectious, which means that only a tiny amount of HCV can cause illness. Hepatitis C is a major public health problem worldwide with far-reaching implications because of the chronicity of the infection that leads to chronic liver disease, cirrhosis, and primary hepatocellular carcinoma.

The role of liquid-based cytology in the investigation of colorectal lesions: a cytohistopathological correlation and evaluation of diagnostic accuracy.

BACKGROUND AND AIMS: The role of cytologic techniques is not widely accepted even if it is well documented that the cytologic investigation of colorectal tract could complement the biopsy and increase the correct diagnosis of carcinomas. This study aims to evaluate the role of Thin-Prep(R) liquid-based cytology in the investigation of colorectal lesions. MATERIALS AND METHODS: We compared the diagnostic accuracy of Thin-Prep(R) with that of biopsy in 158 patients with signs and symptoms of the lower gastrointestinal tract. Each patient underwent colonoscopy, followed by tissue biopsy and brush cytology. Brushing material was obtained and prepared according to the operating manual of Thin-Prep(R). RESULTS: The rate of unsatisfactory smears was 5% (8/158) with liquid-based technique and appeared to be slightly higher than the respective of biopsy [3.2% (5/158) (5 vs 3.2%, P = 0.18)]. Based on the final diagnosis, 89 out of 93 total malignant cases and 53 out of 53 total benign cases were correctly diagnosed with Thin-Prep(R) technique (four false negatives). Accurate diagnosis with biopsy was performed in 87 out of 93 total malignant cases and 53 out of 53 total benign cases with biopsy (six false negatives). Neither in Thin-Prep(R) technique nor in biopsy were false-positive cases observed. The sensitivities of detecting malignancy by Thin-Prep(R) and biopsy were 95.7, and 93.5%, respectively (no significant difference, P = 0.239). The sensitivity was augmented (98.9%) when the two techniques were combined, and this difference was found to be statistically significant (98.9 vs 92.9, P = 0.01, and 98.9 vs 95.7, P = 0.039). CONCLUSIONS: Liquid-based cytology appears to be an easy, highly accurate, and reliable cytologic method for the diagnostic approach of colorectal diseases and could be applied as complementary to biopsy for the improvement of the diagnosis. Moreover, could be used for DNA ploidy analysis and immmunohistochemical studies.

Wandering spleen with torsion of the pedicle.

Wandering spleen is a rare medical entity. It usually occurs at 20-40 years of age, and most cases are seen in women. Clinical diagnosis is difficult due to lack of symptoms, unless splenic torsion has occurred and clinical symptomatology of acute abdomen develops. The diagnosis can be confirmed by imaging techniques. Treatment is operative due to complications of splenic infarction. Splenopexy is the usual treatment, except for cases of splenic infarction. Splenectomy should be carried out when there is no evidence of splenic blood flow after detorsion of the spleen and in cases of excessive splenomegaly.

Hydatid disease of the liver: a continuing surgical problem.

HYPOTHESIS: To study the results of different surgical strategies in the treatment of liver hydatid disease. DESIGN: A retrospective study of 287 patients. SETTING: A university hospital in Athens, Greece. PATIENTS: Two hundred eighty-seven patients with liver hydatid cysts treated surgically 1977-2004. The cysts were located in the right hepatic lobe in 192 cases, in the left lobe in 66 cases, and in both lobes in 29 cases. Eleven patients had concomitant cysts in other organs and 12 patients had multiple intra-abdominal cysts. RESULTS: All patients were treated surgically. Surgical procedures included external drainage, simple closure, marsupialization, partial cystectomy with omentoplasty, radical procedures, laparoscopic drainage, and radiofrequency ablation. The first 3 techniques carried a higher complication rate (36.5%) compared with the other techniques (17.85%; P<.05). However, omentoplasty and external drainage carried a higher recurrence rate (7.42% overall), as compared with radical procedures (3.22%). CONCLUSION: Omentoplasty and radical procedures carry a lower complication rate compared with the formerly used marsupialization and external drainage. Conservative techniques, such as omentoplasty and/or other procedures, offer an effective control of hepatic hydatidosis and are preferred over radical procedures, when possible.

