Ultrasound and color-flow Doppler evaluation for the diagnosis of subclinical hyperthyroidism.

AIM: Clinical significance, population screening and management of subclinical hyperthyroidism (SHyper) are still debated. Although the diagnosis of subclinical hyperthyroidism is, by definition, purely a biochemical one a conventional gray-scale sonography and, more recently, color-flow Doppler sonography (CFDS) have proven to be useful in obtaining information about thyroid morphology and function in thyroid disease, such as SHyper. The objective of this study was to evaluate, using CFDS, the presence and significance of changes in intrathyroidal blood flow and velocity in patients affected by SHyper and, to evalutate the potential diagnostic role of CFDS in mild thyroid disease in absence of a significant alteration in the serum level of circulating thyroid hormones. METHODS: In this study, patients with SHyper (the case group) and euthyroid patients (the control group) were enrolled. All patients from the two groups who were affected by multinodular goiter as preoperative diagnosis, underwent total thyroidectomy. In both groups preoperative examination included a conventional grey-scale sonography, followed by CFDS. Quantitative flow evaluation was performed measuring the maximal peak systolic velocity (PSV) at the level of intrathyroid arteries and inferior thyroid artery. RESULTS: Patients with SHyper showed an increased thyroid vascularization both intranodular and peripheral and the mean PSV values were higher in case patients than in control subjects. CONCLUSION: We have shown that significant changes in thyroid vascularity and blood flow velocity are already present in patients with SHyper. CFDS is a suitable technique to identify SHyper.

Beyond hematoxylin and eosin: the importance of immunohistochemical techniques for evaluating surgically resected constipated patients.

Chronic constipation requiring surgical ablation for intractability is often a frustrating condition from the pathologist's point of view. In fact, limiting the histological examination to only hematoxylin-eosin staining usually yields only the information that there are no abnormalities. By employing some simple and widely available immunohistochemical methods, discussed in this review, it is possible to gather data that may help in explaining the pathophysiological basis of constipation in these patients.

The changing impact of age on colorectal cancer surgery. A trend analysis.

OBJECTIVE: The aim of the study was to evaluate the changing influence of age on the outcomes of colorectal cancer surgery in a retrospective trend analysis. METHODS: Data on 985 patients undergoing colorectal cancer surgery were collected during 1975-1984 and 1995-2004. Variables and outcomes of patients aged < 65, 65-74, 75-84 and 85+ years were compared with intra- and interdecade analyses. Endpoints of the study were postoperative mortality, 5-year overall and cancer-related survivals. RESULTS: The rate of elderly patients undergoing colorectal cancer surgery increased significantly from 1975-1984 to 1995-2004. Distribution of American Society of Anesthesiology score and cancer stage remained unchanged over time. The rate of palliative procedures decreased over time, most significantly in the older age groups. In 1995-2004 the palliation rate was similar across all age groups. The rate of emergency surgery also decreased, but it remained higher in older age groups. Operative mortality rate decreased over time across all age groups, but age-related differences were still observed in the 1995-2004 series. Cancer-related survival after curative surgery increased from 58% in 1975-1984 to 64% in 1995-2004 in 75+ years patients, while it increased from 56% to 78% in patients aged 74 years or younger. CONCLUSIONS: Elderly patients with colorectal cancer benefited substantially from healthcare progress during the last 30 years. The reduction of palliative procedures and the decline in operative mortality document the efficacy of not restricting the access to radical surgery for these patients.

Expression of the Rai (Shc C) adaptor protein in the human enteric nervous system.

The adaptor protein Rai (ShcC/N-Shc) is almost exclusively present in the nervous system, although little is documented about its expression in the gut and the enteric nervous system (ENS). As Rai is a physiological substrate of Ret, an important factor for the development of ENS, we have evaluated the expression of Rai in the ENS in various segments of the human gastrointestinal tract. The expression of Rai was assessed by immunohistochemistry in disease-free human gut samples (oesophagus, stomach, small bowel and colon) obtained from subjects undergoing surgical procedures. Rai was not expressed in the epithelia or lymphoid tissue, whereas a moderate level of expression was observed in the endothelial cells of blood vessels and on the outer membrane of smooth muscle cells in both the muscularis mucosae and the muscularis propria. In the ENS, strong positivity was observed only in enteric glial cells, overlapping with GFAP and S100. In conclusion, Rai is expressed in the human gut, especially in the enteric glial cells. We conclude that Rai may provide an additional marker for this cell type.

