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Neonatal and infantile cholestasis (NIC) can represent the onset of a surgically correctable disease and of a genetic or metabolic disorder worthy of medical treatment. Timely recognition of NIC and identification of the underlying etiology are paramount to improve outcomes. Upon invitation by the Italian National Institute of Health (ISS), an expert working grouped was formed to formulate evidence-based positions on current knowledge about the diagnosis of NIC. A systematic literature search was conducted to collect evidence about epidemiology, etiology, clinical aspects and accuracy of available diagnostic tests in NIC. Evidence was scored using the GRADE system. All recommendations were approved by a panel of experts upon agreement of at least 75% of the members. The final document was approved by all the panel components. This position document summarizes the collected statements and defines the best-evidence diagnostic approach to cholestasis in the first year of life.

Chronic infections by hepatitis B virus (HBV) and hepatitis C virus (HCV) major causes of advanced liver disease and mortality worldwide. Although regarded as benign infections in children, their persistence through adulthood is undoubtedly of concern. Recent advances in HCV treatment have restored the visibility of these conditions and raised expectations for HBV treatment, which is currently far from being curative. Herein we describe direct-acting antivirals available for pediatric HCV (sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir) and their real-world use. A critical review of the HBV pediatric classification is provided. Anti-HBV investigational compounds are reviewed in light of the pathophysiology in the pediatric population, including capsid assembly modulators, antigen secretion inhibitors, silencing RNAs, and immune modifiers. Recommendations for screening and management of immunosuppressed children or those with other risk factors or comorbidities are also summarized.

Objectives The aim of the study was to assess changes in clinical phenotype, and identify determinants of outcome in children with chronic hepatitis B virus (HBV) infection born in HBV-endemic countries followed in 2 Italian tertiary care centers after immigration or adoption. Methods A prospective observational study on hepatitis B e-antibodies-negative chronic hepatitis B children started on 2002. Patients with liver fibrosis, or those needing antiviral treatment were excluded. Immune active patients were defined those with raised transaminases (alanine aminotransferase > 40 IU/L), immune tolerants those having normal alanine aminotransferase, both exhibiting substantial viral replication (HBV DNA >2000 IU/mL). Results Sixty-nine patients (44 boys, median age 4.7 years) had a median follow-up of 53 months. At entry, 18 (26%) children were immune tolerant, 47 (68%) immune active, and 4 had indeterminant immune status. At last follow-up, 14 (78%) of the immune-tolerant patients remained so, whereas only 23 (49%) of the immune active children maintained their initial immune phenotype. Seroconversion to hepatitis B e antibodies (SCHBe) occurred in only 2 (11%) immune tolerants, whereas 13 (28%) immune active patients achieved SCHBe.Ethnicity was the only feature independently correlated to SCHBe: Asian origin reduced by 4.1 times the probability of SCHBe (Asian vs other; odds ratio = 0.24 [95% confidence interval = 0.07-0.76]; P = 0.016) compared to other ethnicities, whereas viral genotype did not influence the outcome. Conclusions Ethnicity and immune status phenotype against HBV, rather than HBV genotype, are the main determinants of SCHBe in foreign-born children with chronic HBV infection.

OBJECTIVES A proportion of children with chronic liver disease have severe portal hypertension (PH) and a preserved synthetic and biliary function. In our institution these children have been managed with transjugular intrahepatic portosystemic shunts (TIPS). We aimed to evaluate the long-term patency of TIPS placed in pediatric patients with PH. METHODS Retrospective study of children who underwent TIPS in the last 15 years. We compared patients with cirrhotic PH to those with noncirrhotic PH, and all with an historical cohort of children who underwent a surgical portosystemic shunt. Kaplan-Meier analysis measured long-term shunt patency. RESULTS Twenty-nine patients were recorded (cirrhotic PH = 11, noncirrhotic PH = 18, mean age 10.3 years[±4.3], mean weight 36.7 kg [±20.1], mean pediatric end-stage liver disease score 4.1 [±7.1]); in 5 TIPS was placed after split liver transplantation. Indication for TIPS was variceal bleeding in 18, refractory ascites in 11. Primary patency rates at 6 months and at 1, 2, and 4 years were 91%, 83%, 60%, and 46%, respectively. At last follow-up (mean of 2.8 years [±2.4, range 0.1-8.1 years]) secondary patency (after radiological revision) was 100%. The patency rate of the historical cohort of patients who underwent a surgical portosystemic shunt was 26 of 31 (82%) at a median follow-up of 12.5 years (1.6-25.8). CONCLUSION TIPS appears to have a high mid-term patency rate, especially if monitored and revised. Its high clinical success rate, along with a minimally invasive approach, suggests that in this setting TIPS should not be regarded only as a bridge to liver transplantation.

