Staging of pancreatic cancer: suggestions for a simplified, reliable modification of the TNM classification system.
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Evaluation Studies as Topic↗
Biomedical subjects
G Serio
Publications and source records attributed to G Serio.
Spindle and giant cell carcinoma of the urinary bladder: a clinicopathological light microscopic and immunohistochemical study.
OBJECTIVE: To evaluate the cellular nature and biological behaviour of spindle and giant cell carcinoma (SGCC) of the urinary bladder. The clinicopathological, light microscopic and immunohistochemical features of seven patients are reported. PATIENTS AND METHODS: Paraffin-embedded tissue was available from each patient for microscopic and immunohistochemical studies. There were five men and two women, ranging in age from 48 to 79 years. Clinical histories and follow-up information were obtained by review of the patients' charts. The clinical outcome was compared with that of transitional cell carcinoma (TCC) and small cell carcinoma (SCC). RESULTS: The tumours were large, polypoid and frequently ulcerated. They diffusely permeated the bladder musculature or the perivesical fat. On microscopic examination five tumours were composed mainly of interlacing sheets of spindle cells and occasional giant cells; two comprised giant cells only. Foci of identifiable TCC (papillary or in situ) were present in four tumours. Immunohistochemistry demonstrated that SGCCs exhibit a phenotype indicative of an epithelial nature. CONCLUSIONS: The median survival (11 months) of the seven patients indicates that SGCCs have a poor prognosis and they are more aggressive than TCCs of the same stage. The unfavourable clinical course is similar to the rapidly fatal outcome of small cell carcinomas of the bladder. The prolonged survival periods of three patients who received additional chemotherapy suggest that this treatment may be profitable.
Aged↗
Multivariate analysis of predictive factors of multiple sclerosis course with a validated method to assess clinical events.
The clinical data of 309 patients with definite multiple sclerosis were recorded in the European data base for multiple sclerosis (EDMUS) to determine the prognostic significance of several demographic and clinical variables. An interview with closed questions structured according to standardised criteria of disease phases and courses was used to assess the clinical course. The reliability was evaluated by four trained neurologists in a sample of 33 patients with multiple sclerosis. Both the within and between rater agreement on data collection was fair to high for the historical variables (K = 0.33-1). Between rater agreement was more variable for the evaluation of 12 different EDMUS event categories (K = 0.3-0.95). The predictive model for the time to reach a secondary progression showed that an age at onset older than 25 (p = 0.006) and an event at onset followed by disability > or = 3 on the Kurtzke expanded disability status scale (EDSS; p = 0.004) were the most unfavourable clinical variables in 249 patients with relapsing remitting (180) or relapsing progressive (69) courses. In the 69 patients with relapsing progressive disease, the time to reach severe disability (EDSS > or = 6) was negatively influenced by a first interval between attacks shorter than one year, a number of bouts with EDSS > 2 in the first two years of the disease, and involvement of the pyramidal system at onset (p < 0.05). In 60 patients with chronic progressive disease this outcome was negatively influenced by pyramidal, brainstem, and sensory involvement at onset (p < 0.01).
Adult↗
ras-family gene mutations in neoplasia of the ampulla of Vater.
Mutations in the first and second exons of Ha-, Ki- and N-ras oncogenes were investigated in 17 epithelial tumors of the ampulla of Vater by single-strand conformation polymorphism analysis and direct sequencing of DNA fragments amplified by polymerase chain reaction. The panel included 12 intestinal-type adenocarcinomas, 3 villous adenomas, 1 papillary carcinoma and 1 neuroendocrine carcinoma. Six cases (35%) contained ras mutations, affecting codon 12 of Ki-ras in 2 adenomas and 3 carcinomas, and of N-ras in 1 adenoma. All mutations were found in adenomas and among cancers with adenomatous areas, whereas none of the cases lacking adenomatous areas contained mutations. This suggested that ampullary cancers represent heterogeneous diseases with respect to the presence or absence of adenomatous areas and, among those with adenomatous areas, with respect to the presence of activated ras genes. Ki-ras mutated cases included 3 of 4 tumors which mainly involved the intraduodenal bile duct, thus suggesting that a proportion of Ki-ras-mutated ampullary cancers might correspond to those originating from the epithelium of the bile duct component of the ampulla.
