H19 expression in hepatic metastases from a range of human carcinomas.

AIMS: To investigate the expression of the imprinted oncofetal H19 gene in hepatic metastases derived from a range of human carcinomas and assess its prognostic value with the view of developing a DNA based treatment for such metastases. METHODS: Non-radioactive in situ hybridisation for H19 RNA was performed on paraffin wax embedded sections of liver biopsies or partial hepatectomy specimens, taken from 80 patients with hepatic metastases derived from carcinomas from several medical centres in Israel. The degree of expression was graded qualitatively according to the number of cells expressing H19 and the intensity of staining. The medical files were searched for demographic data and survival times before and after diagnosis of hepatic metastases. RESULTS: H19 expression was found in the hepatic metastases of 64 of 80 patients. High expression (higher staining grades) of H19 in the metastases was found in 43 of 80 patients. However, H19 expression status in the hepatic metastases did not correlate with either the length of time to development of metastasis or overall survival. CONCLUSIONS: H19 is highly expressed in more than half of hepatic metastases derived from a range of carcinomas. Thus, these metastases may be suitable candidates for H19 DNA based treatment. Further studies are needed to determine whether H19 expression has prognostic value in metastatic liver disease using larger numbers of specific subtypes of primary carcinomas.

The role of laparoscopic ultrasound in the minimally invasive management of symptomatic hepatic cysts.

BACKGROUND: Now that the laparoscopic treatment of symptomatic liver cystic disease has proven feasible and safe, it is gaining wide acceptance. However, due to diagnostic pitfalls and a relatively high recurrence rate, further improvements and refinement of the procedure are still needed. We have evaluated the contribution of laparoscopic ultrasound in the diagnosis and management of patients with symptomatic liver cysts. METHODS: Twelve patients with single or multiple cysts of the liver and two patients with polycystic liver disease were managed laparoscopically. Laparoscopic ultrasound served as an integral part of the procedure in all patients. RESULTS: Patients underwent either complete cyst excision (two cases) or resection of the extrahepatic cystic component (eight cases). Additionally, in two patients, deep cysts not demonstrated by preoperative imaging studies were detected and treated with a combination of laparoscopy and laparoscopic ultrasound. In one patient with a cystobiliary fistula, conversion to an open cystjejunostomy was necessary. Patients with polycystic liver disease underwent a combination of excision and unroofing of both superficial and deeper cysts using laparoscopic contact ultrasound throughout the procedure. Laparoscopic ultrasonography was found to have a significant impact on the operative strategy in five patients (36%) with multiple cysts or polycystic disease. The postoperative course was uneventful in all cases. Thirteen patients remained asymptomatic throughout the follow-up period of 30 months; one patient with polycystic liver disease developed recurrent symptoms after 5 months and was treated with left hepatectomy. CONCLUSION: Additional use of laparoscopic ultrasound enables the detection, differentiation, and treatment of deep, nonvisualized cystic lesions (two patients, 16.6%) and validation of the adequacy of the laparoscopic procedure.

[Aggressive surgical approach in pancreatic cancer--is it justified?].

Resection presents the only possible cure for pancreatic cancer. An aggressive surgical approach may extend the limits of resection and offer cure for more patients. 37 women and 28 men, mean age 67 years (range 33-84) with focal lesions underwent pancreatic resection (1993-1999). Cancer of the pancreatic head was found in 45, in the ampulla in 4 and in the body or tail in 16. There was a tumor larger than 5 cm in 9, vascular involvement in 8, and a combination of both in 6. All were evaluated prior to exploration by standard imaging techniques and 44 by laparoscopic ultrasound. 42 underwent pancreatico-duodenectomy, 16 distal subtotal pancreatectomy and 3 local excision of an ampullary tumor. Benign lesions were found in 8 (focal pancreatitis in 4 and a serous cystic lesion in 4). Curative resection (microscopically negative margins, negative lymph nodes) was achieved in 44. 2 died 1-2 months after operation of septic complications (2% operative mortality). The most frequent complication (in 8) was pancreatic fistula. Additional complications included anastomotic-line bleeding (3), intra-abdominal abscess (2), and 1 developed portal vein thrombosis (treated surgically). 1- and 2-year survival in those after curative pancreatic resection was 81% and 55% respectively. 2-year survival in those after palliative resection (positive resection margins or positive lymph nodes) was 50% and 11%, respectively. After proper selection of those in whom it is possible to perform curative resection, regardless of size or vascular involvement, an aggressive surgical approach is justified.

