Teaching parotid surgery to ENT residents in the era of new technologies: an ex-vivo ovine model.

Surgical training has recently assumed a central role in the otolaryngology field, and the necessity to train residents and fellows' skills in a progressive manner has led to an incredible widespread of ex-vivo animal models for several surgical procedures. To report our experience with an ex-vivo ovine model for parotid gland dissection in a training context. A junior resident (PGY-1) and a post-graduate student with no experience in parotid surgery were guided by a skilled surgeon in the parotid gland dissection for each step of the procedure. Three different adult lamb heads were used for this feasibility study. A specific preparation of the model was performed before the training session. Similarity between the ovine model and the human were recorded. The resident and the post-graduate student were able to carry out a complete parotid gland dissection under supervision. The correct identification of surgical landmarks has led to a proper surgical simulation. The facial nerve dissection was adequately performed, and all branches were isolated. Parotid surgery training on an ex-vivo ovine model is useful, easy repeatable, and low cost. The ovine model presented in this study has similarities in size, structure, and tissue consistence to the human parotid, making it an ideal model for residents to simulate parotid surgery.

Experimental evidence and mathematical modeling of thermal effects on human colonic smooth muscle contractility.

It has been shown, in animal models, that gastrointestinal tract (GIT) motility is influenced by temperature; nevertheless, the basic mechanism governing thermal GIT smooth muscle responses has not been fully investigated. Studies based on physiologically tuned mathematical models have predicted that thermal inhomogeneity may induce an electrochemical destabilization of peristaltic activity. In the present study, the effect of thermal cooling on human colonic muscle strip (HCMS) contractility was studied. HCMSs were obtained from disease-free margins of resected segments for cancer. After removal of the mucosa and serosa layers, strips were mounted in separate chambers. After 30 min, spontaneous contractions developed, which were measured using force displacement transducers. Temperature was changed every hour (37, 34, and 31°C). The effect of cooling was analyzed on mean contractile activity, oscillation amplitude, frequency, and contraction to ACh (10(-5) M). At 37°C, HCMSs developed a stable phasic contraction (~0.02 Hz) with a significant ACh-elicited mean contractile response (31% and 22% compared with baseline in the circular and longitudinal axis, respectively). At a lower bath temperature, higher mean contractile amplitude was observed, and it increased in the presence of ACh (78% and 43% higher than the basal tone in the circular and longitudinal axis, respectively, at 31°C). A simplified thermochemomechanical model was tuned on experimental data characterizing the stress state coupling the intracellular Ca(2+) concentration to tissue temperature. In conclusion, acute thermal cooling affects colonic muscular function. Further studies are needed to establish the exact mechanisms involved to better understand clinical consequences of hypothermia on intestinal contractile activity.

On the electrical intestine turbulence induced by temperature changes.

Paralytic ileus is a temporary syndrome with impairment of peristalsis and no passage of food through the intestine. Although improvements in supportive measures have been achieved, no therapy useful to specifically reduce or eliminate the motility disorder underlying postoperative ileus has been developed yet. In this paper, we draw a plausible, physiologically fine-tuned scenario, which explains a possible cause of paralytic ileus. To this aim we extend the existing 1D intestinal electrophysiological Aliev-Richards-Wikswo ionic model based on a double-layered structure in two and three dimensions. Thermal coupling is introduced here to study the influence of temperature gradients on intestine tissue which is an important external factor during surgery. Numerical simulations present electrical spiral waves similar to those experimentally observed already in the heart, brain and many other excitable tissues. This fact seems to suggest that such peculiar patterns, here electrically and thermally induced, may play an important role in clinically experienced disorders of the intestine, then requiring future experimental analyses in the search for possible implications for medical and physiological practice and bioengineering.

Promyelocytic leukemia (PML) gene expression is a prognostic factor in ampullary cancer patients.