In adults, the absence of a preexisting chronic liver disease (CLD) is required to diagnose acute liver failure (ALF). The pediatric classification does not consider this aspect, thus previous studies pooled together children with ALF and children with unknown CLD presenting with acute hepatic decompensation (ALF-CLD). We aimed to compare prevalence, features, and outcome of children with ALF-CLD to those with a proper ALF.Patients admitted between 1996 and 2017 because of ALF defined by Pediatric Acute Liver Failure criteria (raised transaminases, International Normal Ratio ≥2.0, no history of liver disease) were classified as ALF-CLD if diagnosed with autoimmune hepatitis, Wilson disease, Budd-Chiari syndrome, hepatitis B virus reactivation, inborn errors of metabolism. The others were classified as ALF.Seventy-four children (median age, 4 years; 1.0-8.8; male/female, 36/38] with ALF were found; 18 of1 year of age were excluded. Fifty-six (median age, 6.6 years; 2.7-11.7; male/female, 23/33], 22 with ALF-CLD (autoimmune hepatitis, n = 14; Wilson disease, n = 6; inborn errors of metabolism, n = 2) and 34 with ALF (paracetamol overdose, n = 6; viral infections, n = 3; mushroom poisoning, n = 5; indeterminate, n = 20) were compared. In ALF-CLD, the median age at onset was higher, alanine aminotransferase, albumin, and International Normal Ratio levels were lower, splenomegaly, ascites, and cirrhosis were more common (all P0.01). On multivariate analysis, the diagnosis of ALF-CLD was an independent predictor of transplant-free survival (P = 0.006).In children, ALF-CLD is common, has peculiar features, and is associated with a favorable outcome. This study suggests the need to distinguish this entity from other forms of ALF in children.

Sclerosing cholangitis (SC) is a rare chronic disorder characterised by inflammation and progressive obliterative fibrosis of the intrahepatic and/or extrahepatic bile ducts. Diagnosis is based on cholangiogram showing bile duct dilatation, narrowing and obliteration of the biliary tree, and histologically, on the presence of inflammatory bile duct damage leading to periductal fibrosis. In children the most common SC is associated with strong autoimmune features, overlapping with those of autoimmune hepatitis (AIH); this form is known as autoimmune sclerosing cholangitis, ASC. Conversely, primary SC (PSC), a condition in which the term "primary" indicates that aetiology and pathogenesis are unknown, is rare in paediatrics. Secondary SC (SSC) defines a cholangiopathy associated with an identifiable aetiology such as immunodeficiencies, infections or haematological disorders. ASC and PSC are strongly associated with inflammatory bowel disease (IBD). ASC responds biochemically well to immunosuppressive drugs and ursodeoxycholic acid (UDCA). Primary forms are exclusively managed with oral UDCA, while in the secondary forms the medical treatment depends on the underlying aetiology. Despite treatment, SC often progresses to biliary cirrhosis and end-stage liver disease requiring liver transplantation. The disease can recur after transplant. Better understanding of pathogenic mechanisms and better treatment modalities are needed to improve the prognosis of this invalidating hepatic disorder.

Background: COVID-19, a disease caused by the new coronavirus SARS-CoV-2, spread worldwide, and Bergamo was one of the most affected areas in Europe. Following the first outbreak, more than half of the population of the Bergamo province had been infected. We aimed to describe the patients admitted to our unit shortly after the first outbreak.Methods: we retrospectively reviewed the notes of all pediatric patients diagnosed with COVID-19. We enrolled patients with positive swabs or serology and classified them based on the pattern and the timing of presentation after the first outbreak. This setting was considered a reliable reflection of the consequences of unmitigated SARS-CoV-2 circulation.Results: We diagnosed 35 patients over a 3-month period and we identified six patterns presenting in two temporal phases: Early phase, Group 1 (median of 20 days from epidemic start, IQR: 15–27): neonatal sepsis (n.7), pneumonia (n.5), flu-like symptoms (n.2). Late phase, Group 2 (59:51–66 days, p < 0.001): MIS-C (n.18), neurological manifestations (n.3). Group 1 differed from Group 2 for younger age (1 vs. 8 years, p = 0.02), lower C-reactive protein (0.9 vs. 16.6 mg/dl, p = 0.008), procalcitonin (0.16 vs. 7.9 ng/ml, p = 0.008) and neutrophil count (3,765 vs. 6,780/μl, p = 0.006), higher rate of positive swabs (14/14 vs. 9/21, p < 0.001), higher lymphocyte count (3,000 vs. 930/μl, p = 0.006) and platelet count (323,000 vs. 210,000/μl, p = 0.009).Conclusions: Following an outbreak of unmitigated SARS-CoV-2 diffusion, infected children may present with clinical patterns suggesting two temporal clusters, the first characterized by markers of direct viral injury, the second suggesting an immune-mediated disease.