Adenocarcinoma↗
Serum beta 2-microglobulin in intravenous drug users and its correlation with human immunodeficiency virus infection.
High levels of serum beta 2-microglobulin have been associated with human immunodeficiency virus infection and beta 2-microglobulin has been used with other serological and immunological markers for monitoring disease progression. The usefulness of beta 2-microglobulin as a prognostic marker during human immunodeficiency virus infection has been demonstrated in homosexual men and hemophiliacs; few and contradictory data have been reported in intravenous drug users. We have evaluated a cohort of 160 intravenous drug users (81 seronegative and 79 seropositive for human immunodeficiency virus infection) with normal renal function to assess whether serum beta 2-microglobulin could be used as a serological marker for monitoring infection; 78 healthy subjects were used as controls. Of 79 seropositive drug users, 54 were asymptomatic or had persistent generalized lymphoadenopathy the remaining 25 had the acquired immunodeficiency syndrome. Seropositive patients were tested for CD4+ lymphocyte number, p24 antigen and anti-p24 antibodies. A significant statistical difference was found in mean serum beta 2-microglobulin levels between seronegative and seropositive drug users. Moreover, higher levels of beta 2-microglobulin were observed in acquired immunodeficiency syndrome patients compared with asymptomatic or patients with persistent lymphadenopathy. A significant relationship was also observed between increased concentration of beta 2-microglobulin and the serological and immunological markers which indicate human immunodeficiency virus disease progression.
Acquired Immunodeficiency Syndrome↗
Bone marrow angiogenesis and progression in multiple myeloma.
Tumour growth is angiogenesis-dependent. We found a high correlation between the extent of bone marrow angiogenesis, evaluated as microvessel area, and the proliferating (S-phase) fraction of marrow plasma cells, evaluated as labelling index (LI), in patients with multiple myeloma (MM) and in those with monoclonal gammopathies of undetermined significance (MGUS). Angiogenesis itself was significantly associated with active as opposed to non-active MM and MGUS. The highest microvessel area accompanied rapidly progressive MM with the highest LI. When a cut-off value of 2% or greater of the microvessel area was used, most patients with active MM were classified correctly. The risk of active disease in patients with MM increased in parallel with the microvessel area. A causal relationship between plasma cell growth, activity phase in MM and marrow angiogenesis is suggested. Since angiogenesis proceeds in step with the enlargement of plasma cell tumours and the activity phase in MM, its measurement could be a useful prognostic marker in patients with plasma cell proliferative disorders.
Aged↗
Differential expression of two ICAM-1 epitopes and LFA-1 chains in B-cell non-Hodgkin's lymphomas.
B-cell non-Hodgkin's lymphomas (B-NHL) and B-cell areas of reactive lymphadenopathies were investigated immunohistochemically for expression of two distinct ICAM-1 epitopes, Me14/D12 and P3-58, and the LFA-1 alpha and beta chains. Partial or total loss of expression of one or both epitope(s) and/or chain(s) was evident in all B-NHL in function of increasing Working Formulation (WF) malignancy grade, with most defects in the high-grade tumors, namely the lowest detectability of the ICAM-1 Me14/D12 and LFA-1 alpha chain, the lowest co-expression of ICAM-1 epitopes and LFA-1 chains, and the most frequent simultaneous loss. The ICAM-1 and LFA-1 profiles overlapped within the low- and intermediate-grades, whereas striking differences between the high-grade subtypes were detected. Specifically, Burkitt's and lymphoblastic tumors always lost both epitopes and both chains. Large cell, immunoblastic tumors occasionally did so, and also showed either uncoordinated expression or co-expression of these constituents. It is suggested that expression defects of this type may help differentiate malignant from benign lymphoproliferations, and also be involved in the progression of B-NHL, since most are observed in high-grade tumors, whose ICAM-1 and LFA-1 profiles indicate that their subtypes are the expression of distinct normal B-cell differentiation stages.
Antibodies, Monoclonal↗
Efficacy of different proteolytic treatments for the immunohistochemical stain of cytokeratins.
