Piero Rossi

Percutaneous Liver Biopsy Using an Ultrasound-Guided Subcostal Route

Percutaneous biopsy is considered one of the most important diagnostic tools to evaluate diffuse liver diseases. The introduction and widespread diffusion of ultrasounds in medical practice has improved percutaneous bioptic technique, while reducing postoperative complications. Although ultrasonography has become almost ubiquitous in prebiopsy investigation, only one third of biopsies are performed under ultrasound control. Moreover, the one-day procedure, reported in several studies to be safe and cost effective, accounted for only 4% of biopsies done. We report our experience of 142 percutaneous US-guided biopsies performed on 140 patients affected by chronic diffuse liver disease over a four-year period. Liver biopsies were performed under US guidance at the patients bed using an anterior subcostal route. We evaluated postoperative pain, modifications of blood pressure and red cell count, hospital stay, morbidity and mortality rates, and adequacy of specimens for histologic examination. There was no operative mortality. As for major complications, one case of hemobilia occurred. As for minor complications, two cases of persistent postoperative pain required analgesic therapy. Patients were discharged the day following the procedure in all cases but two, who were discharged on the third and fifth postoperative days. Liver specimens were suitable for histologic diagnosis in all but one case, in which there were no portal spaces. According to our experience, we believe that hepatic biopsy guided by ultrasonography could replace blinded biopsy in the diagnosis of diffuse liver disease. The procedure is suitable to be performed safely on an outpatient basis.

Interleukin-34 Induces Cc-chemokine Ligand 20 in Gut Epithelial Cells.

BACKGROUND AND AIM Production of chemokines by intestinal epithelial cells is a key step in the amplification of the destructive immune-inflammatory response in patients with inflammatory bowel diseases [IBD]. In this study, we examined whether intestinal epithelial cells express macrophage colony-stimulating factor receptor 1 [M-CSFR-1], the functional receptor of interleukin-34 [IL-34], a cytokine that is over-produced in IBD and supposed to sustain inflammatory pathways. METHODS M-CSFR-1 expression was evaluated in intestinal samples of IBD patients, controls, and colon epithelial cell lines by real-time polymerase chain reaction [PCR], immunohistochemistry, and western blotting. DLD-1 cells were stimulated with IL-34 in the presence or absence of MAP kinase inhibitors, chemokine induction was assessed by real-time PCR and enzyme-linked immunosorbent assay [ELISA], and mitogen-activated protein (MAP) kinase activation was monitored by western blotting. The effect of a neutralising IL-34 antibody on CC chemokine ligand (CCL) 20 synthesis was tested in ex vivo organ cultures of IBD mucosal explants. RESULTS Enhanced expression of M-CSFR-1 RNA transcripts was seen in inflamed mucosa of IBD patients as compared with controls. Immunohistochemical analysis confirmed up-regulation of M-CSFR-1 in IBD and showed that both epithelial and lamina propria mononuclear cells expressed this receptor. Stimulation of DLD-1 with IL-34 increased CCL20 production through an ERK1/2-dependent mechanism. Consistently, treatment of IBD explants with anti-IL-34 reduced CCL20 production. CONCLUSIONS These data show that intestinal epithelial cells are a target of IL-34 and suggest that this cytokine contributes to mediating the cross-talk between epithelial cells and immune cells in IBD.

Smad7 knockdown activates protein kinase RNA-associated eIF2α pathway leading to colon cancer cell death

Upregulation of Smad7, an inhibitor of transforming growth factor-β1 (TGF-β1), occurs in sporadic colorectal cancer (CRC) and knockdown of Smad7 inhibits CRC cell growth, a phenomenon that associates with decreased expression of cell division cycle 25 homolog A and arrest of cells in the S phase of the cell cycle. These findings occur in CRC cells unresponsive to TGF-β1, thus suggesting the existence of a Smad7-mediated TGF-β1-independent mechanism that controls CRC cell behavior. Here we show that Smad7 inhibition with a specific Smad7 antisense oligonucleotide upregulates eukaryotic translation initiation factor 2α (eIF2α) phosphorylation, a transcription factor involved in the regulation of cell cycle arrest and induction of cell death, and induces activating transcription factor 4 (ATF4) and CCAAT/enhancer binding protein homology protein (CHOP), two downstream targets of eIF2α. Among the upstream kinases that control eIF2α phosphorylation, the serine–threonine protein kinase RNA (PKR), but not general control non-derepressible 2 (GCN2) and protein kinase RNA-like endoplasmic reticulum kinase (PERK), is activated by Smad7 knockdown. PKR silencing abolishes Smad7 antisense-induced eIF2α phosphorylation and ATF4/CHOP induction, thereby preventing Smad7 antisense-driven cell death. Smad7 inhibition diminishes interaction of PKR with protein kinase inhibitor p58 (p58IPK), a cellular inhibitor of PKR, but does not change the expression and/or activity of other factors involved in the control of PKR activation. These findings delineate a novel mechanism by which Smad7 knockdown promotes CRC cell death.