The use of oxygen in Fournier's gangrene.

Fournier's gangrene is an aggressive form of necrotizing fasciitis of the perineal, perianal or genital regions, usually caused by a polymicrobial infection that includes virulent organisms. Over the last decades, we have treated 9 patients suffering from Fournier's gangrene using systemic chemotherapy with broad-spectrum antibiotics, and with extensive, sometimes serial surgical debridement. Recently in one case, in addition to treatment, we used locally 100% oxygen in daily doses with promising results in healing wound. Herein, we report this case with a brief review of the literature concerning pathogenesis, risk factors, and treatment approaches.

Co-existence of spontaneous splenic rupture and tuberculosis of the spleen.

A rare case of splenic tuberculosis complicated by splenic rupture is reported. A 73-year-old man, hospitalized for peptic ulcer bleeding, presented in oligemic shock, was transferred to the operating room. Hemoperitoneum, due to rupture of an enlarged spleen was detected. The pathology revealed splenic tuberculosis. He had an uneventful recovery. Postoperatively, he received a combination of anti-tuberculous therapy for 6 months.

Benign multicystic peritoneal mesothelioma: a case report and review of the literature.

Benign multicystic peritoneal mesothelioma (BMPM) is a rare tumor that occurs mainly in women in their reproductive age. The pathogenesis of BMPM is unclear and a controversy regarding its neoplastic and reactive nature exists. The biological behavior of BMPM is characterized by its slowly progressive process and high rate of recurrence after surgical resection. In addition this lesion does not present a strong tendency to transform into malignancy. Today approximately 130 cases have been reported. We here report a 62-year-old woman who had diffuse abdominal pain, nausea and vomiting. Physical examination revealed a painful mass in her upper abdomen. She reported a mild dehydration, but the vital signs were normal. Peristaltic rushes, gurgles and high-pitched tinkles were audible. Upright plain abdominal film revealed small bowel loops with air-fluid levels. She was diagnosed having an incarcerated incisional hernia that resulted in intestinal obstruction. The patient underwent surgery during which a cystic mass of the right ovary measuring 6 cm multiply 5 cm multiply 4 cm, four small cysts of the small bowel (1 cm in diameter) and a cyst at the retroperitoneum measuring 11 cm multiply 10 cm multiply 3 cm were found. Complete resection of the lesion was performed. The patient had an uneventful recovery and had no recurrence two years after surgery.

Granuloma of the appendiceal stump. An unusual cause of right hemicolectomy.

Granuloma of the appendiceal stump is not a common surgical entity. However, hemorrhage which may lead to right hemicolectomy is rare in fact. We report this case, in order to avoid this kind of overtherapy.

Congenital duplication of the gallbladder.

Duplication of the gallbladder is a rare congenital anomaly of the biliary system. In this article, two cases of gallbladder duplication are presented. The first case is a patient with double gallbladder and concomitant choledocholithiasis. The probable diagnosis of double gallbladder was made preoperatively by computed tomography. The patient underwent a successful open cholecystectomy and common bile duct exploration. In the second case, two cystic formations in the place of gallbladder are demonstrated with ultrasound scan in a woman with acute cholecystitis. At surgery, two gallbladders were found. A brief review of epidemiology and anatomy of double gallbladder is included, along with a discussion of the difficulties in diagnosis and treatment of this condition.

Adenomatoid hyperplasia of pancreas presenting as tumor.

Adenomatoid hyperplasia belongs to the group of hyperplastic duct lesions of the pancreas. We report a 60-year-old man with adenomatoid hyperplasia of the pancreas, presenting as a mass lesion. The patient underwent pancreatico-duodenectomy uneventfully. The unusual location of the mass in the head of pancreas, the imaging and macroscopic appearance, dense fibrous stroma on histology and prominent expression of p21ras protein point towards a distinct subtype.

