Transhepatic intravascular ultrasound for evaluation of portal venous involvement in patients with cancer of the pancreatic head region.

The aim of this study was to evaluate the ability of intravascular ultrasound to diagnose tumor involvement of the portal and the superior mesenteric veins using the preoperative percutaneous, transhepatic approach, and to compare the findings with those made at concomitant direct portography, surgery, and histopathological examination. Ten patients with a preoperative diagnosis of a resectable tumor in the pancreatic head region were examined with percutaneous transhepatic portography (PTP) and intravascular ultrasound (IVUS). The surgeon's intraoperative evaluation and the histopathological examination in combination revealed tumor involvement of the portal or superior mesenteric veins in six of the ten patients. Percutaneous transhepatic portography suggested tumor involvement of the veins in six patients but two of the examinations were false positive and another two were false negative. Intravascular ultrasound showed signs of tumor involvement in eight patients. The examination was, however, false positive in two patients, but there were no false negatives. Complications of the percutaneous transhepatic procedure occurred in six patients including severe pain, bleeding, and related death. Percutaneous transhepatic IVUS of the portal vein may be a useful tool in the preoperative selection of the subgroup of patients with tumor of the pancreatic head region that could benefit from surgery. There is a need for technical improvement as well as studies with larger patient series to definitely decide the role of the technique.

Extensive cytogenetic heterogeneity in a benign retroperitoneal schwannoma.

A benign retroperitoneal schwannoma from a patient without prior exposure to radiotherapy or chemotherapy was analyzed by chromosome banding after short-term culture. An extensive intratumor heterogeneity in the form of 29 karyotypically related as well as unrelated clones was found. The aberrant clones were diploid or near-diploid and displayed both numerical and structural changes. All chromosomes, except 11, 16, and 20, were affected. Numerical changes included trisomies X, 7, 9, 17, and 18, and monosomies 13 and 18. No clonal loss of chromosome 22, the most characteristic abnormality in schwannomas of other locations, was, however, detected. The structural aberrations resulted in a total of 58 chromosomal breakpoints, with chromosomes 18, 1, and 15 participating in rearrangements most frequently, followed by chromosomes 14, 2, and 22. A striking finding was the clonal involvement of 18p11 in eight rearrangements affecting different chromosomes, suggesting alteration of telomeric function. The molecular mechanisms underlying the observed massive polyclonality in the schwannoma, particularly the presence of cytogenetically unrelated clones, are unknown and probably heterogeneous.

K-ras oncogene subtype mutations are associated with survival but not expression of p53, p16(INK4A), p21(WAF-1), cyclin D1, erbB-2 and erbB-3 in resected pancreatic ductal adenocarcinoma.

Previous studies of molecular prognostic markers following resection for exocrine pancreatic cancer have produced conflicting results. Our aim was to undertake a comprehensive analysis of potentially useful molecular markers in a large, multicentre patient population and to compare these markers with standard pathological prognostic variables. Formalin-fixed, paraffin-embedded specimens of pancreatic ductal adenocarcinoma were analysed from 157 patients [100 men and 57 women with a median (range) age of 60 (33-77) years] who had undergone pancreatectomy. Immunohistochemistry was used to detect expression of p16(INK4), p53, p21(WAF1), cyclin D1, erbB-2 and erbB-3. Mutations in codons 12 and 13 of the K-ras oncogene were detected by SSCP and sequencing following DNA extraction and amplification by PCR. The median (range) survival post-resection was 12.5 (3-83) months. Abnormalities of p16(INK4), p53, p21(WAF1), cyclin D1, erbB-2 and erbB-3 expression were found in 87%, 41%, 75%, 72%, 33% and 57% of cases, respectively. There was no significant correlation between expression of any of these markers and patient survival. K-ras mutations were found in 73 (75%) of 97 cases with amplifiable DNA. The presence of K-ras mutation alone did not correlate with survival, but there were significant differences in survival according to the type of K-ras mutation (p = 0.0007). Reduced survival was found in patients with GaT, cGT and GcT K-ras mutations compared to GtT, aGT and GaC mutations. In conclusion, survival was associated with type of K-ras mutation but not expression of p16(INK4), p53, p21(WAF1), cyclin D1, erbB-2 and erbB-3.

Operations for extrahepatic bile duct cancers: are the results really improving?

