Small bowel intussussception due to metastatic melanoma of unknown primary site. Case report.

Malignant melanoma is characterized by metastases also to the gastrointestinal tract, especially in the small bowel. The diagnosis is often delayed because unspecific clinical presentation (frequently as chronic iron deficiency anemia, rectal bleeding or intestinal obstruction). We present a case of melanoma of unknown primary site, with clinical presentation of intestinal obstruction. A segmental resection of the ileum was performed including mesentery with lymph nodes. Histology revealed metastatic melanoma from unknown primary. PET and MRI confirmed disseminated disease without brain metastasis.

Risk management in surgery.

Malpractice is the responsible for the greatest number of legal claims. At the present time, legal actions against physicians in Italy are 15,000 per year, and a stunning increase about costs to refund patients injured by therapeutic and diagnostic errors is expected. The method for the medical prevention is "Risk Management", that is the setting-up of organizational instruments, methods and actions that enable the measurement or estimation of medical risk; it allows to develop strategies to govern and reduce medical error. In the present work, the reconstruction about the history of risk management in Italy was carried out. After then the latest initiatives undertaken by Italy about the issue of risk management were examined.

Single-incision laparoscopic appendectomy is comparable to conventional laparoscopic and laparotomic appendectomy: our single center single surgeon experience.

Several studies have demonstrated the clinical and technical benefits of the laparoscopic surgery for complicated and uncomplicated appendicitis. Our retrospective study included 12 patient who underwent SILS appendectomy (SILS-A), 14 who received conventional laparoscopic surgery (VL-A), and 12 who received laparotomic appendectomy (OA); performed in all cases by the same surgeon (C.F.). The aim of this study was the comparison between this three different surgical techniques on same features: post operative leukocytosis, post operative pain, need abdominal drainage, esthetic viewpoint, incidence of complication, hospital stay. The results showed no significant differences between SILS-A and VLS-A, while an evident improvement shows versus O-A, even though not statistically significative. SILS was more effective in decreasing the risk of postoperative wound infection.

Technique and outcomes about a new laparoscopic procedure: the Pelvic Organ Prolapse Suspension (POPS).

Pelvic organ prolapse suspension (POPS) is a recent surgical procedure for one-stage treatment of multiorgan female pelvic prolapse. This study evaluates the preliminary results of laparoscopic POPS in 54 women with a mean age of 55.2 and a BMI of 28.3. Patients underwent at the same time stapled transanal rectal resection (STARR) to correct the residual rectal prolapse. We had no relapses and the preliminary results were excellent. We evaluated the patients after 1 year follow-up and we confirmed the validity of our treatment. The technique is simpler than traditional treatments with an important reduction or completely disappearance of the pre-operative symptomatology.

Liver resection for hemoperitoneum caused by spontaneous rupture of unrecognized hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is an increasingly common form of cancer. Although its spontaneous rupture is rare in Western countries, it constitutes a surgical emergency and is associated with high mortality. There is a lack of consensus as to the best approach and what parameters to use in choosing it. The three main approaches are conservative, endovascular and resection - the treatment of choice for acute abdominal bleeding. We report a case of hemoperitoneum following the spontaneous rupture of an unrecognized HCV-related HCC in a patient with no history of liver disease. The patient was successfully treated by emergency surgery, with resection of two segments of the left liver.

Cholecystectomy by single incision laparoscopic surgery (SILS): early experience and technique standardization.

Single Incision Laparoscopic Surgery (SILS) is a recent surgical technique, first described in the 1990s. Its aim is to optimize the esthetic result offered by laparoscopy by minimizing the number of abdominal incisions. Various preliminary studies have been carried out on the application of SILS, especially in cholecystectomy and appendectomy. This study evaluates the preliminary results of cholecystectomy by SILS (SILS™ Port) conducted between October 2009 and February 2011 on 21 patients (4 men and 17 women) with a mean age of 49.9 years and a mean Body Mass Index (BMI) of 22.8. All patients were treated by the same team, which had previously undergone six months' simulator training. There were two main selection criteria, both evaluated intraoperatively: absence of adhesions and of significant inflammatory sequelae from previous cholecystitis; and suitable distance between gallbladder and SILS access port. Conversion to traditional laparoscopy was necessary in just two cases, while an accessory trocar was introduced in another two cases. Conversion to open surgery was not necessary in any case. One case of SILS cholecystectomy was complicated by postoperative bile leakage, which was treated conservatively, as the fistula had a low output. The mean duration of hospitalization was 3.6 days. This preliminary experience led us to conclude that SILS is safe and highly satisfactory in the postoperative phase, thanks to the reduced need for painkillers and the improved esthetic result.

