Cystic lymphangioma of the pancreas: anatomoclinical, diagnostic and therapeutic considerations regarding three personal observations and review of the literature.

Cystic lymphangioma is a very rare pathology and the pancreatic ones represent an exceptional report that must be considered in the differential diagnosis with others and more frequent cystic lesions of the pancreas. In this paper we describe three cases of cystic lymphangiomas of the pancreas observed in our Institute and we report on the literature review. Anatomopathological, clinical and therapeutics aspects of pancreatic cystic lymphangioma were analyzed for a better knowledge of this cystic lesion and to recognize some specific findings that could allow a preoperative diagnosis and, subsequently, a proper treatment.

Do early symptoms of pancreatic cancer exist that can allow an earlier diagnosis?

Diagnosis of pancreatic cancer is made late, and prognosis remains extremely poor. This study was carried out to investigate whether symptoms exist before pain or jaundice that could suggest pancreatic cancer and favor earlier diagnosis. The study involved 305 patients with confirmed pancreatic cancer and 305 controls. All subjects were interviewed personally at least twice about their clinical history; pancreatic cancer patients were asked about any disturbances before abdominal pain or jaundice. Of the 305 pancreatic cancer patients, 151 (49.5%) had some prior disturbances, 108 (35.4%) 6 months or less before pain or jaundice and 43 (14.1%) more than 6 months before. Among the latter, 14 (4.6% of all patients) had had anorexia and/or early satiety and/or asthenia (7-20 months before pain or jaundice), 11 (3.6%) had disgust for coffee and/or smoking and/or wine (7-20 months before), 14 (4.6%) had diabetes (7-24 months before), and four (1.3%) had acute pancreatitis (8-26 months before). Among the controls, the only reports of these symptoms were two (0.7%) cases of asthenia (4 and 6 years earlier), 22 (7.2%) cases of diabetes (of which only two [0.7%] were diagnosed 7-24 months before the interview), and one (0.33%) case of acute pancreatitis (10 years earlier). Apart from acute pancreatitis, all the other differences between patients and controls were statistically significant. In approximately 15% of patients, disturbances existed more than 6 months before pain or jaundice, which, although not specific, could raise suspicion of the possibility of pancreatic cancer. These disturbances could represent the one current opportunity for an earlier diagnosis in a significant minority of pancreatic cancer patients.

Clone heterogeneity in diploid and aneuploid breast carcinomas as detected by FISH.

We investigated the relationship between DNA ploidy and alterations in chromosomes 1, 8, 12, 16, 17, and 18 in 63 breast carcinoma samples by static cytofluorometry and fluorescence in situ hybridization. Thirty specimens were diploid and 33 were aneuploid. In aneuploid samples, the DNA index value ranged from 1.3 to 3.1, with a main peak near tetraploid values. Diploid clones were present in 21 of 33 aneuploid specimens. Fluorescence in situ hybridization analysis showed a heterogeneous degree of alterations in diploid specimens: one sample was normal, 16 samples had one to three chromosome alterations involving mostly chromosomes 1, 16, and 17, and 13 samples an even higher degree of alterations. The 33 aneuploid specimens showed a very high number of signals (four, five, or more). All the investigated chromosomes were affected in 23 of 33 specimens. Alterations in chromosomes 1 and 17 were detected to a similar percentage in diploid and aneuploid samples, whereas chromosome 16 monosomy was more frequent in diploid samples. Overrepresentation of chromosomes 8, 12, 16, and 18 was significantly higher in aneuploid than in diploid samples. Based on these results, we suggest that diploid and aneuploid breast carcinomas are genetically related. Chromosome 1 and 17 alterations and chromosome 16 monosomy are early changes. Allelic and chromosomal accumulations occur during progression of breast carcinoma by different mechanisms. The high clone heterogeneity found in 17 of 33 aneuploid samples could not be completely explained by endoreduplication and led to the suggestion that chromosomal instability concurs with aneuploidy development. This different evolutionary pathway might be clinically relevant because clone heterogeneity might cause metastasis development and resistance to therapy.