Chromosomal study of enteric glial cells and neurons by fluorescence in situ hybridization in slow transit constipation.

The pathogenesis of slow transit constipation is still elusive. However, a genetic basis may be present. We investigated possible chromosomal abnormalities in enteric neurons and glial cells in patients with slow transit constipation. Colonic specimens from 22 patients with slow transit constipation undergoing surgery for intractable symptoms were obtained, and investigated by fluorescence in situ hybridization (FISH) for chromosomal abnormalities (chromosomes 1, 8, 17 and XY). These specimens were compared with of those obtained in 12 control subjects. Data analysis showed that 45.5% of patients displayed significant (>10%) aneusomy of chromosome 1 in enteric neurons. Aneusomy <10% for the same chromosome, but less than the cutoff suggested (10%), was found in enteric glial cells in 45.4% of the same patients. One patient had <10% aneusomy in enteric neurons for chromosome 8. No other abnormalities were found for the remaining probes, and no abnormalities were found in controls. We concluded that in a subgroup of patients with slow transit constipation a genetic basis may be present.

Prognostic value of circulating KRAS2 gene mutations in colorectal cancer with distant metastases.

While tissue KRAS2 mutations have been extensively investigated, the role of circulating mutant KRAS2 gene in patients with colorectal carcinoma remains obscure. The aim of the present study was to explore the prognostic significance of circulating KRAS2 gene mutational status in subjects undergoing primary treatment for colorectal cancer. Codon 12 KRAS2 mutations were examined in DNA samples extracted from the serum of 86 patients with colorectal cancer and were compared with the KRAS2 status of their primary tumors. Tissue and serum KRAS2 status was compared with other clinicopathological variables (including CEA and CA 19-9 levels) and with cancer-related survival. KRAS2 mutations were found in tissue samples of 28 patients (33%); serum KRAS2 mutations were detected in 10 of them (36%). Serum KRAS2 status was significantly associated with Dukes' stage D (p=0.001) and with preoperative CA 19-9 levels (p=0.01). At multivariate analysis, cancer-related survival was associated with Dukes' stage (p<0.0001), CEA level (p=0.02), and mutant circulating KRAS2 (p=0.01). All 7 stage D patients with serum KRAS2 mutations died of the disease within 24 months of primary treatment; cancer-related survival was significantly better in 9 stage D patients without serum KRAS2 mutations, with 5 patients (56%) alive after 24 months and 1 patient (13%) alive after 44 months. Residual disease after surgery was evident in all 7 stage D patients with mutant circulating KRAS2, and in 5 out of 9 stage D patients without serum mutations. Serum KRAS2 status may impact substantially on the management of stage D colorectal carcinoma, since it appears to cor-relate with prognosis in this patient subgroup.

Microsatellite instability and mismatch-repair protein expression in hereditary and sporadic colorectal carcinogenesis.

Aberrant crypt foci (ACF) are microscopic clusters of altered colonic crypts considered premalignant lesions in the large bowel. Genomic instability at short tandem repeats in the DNA, referred to as microsatellite instability (MSI) is the hallmark of hereditary nonpolyposis colorectal carcinoma (HNPCC) caused by mutations in DNA mismatch-repair genes, mostly hMLH1 and hMSH2. In this study, we evaluated for MSI ACF (n = 16), adenomas (n = 18), carcinomas (n =22), and lymph node metastases (n = 3) from 17 patients with colorectal cancer positive for MSI. Ten patients were members of HNPCC families; 7 patients had no family history of cancer. MSI was found in 7 of 7 (100%) ACF and 11 of 12 (91%) adenomas from patients with HNPCC. MSI was not related to histology and size of ACF. A progressive increase in instability as estimated by the number of shifted bands was observed along the ACF-adenoma-carcinoma sequence. In contrast, two of nine (22%) ACF and none of six adenomas from patients with MSI sporadic carcinoma were unstable at microsatellite loci. hMLH1 or hMSH2 protein expression was altered only in MSI-positive premalignant lesions (ACF and/or adenomas), but not in all MSI-positive lesions in patients with HNPCC. These observations provide evidence of the premalignant nature of ACF in HNPCC and suggest that MSI is a very early event both in HNPCC and in sporadic colorectal carcinogenesis, although in the latter it seems infrequent.