[Unusual cause of acute abdomen in adult patient: gallstone ileus]. / Insolita causa di addome acuto in paziente adulto: l'ileo biliare.

INTRODUCTION: Gallstone ileus is a rare complication of cholecystolithiasis. It causes 1-3% of the mechanical obstructions of the small bowel. It often affects patients between 63 and 85 years old. Pre-operative diagnosis is usually delayed 1-10 days because there is not a specific symptomatology. CASE REPORT: The authors report the case of a 50 year-old man with diagnosis of mechanical obstruction of the small bowel caused by a voluminous gallstone. Ileal occlusion was showed by CT. The patient underwent to one-stage emergency surgery with enterolithotomy, cholecystectomy and duodenal fistula repair. Patient's recovery was regular and he was discharged fourteen days after surgery. DISCUSSION: In our case gallstone ileus was diagnosed with a delay of 5 days. Ultrasonography was not able to show the gallbladder. Diagnosis was made by CT, which is the diagnostic gold standard. CONCLUSION: Patient's performance status influences surgical strategy. In our experience, the patient underwent one-stage surgery because he was considered at low risk. Instead staged procedure with enterolithotomy and delayed cholecystectomy and fistula repair, is performed only in patients at high risk.

[Umbilical primary endometrioma. Case report]. / Endometriosi primitiva ombelicale. Caso clinico.

Umbilical primary endometrioma is a rare extra-uterine localization of endometriosis with a documented neoplastic risk. It is often difficult to distinguish primary umbilical endometriosis from other benign and malignant tumors of the abdominal wall. The Authors report a case of umbilical endometriosis in a 36-year old female. Endometriosis was suspected because of the presence of the typical cyclic bleeding and swelling. Abdominal CT excluded the presence of other endometriotic localizations. The umbilical mass was widely excised together with umbilicus, fascia and peritoneum. The tissue defect was primary closed without prosthetic mesh. Histological examination of the specimen showed the presence of endometrial glands with stromal component, compatible with the diagnosis of endometriosis. The Authors suggest that surgery should be performed in the first 3-4 days of the follicular phase, to minimize the risk of diffusion of endometriotic cells. Moreover, the excision should be wide in order to prevent local recurrence.

[Massive haemoperitoneum due to traumatic rupture of multifocal hepatocarcinoma in the right hepatic lobe. Case report]. / Emoperitoneo massivo da rottura di epatocarcinoma multifocale del lobo destro. Case report.

UNLABELLED: Abdominal blunt trauma is the main cause of death in people younger than 40 years old. The liver injury still represents a challenging problem. Isolated hepatic injury is rare and it occurs more frequentely in polytraumatizated patients and causes massive haemoperitoneum. The Authors report a case of a 83 years-old woman admitted to Emergency Department for syncope due to an active bleeding arising from a rupture of a right hepatic lobe unsuspected tumor. The computer tomography (CT) scans showed a clear pattern of liver laceration of the VI segment with contrast enhancement spreading in the surrounding tissues, and detected a multifocal hepatocarcinoma located in the VI, VII and VIII segments. Patient's haemodinamically unstable conditions suggested an urgent laparotomy. An accurate perihepatic packing with sterile-drape were successfully employed to control liver hemorrage. Temporary abdominal closure, followed by hepatic arteriography and the right hepatic artery embolization, completed the damage control. Re-exploration laparotomy after 72 hours confirmed the definitive haemostasis and the pack removal was performed without complications. CONCLUSIONS: CT plays a leading role in the diagnosis of liver damage. The patient's haemodynamic status is the principal criterion determining conservative or operative therapy in blunt liver injury. The early perihepatic packing followed by artheriographic embolization to stop liver hemorrhage showed efficacy and safety for the patient. The packing performed with sterile-drape is able to avoid removal complications and 72 hours timing for the pack removal is effective to avoid re-bleeding.