Quantitative p21(waf-1)/p53 immunohistochemical analysis defines groups of primary invasive breast carcinomas with different prognostic indicators.

We used image cytometry to quantify the immunohistochemical expression of p21(waf-1) and p53 in primary breast carcinoma. Ratio analysis of the quantified p53/p21(waf-1) protein expression allowed us to define 3 groups of carcinomas, each characterized by specific pathological and biological profiles. The negative (NEG) group, characterized by negligible expression of both proteins, comprised small-sized, low-grade tumors associated with high contents of hormonal receptors and low growth fraction. In the NEG group, Ki-67 labelling index area (%LIa) was the only significant prognostic indicator. The P53H group, characterized by prevalence of p53 %LIa, was constituted by large-sized, high-grade tumors showing low hormonal receptor contents and high growth fraction. In the P53H group, both p53 and Ki-67 were inversely associated with both estrogen receptor (ER) and progesterone receptor (PGR), suggesting that extensive p53 immunostaining is related to poor differentiation and high proliferation. Only N status was prognostically significant in the P53H group. The P21H group, characterized by prevalence of p21(waf-1) %LIa, displayed intermediate pathological and biological features. A significant association between p53 and p21(waf-1) expression suggested functional stabilization of wtp53 and therefore possible DNA damage-dependent G1/S arrest (genetic instability) in the P21H group; P21(waf-1)expression was significantly associated with the presence of node metastasis. Patients in the P21H group had a higher recurrence rate and a shorter disease-free time interval from surgery with respect to the NEG group. Proportional hazard regression analysis disclosed Ki-67 %LIa and, to a lesser degree, PGR %LIa as significant relapse-free survival prognostic indicators.

Beta-galactoside alpha2,6 sialyltransferase in human colon cancer: contribution of multiple transcripts to regulation of enzyme activity and reactivity with Sambucus nigra agglutinin.

Colon cancer tissues display an increased activity of beta-galactoside alpha2,6 sialyltransferase (ST6Gal.I) and an increased reactivity with the lectin from Sambucus nigra (SNA), specific for alpha2,6-sialyl-linkages. Experimental and clinical studies indicate a contribution of these alterations to tumor progression, but their molecular bases are largely unknown. In many tissues, ST6Gal.I is transcriptionally regulated through the usage of different promoters that originate mRNAs diverging in the 5;-untranslated regions. RT-PCR analysis of 14 carcinoma samples, all expressing an increased ST6Gal.I enzyme activity, and of the corresponding normal mucosa revealed the presence of at least 2 transcripts. One, containing the 5;-untranslated exons, Y+Z, is thought to represent the "housekeeping" expression, and another previously described in hepatic tissues. Both the Y+Z and the hepatic transcripts were detectable in normal and cancer tissues but that latter form had a marked tendency to accumulate in cancer. The extent of alpha2,6-sialylation of glycoconjugates, as determined by SNA-dot blot analysis, was markedly enhanced in all cancer specimens, but the level of reactivity only partially correlated with the level of enzyme expression. Western blot analysis revealed a strikingly heterogeneous pattern of SNA reactivity among cancer tissues. These data indicate that: i) during neoplastic transformation of colonic cells, ST6Gal.I expression may be modulated through a differential promoter usage; ii) the extent of alpha2,6-sialylation of cancer cell membranes is not a direct function of the ST6Gal.I activity, strongly suggesting the existence of other, more complex mechanisms of regulation.

[Intraoperative echography in biliopancreatic surgery]. / L'ecografia intraoperatoria nella chirurgia bilio-pancreatica.

