Liver focal fatty changes at ultrasound after islet transplantation: an early sign of altered graft function?

AIMS: Few longitudinal imaging studies of liver-engrafted islets after islet transplantation are available for islet-transplant-alone (ITA) and islet-after-kidney (IAK) transplanted patients. Particularly controversial is the link between islet function and the appearance of islet-induced liver focal fatty changes. Aims of this study were to assess liver focal fatty changes at ultrasound after islet transplantation and their relationship with islet function. METHODS: The timing of first ultrasound detection of liver focal fatty changes and the prevalence and duration of these changes were assessed in 30 IAK transplanted patients, in five ITA patients and, retrospectively, in full-, partial- and no-function groups, according to islet function evaluated 1 year after transplantation. Patients with persistent ultrasound detected liver focal fatty changes underwent liver biopsy. Ultrasound positive and negative patients with functioning islets were compared for islet-function and C-peptide-levels during the follow-up. Variations of cholesterol/triglycerides and other metabolic parameters were also recorded at 1 year. RESULTS: Liver focal fatty changes at ultrasound were found in 12 patients (10/30 IAK, 2/5 ITA). First detection was at 6 months in eight cases and at 12 months in four cases. Liver ultrasound changes were of more than 1 year duration in eight cases. Steatosis was found histologically in 8/8 patients. At 12 months, liver ultrasound changes were detected to a greater extent in patients with partial islet function (10/12, eight IAK, two ITA) compared with patients with full islet function. C-peptide-levels were significantly lower in ultrasound-positive than in ultrasound-negative patients. At 18 months, ultrasound- positive patients were more prone to worsening of their function (9/12) compared with ultrasound-negative patients (3/18). No statistically significant differences of cholesterol/triglycerides levels were found in either the total number of patients or the IAK and ITA patients. CONCLUSIONS: Liver focal fatty changes at ultrasound (steatosis) after islet transplantation in IAK and ITA patients may represent an early sign of altered graft function.

Natural killer-cell cytotoxicity in HIV-positive and HIV-negative patients with and without severe course of hepatitis B virus infection.

Natural killer (NK) cells represent the first line of defence against viral infections but, in the case of hepatitis B virus (HBV), may also be involved in liver injury. We here compared NK-cell activity of 11 patients with acute HBV infection, either HIV-positive or HIV-negative, with that of 11 healthy subjects. One of the HIV-positive patients, characterized by a severe immunodeficiency, died 3 weeks after hospitalization for HBV-related fulminant hepatitis (FH). He displayed a remarkable NK-cell cytotoxicity against both cell lines and autologous dendritic cells, whereas the NK-cell activity of the remaining patients was significantly reduced as compared with healthy individuals. Our findings suggest that NK-cell-mediated cytotoxicity could contribute to the development of HBV-related acute liver failure in HIV-positive patients with severe immunodeficiency. An immunopathological model of FH in immunocompromised patients was proposed.

Mutations in the E2-PePHD region of hepatitis C virus type 1b in patients with hepatocellular carcinoma.

An interaction between the protein kinase (PKR)-eIF2-alpha phosphorylation homology domain (PePHD) within the E2 protein of hepatitis C virus (HCV) and cell protein kinase (PKR) may affect the control of protein synthesis and cell growth. In an attempt to investigate the genetic variability of the E2-PePHD domain in hepatocellular carcinoma (HCC), we studied sera and liver tissues from HCC patients. The partial E2-PePHD region was analysed by direct sequencing of the sera of 47 HCCs in cirrhotic livers and 31 cases of chronic active hepatitis (CAH), and tumoral and non-tumoral liver tissues from 13 HCC patients. A similar number of mutations was detected within the E2 domain in the HCC and CAH cases, but nine of the 47 HCCs (19%) showed an amino acid (aa) mutation at position 660, eight of which involved a change in the same aa (alanine instead of serine; A/S). No such mutation was detected in any of the PePHD sequences from the CAH patients: this difference was statistically significant (P = 0.008). The aa change at position 660 was also found in two sequences from tumoral but not non-tumoral tissue from the same liver. The analysis of 461 sequences obtained from GenBank supports the conclusion that the observed aa change is an infrequent event in HCV-infected patients, thus suggesting that it could be associated with HCC.

Impact of HAART on liver histology of HIV/HCV coinfected patients.