The impact of laparoscopy and laparoscopic ultrasonography on the management of pancreatic cancer.

HYPOTHESIS: Laparoscopy and laparoscopic ultrasonographic (LAPUS) examinations combined with a biopsy of the pancreatic lesion contribute significantly in the determination of resectability of pancreatic cancer. DESIGN: A prospective evaluation of the impact of laparoscopy and LAPUS on surgical decision making in patients with pancreatic cancer. SETTING: A general community hospital; the department of surgery serves as referral for pancreatic surgery. PATIENTS: During a 36-month period, 94 patients with pancreatic lesions were prospectively examined. Twenty-seven patients were found to have advanced disease. The remaining 67 patients were examined by laparoscopy and LAPUS to determine the resectability of the pancreatic tumor. RESULTS: Laparoscopy and LAPUS contributed new, additional data in 40 patients (60%). Advanced disease was found in 30 patients, precluding curative resection. The study indicated potentially resectable tumors in 37 patients (55%), including 3 defined by conventional imaging studies as probably unresectable, and these patients were operated on with the intention of curative resection. Thirty-three patients underwent resection, and 4 (6%) were found to have nonresectable disease and form the false-positive group of the study. A summary of the results shows that the study resulted in a change of the decision regarding surgical intervention in 24 patients (36%) and avoided unnecessary laparotomies in 21 (31%). The study had a sensitivity of 100%, a specificity of 88%, and a false-positive rate of 6%. The positive predictive value of the study is 89%, and the negative predictive value is 100%. CONCLUSIONS: Although rather invasive procedures that require general anesthesia and hospitalization, laparoscopy and LAPUS significantly contribute to the staging of patients with potentially resectable pancreatic cancer, avoiding unnecessary explorative laparotomies. These procedures should be performed in all patients with potentially resectable pancreatic cancer before explorative laparotomy.

[Laparoscopic ultrasound in predicting resectability of cholangiocarcinoma].

Cholangiocarcinoma accounts for about 1% of all malignant tumors. They are difficult to diagnose because of their small size and their location. Although surgical resection is the best therapeutic approach, most patients undergo unnecessary exploratory laparotomy due to incorrect preoperative diagnosis. We present our experience with laparoscopic ultrasound (LU) in the evaluation of cholangiocarcinoma and determination of tumor spread and vascular involvement. Of 25 patients referred for surgery, 6 were excluded following LU and were referred instead for palliative treatment. Diagnosis of the tumor was successful in 92%, and vascular involvement was diagnosed in 46%. LU should be an integral diagnostic test in the evaluation of choriocarcinoma.

Black thyroid adenoma. Clinical, histochemical, and ultrastructural features.

A 22-year-old woman with a "hot" thyroid nodule who was being treated with minocycline for severe acne vulgaris is presented. A partial thyroidectomy specimen revealed a black adenoma. Microscopically, the black pigment was found in the follicular cells and the colloid of the adenoma. The pigment was bleached with potassium permanganate and was Fontana-Masson stain positive. It was negative for iron, periodic acid-Schiff, and acid-fast Ziehl-Neelsen stains. All these feature suggest a melanin-like pigment. However, electron microscopic examination revealed a dense osmophilic material present within the lysosomes of the follicular cells. No melanosomes were present. Twenty-six previously reported cases are reviewed, and the possible mechanisms for the deposition of the pigment in the adenoma and its relation to minocycline degradation products are discussed.

[Laparoscopic surgery in treating hepatic cysts].

Solitary and multiple hepatic cysts are now more commonly found because of advances in imaging techniques. Most hepatic cysts are asymptomatic, but when they do cause symptoms they require surgical intervention. The advent of laparoscopy and of laparoscopic ultrasonography allow comprehensive evaluation and treatment of the cysts. 12 patients with hepatic cysts were treated laparoscopically. 8 with single cysts underwent successful subtotal cyst resection without signs of recurrence (up to 20 years of follow-up). 4 with polycystic liver disease underwent sub-total resection of superficial cysts. Deep cysts were unroofed and drained under laparoscopic ultrasound guidance. In this group, 1 experienced recurrence of symptoms and required partial hepatectomy of the involved segment. In another, a connection between a deep cyst and bile ducts was demonstrated and cystojejunostomy was performed. The laparoscopic approach in the management of patients with liver cysts is effective and safe, and we recommend it as the procedure of choice for single hepatic cysts. In polycystic liver disease the procedure is much less successful.

Multinodular goiter: the surgical procedure of choice.