Intraoperative sonography (I.O.S.) with the use of high-frequency probes placed in direct contact with structures in exploration assures a more diagnostic accuracy. I.O.S. is particularly useful in bilio-pancreatic surgery for a more precise diagnostic valuation and an excellent surgical approach. It is fundamental in the lithiasis of the biliary duct, especially hepatic lithiasis, microlithiasis, obstruction of common bile duct of uncertain cause and during laparocholecystectomy. In pancreatic surgery I.O.S. is of great usefulness in the study of acute and chronic pancreatitis and their complications, cysts, pseudocysts and cystic tumors. I.O.S. plays important role both in exocrine pancreatic carcinomas for a correct staging, and resectability decision, and in endocrine functioning tumors, permitting the location of some lesions of little dimension and eventual hormone secreting hepatic or lymph nodal metastases. In laparoscopic mini-invasive surgery, I.O.S. substitutes the palpatory sense of touch in the location and study of anatomic structures, reducing the risks of iatrogenic lesions and allowing, diagnostic accuracy even in some underestimated pathologies.

Treatment of metastatic glucagonoma to the liver: case report and literature review.

Glucagonoma, a rare neuroendocrine pancreatic tumour, is frequently malignant and often accompanied by hepatic metastases. Our aim was to consider the different treatments of metastatic glucagonoma to the liver and their results. A case of glucagonoma with metachronous, small, multiple and bilobar liver metastases is reported. Combined treatment with octreotide and hepatic arterial chemoembolization was applied with good results in terms of symptom relief, plasma glucagon levels and regression of hepatic metastases. Survival rates were also improved. Based on our experience, glucagonoma with metachronous, multiple, diffuse and bilobar hepatic metastases should be treated with octreotide plus hepatic arterial chemoembolization with improved outcome and prognosis.

c-erbB-2 over-expression in amplified and non-amplified breast carcinoma samples.

We investigated c-erbB-2 oncogene amplification and over-expression in 79 invasive breast carcinoma samples using fluorescence in situ hybridization (FISH) and immunohistochemistry, with the aim of studying relationships between neoplasms over-expressing c-erbB-2 with or without amplification and bio-pathological parameters used in clinical breast cancer. Nineteen samples showed amplification, and all of these were positive by immuno-histochemistry. Moderate or intense immunostaining was present in a further 22 samples without c-erbB-2 amplification and was not related to any increased number of c-erbB-2 signals: 15 samples exhibited chromosome 17 polysomy, 3 monosomy and 4 no FISH abnormalities. Thirty-eight samples were immunonegative: 18 exhibited chromosome 17 polysomy, 9 monosomy and 11 no alterations. Samples having c-erbB-2 over-expression associated with amplification showed DNA aneuploidy and hormonal receptor loss to a greater extent than those expressing c-erbB-2 without amplification or immunonegative samples (chi2 test, p = 0.007, 0.008 and 0.008, respectively). The proliferation rate, detected by Ag-NOR staining, was highest in amplified samples (Kruskal Wallis test, p = 0.009). Our results indicate that tumours showing both c-erbB-2 over-expression and amplification exhibit more aggressive biological characteristics than those with only over-expression or immunonegative tumours. Since both c-erbB-2 amplification and over-expression have been related to negative responses to chemotherapy and poor prognosis, these differences might have clinical implications. The combination of FISH and immuno-histochemistry may be helpful to achieve this aim.

Immunohistochemical expression of internal and external ErbB-2 domains in invasive breast cancer.

