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Metastatic adenocarcinoma of an unknown primary site. A comparison of the relative contributions of morphology, minimal essential clinical data and CEA immunostaining status.

Measurement of the relative contributions of morphology alone; minimal essential clinical data; immunohistologic reactivity of a prototypic tumor marker, carcinoembryonic antigen (CEA); and the process by which a pathologist can identify the origin of a metastatic adenocarcinoma of unknown primary site is the subject of this report. To standardize the case material, we used an image digitizing and archival system to present 100 metastatic adenocarcinomas of known primary site as unknowns to two pathologists. The images were selected to show only gland-forming areas of the carcinomas and excluded all normal tissue elements. They were viewed, initially without, and then with, identification of gender and metastatic site. Subsequently, the results of immunoperoxidase staining for CEA, assessed independently by a third pathologist, were provided. Our analysis showed that, overall, the correct primary site was chosen as choice 1, 2, or 3 in 72% and 76%, and as choice 1 in 49% and 47% of cases, respectively. Accuracy was highest for prostatic, ovarian, and breast carcinomas, and lowest for upper-gastrointestinal tract, biliary tract, and pancreatic adenocarcinoma. Statistical analysis showed the largest increments in accuracy in the choice 1 prediction in each tumor category were achieved by provision of minimal essential clinical data. Knowledge of CEA status did not affect overall accuracy; however, it increased the odds of making the correct diagnosis for ovarian, colorectal, and endometrial (both pathologists) carcinomas, and for prostatic, pulmonary and esophago-gastric adenocarcinomas (one pathologist). The study exemplifies a model for the objective measurement of the contribution of ancillary studies, such as immunoperoxidase markers, to the accuracy of pathologic diagnosis.

Adenocarcinoma↗

Histologic growth patterns of metastatic carcinomas of the liver.

One hundred autopsied livers containing metastatic cancers were studied pathologically. Macroscopically, the cancers were of the multinodular type in 65.0% of cases, massive type in 17.0% and portal tract type in 8.0%. Among liver metastases from colon and lung cancers, most cases showed predominantly intraparenchymal growth (92.3% and 87.5%, respectively). In contrast, among liver metastases from gallbladder/bile duct cancer, intraparenchymal growth was less frequent (35.7%). With regard to the histologic growth pattern at the boundary of the liver metastases, in micrometastases less than 1 mm in diameter a replacement growth pattern was predominant among metastases from lung, colon and pancreas cancers (69.7%, 79.3% and 66.7%, respectively), whereas a sinusoidal growth pattern was predominant in those from gastric and gallbladder/bile duct cancers (48.5% and 66.7%). Among macrometastases of the liver over 20 mm in diameter, an expansive growth pattern was predominant, irrespective of the cancer primary site. Thus metastatic liver cancers showed changes in growth patterns according to the size of the metastatic tumors.

Aged↗

CT findings in palpable lesions of the anterior abdominal wall.

Computed tomographic findings are reviewed in 25 patients with a palpable mass in the anterior abdominal wall. Computed tomography allowed a specific diagnosis when the mass was due to a hernia and hematoma. In the other cases a specific diagnosis could not be made but CT allowed a detailed evaluation of the extent of the disease.

Abdominal Muscles↗

Percutaneous biliary metal wall stenting in malignant obstructive jaundice.

BACKGROUND: Most patients with advanced stage malignant obstructive jaundice will be suitable for palliation only. Metallic stents are safe, effective and minimally invasive. DESIGN: A review of case notes of patients who had Wallstents inserted percutaneously from January 1996 to December 2000. RESULTS: Eighty-nine patients with a median age of 72 years underwent percutaneous insertion of biliary metal stents. The diagnoses were cholangiocarcinoma (41.5%), pancreatic carcinoma (40.5%), nodal metastases at the porta hepatis (14.6%) and gall bladder cancer (3.4%). Ninety-six per cent of patients improved their hyperbilirubinaemia to normal levels by 1 month. The median post-procedure hospital stay was 16 days. Early overall complications (within 30 days of stenting) occurred in 30% of patients (70% of these were disease related). The 30 day mortality rate was 20% (n = 18). Fifty (70%) patients were readmitted to hospital, most commonly because of carcinomatosis (16) or stent obstruction (12). The symptom-free period ranged from 2 weeks to 13 months. Median survival for all patients was 3.5 months. Survival correlated inversely with serum bilirubin at presentation (r = -0.34, P = 0.001), but not with other liver function tests. DISCUSSION: Metal wall stenting for malignant obstructive jaundice provides good palliation with low, procedure-related morbidity and mortality, but poor overall survival from disease-related morbidity. Survival significantly correlates with pre-stenting serum bilirubin levels. There is a need to identify the subgroup of patients in whom stenting has no beneficial effect.