Surgical management of multinodular goiter (MNG) poses an ongoing dilemma between radical resection with its associated complications and partial resection, which carries the risk of recurrence and increased morbidity and difficulty for rethyroidectomy. This study was designed to evaluate the recurrence rate and need for reoperation in a carefully selected population of MNG patients, after nontotal thyroidectomy. The study addressed a highly selected population of patients who were treated and thoroughly evaluated at one surgical department for several years. We analyzed the recurrence rate of MNG in 124 patients. The follow-up duration extended from 6 to 516 months (mean 93 months). The general recurrence rate for all nontotal bilateral thyroidectomies was 21% (21/100 patients), increasing from 13.4% to 60% according to the extent of resection. The average time for recurrence was 105 months (8.75 years). Among the patients with recurrent MNG, only 4 (4% of the patients with nontotal bilateral thyroidectomy) required secondary surgical interventions with no resultant morbidity. In our series of very highly selected patients, the recurrence rate for nontotal thyroidectomy was high (21%); however, the need for secondary surgical intervention was low (4%). Thus nontotal thyroidectomy for MNG is legitimate. However, we suggest that the surgical procedure of choice be tailored according to the severity of the disease and the patient's general condition.

The impact of laparoscopy and laparoscopic ultrasound on the management of pancreatic cystic lesions.

HYPOTHESIS: Laparoscopic ultrasound examination combined with biopsy of the cystic wall and aspiration of cystic fluid improves differential diagnosis of pancreatic cystic lesions contributing to surgical decision making. STUDY DESIGN: A prospective evaluation of the impact of laparoscopic ultrasound on surgical decision making in patients with pancreatic cysts. SETTING: A general community hospital; the department of surgery serves as referral for pancreatic surgery. PATIENTS: During a 36-month period, 15 patients with pancreatic cystic lesions were prospectively evaluated by laparoscopy and laparoscopic ultrasound with ultrasound-guided biopsy of the cystic wall and aspiration of cystic fluid for cytologic study, viscosity, and determination of levels of amylase and tumor markers (carcinoembryonic antigen, cancer antigen 19.9). RESULTS: Laparoscopic ultrasound contributed new, additional data in 8 patients (53%) when compared with compiled imaging data obtained by conventional ultrasound, computed tomography, magnetic resonance imaging, and endoscopic ultrasound. A solid cystic component was detected in 6 patients and additional small (<1 cm) cysts in 3 patients. Amylase and tumor marker levels, biopsy of the cystic wall, and cytologic examination had significant impact on surgical decision making in 6 patients. Nine patients underwent resection of the cystic lesion. Three patients diagnosed as having benign cysts had laparoscopy with laparoscopic ultrasound only. Three patients with suspicious lesions refused surgery. Laparoscopic ultrasound predicted correctly the nature of the cyst in 7 of 9 surgically treated patients (sensitivity, 78%). Two patients with serous cystadenoma had high levels of tumor markers (false-positive). CONCLUSION: Although a rather invasive procedure that requires general anesthesia and hospitalization, laparoscopy with laparoscopic ultrasonography was found to significantly contribute to the differential diagnosis of pancreatic cystic lesions.

Interval laparoscopic cholecystectomy in the management of acute biliary pancreatitis.

The timing of laparoscopic cholecystectomy following an attack of acute biliary pancreatitis is controversial. The traditional approach of interval cholecystectomy has been challenged recently. The present study was designed to evaluate the benefits of interval laparoscopic cholecystectomy for patients with mild acute pancreatitis (Ranson less than 3). Nineteen patients with mild pancreatitis underwent ultrasonographic evaluation to confirm the biliary etiology. ERCP was performed in all patients on the first available endoscopy list, and endoscopic sphincterotomy was performed in two patients with calculi or dilated common bile duct on ultrasonographic examination. Medical treatment was administered and laparoscopic cholecystectomy was scheduled after 8-12 weeks to allow the inflammatory process to settle. There were no recurrent attacks of pancreatitis during this period. The degree of difficulty of the laparoscopic procedure was assessed by the presence of adhesions to the gallbladder area, difficulty of dissection in the Calot's triangle, intraoperative bleeding and the need for a drain. Six patients (31.5%) had severe adhesions, difficult dissection of the cystic duct and artery, bleeding and prolonged operating time. In two of these patients (10.5%) the procedure was converted to open cholecystectomy. In conclusion, our results suggest that postponing laparoscopic cholecystectomy in acute pancreatitis patients is not advantageous surgically and does not justify the risk of further morbidity caused by the gallbladder disease.