Background: The global pandemic caused by novel Coronavirus SARS-CoV-2 disease (COVID-19) is a major threat to the general population and for patients with pre-existing chronic conditions. We report data concerning SARS-CoV-2 infection in children with chronic liver disease (CLD).Methods: A literature review using the online database PubMed was performed to summarize available findings on the association between pre-existing liver disease and COVID-19 infection in children.Results: Children with COVID-19 have preserved effector and immunosuppressive components resulting in a milder disease compared to adults. The most common hepatic manifestation is an elevation of hepatic transaminases. Liver damage may be directly caused by viral infection of liver cells, by medications or by the chronic hypoxia seen in COVID-19 patients. A multicenter study reported that the majority of children with a CLD remained healthy during the outbreak. Similarly, studies reported that children on immunosuppressive treatment, including patients with autoimmune liver disease (AILD) and liver transplantation (LT), maintained good health during the outbreak without experiencing major complications even if infected with COVID-19.Conclusion: COVID-19-related liver injury presents with a mild elevation of transaminases, although its clinical significance is unclear. Children with CLD, including those with AILD and post-LT, do not have an increased risk for severe disease course of SARS-CoV-2 infection with little or no liver dysfunction. These data highlight the necessity to ensure normal standards of care while adhering to national Covid-19 guidelines, and particularly to maintain immunosuppressive medication to prevent relapse or rejection. Further research is required to evaluate the differences in clinical course between immunosuppressed adults and children and in particular whether asymptomatic infection is a concern.

International audience; Adeno-associated virus (AAV) vector-mediated gene therapy is currently evaluated as a potential treatment for Crigler-Najjar syndrome (CN) (NCT03466463). Pre-existing immunity to AAV is known to hinder gene transfer efficacy, restricting enrollment of seropositive subjects in ongoing clinical trials. We assessed the prevalence of anti-AAV serotype 8 (AAV8) neutralizing antibodies (NAbs) in subjects affected by CN and investigated the impact of low NAb titers (

Various degrees of biliary changes are considered to be part of the histological picture of children with pediatrics autoimmune liver disease (AILD), but the literature is scarce and confusing. We aimed to describe the characteristics of children with AILD (autoimmune hepatitis, AIH, and autoimmune sclerosing cholangitis, ASC) focusing on the prevalence and type of biliary abnormalities on initial biopsy to see whether ASC was predictable on histological ground. The files of children diagnosed with AILD were reviewed. The Ishak score was used to grade inflammation and fibrosis on biopsy; a biliary score was built to grade bile duct injury. Demographic, laboratory and histological features at diagnosis were reported and compared between the two groups (AIH vs ASC). Forty-one patients were diagnosed with AIH (n = 24), ASC (n = 13) and PSC (n = 4) between 2009 and 2018. Twenty-nine patients [F = 76%, AIH = 20, ASC = 9, median age at diagnosis 11.7 (range 2.2–17.8)] were included in the study; 12 (4 with PSC) were excluded. Prevalence of inflammatory bowel disease was higher in ASC group (56% vs 10% in AIH, p

Objectives Non-cirrhotic portal vein thrombosis (PVT) is a main cause of portal hypertension in children. We describe the characteristics at presentation and outcome of a cohort of patients with PVT to determine clinical features and predictors of outcome. Methods We recorded: (1) Associated factors: prematurity, congenital malformations, neonatal illnesses, umbilical vein catheterization (UVC), deep infections, surgery; (2) congenital and acquired prothrombotic disorders; (3) features at last follow up including survival rate and need for surgery. Results 187 patients, mean age at diagnosis 4 ± 3.7 years, had a history of prematurity (61%); UVC (65%); neonatal illnesses (79%). The diagnosis followed the detection of splenomegaly (40%), gastrointestinal bleeding (36%), hypersplenism (6%), or was incidental (18%). Of 71 patients who had endoscopy at presentation 62 (87%) had oesophageal varices. After 11.3 years’ follow up 63 (34%) required surgery or TIPS. Ten-year survival rate was 98%, with 90% shunt patency. Spleen size, variceal bleeding and hypersplenism at presentation were predictors of surgery or TIPS (p Conclusion PVT is associated with congenital and acquired co-morbidities. History of prematurity, neonatal illnesses and UVC should lead to rule out PVT. Large spleen, variceal bleeding and hypersplenism at presentation predict the need for eventual surgery in a third of cases.

Children with liver disease almost invariably require an admission to pediatric intensive care unit (PICU) during their life. The most common causes are (1) an acute decompensation in a patient with a known chronic liver disease; (2) an episode of acute liver failure presenting with severe coagulopathy and encephalopathy; (3) complications of cirrhosis and portal hypertension, such as variceal bleeding; and (4) an admission following surgical operations such as hepatic resection or liver transplantation.

An integrated treatment strategy using peritonectomy procedures plus hyperthermic intraperitoneal chemotherapy (HIPEC) is now a clinical standard of care in selected patients with peritoneal metastases and primary peritoneal tumors. This comprehensive approach can offer many patients, who hitherto had no hope of cure, a good quality of life and survival despite limited morbidity. The increasingly successful results and chance of interfering in the natural history of disease has prompted research to develop for some clinical conditions a therapeutic strategy designed to prevent malignant peritoneal dissemination before it becomes clinically evident and treat it microscopically (tertiary prevention). The main factor governing successful cytoreductive surgery and predicting outcome is the extent of peritoneal spread assessed with the peritoneal cancer index (PCI). In peritoneal metastases from colorectal and gastric cancer the PCI score acquires a specific role acting as the cut-off between patients who can undergo curative surgery or palliation. Long-term results show that the only group enjoying favorable results are patients with limited disease (a statistical minority). By applying to appropriately selected patients with primary malignancies a proactive management strategy including HIPEC we can treat patients with microscopic peritoneal dissemination and therefore at PCI 0. Among treated conditions pseudomyxoma peritonei enjoys the best results. But a major future advance comes from identifying among lesions at major risk of pseudomyxoma.