The impact of HAART on the progression of HCV related liver disease is controversial. This retrospective study compares the grading and staging of chronic viral hepatitis in HIV/HCV coinfected subjects treated or not with antiretroviral therapy (ART) including protease inibithors (PI). The liver histology of 44 HIV/HCV coinfected patients on ART for more than 12 months, 26 coinfected patients naïve for ART and 31 HCV monoinfected patients were analysed by the Ishak score. None of the multivariate models calculated to test if liver histopathology (Ishak grading or staging) between HIV/HCV coinfected patients versus HCV monoinfected or antiretroviral-treated versus untreated HIV+ subjects showed any statistical difference. No significant difference between grading and staging was evidenced either in PI treated subjects versus patients on ART without PI.

Prognostic value of the modified TNM (Izumi) classification of hepatocellular carcinoma in 53 cirrhotic patients undergoing resection.

BACKGROUND/AIMS: Few studies have assessed the significance of prognostic factors in cirrhotic patients undergoing resection for hepatocellular carcinoma. METHODOLOGY: Overall survival and disease-free survival were evaluated in 53 cirrhotic patients undergoing hepatic resection for supervening hepatocellular carcinoma. The value of the UICC TNM classification, and the Izumi modified staging system on prognosis were analyzed. RESULTS: In multivariate analysis lack of micro/macrovascular invasion were predictive for long-term outcome. The difference between stages 1 and 2 or stage 3 and 4A using the UICC TNM classification was not significant with respect to survival or disease-free survival. UICC TNM classification was modified as follows; stage 1, solitary tumor without vascular invasion; stage 2, solitary or multiple tumor(s) involving adjacent vessel branch; stage 3, tumor(s) involving major vessel branch or with regional lymph node metastases; stage 4, tumor(s) with distant metastases. TNM (modified in accordance with Izumi) showed a significant difference between each stage with respect to survival and disease-free survival. CONCLUSIONS: A uniform tumor classification of hepatocellular carcinoma is advocated. Our results show that the UICC TNM classification for hepatocellular carcinoma is inadequate and may even on occasion lead to unnecessary resection. The modified staging system of Izumi is superior in determining outcome for cirrhotic patients with supervening hepatocellular carcinoma undergoing resection.

Gastric carcinoma detected by cervical cytology.

This paper is a report on a case of gastric carcinoma of diffuse type in a young female patient aged 38. The patient was still asymptomatic at hospital admission, her only pathological sign being the finding of malignant cells of indeterminate origin at a routine Pap-test examination. Subsequent investigations showed the presence of a poorly differentiated gastric carcinoma, with metastatic diffusion to uterus, ovaries and peritoneum. Only a few cases of gastric carcinomas without cervical localization, detected by Pap-test, are reported in literature. A few other cases with cervical localization have been described. The aim of this work is to point out that a Pap-test smear may reveal the presence of extragenital tumors still unappreciated.

Acute renal failure due to idiopathic tubulo-intestinal nephritis and uveitis: "TINU syndrome". Case report and review of the literature.

Acute renal failure due to idiopathic tubulo-interstitial nephritis associated with bilateral uveitis (TINU syndrome) is a rare clinical event, contracted mainly by girls or women. Here we report the clinical follow-up regarding a 22-year-old woman with acute renal failure (creat. clearance 13.5 ml/min) due to idiopathic tubulo-interstitial nephritis documented by renal biopsy, after bilateral uveitis which healed with local prednisone. The clinical history and the clinical follow-up of our patient were typical of the TINU syndrome. We were able to exclude all diseases causing acute tubulo-interstitial nephritis such as systemic infection, hypersensitivity to drugs, Behcet's disease, Sjogren syndrome, sarcoidosis, systemic lupus or vasculitides. The patient recovered after systemic prednisone.

Relationship between the shape and size of radiofrequency induced thermal lesions and hepatic vascularization.

