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Stapling devices introduction in gastroesophageal surgery has allowed better results.An analysis is made of a consecutive series of 108 patients operated on with total gastrectomy and mechanical esophagojejunostomy for gastric neoplasm, in the last decade (1984-1995).The incidence of anastomotic clinical leakage was 2.4% with a perioperative mortality of 0.9% (1 patient) while the incidence of stenosis, treated in every patient with endoscopic dilatation, was 3.2%. These data are in accordance with previous reports. After an accurate analysis of the factors influencing the complication rate pointed out that in most of the cases a technical error in the anastomosis confection is present.The conclusion is drawn that the use of stapling devices in gastroesophageal surgery represents an elective indication. Nevertheless it is mandatory to respect the principles of visceral mechanical anastomosis after an adequate training.

P280, a synthetic peptide composed of 26 aminoacids, has high affinity (Kd = 100 nM) and specificity for the glycoprotein IIb/IIIa (GPIIb/IIIa) receptor expressed on activated platelets. In this study we investigated the potential usefulness of imaging deep vein thrombosis (DVT) and pulmonary embolism (PE) in humans with 99mTc-P280. In 15 patients (9 men and 6 women; mean age +/- s.d.: 49.2 +/- 14.1) with known DVT and/or PE, serial images were acquired within 24 hours of the injection of approximately 200 micrograms of P280 radiolabelled with 10-23 mCi of 99mTc. P280 was labelled with the ligand exchange method using 99mTc-glucoheptonate. Rapid blood clearance (or = 5% ID was still circulating in 1 hour) enabled identification of thrombi as early as 60 minutes after the injection, with significant thrombi-to-background ratios (range: 2-4) in 11/15 patients (73%), in 7/9 with DVT, in 2/3 with PE and in 2/3 patients with both DVT and PE. Radiotracer uptake was clearly detectable also in late scans, which confirms that 99mTc-P280 specifically binds to the thrombi through a receptor-mediated mechanism. PE localizations were detectable 3-4 hours after peptide injection, and in 2 cases SPECT enabled the detection of thrombi missed on planar views. Conversely, the test was negative in 4 patients who had the onset of clinical symptoms and the diagnosis of DVT and/or PE more than 40 days before scintigraphy. The lack of 99mTc-P280 uptake in the latter patients suggested that the peptide does not bind to thrombi when thrombogenesis is not active. These preliminary results clearly indicate scintigraphy with 99mTc-P280 to be a suitable, noninvasive and highly specific tool to image fresh clots causing DVT and/or PE. Thus, this technique might overcome the limitations of the imaging procedures currently in use.

Rectal Prolapse is a rare and distressing condition, with a multifactorial etiopathogenesis. Often, this pathology is associated with fecal incontinence. The recommended approach to the patient with rectal prolapse and fecal incontinence is to repair the prolapse first, then deal particularly with fecal incontinence at a second operation. A retrospective, clinical and manometric study has varying degrees of fecal incontinence. Clinically five of their operation, and a further three patients improved, in two patients the degree of fecal incontinence remained invariable. One patient was worsened after surgery. Manometrically resting and pressure (RAP) was significantly higher in continent patients than in voluntary contraction pressure (MVCP) (p0.05) in preoperative testing. Postoperatively, there was a significant increase in the resting anal pressure as well as in maximum voluntary contraction pressure. Patients who remained incontinent had a significantly lower RAP and MVCP than patients who improved our regained continence. In conclusion this study shows an alteration of internal and external sphincteric function in patients with rectal prolapse. The surgical treatment of this disease improves sphincteric function. Incontinent patients with RAP10 mmHg and MCVP20 mmHg, probably they would be better treated simultaneously either for rectal prolapsus and incontinence. In this kind of patients the perianal proctectomy with total sphincteroplasty could be the elective treatment.