[A case of arterial chemoembolization for hepatocellular carcinoma with 11 years of survival]. / Un caso di epatocarcinoma trattato con chemio-embolizzazione arteriosa transcatetere con sopravvivenza di 11 anni.

Hepatocellular carcinoma (HCC) is the most common malignancy of the liver and the third most common cause of cancer mortality worldwide. The major risk of developing HCC is associated with HBV and HCV hepatitis. Liver transplant (LT) is the gold standard for "small" HCC (HCCs) in Child-Pugh class A cirrhotic patients. However its use has been restricted by the severe shortage of donors, so that hepatic resection (HR) is often performed in these patients. In the last two decades image-guided interventional catheterization and ablative regional treatment procedures have revolutionized the therapy of unresectable primary and secondary liver tumors. The Authors present a case of a 61-years old man with Child-Pugh class A HCCs. The age and the previous history of bladder carcinoma made the patient not suitable for LT. The patient refused HR so that transarterial chemoembolization combined to thermo-ablation therapy and oral intake of tamoxifen were proposed. Patient's tolerance to the treatments has been good. During 11-year follow-up there was earlier intrahepatic progression of the tumor followed by reduction in size and number of the lesions. In spite of the scarce prognosis, chemoembolization and immunotherapy allowed to achieve a satisfactory local control of disease in our patient and guaranteed a good quality of life at long-term follow-up.

[A case of uterine carcinosarcoma]. / Carcinosarcoma dell'utero: descrizione di un caso clinico.

Uterine carcinosarcoma is a highly aggressive neoplasm with tendency to early recurrence and/or metastasis. The neoplasia has both epithelial and stromal malignant components. Clinically, it is characterized by a postmenopausal metrorrhagia, associated sometimes with abdominal pain. The Authors describe a case of carcinosarcoma in a 82-year old woman with a vaginal bleeding since 10 months and an ingravescent hypochromic anemia. The RMN of the abdomen and pelvis showed a mass occupying the whole uterine lumen, without signs of pelvic diffusion. A bilateral hystero-oophorectomy was performed; the patient's critical conditions and a high anaesthesiological risk advised us not to perform a bilateral pelvic lymphadenectomy with aortic sampling. Six months after operation, a clinical follow-up with a total-body CT didn't show any sign of local recurrence and/or distant metastasis. From the analysis of this case report and from the data of the literature some important considerations can be done: a) gynecologic check up in post-menopausal women with associated risk factors (obesity and hypertension) can allow an early diagnosis also in asymptomatic patients; b) sovrapubic and transvaginal US, abdomino-pelvic CT and MRI are essential for a correct clinical staging; c) surgical excision followed by the histological examination of the specimen is mandatory to establish a correct diagnosis.

[A possible cause of misdiagnosis in tumors of the axilla: schwannoma of the brachial plexus]. / Una possibile causa di errore nella diagnosi differenziale delle formazioni ascellari: lo schwannoma asintomatico dei tronchi del plesso brachiale.

The Authors report a rare case of a 57 years old man affected by a left radial nerve schwannoma that occurred as an asymptomatic lesion of the axilla. At clinical examination the lump was undistinguishable from the most common axillary lymphadenopathy. A lymphoadenopathy was erroneously diagnosed with ultrasonography (US). This mistake was due to the low specificity of the instrumental methodology and to the rarity of an asymptomatic schwannoma of the infraclavicular brachial plexus. The neoplasia was excised without using the microscope. In the early post-operative follow up, a "falling" attitude of the wrist, the hand and the fingers appeared, peculiar for a lesion of the radial nerve. Furthermore a hypoaesthesia of the skin of first finger and of the first interosseus space was associated. The sensitive and motor electromyography showed a radial nerve suffering. The "stupor" of the nerve trunk was treated with steroid therapy for 7 days and the patient underwent to some series of neuro-rehabilitative physical therapy for 12 weeks. The postoperative total body CT, showed that the lesion was unique: therefore it was possible to exclude the diagnosis of neurofibromatosis. After 28 months electromyography and axillary US were performed showing the complete resolution of the motor and sensitive deficit and the absence of local recurrence.

Adenovirus as vehicle for anticancer genetic immunotherapy.