We tested three ErbB-2 monoclonal antibodies (MoAbs) specific to the intracytoplasmic internal domain (clone CB 11) and the extracellular glycosylated peptide domain (clones CBE1 and Tab250) in 351 primary invasive breast carcinomas. ErbB-2 immunodetection allowed us to differentiate three main groups: group 1 (62.7%) lacked both MoAb ErbB-2 domains (erb -/-); group 2 stained for both domains (erb +/+) (26.5%); group 3 stained for the internal domain only (erb +/-) (10.8%). The relationships among these groups and nodal status (N) were statistically significant, with N+ cases reaching the highest value (89.2%) in the erb +/- group. Lack of immunostaining in the external domain thus seems to be associated with increased metastatic spread. At variance analysis the difference in hormonal receptor content between groups 1 and 3 was not significant; while between groups 1 and 2 it was. The growth fraction of groups 2 and 3 was significantly higher than that of group 1. Our results showed that anti-ErbB-2 MoAb clone CB 11 was able to detect a higher number of ErbB-2 expressing cases than the two that are specific for the external domain (clones Tab 250 and CBE1). Due to the strong association between group 3 cases and the highest metastatic potential, this aggressive group could be identified only with the use of an internal-domain specific MoAb CB 11, which thus seems to present a better discriminative power as a diagnostic marker in the biopathological characterization of breast carcinoma.

[Role of spiral computerized tomography in the staging of pancreatic carcinoma]. / Ruolo della Tomografia Computerizzata spirale nella stadiazione del carcinoma pancreatico.

INTRODUCTION: Few pancreatic carcinomas (5-22%) are resectable at the time of diagnosis because this lesion is seldom diagnosed in an early stage. Unresectability is mainly due to the presence of metastases to the liver, peritoneum and lymph nodes and to tumor spread especially to the portal mesenteric trunk where it can invade, compress, reduce, or occlude the vessels. We investigated the diagnostic yield of multiplanar and 3D spiral CT in the assessment of pancreatic carcinoma resectability. MATERIAL AND METHODS: Twenty-seven patients with histologically confirmed pancreatic head cancer were submitted to spiral CT and color Doppler US in the Surgical Clinic I of the Bologna University. The examination results were correlated with the intraoperative findings of careful inspection and palpation and of US studies of the pancreatic mass and adjacent structures. The tumors were classified in relation to some CT parameters: tumor size (T), infiltration of the stomach (S) and/or duodenum, lymph nodes (N) or distant (M) metastases, involvement of vascular structures (V), particularly of portal or superior mesenteric vein, or superior mesenteric artery. Five grades of vascular involvement were considered. The results of these techniques were correlated with intraoperative findings from careful inspection and palpation and with US studies of the pancreatic mass and adjacent structures. RESULTS: Spiral CT revealed vascular involvement in 19 of 27 cases (70.4%): involvement of portal and superior mesenteric vein was found in 14 (73.6%), superior mesenteric vein was involved in 2 (10.6%), the portal vein in one (2%) and, finally the portal, superior mesenteric vein and superior mesenteric artery in 2 cases (10.6%). The spiral CT results were confirmed intraoperatively in 26 of 27 cases (96.3%); spiral CT did not reveal hepatic metastasis only in one case. Spiral CT with multiplanar reconstructions had very high specificity and sensitivity (100%) in the assessment of vascular involvement, while color Doppler US had the same specificity but lower sensitivity (84.2%). Spiral CT was less sensitive (80%) in the detection of liver metastases. CONCLUSIONS: We believe that spiral CT is currently the best technique for pancreatic carcinoma staging, providing useful information for correct surgical planning.

Role of color Doppler ultrasonography in the preoperative staging of pancreatic cancer.

We describe our experience with color Doppler ultrasonography (CDU) in the preoperative staging of pancreatic cancer and, particularly, in detecting the involvement of the portal-mesenteric trunk (PMT). Of the 54 patients studied, 43 (79.6%) underwent surgery and 11 (20.4%) did not because of evident infiltration of the PMT. Of the 43 patients operated on, the CDU study was normal in 8 cases (18.6%), abnormal in 33 (76.7%), and not possible in the remaining 2 cases (4.7%). Results of the CDU were confirmed intraoperatively in 39 cases (diagnostic accuracy, 95.1%). In only two cases (4.9%) did the CDU not show involvement of the PMT, which was, instead, demonstrated by intraoperative ultrasonography (false negatives). Of the 11 nonoperated patients, all showed morphological alterations at CDU, while only 7 showed hematic flow changes. The sensitivity of CDU was 94.2% and the specificity 100%. The positive predictive value was 100%; the negative predictive value, 75%. The results indicate that CDU may be the first imaging technique for preoperative assessment of PMT involvement in pancreatic cancer.