Aged↗

Evaluation of the reliability of chromosomal imbalances detected by combined use of universal DNA amplification and comparative genomic hybridization.

Comparative genomic hybridization (CGH) analysis of microscopic tumor samples is allowed by universal DNA amplification using degenerate oligonucleotide primed-PCR (DOP-PCR). To evaluate the reliablity of DOP-PCR CGH, we performed DOP-PCR CGH and standard CGH in parallel using DNAs extracted from 10 malignant tumors of the hepatobiliary tract and pancreas. Similar results were obtained by both methods with a few exceptions, indicating that DOP-PCR CGH provides cytogenetic information equivalent to that obtained from standard CGH. We also investigated the sensitivity of DOP-PCR CGH using sequential dilutions of DNA from microdissected tumor cells. DOP-PCR using 100 to 800 pg of template DNA yielded successful CGH results. However, less than 50 pg of template DNA was not suitable because of the small amount of generated DNA. These findings suggest that DOP-PCR CGH is applicable for CGH analysis of tiny specimens which are too small for standard CGH. Accordingly, DOP-PCR CGH analysis may become a useful method in clinical laboratory examination.

Aged↗

Case report: multiple cancers: hepatocellular carcinoma and adenocarcinomas of the common bile duct and the gall-bladder in a woman with primary biliary cirrhosis.

We present a case of primary biliary cirrhosis associated with simultaneous triple cancers: a hepatocellular carcinoma and adenocarcinomas of the common bile duct and gall-bladder. A 70 year old Japanese woman, who had been diagnosed with primary biliary cirrhosis (stage 2 by Scheuer) 15 years before, was admitted to Koseiren Kamo Hospital in a comatose state. Laboratory data were as follows: the ammonia level was high (164.0 micrograms/dL), the antimitochondrial antibody showed a 320-fold increase, a high level of alpha-fetoprotein was indicated (2677 ng/mL), hepatitis B surface antigen was negative and hepatitis C antibody by enzyme immunoassay was negative, although a test for the RNA of hepatitis C virus by polymerase chain reaction was positive (10(3.5) copies/50 microL). The patient's condition gradually worsened and the patient died of liver failure. Autopsy showed triple cancers in the liver (hepatocellular carcinoma; trabecular type, moderately differentiated), the common bile duct (well-differentiated papillary adenocarcinoma) and the gall-bladder (well-differentiated papillary adenocarcinoma) with primary biliary cirrhosis (stage 4). Primary biliary cirrhosis has been believed to be a low risk for the development of hepatocellular carcinoma, despite the high risk of extrahepatic malignancy. The simultaneous occurrence of triple cancers with primary biliary cirrhosis, to the best of our knowledge, has never been reported. The present case may provide additional evidence for a predisposition to malignancy in primary biliary cirrhosis.

Adenocarcinoma↗

Subcutaneous metastases after laparoscopic resection of malignancy.

Following the introduction and widespread acceptance of laparoscopic cholecystectomy, laparoscopic techniques have been applied to an increasing variety of general surgical procedures. Recently, laparoscopic procedures for resection of malignancy have begun to emerge, in particular laparoscopic assisted colectomy for carcinoma of the colon. In the cases reported here, metastatic tumour in the laparoscopy port sites is described as a potentially serious complication of laparoscopic procedures for resection of malignancy.

Abdominal Neoplasms↗

Synchronous carcinoma of the gall-bladder in patients with bile duct carcinoma.