Intestinal failure-associated liver disease (IFALD) is a threatening complication for children on long-term parenteral nutrition because of intestinal failure. When progressive and intractable, it may jeopardize intestinal rehabilitation and lead to combined liver and intestinal transplantation. The institution of dedicated intestinal failure centers has dramatically decreased the incidence of such complication. IFALD may rapidly fade away if very early management aimed at preventing progression to end-stage liver disease is provided. In this review, we address the etiology and risk factors of IFALD in order to introduce pillars of prevention (nutritional management and catheter-related infections control). The latest evidence of therapeutic strategies, such as medical and surgical treatments, is also discussed.

Objective To evaluate the performance of a diagnostic protocol for neonatal/infantile cholestasis in which the main clinical patterns steered the early use of different genetic testing strategies. Study design An observational study was conducted between 2012 and 2017 in a tertiary care setting on a prospective cohort of children with cholestasis occurring at ≤1 year of age and persisting ≥6 weeks, to measure the detection rate of underlying monogenic diseases. After the exclusion of biliary atresia, a clinically driven genetic testing was performed, entailing 3 different approaches with different wideness: confirmatory single-gene testing; focused virtual panels; and wide search through trio whole-exome sequencing. Results We enrolled 125 children (66 female, median age 2 months); 96 (77%) patients had hypocholic stools and were evaluated rapidly to exclude biliary atresia, which was the final diagnosis in 74 (59%). Overall, 50 patients underwent genetic testing, 6 with single confirmatory gene testing, 38 through panels, and 6 with trio whole-exome sequencing because of complex phenotype. The genetic testing detection rate was 60%: the final diagnosis was Alagille syndrome in 11, progressive familial intrahepatic cholestasis type 2 in 6, alpha-1-antitrypsin deficiency in 3, and progressive familial intrahepatic cholestasis type 3 in 2; a further 7 genetic conditions were identified in 1 child each. Overall, only 18 of 125 (14%) remained with an indeterminate etiology. Conclusions This protocol combining clinical and genetic assessment proved to be an effective diagnostic tool for neonatal/infantile cholestasis, identifying inherited disorders with a high detection rate. It also could allow a noninvasive diagnosis in children presenting with colored stools.

Totally implantable venous access ports (TIVAP) are eventually explanted for various reasons, related or unrelated to the implantation technique used. Having more information on long-term explantation would help improve placement techniques. From a series of 1572 cancer patients who had TIVAPs implanted in our center with the cutdown technique or Seldinger technique, we studied the 542 patients who returned to us to have their TIVAP explanted after 70 days or more. As outcome measures we distinguished between TIVAPs explanted for long-term complications (infection, catheter-, reservoir-, and patient-related complications) and TIVAPs no longer needed. Univariate and multivariate analyses were run to investigate the reasons for explantation and their possible correlation with implantation techniques. The most common reason for explantation was infection (47.6 %), followed by catheter-related (20.8 %), patient-related (14.7 %), and reservoir-related complications (4.7 %). In the remaining 12.2 % of cases, the TIVAP was explanted complication free after the planned treatments ended. Infection correlated closely with longer TIVAP use. Univariate and multivariate analyses identified the Seldinger technique as a major risk factor for venous thrombosis and catheter dislocation. The need for long-term TIVAP explantation in about one-third of cancer patients is related to the implantation techniques used.

We report the case of a 72-year-old woman with metastatic malignant mesothelioma presenting as right colonic polyp. She was diagnosed with malignant pleural mesothelioma 2 years previously and underwent surgery, radiotherapy, and chemotherapy. After 2 years with a negative follow-up, she was admitted to the infectious disease department for malaria and severe anaemia. A computed tomographic scan and a colonoscopy showed a huge bleeding polypoid lesion in the right colon diagnosed as adenocarcinoma. She underwent a right hemicolectomy; a pathologic examination found neoplastic cell population positive to anti-cytokeratin7, anti-calretinin, anti-vimentin, and negative for anti-cytokeratin 20, MOC-31, and thyroid transcription factor 1, providing a diagnosis of metastatic mesothelioma.

The organization that has to face the radiological emergencies in a nuclear disaster or terroristic attack must be carefully planned. In the hospitals with a level one Emergency Department, it is possible to draw a pathway for the contaminated patients, based on internal resources and on the recommendations of the nuclear medicine associations (as AIMN – Associazione Italiana di Medicina Nucleare; SNM – Society of Nuclear Medicine). The “Santi Antonio e Biagio e Cesare Arrigo” hospital in Alessandria is a modern hospital and is the reference of an extended area, for its many highly specialized departments. In this background, and in a hospital with a level one Emergency Department, there are three qualified departments, able to play a primary role in the emergency management of the individuals potentially contaminated by nuclear materials: Emergency Department, Nuclear Medicine Unit and Health Physics Unit. Therefore the Alessandria Hospital is suitable to admit patients potentially contaminated by radioactive material, to determ i n e the level of contamination, to decontaminate them in the emergency decontamination area, to hospitalise and treat them in the nuclear medicine rooms.