Aberrant crypt foci in the human colon: frequency and histologic patterns in patients with colorectal cancer or diverticular disease.

Aberrant crypt foci are considered potential markers of colorectal cancer risk. The aim of this study was to analyze a large series of human aberrant crypt foci according to frequency, distribution, and histology. Aberrant crypt foci were identified in methylene blue-stained colonic mucosa from 103 patients undergoing surgery for colorectal cancer or diverticular disease. Foci were histologically classified into surface hyperplastic type, surface and glandular hyperplastic type, mixed hyperplastic and adenomatous type, and adenomatous type. The mean frequency of aberrant crypt foci (n = 720) was higher in the colorectal cancer group (0.20/cm2) than in the diverticular disease group (0.07/cm2), and in distal colonic segments than in proximal segments. Most of the histologically examined foci (n = 366) were hyperplastic (88.8%). Surface hyperplasia accounted for 30.6% and prevailed in small lesions. Surface and glandular hyperplasia accounted for 58.2% and prevailed in medium-sized to large foci. Partially or totally dysplastic foci accounted for 10.1% of examined lesions (10.8% and 2.8% in the colorectal cancer and diverticular disease groups, respectively). Most of them (94.6%) were composed of mixed hyperplastic and adenomatous crypts and prevailed in large lesions. The higher frequency of aberrant crypt foci in patients with colorectal cancer sustains their putative role as preneoplastic markers. The high rate of mixed hyperplastic and adenomatous lesions supports the possible adenomatous transformation of hyperplastic lesions.

Molecular detection of codon 12 K-RAS mutations in circulating DNA from serum of colorectal cancer patients.

Point mutations of the K-RAS gene at codon 12 are found in about 40% of cases with colorectal cancer. The diagnostic implications of the detection of these mutations and their clinical utility are still unclear. The aim of this study was to test both the feasibility of the detection of the mutated K-RAS gene in serum and its potential role in colorectal cancer detection and monitoring. Codon 12 K-RAS mutations were examined in DNA extracted from the serum of 35 patients with colorectal cancer and were compared with the K-RAS status in the corresponding primary tumor. Molecular detection was performed by the mutant-enriched PCR (ME-PCR) assay, a sensitive method capable of distinguishing a small quantity of mutated DNA in the presence of abundant wild-type DNA. The occurrence of mutations was compared with clinicopathological parameters as well as CEA and CA19.9 serum levels. We found codon 12 K-RAS mutations in the tissue of 13/35 (37%) patients. Serum mutations were detected in 5/13 (38.5%) patients with mutated K-RAS in the tissue. 26/35 (74%) patients showed an identical K-RAS pattern in tissue and serum. No codon 12 K-RAS alterations were found in serum samples of 22 patients with benign gastrointestinal diseases. Elevated serum CEA levels were detected in 16 patients, four of whom also presented serum RAS mutations. Our results confirm that K-RAS mutations can be found in circulating DNA extracted from serum samples of patients with colorectal cancer and show that there is a correspondence between serum and tissue K-RAS patterns.

Cytometric ploidy and proliferative activity in colorectal carcinoma.

Thirty cases of colorectal carcinoma have been evaluated for proliferative activity with the monoclonal antibody Ki 67 and with flow cytometry for ploidy, DNA index and the S-phase fraction. In the series, 30% of tumours were strictly aneuploid, 23.8% tetraploid and 45% diploid: "non diploid" cases accounted for 53.8%. The mean comprehensive values of DNA index, percent S-phase and Ki 67 positive fraction were 1.4%, 11.5% and 50%, respectively. The parameters considered showed no statistically significant correlation with each other or with the common histo-pathologic parameters, such as grading and staging. The prevalent prognostic importance of ploidy compared to DNA index is emphasized, and particular attention is paid to diploid cases with a high growth fraction (S-phase fraction), which could make up an "at risk" category. Therefore, we attempted to identify subsets, within groups of the same histologic stage, with a different evolutive significance in relation to DNA content, percentage of positivity to Ki 67, S-phase fraction and ploidy. With such a multi-parametric approach, particular groups of patients at risk could be defined, which are perhaps more sensitive to specific support therapies.