One hundred and twenty-four patients with bile duct carcinoma treated during 16 years were analysed retrospectively for multiple biliary tract carcinoma. Sixty-two cases had undergone a cholecystectomy either as part of a pancreaticoduodenectomy or a bile duct resection or as part of an internal drainage procedure. Three (5%) were found to have an incidental separate carcinoma of the gall-bladder. The discontinuity between the two sites of cancer was histologically confirmed. Clinical concern was that approximately 5% of patients with bile duct carcinoma had a synchronous carcinoma of the gall-bladder. Thus, careful examination of the entire biliary tract including the gall-bladder is necessary at the time of curative surgery for bile duct carcinoma.

Adenocarcinoma↗

Nonsurgical management of ruptured pseudoaneurysm in patients with hepatobiliary pancreatic diseases.

OBJECTIVE: Rupture of a pseudoaneurysm is an unusual complication after surgical and interventional treatments in patients with hepatobiliary pancreatic diseases. However, it occurs abruptly and often results in a lethal outcome. The aim of this study was to retrospectively analyze our experiences of cases of rupture of pseudoaneurysms for providing appropriate therapeutic planning. METHODS: Between 1985 and 1998, we observed ruptures of pseudoaneurysms in 14 of 910 patients with hepatobiliary pancreatic diseases--six after pancreaticoduodenectomy, three after hepatic resection, two after hepatopancreaticoduodenectomy, two after percutaneous transhepatic biliary drainage, and one after gastrojejunostomy. Thirteen of the 14 patients underwent emergency angiography and transcatheter arterial embolization (TAE) or infusion therapies, and one of the 13 patients underwent surgical hemostasis because of incomplete hemostasis with TAE. The other patient, who did not undergo emergency angiography, had surgical hemostasis initially. RESULTS: TAE achieved hemostasis in 11 of 13 patients (85%), but only incomplete hemostasis in the remaining two patients. Of these two patients, one underwent laparotomy, but died of multiple organ failure (MOF) at 6 days after surgical hemostasis. The other died at 1 day after emergency angiography. Ten of 11 patients who obtained complete hemostasis by means of TAE could later be discharged, but one patient died of liver failure, and/or MOF. One patient who underwent laparotomy initially without angiography died of MOF at 43 days after the operation. The onset of rupture of a pseudoaneurysm was a mean of 35.4 days (range 12-76) after surgical or interventional procedures. The warning prodromal symptoms were upper abdominal oppression, nausea, and backache before the rupture of pseudoaneurysms. Fever, leukocytosis. hyperbilirubinemia, anastomotic leak, and intraabdominal abscess were frequent persistent signs in these patients. CONCLUSIONS: If the warning prodromal symptoms appear in patients along with these persistent signs, the impending rupture of pseudoaneurysms should be suspected. Thereafter, a diagnostic angiography should be performed immediately to enable early diagnosis and embolization therapy for rupture of pseudoaneurysms when hemorrhagic episodes appear in these patients. Early detection and immediate embolization might bring about a favorable outcome in patients with hepatobiliary pancreatic diseases who encounter rupture of pseudoaneurysms after surgical and interventional treatments.

Adult↗

Biliary tract cancer and occupation in Sweden.

Using the Cancer-Environment Registry, which links the incidence of cancer (1961-79) and the 1960 census data on industry and occupation for all employed individuals in Sweden, the occurrence of biliary tract cancer (ICD 7th rev 155.1-.9) was systematically assessed according to occupational and industrial classifications. Data are presented separately for cancer of the gall bladder (ICD 155.1) and other cancers of the biliary tract (ICD 155.2-.9) including cancers of the extrahepatic bile ducts, ampulla of Vater, and unspecified bile passages. Statistically significant increased risks for cancer of the gall bladder were observed for men employed in petroleum refining, papermills, chemical processing, shoemaking, and repairing, and for both men and women employed in textile work. A significant increase in the incidence of other cancers of the biliary tract (mostly cancers of the bile duct) was found for such asbestos related employment as shipbuilding and in the wholesale construction materials industry and among insulation workers. These findings should be considered only as clues to aetiological factors, although several are consistent with earlier observations from other countries.

Biliary Tract Neoplasms↗

Cell proliferation and drug resistance in hepatocellular carcinoma are modulated by Rho GTPase signals.