BACKGROUND: Promyelocytic leukemia (PML) tumor suppressor gene plays a key role in acute PML pathogenesis but its involvement in pathogenesis and prognosis of solid cancers has not been defined yet. PATIENTS AND METHODS: In all, 62 ampullary adenocarcinoma patients who underwent curative surgery between 1996 and 2005 were included. Expression analysis of PML was carried out by immunohistochemical staining and correlated with disease-free survival (DFS) and overall survival (OS). RESULTS: In 24 tumor specimens (38.7%), PML was classified as absent, in 16 (25.8%) as focally expressed and in 22 (35.5%) as diffusely expressed. By univariate analysis, DFS was significantly influenced by pathological T stage (P=0.03), lymph nodal involvement (P=0.002), and PML expression (P=0.001). DFS in patients without PML expression was 28.0 months versus 45.1 and 75.5 for patients with focal and diffuse expression, respectively. OS in the group of patients without PML expression, with focal expression, and with diffuse expression was 40, 48, and 77 months, respectively (P=0.002). By a multivariate analysis, PML expression was the strongest prognostic factor for DFS (P=0.003) and the only statically significant prognostic factor for OS (P=0.009). CONCLUSIONS: Our preliminary data suggest PML as a novel prognostic tool for ampullary cancer patients.

Human equilibrative nucleoside transporter 1 (hENT1) protein is associated with short survival in resected ampullary cancer.

BACKGROUND: Gemcitabine is an acceptable alternative to best supportive care in the treatment of advanced biliary tract cancers. The human equilibrative nucleoside transporter 1 (hENT1) is a ubiquitous protein and is the major means by which gemcitabine enters human cells. Moreover, recent reports indicate a significant correlation between immunohistochemical variations of hENT1 in tumor samples and survival after gemcitabine therapy in patients with solid tumors. MATERIALS AND METHODS: We used immunohistochemistry to assess the abundance and distribution of hENT1 in tumor samples from radically resected cancer of the ampulla, and sought correlations between immunohistochemical results and clinical parameters including disease outcomes. RESULTS: In the 41 individual tumors studied, 12 (29.3%) had uniformly high hENT1 immunostaining. Statistical analysis showed a significant correlation between hENT1 and Ki-67 (P = 0.04). No statistical significant differences were found between immunohistochemical findings and patient characteristics (sex, age, and tumor-node-metastasis). On univariate analysis, hENT1 and Ki-67 expression were associated with overall survival (OS). Specifically, those patients with overexpression of hENT1 showed a shorter OS (P = 0.022) and those with high Ki-67 staining showed a shorter survival (P = 0.05). CONCLUSIONS: hENT1 expression is a molecular prognostic marker for patients with resected ampullary cancer and holds promise as a predictive factor to assist in chemotherapy decisions.

Impaired contractility of colonic muscle cells in a patient with chronic intestinal pseudo-obstruction.

Chronic intestinal pseudo-obstruction represents a cause of persistent functional intestinal failure either "secondary" to specific conditions or "chronic intestinal idiopathic pseudo-obstruction" in origin. The diagnosis is mainly clinical, supported by radiological and/or endoscopic findings excluding any mechanical cause of intestinal obstruction. We reported a case of a 39-year-old woman with chronic intestinal idiopathic pseudo-obstruction, who underwent colectomy with ileorectal anastomosis; histological examination of the surgical specimen did not reveal myogenic or neurogenic defects or other pathological abnormalities indicative of an underlying neuromuscular impairment. Because of the apparent integrity of the gut neuromuscular layer, we tested whether a functional impairment affected colonic single smooth muscle cells. Muscle cells were isolated from the right colon and their contractile response to a receptor-dependent agonist evaluated in comparison to that obtained from controls. The cell contraction induced by acetylcholine in a dose response manner was markedly decreased in the patient affected by chronic intestinal idiopathic pseudo-obstruction compared with cells from controls (percentage of cell shortening with maximal dose of acetylcholine [10(-6)M]: 10.7+/-3% versus 34.2+/-4%, respectively). The present findings indicate a specific defect of colonic smooth muscle cells likely related to an ineffective response to acetylcholine.

Doctor-patient communication tricks. Oncological study at Campus Bio-Medico University of Rome.

OBJECTIVE: Doctor-patient relationship is a very important variable in the oncological clinical consultation. METHODS: We have analyzed 100 outpatients oncological visits (first visits and follow up visits). We conducted an observational study of the extra verbal communication (non-verbal and para-verbal) with a structured observation grid. We have analyzed the three stages of the visit: 1. Patient's admission, 2. Communication flows and 3. Information exchange between doctor and patient. RESULT: In the first visit doctor introduce himself (85%). In the follow-up visit the doctor has received the patient with a handshake (86%) while in the first examination in 100%. In the follow-up visit the short phase of pleasantries was present in 61% of cases, while in the first examination in 45% of cases. Doctor drawn an outline, a design or wrote a note in 45% of first examination and 25% of the follow up. CONCLUSION: Extra verbal communication is more important than the verbal. We suggest useful tips on what "do not" and what "do better" during clinical consultations. CONCLUSION: Against what it is often believed eye contact is not always necessary or useful in establishing a good doctor-patient relationship it depends on the patient's preferred representational system.