Portal hypertension (PH) is a common complication in children with chronic liver disease, and its major manifestation, variceal bleeding, represents a major cause of morbidity in this setting. Although often self-limiting, gastrointestinal bleeding is regarded as a frightening event by patients and carers, giving the impression of impending death. PH and its complications are also among the commonest indications to liver transplantation, therefore having relevance in the management of pediatric chronic liver disease. For these reasons, it is important to raise the awareness on the natural history of PH in children, the utility of tools that help preventing and managing acute bleeding, and the signs predicting a poor outcome, thus indicating surgery. Unlike in adults, in the pediatric setting, there is lack of data on pathophysiology, clinical features, and effective management altering the outcome of PH, and therefore children are often managed according to guidelines developed in adults. In this chapter, we discuss the advances made in the management of PH in children, compare it with the larger adult experience, and propose diagnostic and therapeutic algorithms for acute and chronic complications.

Data regarding agreement on endoscopic features of oesophageal varices in children with portal hypertension (PH) are scant. The aim of this study was to evaluate endoscopic visualisation and classification of oesophageal varices in children by several European clinicians, to build a rational basis for future multicentre trials.Endoscopic pictures of the distal oesophagus of 100 children with a clinical diagnosis of PH were distributed to 10 endoscopists. Observers were requested to classify variceal size according to a 3-degree scale (small, medium, and large, class A), a 2-degree scale (small and large, class B), and to recognise red wales (presence or absence, class Red). Overall agreement was considered fair if Fleiss and Cohen κ test was ≥0.30, good if ≥0.40, excellent if ≥0.60, and perfect if ≥0.80.Agreement between observers was fair with class A (κ = 0.34) and class B (κ = 0.38), and good with class Red (κ = 0.49). The agreement was good on presence versus absence of varices (class A = 0.53, class B = 0.48). The agreement among the observers was good in class A when endoscopic features of severe PH (medium and large sizes, red marks) were grouped and compared with mild features (absent and small varices) (κ = 0.58).Experts working in different centres show a fairly good agreement on endoscopic features of PH in children, although a better training of paediatric endoscopists may improve the agreement in grading severity of varices in this setting.

The role of the pathologist in a team dealing with patients affected by PSM is crucial. The steps of this work are not merely diagnostic; in fact, before diagnosis is achieved, the pathologist must collect a great deal of information necessary for analyzing the individual case to enable the surgeon to interpret correctly the macroscopic pattern presented by the patient. The majority of patients undergoing surgical procedures for PSM have already been given systemic chemotherapy, and the pathological pattern at the time of the surgical intervention is affected by the grade of therapeutic response. In cases in which lesions are not obvious, it is important to detect and analyze all areas of minimal alteration, both in the serosal surface and in deeper locations (as in visceral specimens such as large- and small-bowel tracts, uterus and adnexa, bladder, gall bladder, and other such areas). It is even more important to apply this protocol in cases in which superficial macroscopic lesions have virtually disappeared. For correct staging, it must be determined with as much certainty as possible that no microscopic residue remains.

Peritoneal carcinomatosis (PC) is the most impressive and frequent form of locoregional spread of epithelial ovarian cancer (EOC). For much of its natural history, the disease remains confined to the peritoneal district, thus representing the target for various combinations of surgery and systemic or locoregional chemotherapy (CHT). PC is evident both in the primary setting, i.e., in patients first treated for locally advanced EOC, or as a recurrence in patients previously treated for OC at any Federation Internationale de Gynecologie et Obstetrique (International Federation of Gynecology and Obstetrics) (FIGO) stage.

The term Peritoneal Surface Malignancies (PSMs) identifies a wide range of epithelial or mesenchymal neoplasms that originate from the primitive structure of the peritoneum or spread over and through the peritoneum membrane as metastases deriving from tumors of intra-abdominal, retroperitoneal, or extraabdominal organs or viscera (Table 1.1). PSM evolution depends on the degree of aggressiveness of the various neoplastic forms: in contrast with benign or low malignant forms, aggressive forms are able to produce fast and fatal disease progression. The primitive forms are much rarer than secondary forms, and mesotheliomas and serous tumors of the peritoneum are the most common among them. Colorectal, gastric, and ovarian peritoneal carcinomatosis (PC) are the most frequent forms of PSM arising from intraperitoneal viscera. PSMs originating from retroperitoneal tumors, such as the pancreas, kidneys, or adrenals, are rare and even less frequent are those originating from extra-abdominal tumors, such as breast or lung cancer. Epithelial forms are far more frequent than mesenchymal forms. Primary tumors of the peritoneum and carcinomatosis from gynecological or gastrointestinal tumors are overall the most widespread and common PSMs treated in surgery and oncology. Irrespective of histological differences, most PSMs have a common tendency to grow for a relatively long period of time exclusively in the abdominal cavity, thus representing an ideal target for aggressive locoregional treatments.