[Non-polyposis colorectal cancer in subjects under 55 years of age: frequency and phenotype of hereditary or familial syndromes]. / Il cancro non polipotico del colon e del retto sotto i 55 anni di età: frequenza e fenotipo delle sindromi a predisposizione ereditaria o familiare.

Young age is believed to be a risk factor for hereditary or familial non-polyposis colorectal cancer. Present study analysed frequency, phenotype and familial cancer risk of 82 subjects with colorectal cancer under 55 years of age. According to age and family history, probands have been subdivided into 5 groups: Hereditary Non-Polyposis Colorectal Cancer (HNPCC) (8.2% of cases); Suspected HNPCC (7.3%); Non-specific familial aggregation of colorectal cancer (AFACC) (19.5%); Early-onset colorectal cancer (diagnosis under 35 years of age) (CCG) (6.1%); Sporadic colorectal cancer (CCS) (58.5%). Proportions of probands with multiple colonic tumours were highest in HNPCC (57.1%), but present in AFACC (12.5%) and CCG (20.0%) groups, as well. Extracolonic, in particular endometrial and ovarian cancers have been found in HNPCC and AFACC probands. Tumours of proximal colon were most frequent in HNPCC, suspected HNPCC, CCG patients. Eleven-years survival rate was higher in HNPCC probands then in CCS group. Familial cancer risk in HNPCC was 3 times as much as in CCG + CCS groups. Diagnosis of colorectal cancer under 55 years of age is associated with an high frequency of hereditary or familial cases. Genetic tests, surveillance and screening programs in these patients must be based on extensive phenotype and pedigree analyses. HNPCC is widely represented in young colorectal cancer patients and is associated with a high risk of multiple synchronous or metacronous colonic and extracolonic tumours. Total colectomy and eventual hysterectomy with bilateral oophorectomy seem therefore recommendable options in these patients.

[Severe hypercalcemia due to acute primary hyperparathyroidism: role if parathyroidectomy]. / Ipercalcemia grave da iperparatiroidismo primitivo acuto: ruolo della paratiroidectomia.

Grave hypercalcemia may complicate primary hyperparathyroidism. This clinical condition is potentially life-threatening, if it is untreated. The emergency therapy consist in rehydratation, stimulation of diuresis and somministration of biphosphonates. A urgent surgery is required if conservative therapy is not successful. The Authors herein present a consecutive series of 6 cases with acute hypercalcemic crisis due primary hyperparathyroidism, successful treated with urgent parathyroidectomy after conservative treatment.

[The role of color-Doppler ultrasonography in preoperative study of hyperparathyroidism]. / Ruolo dell'ecocolor-doppler nello studio preoperatorio degli iperparatiroidismi.

The different diagnostic modalities (MIBI scan, ultrasound, CT, MNR) applied in the preoperative study of hyperparathyroidism, have given excellent sensitivity results, only slightly lower than those obtained by surgical exploration performed by experienced surgeons. Yet, their only limitation lies in a lower level of specificity. Other cervical tumours, such as thyroid nodules, lymphoadenopaties, vascular and macular lesions, can in fact be erroneously taken as hyperfunctioning parathyroids. The present paper shows a clinical experience of 27 patients affected by IPT (14 primary IPT, 10 secondary, 3 terziary) who underwent Color-Doppler Ultrasonography and US before surgical exploration. As a result, global sensitivity level reached 81.5%, specificity 100%. In IPT I and III, sensitivity reached 100% while in IPT II it was only 72.2%. In conclusion, Color-Doppler associated with conventional US increases the specificity rate of IPT pre-operative diagnosis.

[Multifocal gastric carcinoid associated with chronic type A atrophic gastritis. Analysis of 2 clinical cases]. / Carcinoide gastrico plurifocale associato a gastrite cronica atrofica di tipo "A". Analisi di due casi clinici.