Adenoviruses (Ads) are in the forefront of genetic immunization methods being developed against cancer. Their ability to elicit an effective immune response against tumor-associated antigens has been demonstrated in many model systems. Several clinical trials, which use Ad as vehicle for immunization, are already in progress. Preclinical studies have also demonstrated the efficacy of combining Ad-mediated immunization with adjuvants such as chemotherapeutic agents and cytokines. Issues related to sero-prevalence and safety of Ads, however, continue to pose a challenge and need to be addressed.

Curcumin inhibits activation of Vgamma9Vdelta2 T cells by phosphoantigens and induces apoptosis involving apoptosis-inducing factor and large scale DNA fragmentation.

Curcumin, in addition to its role as a spice, has been used for centuries to treat inflammatory disorders. Although the mechanism of action remains unclear, it has been shown to inhibit the activation of NF-kappaB and AP-1, transcription factors required for induction of many proinflammatory mediators. Due to its low toxicity it is currently under consideration as a broad anti-inflammatory, anti-tumor cell agent. In this study we investigated whether curcumin inhibited the response of gammadelta T cells to protease-resistant phosphorylated derivatives found in the cell wall of many pathogens. The results showed that curcumin levels > or =30 microM profoundly inhibited isopentenyl pyrophosphate-induced release of the chemokines macrophage inflammatory protein-1alpha and -1beta and RANTES. Curcumin also blocked isopentenyl pyrophosphate-induced activation of NF-kappaB and AP-1. Commencing around 16 h, treatment with curcumin lead to the induction of cell death that could not be reversed by APC, IL-15, or IL-2. This cytotoxicity was associated with increased annexin V reactivity, nuclear expression of active caspase-3, cleavage of poly(ADP-ribose) polymerase, translocation of apoptosis-inducing factor to the nucleus, and morphological evidence of nuclear disintegration. However, curcumin led to only large scale DNA chromatolysis, as determined by a combination of TUNEL staining and pulse-field and agarose gel electrophoresis, suggesting a predominantly apoptosis-inducing factor-mediated cell death process. We conclude that gammadelta T cells activated by these ubiquitous Ags are highly sensitive to curcumin, and that this effect may contribute to the anti-inflammatory properties of this compound.

Developmental plasticity of CNS microglia.

Microglia arise from CD45(+) bone marrow precursors that colonize the fetal brain and play a key role in central nervous system inflammatory conditions. We report that parenchymal microglia are uncommitted myeloid progenitors of immature dendritic cells and macrophages by several criteria, including surface expression of "empty" class II MHC protein and their cysteine protease (cathepsin) profile. Microglia express receptors for stem cell factor and can be skewed toward more dendritic cell or macrophage-like profiles in response to the lineage growth factors granulocyte/macrophage colony-stimulating factor or macrophage colony-stimulating factor. Thus, in contrast to other organs, where terminally differentiated populations of resident dendritic cells and/or macrophages outnumber colonizing precursors, the majority of microglia within the brain remain in an undifferentiated state.

Activation of C-C beta-chemokines in human peripheral blood gammadelta T cells by isopentenyl pyrophosphate and regulation by cytokines.

Human gammadelta T lymphocytes respond to viral, bacterial, protozoal, and tumoral antigens, but their precise function remains unknown. In adults the major circulating gammadelta T-cell subset expresses the Vgamma9Vdelta2 T-cell receptor and responds to protease-resistant phosphorylated derivatives found in many pathogens. In this study we show that activation of Vdelta2(+) cells with the nonpeptidic antigen isopentenyl pyrophosphate (IPP) rapidly induces (within 4-12 hours) the C-C chemokines MIP-1alpha, MIP-1beta, and lymphotactin but not MCP-1. The most robust response was obtained for MIP-1beta. IPP induction of MIP-1alpha and MIP-1beta was not affected by costimulation with interleukin-4 (IL-4), IL-10, TGF-beta, or interferon-gamma (INF-gamma). However, IL-12 significantly enhanced IPP-induced expression and release of MIP-1alpha that was down-regulated by TGF-beta whereas the induction of MIP-1beta by IPP+IL-12 was refractory to cotreatment with TGFbeta indicating that these chemokines are differentially regulated by these cytokines. Vdelta2(+) T cells also expressed a wide range of C-C chemokine receptors including CCR1, CCR5, and CCR8, all of which were down-regulated following activation. We conclude that Vdelta2(+) cells can be rapidly induced by components of bacterial cell walls to express high levels of proinflammatory chemokines, supporting an important role for these cells in the early stages of the inflammatory responses to many common pathogens. (Blood. 2000, 95:39-47)

Antigen presenting capacity of brain microvasculature in altered peptide ligand modulation of experimental allergic encephalomyelitis.