Aim of the present study was to investigate the efficacy of 4 different proteolytic treatments (Ficin, Protease type XIV, Microwave irradiation in Citrate buffer and Microwave irradiation in Lead Tiocyanate), compared to the incubation with buffer only, for the detection of cytokeratins in 10 cases of carcinomas from different organs. The same anti-cytokeratin antibody was applied to two sets of tissue sections, after proteolytic treatment, and the reaction was developed by using a different method (ABC or APAAP) for each set of slides. The semiquantitative evaluation of the specimens demonstrated that the higher number of immunoreactive tumor cells was present after Microwave irradiation in Lead Tiocyanate and, to quite a lesser extent, in Citrate buffer. Ficin and Protease type XIV appeared less effective and in some circumstances, the enzymatic digestion of tumor cells seemed to negatively affect the quality of immunostain. When buffer only was used the percentage of immunoreactive tumor cells was considered to be unreliable for diagnostic purposes. The results of the study seem to suggest that proteolytic pretreatment is essential to avoid false negative results when cytokeratin immunostain is essential in histopathology and that Microwave irradiation in Citrate buffer is eligible as the best procedure.
Carcinoma↗
Size and shape evaluation of astrocytoma nuclei with the shape analytical morphometry software system.
Eighteen cases of astrocytomas diagnosed as grades 1-3 of malignancy were studied with analytical morphometry to determine if different grades can be discriminated by size and shape parameters related to the nuclei. The shape analytical morphometry system was used to calculate dimensional measurements and express shape irregularities through quantitative parameters. With the shape asymmetry evaluator procedure, nuclear symmetry was evaluated. All parameters subjected to univariate and multivariate strategies were the same in easily distinguishing grade 1 from the others. Grades 2 and 3 could not be discriminated completely by either dimensional or with analytical parameters revealing strong similarities of nuclear shape and dimensions.
Astrocytoma↗
Retroperitoneal paragangliomas: role of immunohistochemistry in the diagnosis of malignancy and in assessment of prognosis.
OBJECTIVE: To present our experience of 10 patients with extra-adrenal retroperitoneal paragangliomas, and assess prognostic tests. DESIGN: Retrospective study of casenotes. SETTING: University hospital, Italy. SUBJECTS: 10 Patients who presented with paragangliomas between 1970 and 1991. MAIN OUTCOME MEASURES: Histological and immunohistochemical results, and outcome. RESULTS: All tumours were completely resected and there was no operative mortality. Of the 8 patients who had no metastases at presentation 3 died of recurrence 3, 5, and 10 years later, respectively; 4 were alive and free of disease 2-7 years after diagnosis. The 2 patients with synchronous bone metastases at presentation died 1 and 4 years later. Immunohistochemical analysis of type I cells (chromogranin A and neurone-specific enolase) showed little correlation with progression of disease, but there was a correlation between the presence of type II cells (S100 protein) and good prognosis. CONCLUSIONS: Excision is the treatment of choice for paraganglioma. Immunohistochemical techniques may provide useful information about prognosis, in particular about those patients who are at increased risk of recurrence. Long term follow up is essential, because successful management of recurrence is dependent on early recognition.
Adult↗
PCNA/cyclin expression in transitional cell carcinomas of the human bladder: its correlation with Ki-67 and epidermal growth factor receptor immunostainings.
Cell kinetic data are an important adjunct to histologically based tumor classifications and provide reliable information about future tumor behaviour. The growth fraction of 62 transitional cell carcinomas was assessed using Ki-67 and PCNA (Proliferating cell nuclear antigen/cyclin) immunostainings. Ki-67 recognises an unknown nuclear antigen expressed in dividing cells and requires the use of frozen sections. PCNA, a non histone nuclear protein, identifies proliferating cells within fixed, embedded tissue sections. The percentage of labeled cells was expressed as the labeling index (LI). The median LI in normal urothelium and transitional cell carcinoma were 0.5% and 8%, respectively for Ki-67, and 1.5% and 12% for PCNA. A general agreement between indices of cell proliferation and histological grade and stage was demonstrated. Although some discrepancies were observed, there was a strong correlation between Ki-67 and PCNA Lis (r = 0.8308, P < 0.01). In addition, tumor EGFR positive had PCNA values greater than those found in cancer EGFR negative (P = 0.01). These findings suggest that immunohistochemical nuclear labeling with anti-PCNA on routinely processed tissue is a simple technique for the assessment of transitional cell carcinomas.