Short-term ursodeoxycholic acid treatment improves gallbladder bile turnover in gallstone patients: a randomized trial.

UNLABELLED: Ursodeoxycholic acid (UDCA) prevents in vitro gallbladder (GB) muscle damage caused by acute cholecystitis and reduces risk of biliary pain and complications in gallstone (GS) patients. These effects could be partially explained by the improved GB bile turnover. OBJECTIVES: To assess the effect of short-term UDCA treatment on GB motility and bile turnover. METHODS: Ultrasonographic (US) assessment of GB volumes was performed in 16 GS patients, in the postprandial phase, for 90 min with a time sampling of 1 min, before and after 30 days of UDCA (10 mg kg(-1) die(-1)) or placebo, randomly assigned. US data were analysed with statistical tools and with computer fluido-dynamic (CFD) software Fluent(TM) to simulate GB bile flow. RESULTS: After therapy, fasting volume (FV) increased from 21.6 +/- 9 to 28.2 +/- 12 mL (p < 0.001) while the ejection fraction (EF) remained unchanged (44.5 +/- 17% vs 45.1 +/- 20%; p: ns). Volumes before and after treatment were poorly correlated (0.02 < r < 0.35), unlike those in placebo patients (r > 0.6). The average GB volume was increased in 7 out of 10 patients following UDCA (range 7-67%). CFD analysis supports the finding of improved bile flow after treatment. CONCLUSIONS: Unlike results of conventional US parameters of GB motility, CFD analysis shows that UDCA improves GB bile turnover in GS patients.

Ultrasonographic assessment of gallbladder bile exchanges in healthy subjects and in gallstone patients.

Impaired gallbladder motility may contribute to gallstone pathogenesis by providing time for nucleation and aggregation of cholesterol crystals. Simultaneous scintigraphic-ultrasonographic techniques have been proposed to assess alternating phases of gallbladder emptying and filling. To evaluate patterns of gallbladder motility and of postprandial bile flow by means of a single ultrasonographic technique, 12 healthy volunteers and 20 gallstone patients underwent minute-by-minute gallbladder ultrasonography for 3 h postprandially. Mathematical analysis of volume measurements was used to estimate hepatic and cholecystic bile flux through the gallbladder. Compared to controls, gallstone patients showed greater amounts of unexchanged cholecystic-to-hepatic bile (11% vs. 1%, p <.001) and most of them showed impaired gallbladder washout efficacy. Utrasonographic values of bile exchanges were similar to those derived from scintigraphic-sonographic studies in comparable groups of subjects. This study provides new ultrasonographic variables, which better express gallbladder bile retention in gallstone patients and strongly discriminate gallstone patients from controls.

[Clinical manifestations and diagnosis of hemorrhoids]. / Manifestazioni cliniche e diagnosi delle emorroidi.

Haemorroidal disease has often typical presentation with rectal bleeding, anal prolapse and pain. Practitioners and patients usually underestimate the symptoms; in adults and older people the same symptoms may suggest neoplastic disease, which may be synchronous. Proctoscopy is the main diagnostic test for staging; endoscopic examination with biopsy is helpful to differentiate neoplastic, granulomatous and inflammatory anorectal lesions. In our mind, a complete study of anorectal function and morphology is necessary for a correct diagnosis.

[Preoperative staging of gastric carcinoma using endosonography (EUS)]. / Stadiazione pre-operatoria del carcinoma gastrico mediante endosonografia (EUS).