OBJECTIVE: To find out if our results for the treatment of extrahepatic bile duct cancer have improved we reviewed our latest patients as a comparison to a previously reported series from this department. DESIGN: Retrospective study. SETTING: Tertiary referral centre, Sweden. SUBJECTS: 102 patients who presented with extrahepatic bile duct cancer 1979-1995. MAIN OUTCOME MEASURES: Morbidity, mortality, and short and long term survival. RESULTS: 16 patients had various types of resection, which were radical in 14 according to the surgeon and in 10 according to the pathologist. One patient (6%) died in hospital, and 1 (44%) developed complications. 13 patients had other operations that did not involve resection, 23 had laparotomy alone, 61 had biliary drainage either by percutaneous transhepatic cholangiography (PTC) or endoscopy, and 10 had no active treatment. One patient of the 16 (6%) who had resections has survived for more than five years and another one is still alive after 40 months. CONCLUSION: Long term survival has not improved for patients with extrahepatic bile duct cancer in our hospital during the last decades.

Adult rhabdomyoma in fine needle aspirates. A report of two cases.

BACKGROUND: Adult rhabdomyoma (ARh) is a rare, benign tumor arising most frequently in the head and neck region and sometimes mimicking malignant tumors clinically. Correct preoperative evaluation of this tumor is of crucial importance as its treatment is complete excision only and not radical surgery. CASES: Two patients with ARh, one tumor presenting near the submandibular gland and the other in the thyroid area, are reported. The first tumor was correctly diagnosed by fine needle aspiration cytology. The second, clinically suspected to be a colloid goiter, was preoperatively diagnosed as such cytologically as well. After the tumor was excised, reexamination of the cytologic specimen disclosed follicle cells admixed with single cells from ARh; these had been interpreted as colloid fragments at the time of primary evaluation. CONCLUSION: Fine needle aspiration evaluation of ARh may be problematic due to the rarity of the tumor and to the similarity of the tumor cells to normal striated muscle and to other tumors in which cells with abundant granular cytoplasm are characteristic. With an awareness of the cytologic features of this uncommon tumor, cytopathologists can render a correct diagnosis.

Serous and mucinous cystadenoma/cystadenocarcinoma of the pancreas.

Twenty cases of cystic pancreatic neoplasms were examined over a 10-year period by the Department of Radiology, University Hospital, Lund, Sweden. Four patients had serous cystadenoma, seven had mucinous cystadenoma, and seven had mucinous cystadenocarcinoma. One patient had a mucin-producing ductal carcinoma, and one patient had a benign mucus cyst. The various types of tumor are illustrated, and the difficulty in differentiating the subtypes is stressed.

Pancreatic biopsy: why? When? How?

For final diagnosis of pancreatic cancer histologic or cytologic confirmation is needed. Tissue or cell material can be achieved by percutaneous puncture as part of the preoperative workup. During operation core-needle, incisional, and wedge biopsies or fine-needle aspiration cytology (FNAC) can be chosen. Sensitivity and diagnostic accuracy are high for both histologic and cytologic examinations, and false-positive results are exceptional, giving a specificity of 100% in most published series. The complication rate is low, also for knife biopsies in recent reports, provided biopsy of seemingly normal tissue is avoided. Percutaneous puncture is currently restricted to patients found to have advanced disease and who are not candidates for laparotomy. Microscopic confirmation is required in all patients in whom chemotherapy, radiotherapy, or both are planned. However, for attempted radical surgery per se, biopsy is not mandatory if the clinical suspicion of cancer is high and the surgical team has documented low postoperative mortality and morbidity rates.

Molecular analyses of the 15q and 18q SMAD genes in pancreatic cancer.