AIMS AND BACKGROUND: The aim of this study was to evaluate the relationship between hepatic vascularisation and the final size and shape of radiofrequency (RF) induced thermal lesions. METHODS: Series of four RF thermal lesions were created in explanted calf livers and in pig livers maintaining the following experimental conditions throughout the procedure: normal hepatic perfusion, occlusion of the hepatic artery, occlusion of the portal vein, occlusion of both hepatic artery and portal vein (Pringle maneuver) and subtotal occlusion of the hepatic veins. A 14G expandable needle electrode was used to make the thermal lesions. Each lesion was created applying predetermined temperatures ranging between 95 and 115 degrees C and an exposure time of 20 minutes. RESULTS: Occlusion of the hepatic artery during the RF procedure resulted in moderate and not significant increases in thermal lesion diameter compared with those obtained in normally perfused liver (3.0 +/- 0.4 cm vs 3.0 +/- 0.2 cm), while occlusion of the portal vein resulted in larger lesion diameters (3.5 +/- 0.3 cm). In both these cases the diameters of the thermal lesions were smaller than those obtained in explanted calf liver (4.0 +/- 0.3 cm) and their shape showed peripheral irregularities. Thermal lesions larger than those seen in normally perfused liver and equaling those observed in explanted calf liver were created both during the Pringle maneuver (4.0 +/- 0.2 cm) and after subtotal occlusion of the hepatic veins (4.0 +/- 0.3 cm). In both these cases the thermal lesions were regular in shape. CONCLUSIONS: Occlusion of the blood flow during the RF procedure avoids heat loss by convection, resulting in the creation of larger thermal lesions than those obtained in normally vascularized liver using the same electrode, temperatures and exposure time. This technique could therefore be employed in humans to destroy large hepatic tumor nodules.

Emergency liver resection for ruptured hepatocellular carcinoma complicating cirrhosis.

BACKGROUND/AIMS: From a consecutive series of 51 patients surgically treated from January 1993 to August 1997 for hepatocellular carcinoma (HCC) complicating cirrhosis, 6 subjects (12%) presented with acute hemoperitoneum due to spontaneous rupture of the tumor: 3 patients were suffering from chronic hepatitis C, 2 were affected by alcoholic cirrhosis, and one by chronic hepatitis B. The present paper reports experience of the treatment of ruptured HCC complicating cirrhosis in 6 patients undergoing emergency hepatectomy. METHODOLOGY: Hemoperitoneum was successfully diagnosed pre-operatively with the combination of abdominal ultrasound (US) and paracentesis. All subjects had a known history of chronic liver disease, but undiagnosed HCC. Child-Pugh classification assessed the hepatic functional reserve to predict operative risk. Surgical indication was based on hemodynamic instability and/or persistent bleeding. Time from admission to operation was recorded as well as tumor site, size and number, the site of bleeding, and the duration of surgery and hepatic devascularization. Tumor location was defined according to segmental anatomy. All patients underwent one-stage liver resection (segmentectomy VII-VIII in one patient; non-anatomical wedge resections in 5). Operative mortality was defined as death within 30 days of surgery. RESULTS: No intra-operative death occurred. In 4 patients the post-operative course was uneventful. Two patients died 2 weeks after surgery from liver failure (one patient) eventually complicated by renal failure (one patient). Three patients are alive and 2 of them disease-free at 24 months after surgery, whilst one patient has died from liver failure 21 months after surgery in the presence of intrahepatic recurrence of HCC. CONCLUSIONS: Present experience, combined with a literature review on 755 ruptured HCC cases, indicates that emergency liver resection is feasible in patients with limited tumor and preserved liver function (Child-Pugh A or B grade); surgical resection is the only procedure possibly associated with long-term survival, as shown by 4/6 patients of ours surviving more than 12 months, with 2 subjects disease-free at 24 months. Conservative management, such as surgical/radiological devascularization, packing or plication, can be conducted on high risk patients, though long-term survivors have not been reported.

Extramedullary plasmacytoma in a patient with AIDS: report of a case and review of the literature.

Human immunodeficiency virus (HIV) is likely to play a role in the onset of plasma cell tumors (PCT). In fact, HIV could be involved in plasmacytomagenesis in several ways: it has the ability to lessen the immunosurveillance to such a degree as to impair the immune response against tumor cell growth. This decreased immunosurveillance could further facilitate the transforming malignant role of possible Epstein-Barr virus (EBV) infection occurring in this setting. Lastly, a murine retrovirus has been shown to be able to accelerate plasmacytomagenesis in mice, thus indicating that these viruses may be directly involved in the onset of PCT. According to cases previously reported in the literature, the clinical features of this case of HIV-associated PCT were more aggressive and the survival was shorter than expected for PCT cases in the general population. Further, the pattern of alteration of gammaglobulinemia differed in this setting. These alterations strongly suggest a direct role of HIV in PCT. Further in-depth investigations are therefore warranted to elucidate this issue.

Benefits of using telemedicine and first results in Bosnia and Herzegovina.