Surgical management of choledochal cysts in adults.

BACKGROUND/AIMS: Choledochal cysts are congenital malformations of the pancreatico-biliary system. Some aspects of optimal surgical management of choledochal cysts remain controversial. The purpose of this paper is to present our series of 14 patients with choledochal cysts, analyzing surgical management and long-term results. METHODOLOGY: Between January 1975 and December 2001, 15 adult patients with choledochal cysts were treated at our Department. Sex, age, clinical symptoms, associated diseases, surgical management and postoperative morbidity and mortality were reviewed. Choledochal cysts were classified according to the Alonso-Lej classification with Todani et al.'s, modification, based on radiographic and operative findings. RESULTS: There were 15 patients, 6 males and 9 females, with an age ranging from 28 to 82 years and a mean age at the time of surgery 58.3 years. Seven patients had a solitary fusiform extrahepatic cyst (Type I), five patients had an extrahepatic supraduodenal diverticulum (Type II), one patient had a choledochocele (Type III), while two patients had a Type IVB cyst. Symptoms were vague and intermittent. Recurrent upper abdominal pain, jaundice, fever, nausea and vomiting were the most common findings, usually occurring in combination. Two patients presented with cholestatic cirrhosis. Five patients had laboratory evidence of hepatocellular dysfunction and two patients had hyperamylasemia. A variety of operations was performed such as cystoduodenostomy, cyst excision and hepaticojejunostomy, cyst excision and choledochoduodenostomy. Postoperative follow-up ranged from 30 months to 12 years in all patients except of two patients who were lost to follow-up. CONCLUSIONS: Total or partial excision of the choledochal cysts is the optimal treatment because of the lower incidence of postoperative complications and the better survival rate after the operation.

Clinical considerations of primary hydatid disease of the pancreas.

BACKGROUND: The pancreas is a rare primary location of hydatid disease. The purpose of our study is to gain more insight into this entity and to focus on the management and the diagnostic approach to the disease. METHODS: The medical records of 5 patients with hydatid cysts of the pancreas were reviewed. RESULTS: Four of the cysts were primary, while in 1 case a coexisting cyst was found in the liver. The body and tail of the pancreas were the most common locations. Clinical presentation varied according to the anatomic location of the cyst. Abdominal pain, discomfort and vomiting were the main clinical symptoms. One patient presented with obstructive jaundice, while another patient manifested a mild episode of anaphylactic shock. The indirect hemagglutination test was positive in 3 of 4 cases. A computed tomography scan successfully imaged all cysts and calcification of the cystic wall was found in 3 of 4 cases. All patients underwent surgical therapy. Hydatid cysts in the tail of the pancreas were successfully treated with distal pancreatectomy, while cysts in the body and head of pancreas were treated with proper evacuation, pericystectomy and omentoplasty. The postoperative course was uneventful in all patients except 1 who presented a pancreatic fistula and was re-operated. The mean length of hospitalization after surgery was 11-12 (range 10-13) days, except for the patient who needed to be re-operated. No evidence of cyst recurrence was observed during the follow-up period. CONCLUSIONS: Hydatid cystic masses of the upper abdomen might also originate from the pancreas especially in endemic countries. Surgical excision of the entire cystic lesion remains the optimal treatment, offering hope for a complete cure.

A new technique for the palliative treatment of high bile duct cancer.

In case of advanced unresectable hilar cholangiocarcinoma palliative procedures can offer a good quality of life. Palliative techniques include surgical intubation with a U tube or transhepatic ring catheters, nonoperative intubation with an endoprosthesis and biliary-enteric bypass techniques. We present a new surgical procedure for the palliative treatment of high bile duct cancer, in which the gallbladder is used as a conduit for a biliary-enteric bypass. Hepatico-cholecysto-jejunostomy is a safe, rapid and easy method that could be alternatively and successfully used for surgical palliation of unresectable hilar cholangiocarcinoma.