Although the technique for the surgical repair of rectal prolapse has advanced over the years, no ideal procedure has been found. We aim to test a new surgical procedure for abdominal rectopexy that uses the greater omentum to support the rectum below the rectopexy, to reconstruct the anorectal angle and dispense with the need for synthetic mesh, thus reducing the risk of infection. A series of ten patients, all young and medically fit, underwent repair surgery for rectal prolapse with the new rectopexy technique. Some patients had concomitant sigmoidectomy. Preoperative and postoperative assessment included a clinical examination, anal manometry and defecography. Follow-up lasted a mean of 56.4 months. None of the patients had recurrent rectal prolapse or infection. Postoperative assessment at 24 months disclosed significant improvements in all the bowel and sphincter variables assessed. The 8 patients who had severe incontinence preoperatively had notably improved and 4 were fully continent, 3 moderately incontinent, and only 1 patient had persistently high levels of incontinence. In only 1 patient who initially had severe incontinence, continence completely regressed and severe constipation developed. Maximal basal pressure values increased significantly after surgery (p=0.0025), although they increased slightly less evidently in patients in whom marked incontinence persisted at postoperative follow-up. Maximal voluntary contraction pressure also increased significantly after surgery (p=0.0054), although the values changed less than those for basal pressure. During rest, squeeze and straining, and in all the patients who regained continence, even those who recovered it only partly, surgery substantially reduced the anorectal angle. The reduction during rest was statistically significant (p=0.0062). The rectopexy technique we tested in patients with rectal prolapse avoids the need for synthetic mesh, and provides good results in terms of bowel and sphincter function, without infection or recurrence.

BACKGROUND Numerous studies have investigated locoregional immune responses and long term survival in patients with various types of cancer; few have focused on patients with lung carcinoma. The current study was designed to assess the prognostic value of immunomorphologic changes in locoregional lymph nodes and lymphocytic infiltration of primary tumor (LI) in patients who undergo resection for bronchogenic carcinoma. METHODS In a retrospective analysis, immune responses in locoregional lymph nodes and at primary tumor sites were studied histologically in 172 selected patients. Lymph node morphology was studied according to the system of Cottier et al. Sinus histiocytosis and paracortical lymphoid cell hyperplasia were considered to be cellular immune responses, and follicular hyperplasia of the cortical area was considered to be a humoral reaction. LI was classified with Black's method. The survival rate was estimated by using the Kaplan–Meier product-limit method. The log rank test and the Cox proportional-hazards model were used to determine statistical significance in univariate and multivariate survival analyses. RESULTS Among the 172 patients, 35.5% had no evident response in regional lymph nodes, 19.8% had a marked cellular response, 11% had a marked humoral response, and 33.7% had a mixed cellular and humoral response. LI was intense in 36.6% of patients and was absent or scarcely evident in 63.4%. A lymph node cellular response and marked LI improved long term survival rates even in patients with regional lymph node metastases. Multivariate analysis identified two independent variables that had high prognostic value: lymph node immunoreactivity and LI. CONCLUSIONS Lymph node immunoreactivity and LI significantly influence long term survival after curative surgery for patients with carcinoma of the lung and may be useful in stratifying patients for prospective trials of adjuvant treatment, including immunotherapy. Cancer 2000;89:2038–45. © 2000 American Cancer Society.

Background More information is needed on the anatomopathological outcome variables indicating the appropriate surgical strategy for the colorectal resections often needed during cytoreduction for ovarian cancer. Methods From a phase-II study cohort including 70 patients with primary advanced or recurrent ovarian cancer with diffuse peritoneal metastases treated from November 2000 to April 2009, we selected for this study the 52 consecutive patients who needed colorectal resection. Data collected included type of colorectal resection, peritoneal cancer index (PCI), histopathology (depth of bowel-wall invasion and lymph-node spread), cytoreduction rate and outcome. Correlations were tested between possible prognostic factors and Kaplan-Meier five-year overall and disease-free survival. A Cox multivariate regression model was used to identify independent variables associated with outcome. Results In the 52 patients, the optimal cytoreduction rate was 86.5% (CC0/1). In all patients, implants infiltrated deeply into the bowel wall, in 75% of the cases up to the muscular and mucosal layer. Lymph-node metastases were detected in 50% of the cases; mesenteric nodes were involved in 42.3%. Most patients (52%) had an uneventful postoperative course. Operative mortality was 3.8%. The five-year survival rate was 49.9% and five-year disease-free survival was 36.7%. Cox regression analysis identified as the main prognostic factors completeness of cytoreduction and depth of bowel wall invasion. Conclusions Our findings suggest that the major independent prognostic factors in patients with advanced ovarian cancer needing colorectal resections are completeness of cytoreduction and depth of bowel wall invasion. Surgical management and pathological assessment should be aware of and deal with dual locoregional and mesenteric lymphatic spread.