In October 1996 the Institute of Pathology with the Radiology and Ophthalmology Clinic of the university hospital of Sarajevo joined the experimental telemedicine project SHARED. Two months after the project began, dermatology, paediatrics and haematology were also included. During the first phase we had 40 teleconsultations that showed us the benefits of using telemedicine. Our opinions and the opinions of the pathologist in Milan were similar for most of the biopsies (78%). The total time required for the consultation for the first 40 cases was 372 min, or 9.3 min each, on average. The longest consultation time was 25 min. The largest number of images was 44 per case, the smallest four. Because of problems of infrastructure and lack of experts, telemedicine will be important to a small country like Bosnia and Herzegovina.

Percutaneous RF interstitial thermal ablation in the treatment of hepatic cancer.

OBJECTIVE: The aim of this study was to evaluate the usefulness of RF interstitial thermal ablation for treating hepatic cancer. SUBJECTS AND METHODS: Fifty patients, 39 who had 41 hepatocellular carcinoma nodules and 11 who had 13 hepatic metastatic nodules, underwent RF interstitial thermal ablation. In all but one, a thermal necrosis volume greater than the tumoral nodule volume was created to obtain total tumor destruction. One large tumor was treated for debulking purposes. RESULTS: Hepatocellular carcinoma nodule destruction was achieved in a mean of 3.3 sessions of RF interstitial thermal ablation. During a mean follow-up of 22.6 months (range, 3-66 months), 16 (41%) of 39 patients had recurrences; two (5%) of these patients showed local recurrences and the remaining 14 (36%) had new lesions. Nine of these 16 patients underwent further RF interstitial thermal ablation that proved effective. RF interstitial thermal ablation was also successfully repeated in four patients who had a second recurrence. With RF interstitial thermal ablation, we treated 54 hepatocellular carcinoma nodules in 39 patients. Eleven (28%) of the 39 patients died: five from hepatic failure due to advanced cancer and six from causes other than cancer. Autopsy was performed on three patients who died from causes other than cancer, one had had two new courses of RF interstitial thermal ablation for two new lesions. Gross examination failed to detect two treated tumor nodules; histologic examination of three other treated tumor nodules showed total necrosis in two nodules and a 3-mm focus of viable cancer cells in the other nodule. Cumulative survival curves showed the median survival time to be 44 months. The survival rate for the first year was 0.94, 0.86 for the second year, 0.68 for the third year, and 0.40 for the fourth and fifth years. In the patients treated for metastatic nodules, posttreatment imaging studies showed necrosis that varied from 80% to 100% in all cases. Pathologic studies performed on two patients who underwent surgery after RF interstitial thermal ablation showed 100% necrosis in one case and 80% necrosis in the other. CONCLUSION: RF interstitial thermal ablation is a useful percutaneous treatment for hepatic cancer.

[Angiodysplasia of the right colon]. / Angiodisplasia del colon destro.

Ascending colon angiodysplasia is a frequent cause of colorrhagia or chronic blood loss in old patients, but also possible under the age of 55. Angiodysplasia diagnosis is often underestimated. For a long time colorrhagia or lower intestinal bleeding were generally diagnosed like diverticular bleeding. This conclusion was the result of several conditions: the conservative management of distal gastrointestinal bleeding is in most cases successful; the double dye clysma was the first and the main diagnostic procedure for many years and the result was a not correct diagnosis of diverticular bleeding since large bowel diverticulosis is always present in the elderly. The authors report on three cases of low intestinal bleeding where the diagnosis of angiodysplasia in the first patient was performed by upper mesenteric artery arteriography, in the second by preoperative colonoscopy and after confirmed by the histology of the specimen and in the last one by colonoscopy performed in emergency and after intestinal irrigation. The first patients refused the operation; the second had right hemicolectomy and the third one had a spontaneous stop of bleeding. According to their clinical experience the authors suggest that colonoscopy performed in emergency or intraoperative is the first choice diagnostic procedure: it can detect the source of bleeding between right or left colon. Arteriography often shows vascular images characteristic for angiodysplasia or other vascular malformations but, in our experience, it may be absolutely not diagnostic. Colonoscopy performed in emergency during bleeding or per-operative is the best procedure in order to diagnose the source of bleeding. Emergency colonoscopy can distinguish if the blood is coming from the right or left colon and in our experience, colonoscopy during bleeding is always possible because blood has a cathartic effect. In case of emergency operation pre-operative colonoscopy can usually detect the source of bleeding. A double dye clysma, whether barium or hydrosoluble doesn't give a diagnostic support in low intestinal bleeding; on the contrary it can prevent a correct arteriographic and endoscopic evaluation. At last histopathological findings on the specimen are conclusive for the diagnosis.