Accurate staging of gastric malignancy can only be obtained at surgery and after detailed histological examination of the resection specimen. Endoscopic ultrasonography may provide accurate detection and staging of gastric cancer because of its ability to visualize both the intramural and extramural extent of the lesion and any adjacent lymph node involvement. From february 90 to april 91, 29 patients with a gastric carcinoma were studied endosonographically before surgery. All studies were performed with an Olympus EU-M3. Preoperative TNM classification and a prediction of the resectability of gastric cancer were done in every patient. The results were matched with those obtained with the histology of resected specimens according to the TNM classification 1987. Endoscopic ultrasonography was accurate in assessing the extent and depth of tumor infiltration. The overall accuracy rate was 90.5% (19 out of 21 patients). Overstaging occurred in 9.5% of the cases (2 patients); none understaging occurred. EUS was less accurate in assessment of lymph node metastasis; the overall accuracy rate was 57.1%. Distinction between reactive lymph node and small micrometastatic lymph node involvement could be hard. Local resectability was correctly diagnosed with EUS in each of 23 patients; in two patients an intramural mass with a deep infiltration into the surrounding tissue was correctly diagnosed. In our opinion EUS is an essential diagnostic procedure in the clinical staging of the gastric cancer.

[Multifocal inflammatory pseudotumor of the liver]. / Pseudotumore infiammatorio multifocale del fegato.

Inflammatory pseudotumor of the liver is a rare entity of unknown etiology; fewer than 80 cases have been reported in the world literature. Its appearance on the computerized tomography, ultrasound and magnetic resonance have been previously described as nonspecific, and clinical presentation is not helpful in the diagnosis. This is why the diagnosis usually is made after laparotomy and often after the excision of the tumor. Several recent reports show that drug therapy is effective and lead to tumor regression, while other authors believe that an aggressive approach should be taken, due to the potential adverse impact of its vascular invasive and biliary obstructive nature. Herein we describe a case of this clinical entity, which occurred in a 52 years old patient, where the operative examination showed bilobar involvement, treated with right hepatectomy and contra-lateral tumor excision in the clinical suspect of hepatocellular carcinoma. The detailed clinical, radiological and pathological picture is described. At 6 months follow-up the patient conditions are excellent. On the basis of the available literature, we discuss the clinical features and the therapeutical problems of such rare clinical entity, and propose a selected use of liver biopsy when the clinical suspicion of pseudotumor can be considered, in order to achieve a preoperative diagnosis and therefore to avoid surgery.

[Cancer of the gallbladder]. / II cancro della colecisti.

The Authors report their experience about 20 patients operated on since 1975 for primary carcinoma of the gallbladder. They remark their disappointment because of the poor percentage of preoperative and early diagnosis, that only allows a radical surgical therapy. More attention, therefore, should be payed to this not so rare pathology in the hope the survival of the patients radically operated will increase.

Effect of ursodeoxycholic acid on inflammatory infiltrate in gallbladder muscle of cholesterol gallstone patients.

BACKGROUND: Reduced gallbladder (GB) contractility and chronic inflammatory changes in the mucosa have been reported in patients with cholesterol gallstones (GS). Ursodeoxycholic acid (UDCA) restores GB contractility and antagonises liver macrophage activation. In the colon, hydrophobic bile acid, not hydrophilic UDCA, induces mast cell degranulation. We studied the presence of monocyte/macrophage infiltrate, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) expression, the number of total and degranulated mast cells in the GB muscle layer of cholesterol GS patients, and the effect of UDCA administration. METHODS: Gallbladder tissue was obtained from cholesterol GS patients, either treated or untreated with UDCA (10 mg kg(-1) day(-1)) for 30 days prior to surgery. Gallbladders removed for neoplastic diseases, not involving GB, were evaluated for control purposes. The presence of monocytes/macrophages (CD68 positive), granulocytes, and mast cells, and the COX-2 and iNOS expression, was determined immunohistochemically. KEY RESULTS: The number of CD68, granulocytes, mast cells, COX-2 and iNOS positive cells was significantly higher in the muscle layer of GS patients than in controls. Compared to untreated patients, those treated with UDCA showed significantly lower levels of CD68, COX-2 positive cells and degranulated mast cells and a lesser number of iNOS positive cells and granulocytes. CONCLUSIONS & INFERENCES: An inflammatory monocyte/macrophage, mast cell and granulocyte infiltrate is present in the GB muscle layer of GS patients. Ursodeoxycholic acid decreases macrophages, degranulated mast cells and COX-2 expression. These results suggest that monocytes/macrophages and degranulating mast cells contribute to muscle cell dysfunction in cholesterol GS patients and support the anti-inflammatory effect of UDCA.

Human equilibrative nucleoside transporter 1 and carcinoma of the ampulla of Vater: expression differences in tumour histotypes.