[Evaluation of laparoscopy and laparoscopic ultrasound in diagnosis and treatment of pancreatic lesions].

Pancreatic lesions present a diagnostic challenge. Even modern imaging techniques are not sensitive enough in determining resectability of pancreatic tumors. A substantial proportion of patients therefore undergo unnecessary surgical exploration. We determined the impact of laparoscopy and laparoscopic ultrasound (LAPUS) examinations on surgical decision-making in 60 patients with pancreatic lesions. Of 48 with solid pancreatic lesions, 22 were defined by LAPUS as having nonresectable tumors, while conventional imaging studies defined only 9 of them as such. 3 of these 9 underwent successful resections of the pancreatic mass. Surgical intervention was ruled out by LAPUS in 16 patients (33.3%) but 26 had resectable lesions of whom 25 underwent surgery. 3 of this group were found to have nonresectable tumors at surgery, a false-positive rate of 6.2%. Overall sensitivity of LAPUS in our series was 88%. In 12 patients with cystic pancreatic lesions LAPUS contributed significantly to the preoperative decision due to clear imaging of the cystic lesion. Additional information was obtained from ultrasound guided-biopsy of the cyst wall, as well as determination of tumor-marker levels in the cystic fluid aspirate. LAPUS contributed significantly to operative management in 58%.

A bizarre bezoar: case report and review of the literature.

A bizarre case of a foreign-body bezoar is presented. A 16-year-old girl swallowed large amounts of toilet paper as a means of dieting. She presented with a palpable abdominal mass, multiple bezoars in the bowel, and paper excretion in the feces before admitting intentional ingestion of toilet-paper balls. Administration of Gastrografin via a nasogastric tube and enemas resulted in gradual excretion of the paper balls.

Correct preoperative localization: does it permit a change in operative strategy for primary hyperparathyroidism?

BACKGROUND: A meticulous bilateral neck exploration by an experienced endocrine surgeon offers a high cure rate with low morbidity for patients with primary hyperparathyroidism. The advent of localizing studies raises the possibility of unilateral neck exploration. The cost-effectiveness of preoperative localizing studies and unilateral neck exploration in primary hyperparathyroidism are controversial issues. This study was designed to determine the risks of missing a contralateral pathologic parathyroid gland in patients with preoperative localization that was confirmed at neck exploration. METHODS: Preoperative studies (ultrasonography, nuclear radioactive imaging scan, or both) were performed in 79 patients with primary hyperparathyroidism. In 58 patients a definite localization of an enlarged parathyroid gland was confirmed at operation. All patients underwent a meticulous bilateral neck exploration. RESULTS: Unilateral neck exploration was feasible only in 73.4% of the patients, according to our localizing modalities, and an additional enlarged parathyroid gland on the contralateral side, not detected before operation, was revealed in five patients (8.6%). False-positive rates were 1.7% for ultrasonography and 13% for scan. CONCLUSIONS: These results indicate an unacceptably high surgical failure rate for unilateral neck exploration guided by preoperative localizing studies compared with a bilateral neck exploration by an experienced endocrine surgeon, questioning the cost-effectiveness of preoperative localizing studies.

Total proctocolectomy, pancreaticoduodenectomy and total gastrectomy for multiple carcinomas in a patient with familial adenomatous polyposis.

A unique case of familial adenomatous polyposis presenting with simultaneous adenocarcinoma of the periampullary region, gallbladder and several gastric lesions, 10 years after a total proctocolectomy, is reported. Multiple gastrointestinal carcinomas associated with familial polyposis have been reported sporadically. However, this is the only known patient who successfully underwent a pancreaticoduodenectomy (Whipple procedure) and a total gastrectomy in addition to a previous total proctocolectomy.

Analysis of peripheral blood lymphocyte cell surface density of functional and activation associated markers in young and old hemodialysis patients.