Co-immunization with an altered peptide ligand (LR) partially protects SJL mice from proteolipid protein peptide 139-151-induced experimental allergic encephalomyelitis [Kuchroo, V.K., Greer, J.M., Kaul, D., Ishioka, G.Y., Franco, A., Sette, A., Sobel, R.A., Lees, M.B., 1994. A single TCR antagonist peptide inhibits experimental allergic encephalomyelitis mediated by a diverse T cell repertoire. J. Immunol. 153, 3326-3336; Santambrogio, L., Lees, M.B., Sobel, R.A., 1998. Altered peptide ligand modulation of experimental allergic encephalomyelitis: immune responses within the CNS. J. Neuroimmunol. 81, 1-13]. Clinical protection was noted despite extensive central nervous system inflammation observed after co-immunization with native and altered peptides. To extend our previous reports on this model, we now compare MHC class II expression and antigen presenting cell activity of cells associated with the blood-brain barrier in diseased and protected mice. Immunohistochemical studies identified MHC class II products on both the endothelial and microglial/macrophage populations. Ex vivo experiments suggested a correlation between the reduced clinical disease observed in the co-immunized mice and the antigen presenting activity of cells at the blood-brain barrier. The results suggest that antigen presenting activity is primarily mediated by macrophage-lineage cells of the central nervous system.

Cytokine, chemokine and chemokine receptor mRNA expression in different strains of normal mice: implications for establishment of a Th1/Th2 bias.

The resistance or susceptibility of inbred strains of mice to various pathogens and autoimmune diseases such as EAE has been linked to differences in the balance between cytokines associated with Th1- and Th2-type immune responses. Previous work from this laboratory on the mouse strain specific resistance to mouse adenovirus type I (MAV-1)-induced encephalopathy revealed subtle differences in the transcription rates of several immunologically important molecules that was evident prior to infection. In this study, we show striking differences in cytokine, chemokine and chemokine receptor mRNA expression in the spleens of normal, immunologically naive C57BL/6J, BALB/cJ and SJL/J mice. Messenger RNAs for interferon (IFN)-gamma and the chemokine IFN gamma inducible protein (IP)-10 were preferentially expressed in C57BL/6J spleens, whereas in BALB/cJ spleens mRNAs for lymphotoxin-beta, interferon-beta, transforming growth factor-beta, and the chemokine receptors CCR3 and CXCR4 predominated. A unique profile of chemokine receptors was found in spleens from normal SJL/J mice that correlated with the presence of polymorphisms within the CCR-3 gene. The patterns of gene expression fit well into the Th1/Th2 paradigm for C57BL/6J and BALB/cJ strains and suggest an important role for chemokines, as well as cytokines, in contributing to the genetic basis of the immune response.

CD94/NKG2 inhibitory receptor complex modulates both anti-viral and anti-tumoral responses of polyclonal phosphoantigen-reactive V gamma 9V delta 2 T lymphocytes.

Viral, bacterial, protozoal, and cancer-associated Ags elicit strong responses in human gammadelta T lymphocytes. The majority of these cells in the peripheral blood express the Vgamma9Vdelta2-encoded TCR and recognize nonpeptidic phosphoantigens without an apparent MHC restriction. We have shown that Vgamma9Vdelta2 T cells express the inhibitory CD94/NKG2 receptor for HLA class I molecules. The anti-CD94 mAb inhibits 1) the Vgamma9Vdelta2 T cell proliferation in response mycobacterial phosphoantigens and 2) the HIV-induced Vgamma9Vdelta2 T cell expansion. Vgamma9Vdelta2 T cells stimulated with nonpeptidic mycobacterial antigens produce IFN-gamma and TNF-alpha. Signaling through the CD94/NKG2 receptor interferes with the synthesis of these cytokines. The CD94/HLA class I interaction is also involved in the cytotoxic activity of Vgamma9Vdelta2 T cells. The Vgamma9Vdelta2 T cell regulation through the CD94 receptor may be important for the potentially dual function in innate immunity, i.e., 1) NK-like and 2) TCR ligand-induced cytolytic activities.