Hepatocellular carcinoma is highly resistant to chemotherapeutic agents, thus the need to discover effective therapeutic molecules to suppress cancer cell growth and to overcome drug resistance is urgent. The Rho GTPase is implicated in cancer and metastasis and is directly activated by the Lymphoid blast crisis (Lbc) protooncogene, a Rho guanine-nucleotide exchange factor. The aim of the study was to analyze the expression of Lbc in hepatocarcinoma and to determine the effect of Lbc-induced Rho signaling on expression, growth rate and resistance to genotoxic stress. We found, by immunohistochemical analysis of biopsy samples and Northern and Western blot analyses of cell lines, that Lbc is absent in normal adult liver but is abundantly expressed in hepatocarcinoma, implying an increased Rho pathway signaling. Lbc stably transfected hepatocarcinoma cells exhibit increased proliferation and levels of ERK and cyclin D1 activation, which are blocked by a Rho inhibitor. In contrast, AKT activation was not altered. Moreover, Lbc expression confers increased resistance to genotoxic stress induced by doxorubicin, which is associated with upregulation of Bcl-2 and BAD phosphorylation, and this is reversed by a Rho inhibitor. In conclusion, these data support a role for Rho in liver cancer progression and resistance to therapy and may provide a basis for developing effective treatment for hepatocarcinoma.

A Kinase Anchor Proteins↗

Biliary tract malignancy and chronic inflammation from the perspective of pancreaticobiliary maljunction.

This is a brief review of pancreaticobiliary maljunction. The basic treatment for this condition includes either cholecystectomy or extrahepatic bile duct resection. When the condition is accompanied by malignancies, a radical operation should be the first treatment option. Knowledge on molecular pathogenesis is gradually increasing. However, studies should be expanded to include larger patient cohorts, and other types of molecules should be carefully investigated and analyzed.

Bile Duct Diseases↗

Ki-ras mutations as a prognostic factor in extrahepatic bile system cancer. PANK-ras I Project Investigators.

PURPOSE: To assess the prevalence and prognostic significance of Ki-ras codon 12 mutations in extrahepatic biliary system cancer (EBSC). PATIENTS AND METHODS: Patients diagnosed with EBSC between 1980 and 1990 (N = 111) were selected from two hospitals. DNA was amplified from paraffin-embedded tissues and mutations in codon 12 of Ki-ras were detected using the artificial restriction fragment-length polymorphism (RFLP) technique. RESULTS: Tissue was available from 68.5% of patients. The prevalence of mutations was 41%. There was no association between mutations and clinical and pathologic characteristics; however, mutations in Ki-ras were associated with survival, with a median survival duration of 7.7 months for patients with wild-type Ki-ras and 1.7 months for patients with mutated tumors (hazards ratio [HR] = 1.67; P = .075). Among patients with stage I to II tumors, the chance of dying of patients with the mutation was 7.8 times higher than that of patients without the mutation (P = .087); the corresponding HR for patients with stage III to IV disease was 2.9 (P = .003). After adjusting for age, tumor site, histology, differentiation, and stage, the HR for Ki-ras mutations was 2.12 (P = .026). CONCLUSION: Ki-ras codon 12 mutations are an independent prognostic indicator in patients with EBSC. Mutation detection may be of help in the management of these patients.

Adenocarcinoma↗

Metastatic seeding along the small bowel mesentery. Roentgen features.

1. Intra-abdominal malignant seeding along the small bowel mesentery is roentgenologically identifiable. 2. The anatomic features of the small bowel mesentery and the pathways of flow of ascitic fluid along its peritoneal recesses determine the depostion and growth of seeded metastases. 3. Seeded deposits lodge particularly within the lower recesses of the small bowel mesentery and are reflected by typical changes involving distal ileal loops or the cecum. 4. These are characterized by (a) palisading, arcuate scalloped deflections or gross mass displacement of distal small bowel loops in the right lower quadrant, or (b) extrinsic indentations upon the medial and inferior contours of the cecum. Associated desmoplastic reaction may result in tethering of mucosal folds and angulated fixation of bowel loops.

Adenocarcinoma, Mucinous↗