Aging has been associated with specific shifts in various peripheral blood immune competent cell subsets. As part of pre-transplant immune profile evaluation possible parallel age-related changes in mean T-cell surface density of several cluster differentiation and activation linked antigens were into 2 groups: group 1-114 patients 40 years old or younger and group 2-36 patients 55 years old or older. Peripheral blood CD3+, DR+, CD3+DR+, CD4+, CD4+DR+, CD8+, CD8+DR+, CD56+, CD8+CD56+, CD3+IL-2-R+ and CD3+TR+ (interleukin-2 and transferrin receptors bearing CD3+ cells respectively), all mononuclear cells expressing IL-2-R and TR, and CD4+CD45+ cell subsets were analyzed and enumerated by 2-color flow cytometry. Subset relative levels as well as absolute counts were recorded. Cell surface density computation was performed using a computerized mathematical model based on fluorescence intensity vector analysis and cell size score determination based on light scatter pattern from raw data obtained by flow cytometry studies. Younger age was significantly associated with higher absolute cell count of CD3+ (p < 0.001), DR+ (p < 0.05), CD4+ (p < 0.01), CD8+ (p < 0.005), CD3+IL-2-R+ (p < 0.05), CD3+TR+ (p < 0.03) and IL-2-R+ (p < 0.05). Older patients had a slightly higher mean absolute count of CD4+CD45+ subset (p not significant) and significantly higher mean count for CD8+CD56+ cell subset (p < 0.001). When cell subset levels were compared between the 2 groups as the relative fraction of cells expressing a given marker out of all mononuclear cells gated out by flow cytometry, younger age was significantly associated with higher levels of CD3+ (p < 0.005), CD8+ (p < 0.001), CD4+DR+ (p < 0.004), CD3-TR+ (p < 0.05) and CD8+IL-2-R+ (p < 0.05). In contrast, slightly higher subset levels of CD56+ (p not significant), and significantly elevated levels of CD8+CD56+ (p < 0.0019) and CD4+CD45+ (p < 0.004) were observed in the older patients. Cell surface density analysis showed that younger patients had higher mean density per cell of CD3 (p < 0.05), CD8 (p < 0.001), IL-2-R on CD3+ cells (p < 0.05) and TR on CD3+ cells (p < 0.05). Mean cell surface density of CD56 on all CD56+ cells as well as on CD8+ cells was higher in older individuals (p < 0.001 and p < 0.003, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Non-autonomy of parathyroid hormone secretion in acute primary hyperparathyroidism.

A patient with acute primary hyperparathyroidism treated with mithramycin preoperatively, underwent neck exploration and two enlarged parathyroid glands were excised: one huge adenoma (6g) and another smaller gland. Mithramycin was administered preoperatively to lower life-threatening hypercalcaemia, and parathyroid slices from the huge adenoma removed at surgery were submitted in vitro to various calcium concentrations in the media to determine the influence of calcium on parathyroid adenoma secretory pattern in acute primary hyperparathyroidism. Mithramycin induced a significant decline in calcium levels and significant elevations of calciotrophic hormones (intact PTH, mid-region specific PTH, calcitonin and calcitriol). Significant suppression in PTH output in vitro was achieved by increasing calcium levels in the media. These results exclude autonomous PTH secretion (non-calcium dependent) as a possible aetiology of acute primary hyperparathyroidism. We suggest that a sudden increase in the set-point of the diseased parathyroid cells in the presence of a huge cell mass accounts, in large part, for both the marked hypercalcaemia and elevated PTH levels in this patient.

The role of circulating N-terminal parathyroid hormone fragments in the early postparathyroid adenomectomy period.

Calcium metabolism and hormonal control after parathyroid adenomectomy are poorly understood. During the first postoperative hours, biologically active intact parathyroid hormone (PTH) (hPTH 1-84) levels are subnormal and, in spite of down-regulation of PTH peripheral receptors (caused by hypercalcemia before surgery), total and ionized calcium concentrations are maintained in the normal range. Serum samples from 20 patients with primary hyperparathyroidism were collected in the immediate preoperative period and 4 and 48 hours after excision of one parathyroid adenoma. Total and ionized calcium, intact (iPTH), midregion (mrPTH) specific PTH (hPTH 53-68), and N-terminal PTH (N-PTH) serum concentrations were determined. Levels of N-PTH were obtained with a radioimmunoassay by a modified reverse immunoextraction procedure that measures N-PTH fragments after exclusion of the interfering iPTH. No significant correlation was found between ionized and total calcium, mrPTH, and iPTH. However, total and ionized calcium levels correlated well with N-PTH (r = 0.9999, p = 0.0054, and r = 0.9993, and p = 0.0226, respectively). The data suggest that the relatively moderate decrease in calcium levels, in spite of marked decrease in circulating iPTH during the first postoperative hours, may be attributable to the minimal decrease of the bioactive N-PTH epitope concentrations. We would hypothesize that hPTH (1-34) fragments may play a significant role in regulating serum calcium levels in the early postoperative period.

Radiation associated malignant pleural mesothelioma.

Malignant pleural mesothelioma of epithelial type developed in a 24 year old woman, 20 years after radiotherapy for Hodgkin's disease. This case and a review of published cases indicate that radiation may induce malignant mesothelioma.