Although peritoneal carcinomatosis from breast cancer is a rare event it frequently causes morbidity and mortality. Current literature provides scarce information on its management. We report outcomes in 5 patients (mean age 59.4 years) with peritoneal carcinomatosis from breast cancer treated with maximal cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) by the closed technique, at 40 °C for 1 h with cisplatin 75 mg/m(2). The primary breast cancer was a ductal carcinoma in 3 patients and a lobular carcinoma in 2. Mean peritoneal cancer index was 20.2. In 4 of the 5 patients surgery achieved macroscopic complete cytoreduction. One patient died of disease at 56 months, 4 are alive and disease-free at 13, 45, 74 and 128 months. These encouraging outcomes suggest that cytoreduction and HIPEC is a promising approach to offer to highly selected patients with peritoneal carcinomatosis from breast cancer and that this approach merit investigation in a larger series.

The study compared the outcome in patients with advanced colonic cancer at high risk of peritoneal metastases (mucinous or signet-ring cell) without peritoneal or systemic spread, treated with standard colectomy or a more aggressive combined surgical approach. The study included patients with colonic cancer with clinical T3/T4, any N, M0, and mucinous or signet ring cell histology. The 25 patients in the experimental group underwent hemicolectomy, omentectomy, bilateral adnexectomy, hepatic round ligament resection, and appendectomy, followed by HIPEC. The control group comprised 50 patients treated with standard surgical resection during the same period in the same hospital by different surgical teams. Outcome data, morbidity, peritoneal recurrence rate, and overall, and disease-free survival, were compared. Peritoneal recurrence developed in 4% of patients in the experimental group and 22% of controls without increasing morbidity ( 𝑃 < 0 . 0 5 ). Actuarial overall survival curves disclosed no significant differences, whereas actuarial disease-free survival curves showed a significant difference between groups (36.8 versus 21.9 months, 𝑃 < 0 . 0 1 ). A more aggressive preventive surgical approach combined with HIPEC reduces the incidence of peritoneal recurrence in patients with advanced mucinous colonic cancer and also significantly increases disease-free survival compared with a homogeneous control group treated with a standard surgical approach without increasing morbidity.

Spinal muscular atrophy type 0 is a severe form of spinal muscular atrophy that is usually fatal in the first months of life. These children present with arthrogryposis multiplex congenita and respiratory compromise. We describe a child with spinal muscular atrophy and arthrogryposis multiplex congenita who has had a much better course and is alive without ventilator support at age 6 years. This case illustrates that the prognosis for spinal muscular atrophy and arthrogryposis multiplex congenita cannot always be predicted with certainty. (J Child Neurol 2001;16:934-936).

J Thorac Cardiovasc Surg 2001;122:1034-6

Brenner tumor and struma ovarii, two uncommon ovarian tumors arising alone or together with dermoid cysts or adenomas, are both rare entities. Both tumors rarely become malignant and rarely metastasize. Few published reports describe coexisting Brenner tumor and malignant struma ovarii. Patients in whom these malignancies coexist only occasionally have peritoneal spreading, strumosis, or a history of thyrotoxicosis. The patient we describe, a 74-year-old woman, presented with a 2 months' history of lower abdominal pain and episodic intestinal subocclusion due to a complex pelvic mass. The mass consisted predominantly of a Brenner tumor associated with struma ovarii containing a single small island of thyroid tissue that had undergone malignant transformation into a well-differentiated papillary carcinoma and also normal thyroid tissue that had spread to the peritoneum. The patient underwent radical surgical treatment and after 7 years follow-up is disease free.

Until recent years a diagnosis of peritoneal carcinomatosis (PC) from intra-abdominal solid tumors carried a uniformly fatal prognosis, often within weeks or months. Since the 1980s, following the intuition of an American surgeon, Paul Sugarbaker, combined treatment modalities of PC have developed considerably. Since the first pioneering approaches on the treatment of “pseudomyxoma peritonei”

BACKGROUND. Because of scarce data from larger series and nonhomogeneous selection criteria, further information is needed on peritonectomy with hyperthermic intraperitoneal chemotherapy (HIPEC) in managing patients with ovarian peritoneal carcinomatosis. METHODS. In an open, prospective, single-center nonrandomized phase 2 study conducted from November 2000 to April 2007, 47 patients with primary advanced or recurrent ovarian cancer and diffuse peritoneal carcinomatosis were enrolled; 22 underwent primary and 25 secondary cytoreduction plus immediate HIPEC followed by systemic chemotherapy. RESULTS. The overall mean Sugarbaker peritoneal cancer index was 14.9 (range, 6–28). A mean of 6 surgical procedures were required per patient (range, 4–10). In 87.3% of the patients debulking achieved optimal cytoreduction (Sugarbaker completeness of cytoreduction [CC] score 0–1), whereas in 12.7% it left macroscopic residual disease (CC-2 or CC-3). Major complications developed in 21.3% of the patients and the in-hospital mortality rate was 4.2%. The mean overall survival was 30.4 months, median survival was 24 months, and mean disease-free survival was 27.4 months. Five-year survival was 16.7%. Univariate (log-rank test and analysis of variance) and multivariate analyses (Cox proportional-hazard model) identified the CC score as the main factor capable of independently influencing survival. CONCLUSIONS. Peritonectomy procedures combined with HIPEC offer promising long-term survival in patients with diffuse peritoneal ovarian carcinomatosis. They achieve high adequate primary and secondary surgical cytoreduction rates with acceptable morbidity and mortality. Cancer 2008. © 2008 American Cancer Society.