Adult↗
[Surgical resection for pancreatic neoplasms in the past 20 years].
Over the last 20 years there has been substantial progress in histopathological and biological understanding of pancreatic tumours. This has allowed surgical removal to be planned according to the aggressiveness and natural history of the tumours with benign (cystoadenomas, insulinomas) or low grade tumours (borderline mucin producing tumours, cystic papillary tumours), the trend towards cost effective surgery (conservative pancreatectomy) may be linked to the neighbouring organs (spleen, stomach, duodenum) in an attempt to bring about more rapid functional recovery for the patient and an improvement in the quality of life. On the other hand, the drastic reduction in operative mortality, which is currently less than 5% of cases following duodeno-pancreatectomy, has encouraged a more aggressive surgical technique in order to increase radical resectability for malignant tumours. Moreover, for highly malignant tumours such as ductal adenocarcinoma, the role of pancreatic resection for palliative purposes, in order to improve the quality of life with an acceptable operative risk, has been confirmed. It is foreseeable that as a result of a more accurate selection and grading of patients for surgery, there may in the future be improvements in survival even in those patients operated on for ductal adenocarcinoma. Until now, these patients have received no significant benefit from the undoubted progress achieved in diagnostic and operative techniques.
Humans↗
[Anatomo-surgical notes on splanchnicectomy: original research on 15 autopsy observations].
Surgical splanchnicectomy for the relief of neoplastic pain is a palliative strategy in cases of unremovable pancreatic cancer. The first step in the achievement of satisfactory and long-lasting relief of pain is the correct identification of semilunar ganglia and splanchnic nerves during laparotomy. In this light, we tried to estimate the exact location, number, shape, and length of splanchnic nerves and ganglia in 15 corpses (mean age 39.9 years, range 21-74, F/M/ = 5/10). Right and left splanchnic nerves always pierce the diaphragm laterally to the crus. On the right side, the splanchnic nerve always enters the abdomen posterior to the inferior vena cava, on the right edge in 10%, on the middle in 73%, on the left in 17% of the cases. On the left side, the splanchnic nerve pierces the diaphragm strictly thickened to the left edge of the aorta in 66.6% of the cases, close to the left edge in 26.6%, and close to the right edge of the left adrenal gland in 6.8%. The right splanchnic nerve slides almost horizontally on the diaphragmatic bundles, and reaches an area delimited by the coeliac trunk and the superior mesenteric artery. The length of the right splanchnic nerve is 41 mm of the mean (range 20 to 55 mm): the thickness is between 4 and 6 mm. The left splanchnic nerve is shorter (mean 24 mm, range 15; 30 mm). The right splanchnic nerve varies from 2 to 6 ganglionar bodies and varies in size from 4.5 mm to 30 mm; the left nerve varies form 2 to 4 (sizes between 4 mm to 26 mm).(ABSTRACT TRUNCATED AT 250 WORDS)
Algorithms↗
[Repeated liver resections for metastases from colorectal carcinoma: the experience of 23 cases].
One hundred and thirteen patients with metastases from colorectal carcinoma underwent liver resection. The authors report their experience with respect to 23 repeated hepatic resections (or metastases from colorectal carcinoma). The calculated actuarial survival from the first operations is 100% at 12 months, 67% at 24 months, 48% at 36 months and 26% at 60 months. In 90 patients who underwent a single liver resection during the same period, 76% were alive at 12 months, 40% at 24 months, 27% at 36 months and 14% at 60 months (p = 0.03). Survivals calculated from the second operation were 67% at 12 months, 41% at 24 months and 11% at 35 months. There was no operative mortality with morbidity added to that of the first operation. None patients had extrahepatic disease at the second operation: this was resected. Seven patients were treated with neo adjuvant chemotherapy; six with systemic adjuvant chemotherapy; in one this was associated with loco-regional chemotherapy. The number of lesions (single versus multiple), the presence or absence of extrahepatic disease, neo-adjuvant chemotherapy and adjuvant chemotherapy did not seem to influence the prognosis. Average survival calculated from the appearance of the first metastasis in the liver is better in patients with a synchronous lesion compared to the patients with a metachronous lesion (48.1 months versus 29.3). The authors claim that surgery is indicated, when technically possible, in the hepatic recurrence of disease. The results are not as good as those obtained following the first liver resection, with a probability of earlier recurrence of disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[The therapeutic strategy in benign liver tumors: a 20-year experience].