In this study, 35 patients (11 men and 24 women, mean age 47 +/- 16 years) with unilateral adrenal masses underwent nor-cholesterol (nor-Chol) (n = 11), metaiodobenzylguanidine (MIBG) (n = 15) or nor-Chol and MIBG (n = 9) radionuclide studies. In all patients Magnetic Resonance (MR) adrenal imaging was also performed. In 19 (54%) patients, no laboratory abnormalities of adrenal function were observed. In the other 16 (46%) patients, adrenal hyperfunction was found. In 21 lesions, histology showed 10 pheochromocytomas (Pheos), 6 adenomas, 3 metastases, 1 cyst and 1 nodular focal liver hyperplasia. In the remaining 14 lesions, increased cortisol (n = 4) or aldosterone (n = 2) levels and/or intense nor-Chol uptake (n = 14) were considered suggestive of adenoma. Diagnostic accuracy of both nor-Chol and MIBG radionuclide studies in correctly identifying adenoma or Pheos was 100%. Conversely, qualitative MR signal intensity (SI) analysis on T2-weighted images did not allow to accurately distinguish lesions of different nature. In particular, 10 Pheos, 8 adenomas, 3 mestastasis and 1 cyst clearly showed on T2-weighted images higher SI than the liver; 5 adenomas had a slight higher SI; the remaining lesions (7 adenomas and 1 liver hyperplasia) exhibited low SI. In conclusion, adrenal scintigraphy using nor-Chol or MIBG allows to identify adenomas and Pheos, respectively. Conversely, qualitative MR SI analysis cannot differentiate different adrenal lesion (Pheos, adenoma, metastasis and cyst) and yields heterogeneous results in adenomas.

Parathyroid carcinoma is a rare malignancy. We report the case of a 66 years old man referred to our department for a large substernal goiter suspected as a thyroid cancer associated with severe hyperparathyroidism. After normalization of serum levels of calcemia, total thyroidectomy and subtotal parathyroidectomy was performed. Histopathology revealed a parathyroid cancer of 450 g.

Cutaneous squamous cell carcinoma (SCC) is, in its most frequent presentation, a moderately aggressive neoplastic disease. It can, however, present in a moltitude of clinico-pathological variants, some of which are characterized by a more malignant attitude. It is important to determine which tumors, among the various histophenotypes, are high risk in order to establish the appropriate treatment and follow-up. Histologic subtype has been considered as a possible variable in determining the prognosis of cutaneous SCC. We report our experience with 3 cases of peculiar variants of cutaneous SCC.

Solitary metastases to the small bones and/or to the soft tissue of the hands and feet (acrometastases) are rare. We report a case of renal cell carcinoma (RCC) with big toe metastasis revealed before the primary tumor became apparent. The best treatment for a single metastasis is always surgical excision, regardless of the lesion being synchronous or metachronous. The biological behavior of metastatic RCC is unpredictable and only early diagnosis and treatment may favorably affect patient survival. Thus, metastatic RCC should be included in the differential diagnosis of all enlarging cutaneous nodules, wherever they develop.

Purpose: Factors that are predictive of prognosis in patients who are diagnosed with malignant melanoma (MM) are widely awaited. Detection of circulating melanoma cells (CMCs) by reverse transcriptase-polymerase chain reaction (RT-PCR) has recently been postulated as a possible negative prognostic factor. Two main questions were addressed: first, whether the presence of CMCs, defined as the patient being positive for any of the three markers, had a prognostic role; and second, what the predictive value of each individual marker was. Patients and Methods: A consecutive series of 200 melanoma patients observed between January 1997 and December 1997, with stage of disease ranging from I to IV, was analyzed by semiquantitative RT-PCR. Tyrosinase, p97, and MelanA/MART1 were used as markers to CMCs on baseline peripheral blood samples. Progression-free survival (PFS) was used as a unique end point and was described by the product limit method. Multivariable analysis was applied to verify whether the auspicated prognostic value of these markers was independent of the stage of disease, and a subgroup analysis was performed that excluded patients with stage IV disease. Results: Overall, 32% (64 of 200) of patients progressed, and a median PFS of 52 months in the whole series was observed. The presence of CMCs and the markers individually or combined was predictive of prognosis in the univariate analysis but did not provide additional prognostic information to the stage of disease in multivariable models. In the subgroup analysis of stage (ie, I–III subgroup), similar results were observed. Conclusion: Detection of CMCs in peripheral blood samples at the time of MM diagnosis by semiquantitative RT-PCR does not add any significant predictive value to the stage of disease. Thus, this approach should not be used in clinical practice, and further studies are required to determine its usefulness.