SMAD4 (DPC4) is part of the TGFB signaling pathway and is frequently inactivated in pancreatic carcinomas. TGFB signals from the membrane to the nucleus via SMAD proteins. TGFB receptor activation results in SMAD2 and SMAD3 phosphorylation, which then form heteromeric complexes with SMAD4. Inhibitory SMADs, SMAD6 and SMAD7, can prevent TGFB signaling by interacting either with the receptor or with SMAD2 and SMAD3. The encoding sequences for these proteins are organized in two gene clusters, one at 18q21 (SMAD2, SMAD4, and SMAD7) and the other at 15q21-22 (SMAD3 and SMAD6). Losses of 15q and 18q material are frequent in pancreatic carcinomas, and in order to map the extent of 15q and 18q deletions and to investigate further the involvement of SMAD4 and the possible function of SMAD2 and SMAD3 as tumor suppressor genes in pancreatic carcinoma, we performed loss of heterozygosity studies as well as mutation and expression analyses of SMAD4, SMAD2, and SMAD3 in 13 low-passage cell lines from 12 pancreatic carcinoma patients. To investigate possible amplifications of SMAD6 and SMAD7, the genomic organization and the expression levels of these genes were analyzed. One tumor with homozygous loss of SMAD4 was detected, and mutations of this gene were found in four of the 12 carcinomas; no SMAD2 or SMAD3 inactivating genomic alterations were found. In none of the cases was transcriptional silencing seen. No genomic amplifications, mutations, or increased expression of SMAD6 and SMAD7 were detected. These results suggest that functional abrogation of SMAD2 or SMAD3 and increased expression of SMAD6 or SMAD7 are infrequent in pancreatic carcinomas and further stress the particular importance of SMAD4 inactivation in pancreatic carcinogenesis.

Cytogenetic analysis of pancreatic carcinomas: intratumor heterogeneity and nonrandom pattern of chromosome aberrations.

Twenty-nine nonendocrine pancreatic carcinomas (20 primary tumors and nine metastases) were studied by chromosome banding after short-term culture. Acquired clonal aberrations were found in 25 tumors and a detailed analysis of these revealed extensive cytogenetic intratumor heterogeneity. Apart from six carcinomas with one clone only, 19 tumors displayed from two to 58 clones, bringing the total number of clones to 230. Karyotypically related clones, signifying evolutionary variation, were found in 16 tumors, whereas unrelated clones were present in nine, the latter finding probably reflecting a distinct pathogenetic mechanism. The cytogenetic profile of pancreatic carcinoma was characterized by multiple numerical and structural changes. In total, more than 500 abnormal chromosomes, including rings, markers, homogeneously stained regions, and double minutes, altogether displaying 608 breakpoints, were detected. This complexity and heterogeneity notwithstanding, a nonrandom karyotypic pattern can be discerned in pancreatic cancer. Chromosomes 1, 3, 6, 7, 8, 11, 12, 17, and 19 and bands 1q12, 1q21, 3q11, 6p21, 6q21, 7q11, 7q22, 7q32, 11q13, 13cen, 14cen, 17q11, 17q21, and 19q13 were most frequently involved in structural rearrangements. A total of 19 recurrent unbalanced structural changes were identified, 11 of which were not reported previously: del(1)(q11), del(3)(p11), i(3)(q10), del(4)(q25), del(11)(p13), dup(11)(q13q23), i(12)(p10), der(13;15)(q10;q10), del(18)(q12), del(18)(q21), and i(19)(q10). The main karyotypic imbalances were entire-copy losses of chromosomes 18, Y, and 21, gains of chromosomes 7, 2, and 20, partial or whole-arm losses of 1p, 3p, 6q, 8p, 9p, 15q, 17p, 18q, 19p, and 20p, and partial or whole-arm gains of 1q, 3q, 5p, 6p, 7q, 8q, 11q, 12p, 17q, 19q, and 20q. In general, the karyotypic pattern of pancreatic carcinoma fits the multistep carcinogenesis concept. The observed cytogenetic heterogeneity appears to reflect a multitude of interchangeable but oncogenetically equivalent events, and the nonrandomness of the chromosomal alterations underscores the preferential pathways involved in tumor initiation and progression.

Cytogenetic and FISH analyses of pancreatic carcinoma reveal breaks in 18q11 with consistent loss of 18q12-qter and frequent gain of 18p.

Chromosome 18 was analysed using a banding technique and fluorescence in situ hybridization (FISH) in 13 pancreatic carcinoma samples. The cytogenetic analysis revealed that chromosome 18 abnormalities were present in all cases and that several different rearrangements, such as translocations, deletions, dicentrics and ring chromosomes, were often found together. FISH mapping using 18q YAC probes showed that all tumours had lost at least one copy of 18q and that 18p was over-represented in 6 of the 13 cases. Furthermore, out of 13 identified deletion breakpoints on 18q, 11 were mapped to 18q11. The clustering of breaks close to the centromere indicates that loss of genes in bands 18q11 and 18q12, in addition to those located in 18q21, e.g. DPC4 and DCC, are important in the development of pancreatic tumours.