Gastric carcinoid is a rare disease, representing less than 1% of gastric tumours and 11-41% of all gastrointestinal carcinoids. The recent Solcia's classification distinguishes three subtypes of these neoplasms, which show specific clinical and pathological features. Type one arises in patients with chronic atrophic gastritis (CGA), achlorhydria, hypergastrinemia and consequent enterochromaffin-like cell hyperplasia and dysplasia. Type two is related to Zollinger Ellison syndrome and type three represents the sporadic kind. We report two cases of multifocal gastric carcinoid associated to CGA, one of them with pernicious anemia. Both patients had aspecific abdominal symptoms; the diagnosis was suspected by upper endoscopy and confirmed by histological examination. Patients were submitted to total gastrectomy. They are still alive six years after surgery, without signs or symptoms of recurrences. Treatment of these tumours is controversial, because of their uncertain biological and clinical behaviour. Some Authors propose a conservative strategy (only endoscopic surveillance or removal); others stress importance of surgery (antrectomy or gastric resection). We discuss and underline the role of surgical therapy and the relevance of radical approach.

[Hypoparathyroidism following total thyroidectomy: prognostic value of intraoperative parathyroid hormone assay]. / Ipoparatiroidismo dopo tiroidectomia totale: utilità prognostica del dosaggio intraoperatorio del paratormone.

Transient and definitive hypoparathyroidism represent a frequent complication after thyroid surgery. Recently some authors proposed the use of intraoperative parathyroid hormone assay for the rapid detection of this complication. In this paper the authors describe the data obtained from 42 total thyroidectomies with intraoperative measurements of parathyroid hormone. When parathormone decrement was over 75% during thyroidectomy, the hypocalcemic symptomatology was found in all cases during postoperative observation. The authors emphasize intraoperative PTH dosage for immediate identification of patients at risk for postoperative hypoparathyroidism. In this cases parathyroid autotransplantation is suggested to prevent postoperative hypoparathyroidism.

Distribution of 1,2 DMH-induced colonic aberrant crypt foci after administration of a gastrin receptor antagonist (CR2945), in the murine model.

Our previous experimental data demonstrated that a new gastrin receptor antagonist (CR2945) has a chemopreventive effect on dimethylhydrazine-induced colon cancer in mice. The aim of this study is to test the effect of CR2945 on the appearance and distribution of aberrant crypt foci (ACF), proposed as early "preneoplastic" lesions in colon carcinogenesis, in the murine model. 176 CD1 male mice were randomly divided into 4 groups: group 1, sham group received 2 daily intra-peritoneal injections of saline solution; group 2 received 1 weekly intra-peritoneal injection of DMH 20 mg/kg, for 5 weeks, and 2 daily intra-peritoneal injections of equal volume of NaCl 0.9%; group 3 and 4 received the same weekly dose of DMH and 2 daily injections of CR2945 at the respective doses of 2.5 and 7.5 mg/Kg for 5 weeks. The rodents were sacrified 15, 20, 25, and 38 weeks after receiving the first injection. The number of ACF per area (ACF frequency), their multiplicity (number of crypts per focus), ACF frequency according to each colonic site were recorded. No ACF were found in the sham group. No substantial differences were observed in ACF distribution between the remaining groups. Our hypothesis is that CR2945 does not alter the final number of ACF but might induce a regression of some dysplastic ACF.

[Billiopancreatic diversion with preservation of the duodenal bulb and transitory gastroplasty in the treatment of morbid obesity. Our experience]. / La diversione bilio-pancreatica con conservazione del bulbo duodenale e gastroplastica transitoria nel trattamento dell'obesità patologica. Nostra esperienza.

We present our experience in malabsorbitive procedure in bariatric surgery based on Biliopancreatic Diversion (BPD) with transitory gastroplasty. Since 1995 we operated on 74 patients with BPD coupled with gastroplasty which is transitory due to the presence of a band in polidioxanone (PDS). The technique, proposed by Vassallo et al. in 1992, involve the respect of the duodenal bulb (5 centimeter from the pylorous) making an end-to-side duodeno-ileal isoperistaltic anastomosis. The initial excess weight loss was satisfactory (69.8% +/- 11.4% after 1 year) and it kept being stable during all the follow-up (75.2% +/- 6.4% after 5 years). The mortality was absence. We didn't observe ipoalbuminemia, diarrhea or halitosis in any patients. Only 1 patient (1.3%) developed an anastomotic ulcer. After 5 years follow-up we observed 2 cases (12.5%) of chronic hypochromic anemia and 1 case (6.2%) of hypocalcemia. We didn't perform any restorative operation. We consider this technique a good malabsortive procedure able to obtain a satisfactory and stable weight loss, with a low incidence of complications. Moreover it could be applied in patients previously treated by an ineffective gastroplasty.