Local recurrence following curative low anterior resection for rectal carcinoma.

BACKGROUND/AIMS: Local recurrence is a formidable problem after potentially curative resection for rectal cancer. We attempted to identify possible factors affecting the frequency of local recurrence, focusing on the clearance of the tumor and the margin of resection. METHODOLOGY: The clinical cohort consisted of 66 patients suffering from rectal carcinoma. All patients underwent a low anterior resection with meticulous pelvic preparation and dissection. The proximal and distal margins of the tumor were measured before fixing for permanent sections. RESULTS: Analysis by distance of the tumor from the anal verge revealed that 5 out of 33 patients (15.15%) from the upper rectal group and 7 out of 19 patients (36.8%) from the mid rectal group developed local recurrences (36.8% vs. 15.15% P=0.0369). Analysis by distance of the distal resection margins revealed that 8 out of 12 patients with local recurrence had distal margins less than 2cm, whereas 7 out of 40 patients free of local relapse had margins less than 2cm. Therefore 8 out of 15 patients with distal margins less than 2cm developed local recurrence (53.5%) whereas 4 patients among 37 with margins greater than 2cm developed a local failure (10.8%) (53.5% vs. 10.8% P=4.88E-04). The median survival in all patients of our series was 23 months. The median survival in 52 patients who underwent a potentially curative resection was 42 months. CONCLUSIONS: Tumors located in the upper portion of the rectum presented a minor tendency for local recurrence compared to tumors located in the middle of the rectum. Our study provides strong indications that high rate of local recurrences are probably related to the limited anatomic margins that can be obtained in the pelvis during primary resections.

Carcinoid tumors of the appendix. Prognostic factors and evaluation of indications for right hemicolectomy.

BACKGROUND/AIMS: Carcinoid tumors of the appendix are thought to be the most common type of appendiceal neoplasms. Although the vast majority of appendiceal carcinoids behave in a benign fashion, they are considered malignant because they all have the potential for invasion, metastasis and production of physiologically active substances. The aim of our study is to evaluate the gravity of the prognostic factors and the indications for extended surgical treatment. METHODOLOGY: Twenty-four patients, six male (aged from 18 to 59 years) and eighteen female (aged from 16 to 27 years) are included in our study. All these patients were managed and followed-up in our section during the last 17 years (follow-up range 10-17 years). Following confirmation of the diagnosis, secretion of 5-HLAA (5-Hydroxy-Inndole-Acetic Acid) was measured after a 24-hour collection of urine. Moreover, ultrasound (US) examination of the liver and computerized tomography (CT) scanning of the upper abdomen were performed after the operation in all patients. Also, patients with tumor size more than 1cm underwent a Somatostatin Receptor Scintigraphy (Octreoscan). The follow-up data of all patients included measurement of 5-HLAA and US examination every six months. RESULTS: The most common site for the tumors was the tip of the appendix (18/22). In the rest of the cases, the neoplasms were located in the base (4/22) and in the body (2/22), while in one patient the mesoappendix was invaded. In sixteen patients the tumor size was less than 1cm, in seven patients the tumor diameter was measured to be 1 to 2cm and in one patient the tumor was 3cm. Most of our patients (16/22) underwent only an appendicectomy, while in the rest of them (in the patients with tumor size between 1-2cm and in the patient with invasion of mesoappendix) a right hemicolectomy was performed. No patient was found to have metastatic disease during the operation, while the patient with invasion of the mesoappendix developed metastases in the lung, two years after the operation. CONCLUSIONS: Carcinoid tumors of the appendix, in most cases, are found incidentally during appendicectomies, especially in young females and usually are less than 1cm in size, which is probably the reason of the absence of metastases in all cases. Histological examination and size of the tumor are important factors that contribute to the selection of the surgical treatment and both must be estimated by the surgeons to make the final choice.