Therapeutic choices for benign liver tumours have changed over the last 20 years. From 1975 to December 1993, we observed 145 hemangiomas (HMG) (57.2% females-mean age 47.3 years, 42.8% males-mean age 50.4 years): we resected 42 symptomatic hemangiomas: mortality rate was 2.3%. 93 HMG without symptoms were only followed-up: 5 of these increased in size and were resected. 27 symptomatic cases over 50 focal nodular hyperplasia (FNH) were resected, 7 cases were resected and 3 biopsied during laparotomy performed for other pathology. Postoperative mortality was nil. 13 cases were only followed-up after diagnosis by imaging techniques and fine needle biopsy: over a mean period of 23 months. No variations have been recorded. Increases in GGT and ALP were present respectively in 34% and 22% of FNH-cases. Scintigraphic techniques were the most diagnostically accurate (96.2%). All 16 hepatocellular adenomas (HCA) were removed (11 females, 5 males), postoperative mortality was nil: oestrogen administration was present in 36.4% of female cases, histological diagnosis v/s well differentiated hepatocellular carcinoma was difficult in 2 cases, whilst 3 cases had spontaneous rupture. We resected also 8 cases of biliary adenomas in order to determine a precise diagnosis v/s liver metastases, and 4 biliary cystadenomas for their malignant potential. Asymptomatic HMG and FNH for their low tendency to increase, can be only observed, whilst HCA must be fully resected for risk of bleeding and misdiagnosis v/s well differentiated hepatocellular carcinoma.
Adenoma, Liver Cell↗
Melanocyte tumor progression is associated with changes in angiogenesis and expression of the 67-kilodalton laminin receptor.
BACKGROUND: A number of experimental studies have substantiated changes in angiogenesis and in laminin/laminin-receptor interactions during tumorigenesis and tumor progression. However, these observations have never been verified objectively in tissues from a well-defined model of tumor progression. METHODS: Tissues from 97 proliferative lesions of the melanocyte lineage defining distinct steps in tumor progression were investigated immunohistochemically for changes in angiogenesis and expression of the laminin receptor (67-kilodalton molecule). RESULTS: Although the microvessel number was low in common nevi, it increased significantly in nevi with architectural disorder with varying degrees of melanocytic atypia (termed "nevi with ADMA"), and these changes persisted during transformation. Progression to primary melanomas was accompanied by a high microvessel number and progression to metastases by another significant increase. The number and diameter of microvessels were significantly higher at the lesion base than at the adjacent dermis of primary melanomas and higher in the lesion than in the adjacent tissue of metastatic foci. Expression of the laminin receptor, evaluated as percentages of positive lesions and positive cells per lesion, underwent upregulation in the course of progression. Changes in expression were associated mostly with nevi with ADMA, transformation, and deepening of the tumors into the dermis. CONCLUSIONS: These in situ data suggest that more frequent interactions between melanocytic cells and their microvasculature via adhesion protein laminin occur during tumor progression.
Adult↗
Dermoid cyst of the head of the pancreas area.
We report a case of dermoid cyst of the head of the pancreas area in a 26-yr-old woman radically treated with pancreatoduodenectomy and alive with no recurrence at 6-yr follow-up. The diagnostic and surgical procedures are described, and the literature is reviewed.
Adult↗
Different assays for HER-2/neu evaluation in breast cancer.
To evaluate different methodologic approaches for HER-2/neu analysis, we performed Southern, Northern, Western blot and histochemical assay on 112 samples from 86 primary tumors and 26 synchronous axillary metastatic lymph nodes of patients affected by operable breast cancer. Simultaneous statistical analysis of data obtained with the four methods (31 samples) showed that Western blot detected a higher percentage of alterations than the other assays (Cochran and Victor tests, 0.01 less than p less than 0.05). The same result was emphasized by pair analysis (McNemar, p less than 0.05), which evaluated the assay data two by two. Immunohistochemical evaluations were more in accord with immunoprecipitation data when performed on frozen or Bouin-fixed, paraffin-embedded tissues than on formalin-fixed, paraffin-embedded tissues.
Blotting, Northern↗