The human equilibrative nucleoside transporter 1 (hENT1) is the major means by which gemcitabine enters human cells; recent evidence exists that hENT1 is expressed in carcinoma of the ampulla of Vater and that it should be considered as a molecular prognostic marker for patients with resected ampullary cancer. Aim of the present study is to evaluate the variations of hENT1 expression in ampullary carcinomas and to correlate such variations with histological subtypes and clinicopathological parameters. Forty-one ampullary carcinomas were histologically classified into intestinal, pancreaticobiliary and unusual types. hENT1 and Ki67 expression were evaluated by immunohistochemistry, and apoptotic cells were identified by the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate biotin nick end labelling (TUNEL) method. hENT1 overexpression was detected in 63.4% ampullary carcinomas. A significant difference in terms of hENT1 and Ki67 expression was found between intestinal vs. pancreaticobiliary types (P=0.03 and P=0.009 respectively). Moreover, a significant statistical positive correlation was found between apoptotic and proliferative Index (P=0.036), while no significant correlation was found between hENT1 and apoptosis. Our results on hENT1 expression suggest that classification of ampullary carcinoma by morphological subtypes may represent an additional tool in prospective clinical trials aimed at examining treatment efficacy; in addition, data obtained from Ki67 and TUNEL suggest a key role of hENT1 in tumour growth of ampullary carcinoma.

[Pancreatic tumor: unusual onset of Von-Hippel Lindau syndrome]. / Tumore del pancreas un raro esordio di sindrome di Von-Hippel Lindau.

The Von-Hippel Lindau (VHL) disease is a rare genetically determined syndrome. Clinical course depends on the occurrence of multiple tumors as central nervous system tumors, phaeochromocytoma and renal cell carcinoma. We describe the second case in the literature reporting about a patient affected by a pancreatic neuroendocrine tumor as the first clinical sign of VHL disease. It has been showed that only a strict follow-up can effectively improve survival. Based on the present case, the follow-up of patients affected by VHL syndrome should routinely include functional tests and imaging exams of the pancreas.

[Xanthogranulomatous pyelonephritis and renal carcinoma. Report of a clinical case and review of the literature]. / Pielonefrite xantogranulomatosa e carcinoma renale. Presentazione di un caso clinico e revisione della letteratura.

Xanthogranulomatous pyelonephritis is a rare disease of the kidney; renal parenchyma is replaced by lesions radiologically simulating clear cell carcinoma. We present a case of a 62-year-old diabetic woman observed at our institution for the appearance of back pain and dysuria. A CT scan revealed a large lesion of left kidney with psoas muscle infiltration and the patient undrwent a nephrectomy. Histology surprisingly showed a xanthogranulomatous pyelonephritis. Though recent reports demonstrated the feasibility of conservative management of XGP with antibiotics, the use of pre-operative biopsy is still limited by the risk of seeding and the high false-negative results. How to distinguish xanthogranulomatous pyelonephritis from renal cancer?

Gastric submucosal neoplasms: new diagnostic and therapeutic procedures.

Submucosal neoplasms can be found in the esophagus and stomach during radiologic or endoscopic examination; histological diagnosis, however, is not significant in many cases because sampling is difficult. Endoscopic biopsies usually do not allow to obtain tissue from the submucosal layer nor other techniques prove to be reliable enough. 23 patients, aged between 21 and 76 were studied over a period of 5 years; in 1 male large gastric folds were observed. Of the 22 patients affected by benign submucosal neoplasms, 2 underwent surgical operation; no significant samples were obtained in any of the 11 cases in which biopsy forceps had been used. In the remaining patients an electrosurgical snare for polypectomy was used; this technique proved to be successful in 77.8% of cases. It is often shown to be also a therapeutic method when polypoid neoplasms are found.

Opsoclonus in a patient with cerebellar dysfunction.

After two days of malaise, headache, nausea, and vomiting, a 26-year-old man suddenly developed opsoclonus and stance and gait ataxia, without myoclonus. Having excluded a paraneoplastic etiology, we assumed that the disorder was probably related to a viral infection. Spontaneous resolution occurred in about two months. Opsoclonus became flutter dysmetria and then resolved. Saccadic eye movement recording disclosed the occurrence of hypermetria, increased velocity, and delayed latency, which also resolved. In this patient, the correspondence between clinical and ocular motor abnormality courses suggests a transient cerebellar dysfunction as the possible pathophysiologic mechanism for opsoclonus.