Natural humoral immune response to ribosomal P0 protein in colorectal cancer patients

BackgroundTumor associated antigens are useful in colorectal cancer (CRC) management. The ribosomal P proteins (P0, P1, P2) play an important role in protein synthesis and tumor formation. The immunogenicity of the ribosomal P0 protein in head and neck, in breast and prostate cancer patients and the overexpression of the carboxyl-terminal P0 epitope (C-22 P0) in some tumors were reported.MethodsSera from 72 colorectal tumor patients (67 malignant and 5 benign tumors) were compared with 73 healthy donor sera for the presence of antibodies to CEA, EGFR, ErbB2 and ribosomal P proteins by western blotting or ELISA. Expression of the C-22 P0 epitope on tissues and colon cancer cells was determined by immunoperoxidase staining and indirect immunofluorescence/western blotting, respectively, employing MAb 2B2. Biological effects of MAb 2B2 on colon cancer cells were assessed by the Sulforhodamine B cell proliferation assay, trypan blue exclusion test and cleaved caspase-3 detection. Fisher’s exact test was used to compare the number of auto-antibodies positive patients with healthy donors. Variation in the C-22 P0 expression, and in the number of apoptotic cells was evaluated by Student’s t-test. Variation in cell survival and cell death was evaluated by Newman-Keuls test.ResultsNo significant humoral response was observed to CEA, EGFR and ErbB2 in CRC patients. Conversely, 7 out of 67 CRC patient sera reacted to ribosomal P proteins. The prevalence of P proteins auto-antibodies in CRC patients was significant. Five patients showed restricted P0 immunoreactivity, while two patients reacted simultaneously to all P proteins. The C-22 P0 epitope was homogenously expressed both in malignant tumors and the adjacent mucosa, but the intensity of expression was higher in the tumor. Starved colon cancer cells showed a higher C-22 P0 epitope plasma membrane expression compared to control cells. MAb 2B2 inhibited colon cancer cell growth and induced cell death in a dose dependent manner.ConclusionsOur study shows a spontaneous humoral immune response to ribosomal P0 protein in CRC patients and the inhibition of in vitro cancer cell growth after C-22 P0 epitope targeting. The ribosomal P0 protein might be a useful immunological target in CRC patients.

Surgical treatment of gastric outlet obstruction due to gastroduodenal tuberculosis.

Gastroduodenal tuberculosis is a very rare location of abdominal tuberculosis; it is usually secondary to pulmonary tuberculosis and is often associated with HIV infection. We report a case of a 45-year-old woman with no HIV infection and no evidence of pulmonary tuberculosis, with a history of duodenal ulcer treated for several months, who presented at the emergency department with severe gastric outlet obstruction of recent onset caused by ulcerohypertrophic antroduodenal tuberculosis. The lesion was misdiagnosed at endoscopy as a malignancy, although histological examination of biopsies showed only chronic inflammation. The diagnosis was established at surgery, when a frozen section of an enlarged lymph node showed the presence of giant cells and caseating granuloma. The treatment was gastric resection with Roux-en-Y gastrojejunal anastomosis. In this patient the rare gastroduodenal location of tuberculosis occurred as primary disease in the absence of other organ involvement.

Activated c-Kit receptor in the heart promotes cardiac repair and regeneration after injury

The role of endogenous c-Kit receptor activation on cardiac cell homeostasis and repair remains largely unexplored. Transgenic mice carrying an activating point mutation (TgD814Y) in the kinase domain of the c-Kit gene were generated. c-KitTgD814Y receptor was expressed in the heart during embryonic development and postnatal life, in a similar timing and expression pattern to that of the endogenous gene, but not in the hematopoietic compartment allowing the study of a cardiac-specific phenotype. c-KitTgD814Y mutation produced a constitutive active c-Kit receptor in cardiac tissue and cells from transgenic mice as demonstrated by the increased phosphorylation of ERK1/2 and AKT, which are the main downstream molecular effectors of c-Kit receptor signaling. In adult transgenic hearts, cardiac morphology, size and total c-Kit+ cardiac cell number was not different compared with wt mice. However, when c-KitTgD814Y mice were subjected to transmural necrotic heart damage by cryoinjury (CI), all transgenic survived, compared with half of wt mice. In the sub-acute phase after CI, transgenic and wt mice showed similar heart damage. However, 9 days after CI, transgenic mice exhibited an increased number of c-Kit+CD31+ endothelial progenitor cells surrounding the necrotic area. At later follow-up, a consistent reduction of fibrotic area, increased capillary density and increased cardiomyocyte replenishment rate (as established by BrdU incorporation) were observed in transgenic compared with wt mice. Consistently, CD45−c-Kit+ cardiac stem cells isolated from transgenic c-KitTgD814Y mice showed an enhanced endothelial and cardiomyocyte differentiation potential compared with cells isolated from the wt. Constitutive activation of c-Kit receptor in mice is associated with an increased cardiac myogenic and vasculogenic reparative potential after injury, with a significant improvement of survival.