Retinoblastoma (RB1) gene product expression in breast carcinoma. Correlation with Ki-67 growth fraction and biopathological profile.

AIMS: To investigate the expression of retinoblastoma protein (pRb) in invasive breast tumours and compare its expression with the major biopathological prognostic indicators to identify more aggressive subgroups. MATERIAL: Archival paraffin embedded tissues from 153 consecutive primary breast carcinomas. METHODS: pRb, Ki-67, and oestrogen receptor/progesterone receptor proteins were identified by immunohistochemistry and score values were recorded by image cytometric analysis; p53 and EGFr expression was also evaluated. RESULTS: pRb scores correlated strongly with proliferation activity as determined by Ki-67 staining. Positive relations were also observed between pRb scores, tumour size, nuclear and histological grade, and oestrogen receptor/progesterone receptor content, while abnormal p53 accumulation was not associated with pRb expression. Among the high proliferating carcinomas it was possible to identify 13 cases with loss of pRb expression. CONCLUSIONS: pRb expression paralleled proliferative activity in the majority of breast carcinomas examined, suggesting that in these cases the protein behaves normally in regulating the cell cycle. Conversely in cases with loss of pRb immunostaining, the combined expression of specific highly aggressive factors (EGFr and p53 expression, oestrogen receptor/progesterone receptor negative status, and high K67) seems to characterise a more aggressive phenotype showing growth advantage and cellular "progression" rather than significant nodal involvement.

Late stage congestive gastropathy.

Gastric mucosal abnormalities resulting from portal hypertension are defined as "congestive gastropathy". A case of congestive gastropathy with unusual features, in a 63 year old man with a history of excessive alcohol intake and cirrhosis, is described. The patient underwent a subtotal gastrectomy because of profuse bleeding from a gastric ulcer, providing a large surgical specimen for examination. Unusual gross and histological findings included prominent arterial intimal hyperplasia, and diffuse duplication and focal fragmentation of the internal lamina elastica. The differential diagnosis of this condition includes primary angiodysplastic gastropathy such as Dieulafoy's disease. The similarity with Dieulafoy-like angiodysplasia emphasises that clear cut criteria to define gastric vascular lesions do not yet exist.

The role of ultrasound in the differential diagnosis of serous and mucinous cystic tumours of the pancreas.

OBJECTIVE: To evaluate the usefulness of a series of ultrasound parameters in the differential diagnosis between serous and mucinous forms of cystic tumours of the pancreas. SETTING: Retrospective comparative study between the histological analysis of surgical specimens from cystic tumours of the pancreas (4 serous cystadenomas, 6 mucinous cystadenomas and 11 mucinous cystadenocarcinomas) and ultrasound evaluation. METHODS: The ultrasound images of the 21 tumours were analysed by an operator who did not know the result of the histological diagnosis and were divided according to Johnson's criteria (number of cysts > 6 and diameter < 2 cm for serous tumours; number of cysts <6 and diameter >2cm for mucinous tumours) and according to other anatomicopathological parameters such as the presence of septae, endocystic projections, central scar, central calcification and/or in the tumour wall. RESULTS: The ultrasound study gave a correct diagnosis in two out of the four (50%) serous cystic tumours. A central scar and internal calcification was present in one of them. Fifteen (88.2%) of the 17 mucinous tumours were correctly diagnosed; one presented peripheral calcifications and three endocystic projections. CONCLUSION: Ultrasound has a high degree of sensitivity in the differential diagnosis of serous and mucinous cystic tumours of the pancreas if the ultrasound aspects corresponding to the anatomicopathological structure of the neoplasms are correctly evaluated.

Macrocystic serous cystadenoma of the pancreas. Diagnostic, therapeutic and pathological considerations of three cases.