[Course and natural history of idiopathic ulcerative proctitis in adults]. / Decorso e storia naturale della proctite ulcerosa idiopatica nell'adulto.

BACKGROUND AND AIMS: Epidemiological studies have shown that ulcerative proctitis represents 25-55% of ulcerative colitis. In western countries, the incidence of ulcerative proctitis has been increased, while the incidence of more extensive colitis remained unchanged. Compared with extensive ulcerative colitis, the idiopathic proctitis seems to be a benign disease, with an extension to proximal segments in less than 30% of cases, low surgical and cancer risk. On the basis of epidemiological studies, not confirmed by endoscopic and histological features, it has been hypothesized that ulcerative colitis and proctitis could represent two different clinical entities. The aim of the study was to evaluate some clinical and demographic features related to the two different localizations, colitis and proctitis, in the attempt to clarify the above mentioned issues. METHODS: Demographic data of 156 patients observed in our institution from 1982 to 1999, were retrospectively analysed. Diagnosis, extension and severity of ulcerative procto-colitis were based on endoscopic and histological criteria. Local and systemic symptoms, extraintestinal manifestations, surgical and cancer risk, were also recorded. RESULTS AND CONCLUSIONS: Ulcerative proctitis has shown to be a benign disease, with a prevalence of local symptoms, less systemic and extraintestinal manifestations, and low endoscopic grades of activity. Furthermore no surgical intervention and cancer development were recorded. Extension to proximal segments was observed in 10.25% of cases. Young age of onset of symptoms,-smoking and appendectomy were associated to an higher risk of extension of the disease.

[The role of color flow-Doppler ultrasonography in the diagnosis of nodular goiter]. / Ruolo dell'ecocolordoppler nello studio del gozzo nodulare.

Sixtysix patients were submitted to color Doppler ultrasonography, with flowmetric analysis, in the preoperative work up of their thyroid nodules. Three different groups (and two subsets) were so identified, corresponding to the different pathological nodule types: hyperplasia, adenoma, and cancer. The data obtained were then compared to the final pathological results. The color Doppler ultrasonography showed a diagnostic accuracy rate of 87.8%. An evaluation of the peak systolic velocity proved to be very useful in the differential diagnosis between adenomas and cancers. The color Doppler ultrasonography represents a sound method for evaluating thyroid nodules.

[Surgery in severe ulcerative colitis: our experience]. / La chirurgia nella rettocolite ulcerosa grave: nostra esperienza.

BACKGROUND AND AIMS: The mortality in severe episodes of ulcerative colitis (UC) has been reduced from 31-61% in the 1950 to 1-3%. Nevertheless it remains high in non specialist centers. Simple criteria are necessary to predict the outcome of severe ulcerative colitis. METHODS: 14 patients hospitalized for severe disease (Truelove and Witts criteria) from 1996 to 2000 were retrospectively analyzed. Patients were divided into two groups: 1. Group A: patients with severe disease surgically treated. 2. Group B: patients with severe disease responders to medical therapy Sex, age, length of steroids medical therapy, fever, stool frequency, CRP, ESR, haemoglobinemia, leukocytes, serum albumin values in the three days before the operation or during the hospitalization were collected. RESULTS: Total colectomy with ileostomy was necessary in 8 patients (57.1%), while 6 patients (42.90%) were responders to medical therapy. No perioperative mortality was recorded. Stool frequency, CRP, ESR, haemoglobinemia, serum albumin were significantly related to surgical operation. CONCLUSIONS: 1. No uniform criteria off severe attacks, are clearly defined in Literature. 2. The length of pre-operative medical therapy has a tendency to be too high (in our series 19 + 8.2 days). 3. Stool frequency, CRP, ESR, haemoglobinemia, serum albumin were significantly modified in operated patients.