Familial colorectal cancer screening: When and what to do?

Colorectal cancer (CRC) is the third leading cause of death worldwide and represents a clinical challenge. Family members of patients affected by CRC have an increased risk of CRC development. In these individuals, screening is strongly recommended and should be started earlier than in the population with average risk, in order to detect neoplastic precursors, such as adenoma, advanced adenoma, and nonpolypoid adenomatous lesions of the colon. Fecal occult blood test (FOBT) is a non invasive, widespread screening method that can reduce CRC-related mortality. Sigmoidoscopy, alone or in addition to FOBT, represents another screening strategy that reduces CRC mortality. Colonoscopy is the best choice for screening high-risk populations, as it allows simultaneous detection and removal of preneoplastic lesions. The choice of test depends on local health policy and varies among countries.

Spontaneous intraperitoneal rupture of pyonephrosis in a patient with unknown kidney carcinosarcoma: a case report

Seventeen cases of peritonitis due to rupture of a pyonephrosis have been reported. The majority of these cases occur secondary to renal stones. Only two cases of ruptured pyonephrosis with concurrent kidney neoplasm have been described and only one of these presented as an acute peritonitis. In this presentation we discuss an unusual case of a 68 year old man with a chronic history of bilateral nephrolithiasis and recent pyonephrosis. He presented acutely with peritonitis and was later found to have a carcinosarcoma of the kidney. The case highlights the importance of recognizing the possibility of underling renal carcinoma in patients presenting with a ruptured pyonephrosis and discuss steps to avoid this serious complication.

Radio frequency interstitial thermal ablation of metastatic liver tumours

Introduction: Radio frequency thermal ablation (RFA) of focal liver metastatic lesions has received much recent attention as minimally invasive treatment of such pathologic entities. The purpose of the study was to evaluate the efficacy of RFA in the treatment of liver metastases from different tumors. Methods: In the period October 1998–January 2001, 29 patients affected by 38 focal lesions, age range 31–86 years old, 16 males and 13 females were treated in our Institution by RFA. Sixteen patients had liver metastases from colorectal cancer, four from gastric cancer, three from breast, two from kidney, one from anal carcinoma, one from esophageal cancer, one from pancreas, and one undetermined. Average metastases size was 3.22 cm (range 1.7–6 cm). All patients, except three, had the primary tumor already resected before the treatment of liver metastases. In six cases, RFA was repeated to complete ablation for a total of 35 procedures. Eight treatments were performed under general anesthesia after laparotomy, 27 ultrasound-guided procedures were performed percutaneously, 6 of them in general and 21 under local anesthesia. Results: Mean follow up was 12.9±6.9 months (range 2–27 months). One patient who underwent liver resection plus RFA of a second lesion, had a subphrenic abscess treated by percutaneous computed tomography (CT)-guided drainage, another patient had left intra-hepatic portal branch thrombosis, which recovered spontaneously. One patient died 11 months after treatment, a second patient died after 6 months. A follow up CT scan was done in 25 of 29 patients. In those 25 patients, 31 focal lesions were treated. The amount of focal lesion necrosis based on CT scan was complete (100%) in 24 lesions, nearly complete (90–99%) in 1 lesion, and partial in 6 lesions (50–89%). Conclusion: RFA is an effective and safe treatment modality for metastatic liver tumors. Larger future studies and longer follow up will be needed to evaluate the impact on survival with respect to surgical resection.

Solitary skin metastasis from sarcomatoid carcinoma of the bladder: a case report

IntroductionCutaneous metastases from carcinomas of the bladder are very rare. They are related to advanced stages of the disease and have poor prognosis with low survival rates. The common treatment modality of cutaneous metastases from a primary bladder cancer is wide local excision followed by chemotherapy.Case presentationWe report a case of solitary skin metastasis from a rare type of urinary bladder carcinoma in a 68 year-old Caucasian man. Urinary bladder carcinoma metastasizing to the skin is an uncommon finding despite the high incidence of this tumor. Skin metastasis generally presents in the late stages of this disease and indicates a poor outcome.ConclusionsBecause of the extremely aggressive malignant potential of sarcomatoid carcinomas, the indications for a transurethral resection of the bladder should be carefully assessed and suitable therapeutic strategies should be examined further.