Skeletal muscle metastases from lung cancer are rare, and the optimal treatment strategy is unknown. Three cases of skeletal muscle metastases from lung cancer are described. In 2 patients surgical biopsy of muscle swelling disclosed the presence of the lung tumor; the first patient underwent lung resection to remove the primary lesion, the second was not operable because of the metastatic extension of the disease. In the third patient muscle metastasis was observed and excised after lung resection. Adenocarcinoma, squamous cell, and small cell carcinoma were the histologic types diagnosed. Various regimens of radiotherapy and chemotherapy were adopted. Survival times were 3, 6, and 30 months.

Objective: To develop a simple and accurate technique of incisional biopsy under ultrasonographic guidance to aid the histological diagnosis of non-palpable lesions of the breastDesign: Open prospective study.Setting: Teaching hospital, Italy.Subjects: 35 patients who presented to this hospital with 42 non-palpable lesions diagnosed by echography or mammography during 18 month period 1995&1996.Interventions: Creation of a pocket in the breast in which the transducer of the ultrasound scanner was inserted to guide the surgeon while an excision biopsy was taken.Main outcome measures: Histological diagnosis, and quality of scar.Results: Mean (SD) diameter of the lesions was 11.6 (3.15) mm on the ultrasound scan, that of the biopsy specimens was 18.1 (5.82) mm, and that of the histological specimens 9.7 (3.52) mm. 29 lesions showed fibrocystic mastopathy with apocrine metaplasia, 10 fibroadenomas, 2 invasive ductal carcinoma, and 1 atypical duct hyperplasia. There were no unsightly scars.Conclusions: We have ...

The authors report on a typical case of melorheostosis observed in an 18-year-old man, localized in the II digit of the right hand causing tumefaction and irregular pain. At 20-year follow-up, the patient showed a radiographical slight worsening of the lesion. Radiographic examination showed a mild increase in cortical and endosteal hyperostosis with bone shape alteration in the II digit of the right hand, slight cortical and endosteal hyperostosis at the level of right shoulder girdle involving the humerus. The other part of the skeleton was not affected. Clinical examination revealed swelling and tumefaction of the forefinger of the right hand and reduced articular motion both in proximal and distal interphalangeal joint and metacarpal phalangeal joint. The reminder of the clinical examination was normal. Melorheostosis is an uncommon mesenchymal disorder characterized by a chondral hyperostosis of the long bones associated to a sclerosis of the spongious bone. The etiology of this affection is unknown: the most accredited hypothesis is a developmental anomaly with a sequential sclerotomes distribution. Both genders may be affected, with the long tubular bones of the lower limbs more involved. This anomaly is often asymptomatic but maybe accompanied by pain with a smooth symptom progression and periodic exacerbations. Therapy is mainly symptomatic and comprises anti-inflammatory drugs or surgical approach for removal of soft tissue that may preclude daily activities. This case report demonstrates that melorheostosis is a relatively benign disorder with mildly progressive course.

Background Peritoneal metastasis (PM) is considered a terminal and incurable disease. In the last 30 years, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) radically changed the therapeutic approach for these patients and is regarded as the standard of care for pseudomyxoma peritonei from appendiceal cancer and peritoneal mesotheliomas. Improved survival has also been reported in treating PM from ovarian, gastric, and colorectal cancers. However, PM often seriously complicates the clinical course of patients with other primary digestive and non-digestive cancers. There is increasing literature evidence that helped to identify not only the primary tumors for which CRS and HIPEC showed a survival advantage but also the patients who may benefit form this treatment modality for the potential lethal complications. Our goal is to report our experience with cytoreduction and HIPEC in patients with PM from rare or unusual primary tumors, discussing possible “unconventional” indications, outcome, and the peculiar issues related to each tumor. Methods From a series of 253 consecutive patients with a diagnosis of peritoneal carcinomatosis and treated by CRS and HIPEC, we selected only those with secondary peritoneal carcinomatosis from rare or unusual primary tumors, excluding pseudomyxoma peritonei, peritoneal mesotheliomas, ovarian, gastric, and colorectal cancers. Complications and adverse effects were graded from 0 to 5 according to the WHO Common Toxicity Criteria for Adverse Events (CTCAE). Survival was expressed as mean and median. Results We admitted and treated by CRS and HIPEC 28 patients with secondary peritoneal carcinomatosis from rare or unusual primary tumors. Morbidity and mortality rates were in line with those reported for similar procedures. Median survival for the study group was 56 months, and 5-year overall survival reached 40.3 %, with a difference between patients with no (CC0) and minimal (CC1) residual disease (52.3 vs. 25.7), not reaching statistical significance. Ten patients are alive disease-free, and eight are alive with disease. Conclusions Cytoreduction and HIPEC should not be excluded “a priori” for the treatment of peritoneal metastases from unconventional primary tumors. This combined therapeutic approach, performed in an experienced center, is safe and can provide a survival benefit over conventional palliative treatments.