Background: Locally advanced rectal cancer (LARC) is a heterogeneous group of tumors where a risk-adapted therapeutic strategy is needed. Short-course radiotherapy (SCRT) is a more convenient option for LARC patients than preoperative long-course RT plus capecitabine. Histone-deacetylase inhibitors (HDACi) have shown activity in combination with RT and chemotherapy in the treatment of solid tumors. Valproic acid (VPA) is an anti-epileptic drug with HDACi and anticancer activity. In preclinical studies, our group showed that the addition of HDACi, including VPA, to capecitabine produces synergistic antitumour effects by up-regulating thymidine phosphorylase (TP), the key enzyme converting capecitabine to 5-FU, and by downregulating thymidylate synthase (TS), the 5-FU target. Methods/Design: Two parallel phase-1 studies will assess the safety of preoperative SCRT (5 fractions each of 5 Gy, on days 1 to 5) combined with (a) capecitabine alone (increasing dose levels: 500–825 mg/m2/bid), on days 1–21, or (b) capecitabine as above plus VPA (oral daily day −14 to 21, with an intra-patient titration for a target serum level of 50–100 microg/ml) followed by surgery 8 weeks after the end of SCRT, in low-moderate risk RC patients. Also, a randomized phase-2 study will be performed to explore whether the addition of VPA and/or capecitabine to preoperative SCRT might increase pathologic complete tumor regression (TRG1) rate. A sample size of 86 patients (21-22/arm) was calculated under the hypothesis that the addition of capecitabine or VPA to SCRT can improve the TRG1 rate from 5% to 20%, with one-sided alpha = 0.10 and 80% power. Several biomarkers will be evaluated comparing normal mucosa with tumor (TP, TS, VEGF, RAD51, XRCC1, Histones/proteins acetylation, HDAC isoforms) and on blood samples (polymorphisms of DPD, TS, XRCC1, GSTP1, RAD51 and XRCC3, circulating endothelial and progenitors cells; PBMCs-istones/proteins acetylation). Tumor metabolism will be measured by 18FDG-PET at baseline and 15 days after the beginning of SCRT. Discussion: This project aims to improve the efficacy of preoperative treatment of LARC and to decrease the inconvenience and the cost of standard long-course RT. Correlative studies could identify both prognostic and predictive biomarkers and could add new insight in the mechanism of interaction between VPA, capecitabine and RT. EudraCT Number: 2012-002831-28. Trial registration: ClinicalTrials.gov number, NCT01898104

We investigated the role of radiolabeled somatostatin analogs (SAs) in adrenal imaging. We evaluated 15 patients (6 men and 9 women, mean age 47 ± 17 years) with imaging-detected adrenal tumors. Patient population was divided into two groups on the basis of the nature of adrenal lesions. Group 1 consisted of patients with benign adrenal lesions ( n = 10). Group 2 consisted of patients with malignant adrenal lesions ( n = 5). Pathology examinations were obtained in 13 cases: 7 pheochromocytomas, 2 adenomas, 2 cysts, 1 carcinoma, and 1 fibro-histiocytoma. One patient had a proven diagnosis of non-small-cell lung cancer associated with the presence of a right adrenal mass. The last patient had a clinical diagnosis of Werner syndrome associated with the presence of a large left adrenal mass. All patients underwent scintigraphic studies using radiolabeled SAs, of which indium-111 (In-111) pentetreotide was used in 11 cases and technetium-99m (Tc-99m)-labeled peptides (P-587 or P-829) were used in the remaining four cases. No significant labeled SAs uptake was observed in the majority (8 of 10, 80%) of the benign adrenal lesions (Group 1); however, increased uptake was found in two benign pheochromocytomas. Conversely, significant labeled SAs uptake was observed in the majority (4 of 5, 80%) of the malignant adrenal lesions (Group 2); however, the last lesion (carcinoma) did not show abnormal uptake. Results of this study show that the majority of benign adrenal tumors do not concentrate radiolabeled SAs; conversely, the majority of malignant adrenal lesions show significant SAs uptake, suggesting the presence of somatostatin receptors. This finding may allow the use of somatostatin as a treatment agent in malignant adrenal tumors. Thus, the main role of labeled SAs in adrenal imaging consists of lesion characterization rather than tumor detection and localization.

Purpose The prevalence of BRAF, NRAS, and p16CDKN2A mutations during melanoma progression remains inconclusive. We investigated the prevalence and distribution of mutations in these genes in different melanoma tissues. Patients and Methods In all, 291 tumor tissues from 132 patients with melanoma were screened. Paired samples of primary melanomas (n = 102) and synchronous or asynchronous metastases from the same patients (n = 165) were included. Tissue samples underwent mutation analysis (automated DNA sequencing). Secondary lesions included lymph nodes (n = 84), and skin (n = 36), visceral (n = 25), and brain (n = 44) sites. Results BRAF/NRAS mutations were identified in 58% of primary melanomas (43% BRAF; 15% NRAS); 62% in lymph nodes, 61% subcutaneous, 56% visceral, and 70% in brain sites. Mutations were observed in 63% of metastases (48% BRAF; 15% NRAS), a nonsignificant increase in mutation frequency after progression from primary melanoma. Of the paired samples, lymph nodes (93% consistency) and visceral metastases (96% consistency) presented a highly similar distribution of BRAF/NRAS mutations versus primary melanomas, with a significantly less consistent pattern in brain (80%) and skin metastases (75%). This suggests that independent subclones are generated in some patients. p16CDKN2A mutations were identified in 7% and 14% of primary melanomas and metastases, with a low consistency (31%) between secondary and primary tumor samples. Conclusion In the era of targeted therapies, assessment of the spectrum and distribution of alterations in molecular targets among patients with melanoma is needed. Our findings about the prevalence of BRAF/NRAS/p16CDKN2A mutations in paired tumor lesions from patients with melanoma may be useful in the management of this disease.