BACKGROUND: Macrocystic serous cystadenoma (MSC) of the pancreas is a new entity that has recently been well recognised. This tumour is quite similar in aspect to the mucinous cystic tumours (MCT) but its prognosis is much better, so that a correct diagnosis before surgery is important. PATIENTS: Three patients undergoing surgery in the 1st Surgical Clinic of the University of Bologna for suspected cystic lesions were found to have macrocystic serous cystadenoma (MSC) of the pancreas. In two cases a biopsy was performed during surgery, but in only one was a correct diagnosis of MSC made; in the other the diagnosis was lymphangioma. In the remaining case a biopsy was not performed because the high 19/9 CA level in the blood suggested a diagnosis of MCT of the pancreas. In all 3 cases the tumour was successfully removed by surgery. CONCLUSIONS: Macrocystic serous cystadenoma (MSC) of the pancreas represents a variant of the serous cystic tumors, which encompass microcystic adenoma and serous cystadenocarcinoma. MSC must be distinguished from MCT because it exhibits a different biological pattern and requires a different surgical approach. Therefore, we would underline the importance of a biopsy in making the differential diagnosis.

Role of reoperation in recurrence of adrenal cortical carcinoma: results from 188 cases collected in the Italian National Registry for Adrenal Cortical Carcinoma.

BACKGROUND: Recurrence of adrenal cortical carcinoma (ACC) after radical surgery is a common finding. Although successful reoperations have been reported with encouraging results, most published experiences are anecdotal and based on few cases. We report the results of surgical treatment for recurrent ACC in a multiinstitutional series. METHODS: One hundred eighty-eight cases of ACC were collected in a national registry. A complete follow-up was obtained in 179 cases. At initial diagnosis 92 patients had local disease (stage I or II). One hundred seventy patients underwent surgical treatment, considered radical in 140; in this group, recurrent disease was observed in 52 cases (37%) after a mean disease-free interval of 21.7 months. RESULTS: Adjuvant chemotherapy was ineffective in ameliorating the prognosis. The mean survival in 20 patients who underwent reoperation was significantly higher (15.85 +/- 14.9 months) than in nonreoperated cases (3.2 +/- 2.9 months). Five-year actuarial survival in reoperated patients is significantly better than in nonreoperated patients (49.7% versus 8.3%, respectively). CONCLUSIONS: Although the prognosis of this tumor is still poor, surgery is the only effective therapy; reoperation allows survival comparable to that observed in patients without recurrent disease. An aggressive strategy for recurrent ACC is advisable until prospective studies demonstrate a real effectiveness for chemotherapy.

Gastrointestinal autonomic nerve tumor of the jejunum. Case report and review of the literature.

Gastrointestinal autonomic nerve tumor is very rare and it is difficult to distinguish this tumor from other gastrointestinal tumors due to the absence of clinical, instrumental and macroscopic features which allow pre- or intraoperative diagnosis. Our aim was to recognize the characteristic features (preoperative, intraoperative, pathological) that would allow diagnosis of gastrointestinal autonomic nerve tumor. A case of gastrointestinal autonomic nerve tumor of the jejunum is reported. Surgical specimen was routinely processed. Immunohistochemical staining was performed according to modified immunoperoxidase Avidin-Biotin-Peroxidase Complex method. An electron microscopy study was also performed. The tumor mass showed some characteristic pathological findings: histologically, it was composed of spindle cells and epithelioid cells; immunohistochemically, a focal positivity for Neuron Specific Enolase was shown, and finally, ultrastructural examination showed neuron-like cells with long cytoplasmic processes containing microtubules and bulbouns synapse-like structures with dense core neurosecretory-type granules. Preoperatively gastrointestinal autonomic nerve tumor of the jejunum must be considered and treated as a malignant tumor. A correct diagnosis is possible only with immunohistochemical and ultrastructural studies. It is probable that this tumor is more common than previously thought.