Simultaneous relapse of liver cell carcinoma and non-Hodgkin's lymphoma in the liver. Report of a case with diagnosis by ultrasonically guided fine needle aspiration biopsy.

A 50-year-old man was diagnosed with non-Hodgkin's lymphoma (NHL) in 1980; he was treated with chemotherapy and achieved complete remission. Six years later he reported upper abdominal pain. Ultrasound (US) showed a 3-cm mass in the right lobe of the liver. Needle aspiration showed hepatocellular carcinoma (HCC). The patient was treated with radical resection of the tumor. Three years later (June 1989), abdominal US showed two lesions in the right lobe of the liver. Needle aspiration and tissue core biopsy showed NHL in one lesion and HCC in the other. The lymphomatous lesion resolved after chemotherapy. The patient died 30 months later (January 1992) from a gastrointestinal hemorrhage; the NHL was in complete remission. This case of the simultaneous presence of HCC and hepatic lymphoma is, to our knowledge, the first diagnosed in vivo.

Isolated kidney localization of invasive Aspergillosis in a patient with AIDS.

Although the importance of Aspergillus in AIDS is now increasing, extra-pulmonary disease is still an unusual event, especially when a single localization occurs. A case of isolated renal aspergilloma in an AIDS patient is described. At onset, no recognized risk factors were present in our patient. An early surgical approach combined with antifungal chemotherapy (amphotericin B, Itraconazole) led to a good control of the disease, with no evidence of recrudescence at 8 months' follow-up.

Apocrine carcinoma of the skin. A clinicopathologic, immunocytochemical, and ultrastructural study.

BACKGROUND: Apocrine carcinomas of the skin are rare and incompletely studied neoplasms. METHODS: An immunohistochemical and ultrastructural study is reported of specimens from six patients with apocrine skin carcinoma in various body sites. Three tumors were in the axilla; one, the eyelid; one, the ear; and one, the scalp. There were three local recurrences and three regional lymph node metastases, but no patient died of cancer (follow-up, 2-10 years). RESULTS: The most reliable histopathologic criteria for identifying apocrine skin carcinoma appear to be decapitation secretion, periodic acid-Schiff-positive diastase-resistant material in the cells or lumen, and immunoreactivity with gross cystic disease fluid protein 15. All specimens expressed common epithelial antigens (cytokeratins, carcinoembryonic antigen, and epithelial membrane antigen) and histiocytic-secretive antigens (Leu-M1, lysozyme, LN5, alpha-1-antitrypsin, and alpha-1-antichymotrypsin). S-100 protein was found in the three nonaxillary tumors. Ultrastructurally, the primary tumors, and especially the secondary lesions, were dedifferentiated compared with normal apocrine glands. CONCLUSIONS: Apocrine differentiation in skin tumors does not indicate an exclusive origin from the apocrine sweat glands; these neoplasms usually have an indolent clinical course.

Multidirectional carcinoma of the thymus with neuroendocrine and sarcomatoid components and carcinoid syndrome.

We report a case of metastatic thymic neoplasm occurring in a 62-year-old Caucasian man. The tumor was polymorphic, with intimately admixed carcinoid, sarcomatous and undifferentiated components. Sarcomatous cells were spindle-shaped and immunoreactive for vimentin, actin and desmin. Carcinoid cells reacted for cytokeratin as well as with a panel of general neuroendocrine markers, including chromogranins A and B, synaptophysin, protein gene product (PGP) 9.5, neuron specific enolase (NSE), Leu 7 and Grimelius' silver. The endocrine nature of the latter cells was confirmed by ultrastructural evidence of abundant electron-dense granules 100 to 300 nm in size. Among the various hormones investigated immunohistochemically only the alpha chain of human chorionic gonadotropin (alpha-hCG) was detected in tumor cells. The neoplasm recurred after surgical resection and caused a typical carcinoid syndrome with skin flushing and increased urinary 5-hydroxyindolacetic acid (5-HIAA). The diagnosis of multidirectional thymic carcinoma with two lines of differentiation, of carcinoid and sarcomatoid type, was made.