Lack of technetium-99m methoxyisobutylisonitrile ((99m)Tc-MIBI) uptake is consistently reported to predict poor response to subsequent chemotherapy in a variety of human malignant tumours. Since (99m)Tc-MIBI accumulates within mitochondria, which also play a central role in apoptosis through the integration of death signals by Bcl-2 family members, we tested whether early (99m)Tc-MIBI uptake is affected by alterations of the apoptotic pathway. Forty-two breast cancer patients were intravenously injected with 740 MBq of (99m)Tc-MIBI and planar images were obtained 10 min post injection with the patients in the prone lateral position. Ten carcinomas failed to accumulate (99m)Tc-MIBI and could not be visualised on scintigraphic images despite being larger than 1.8 cm (MIBI negative). Thirty-two of the 42 breast carcinomas showed focal uptake of (99m)Tc-MIBI (MIBI positive), and 10 min tumour-to-background ratios (T/B) varied between 1.14 and 6.93. The apoptotic index, the rate of proliferation, and the expression of the anti-apoptotic Bcl-2 protein and pro-apoptotic Bax protein were assessed in surgically excised tumours. All MIBI-negative carcinomas showed a dramatic and statistically significant reduction in the apoptotic index as compared with MIBI-positive lesions (mean+/-SD, 0.14+/-0.15 vs 1.28+/-0.83, P

Characteristic patterns of regional cerebral blood flow (rCBF) reduction, as detected by technetium-99m hexamethylpropylene amine oxime ((99m)Tc- HMPAO) single-photon emission tomography (SPET), may help clinicians in differentiating patients with frontotemporal dementia (FTD) from those with Alzheimer's disease (AD). However, in some cases these patients may share common rCBF abnormalities and the visual analysis and/or the region of interest (ROI) approach may not sensitively detect more localised focal changes that could be more specific for each pathology. Recently, automated voxel-by-voxel statistical analysis of perfusion brain maps has been applied to SPET images. This method has the advantage of including the rCBF information for the whole brain for statistical analysis without any a priori hypothesis regarding the regions possibly involved. This could result in a better characterisation of rCBF differences in brain regions while also reducing the operator's subjectivity and the time required for data analysis. The purpose of this study was to apply such a technique to highlight the specific brain areas showing a relative functional involvement in FTD and AD. Thus, we compared the relative rCBF patterns obtained in eight FTD patients with those obtained in 21 AD patients using (99m)Tc-HMPAO SPET and statistical parametric mapping (SPM). When FTD patients were compared with AD patients, relatively lower rCBF was observed in right medial frontal cortex (BA 8, 9, 10), right anterior cingulate cortex (BA 32), right temporal cortex (BA 21/22), right orbitofrontal cortex (BA 11) and ventrolateral prefrontal cortex (BA 47); in BA 47 the reduction was evident bilaterally but was more marked on the right side. On the other hand, when AD patients were compared with FTD patients, a significant relative rCBF decrease was found in the bilateral superior parietal cortex (BA 7); this decrease was more extensive on the left side, where it also included the inferior parietal (BA 40), superior occipital (BA 19) and temporo-occipital regions (BA 39, 19). The results of this study confirm the preferential involvement of the frontotemporal regions in FTD patients and of the temporoparietal regions in AD patients. Furthermore, they highlight the networks that are more specifically impaired in these disorders and that could be implicated in the emotional- behavioural and cognitive disturbances that characterise FTD and AD respectively.

The authors explain their experience about 136 patients affected by differentiated thyroid carcinoma. They compare different surgical procedure (total thyroidectomy vs conservative surgery). Although the surgical significance above the survival is discuss again, the authors, analysing the prognostic factors and the long term results, identify the total thyroidectomy maybe associated to lymphectomy and radioiodine therapy like the best treatment for this pathology.

Iodine-131 metaiodobenzylguanidine (MIBG) scintigraphy, computed tomography (CT) and ultrasonography (US) were used to localize tumour lesions in 28 children with histologically proven neuroblastoma. Overall, a total of 73 lesions were detected on imaging studies. MIBG scintigraphy, CT and US localized 63 (86%), 49 (67%) and 36 (49%) of these lesions, respectively. The findings of the three imaging techniques were concordant in respect of only 31 (42%) of the lesions. The best agreement among MIBG scintigraphy, CT and US was observed for abdominal lesions (the techniques were concordant for 22 of 23 lesions, i.e. 96%). MIBG scintigraphy detected nine out of ten (90%) liver metastases, but agreement with CT and US was observed in only six instances (60%). The imaging findings were concordant in respect of only two (33%) out of six lymph node metastases; the MIBG scan was normal in the other four cases. Imaging agreement was observed for a lesion located in the pelvis. MIBG and CT findings were concordant in four lesions located in the chest, but US was not performed. MIBG scintigraphy depicted the majority (96%) of the skeletal lesions (23/24); CT showed five of these, but, again, US was not performed. The imaging findings were not concordant as regards the remaining five lesions located in different anatomical sites. The results indicated that MIBG imaging is more sensitive that CT and US in localizing the majority of neuroblastoma lesions. Since the metastatic spread of neuroblastoma is unpredictable, we recommend MIBG scintigraphy as the initial imaging modality for staging of these patients. US and, particularly, CT should be performed thereafter to clarify the anatomical detail of the lesions detected on MIBG scans, or when MIBG findings are normal or equivocal.

The results of 131I metaiodobenzylguanidine (MIBG) and Computed Tomography (CT) scans in a group of patients with clinically suspected pheochromocytoma were evaluated and compared with biohumoral parameters. We studied 24 consecutive patients (7 M and 17 F; age range 20-66 years). 131I-MIBG scintigraphy and CT were in agreement in 19 patients (79%): of them 7 cases were true positive, and 12 were true negative. Disagreement between the two imaging techniques was observed in 5 patients (21%). In this group, one patient, with positive CT scan, had false negative MIBG study, while 4 patients with negative MIBG scan, had false positive CT. MIBG showed significantly higher (p less than 0.05) specificity (100%), positive predictive value (100%), and accuracy (96%) than CT (75%, 67%, and 83%, respectively). 131I-MIBG scintigraphy is an accurate, noninvasive technique for localizing pheochromocytoma and providing direct tissue characterization, while CT provides more accurate spatial information. In conclusion, CT and MIBG studies are complementary in the evaluation of patients with suspected pheochromocytoma.

Many tumors with neuroendocrine characteristics express high amounts of somatostatin receptors that enable in vivo imaging with [(111) In-DTPA-D-Phe(1)]-octreotide. In this study, we have analyzed the feasibility in detecting and characterizing thymic masses by somatostatin receptor scintigraphy (SRS), Methods: Eighteen patients (13 women, 5 men, ages 18-78 yr; mean +/- s.d. = 42.1 +/- 17.6 yr) were enrolled in this study, Eleven patients were studied during diagnosis and seven during routine follow-up, In seven patients, myasthenia gravis was the presenting symptom. SRS was performed within 4 wk after CT and/or MRI, Planar and tomographic images were acquired within 24 hr after the injection of approximately 111 MBq of [(111) In-DTPA-D-Phe(1)]-octreotide. The scintigraphic results were categorized according to the histologic findings, Results: Histology diagnosed 10 mixed epithelial/lymphoid thymomas (8 with prevalent epithelial component), 2 thymic carcinomas, 1 thymic carcinoid, 1 lymphangioma and 4 thymic hyperplasias. Two thymoma were Stage I, 3 were Stage II, 2 were Stage III and 5 were Stage IV, as was the thymic carcinoid. Indium-111-DTPA-D-Phe(1)-octreotide concentrated in primary and/or metastatic sites of thymic tumors, thereby enabling successful external gamma imaging of sites greater than 1.5 cm in size, Tumor-to-lung (T/L) ratios were as high as 7.6-fold (range 1.7-7.6). Untreated thymomas showed higher T/L (4.34 +/- 1.57) than treated ones (2.68 +/- 1.18). No uptake was detectable in the four patients with benign thymic hyperplasia and the patient with the lymphangioma. Conclusion: Indium-111-DTPA-D-Phe(1)-octreotide is avidly concentrated within thymic tumors, but it is not concentrated by thymic hyperplasia, which allows differential diagnosis. Thus, in patients with myasthenia gravis, SRS may have a role in characterizing thymic masses, thereby overcoming the limits of cross-sectional imaging modalities.