The evolving phenotype of autoimmune hepatitis across the millennium: The 40-year experience of a referral centre in Italy.

BACKGROUND AND AIMS: During recent years, there have been major insight into the pathogenesis, diagnosis and treatment of autoimmune hepatitis (AIH). We aim to evaluate modifications of the clinical-epidemiological phenotype of AIH patients from 1980 to our days. METHODS: Single-centre, tertiary care retrospective study on 507 consecutive Italian patients with AIH. Patients were divided into four subgroups according to the decade of diagnosis: 1981-1990, 1991-2000, 2001-2010 and 2011-2020. We assessed clinical, laboratory and histological features at diagnosis, response to treatment and clinical outcomes. Acute presentation is defined as transaminase levels >10-fold the upper limit and/or bilirubin >5 mg/dL. Complete response is defined as the normalization of transaminases and IgG after 12 months. Clinical progression is defined as the development of cirrhosis in non-cirrhotic patients and hepatic decompensation/hepatocellular carcinoma development in compensated cirrhosis. RESULTS: Median age at diagnosis increased across decades (24, 31, 39, 52 years, p < .001). Acute onset became more common (39.6%, 44.4%, 47.7%, 59.5%, p = .019), while cirrhosis at diagnosis became less frequent (36.5%, 16.3%, 10.8%, 8.7%, p < .001). Complete response rates rose (11.1%, 49.4%, 72.7% 76.2%, p < .001) and clinical progression during follow-up decreased (54.3%, 29.9%, 16.9%, 11.2%, p < .001). Anti-nuclear antibodies positivity increased (40.7%, 52.0%, 73.7%, 79.3%, p < .001), while IgG levels/upper limit progressively decreased (1.546, 1.515, 1.252, 1.120, p < .001). Liver-related death and liver transplantation reduced from 17.1% to 2.1% (p < .001). CONCLUSIONS: In the new millennium, the typical AIH patient in Italy is older at diagnosis, more often presents with acute hepatitis, cirrhosis is less frequent and response to treatment is more favourable.

Paraneoplastic Anti-Tif1-gamma Autoantibody-positive Dermatomyositis as Clinical Presentation of Hepatocellular Carcinoma Recurrence.

Hepatocellular carcinoma (HCC) is rarely associated with autoimmune paraneoplastic syndromes. We report a case of anti-transcriptional intermediary factor-1 gamma (TIF1-γ)-positive dermatomyositis (DM) as clinical presentation of HCC recurrence in a 72-year-old male patient admitted to our hospital due to fatigue, myalgia, and typical skin rash. His medical history was notable for hepatitis C-related cirrhosis, successful treatment with direct-acting antiviral agents, and previously efficacious treatment of HCC. Laboratory testing showed significant rhabdomyolysis with anti-TIF1-γ antibodies at high titer, and DM was diagnosed. After a careful diagnostic workup, HCC recurrence was diagnosed. After first-line corticosteroid treatment, azathioprine and intravenous immunoglobulin treatments were administered; unfortunately, he mounted only partial response. Owing to the compromised performance status, no HCC treatment was feasible, and, according to international guidelines, he received only best supportive care. Here, we discuss the diagnostic, prognostic, and pathogenic roles of anti-TIF1-γ antibodies associated with paraneoplastic DM and the scant literature data on its occurrence in HCC patients. Considering the TIF1 gene family's established role in oncogenesis, we also review the role of TIF1-γ as a tumor-related neoantigen, leading to the development of clinically overt anti-TIF1-γ antibodies-positive DM.

Porto-sinusoidal vascular disorder, report of a novel association with POEMS syndrome. Future challenge for the hepatologist.

Porto-Sinusoidal Vascular Disorder (PSVD) is a recently introduced clinical entity. Since it is rare and often underrecognized, there is growing interest in identifying patients at increased risk. We present a case of a 59-years-old male with refractory ascites, pleural effusion, and high-risk varices meeting the diagnostic criteria for PSVD with a concomitant diagnosis of POEMS syndrome. The possible association between PSVD and POEMS syndrome has been described only in eight reports in literature, but it may be underrecognized due to the clinical manifestations overlap. To gain a wider comprehension of PSVD, it is fundamental to cooperate using international networks.

Abdominal ultrasound in the characterization of branch-duct intraductal papillary mucinous neoplasms: A new tool for surveillance of low-risk patients?

BACKGROUND: Magnetic resonance imaging (MRI) is regarded as gold-standard for intraductal papillary mucinous neoplasms (IPMNs) follow-up. Given the low risk of transformation and the increasing population under surveillance, there is growing interest in identifying optimal follow-up strategies. AIM: To evaluate reliability of abdominal ultrasound (US) for characterization of low-risk IPMN, compared to MRI. METHODS: Prospective monocentric study among 79 consecutive patients with a suspected BD-IPMN on US. Each patient underwent confirmatory MRI. We evaluated Cohen's kappa statistic and concordance rate (CR) between MRI and US. RESULTS: Of 79 suspected IPMNs on US, MRI confirmed 71 BD-IPMNs. There was high agreement for cyst location and number (CR and kappa of 77.5 % and 81.7 % and 0.66±0.08 and 0.62±0.11 respectively). We found high agreement for cyst size (CR=96.5 %, kappa=0.93±0.05) and main pancreatic duct (MPD) dilatation (CR=100 %, kappa=1). There was a good agreement for thickened septa (CR=80.3 %, kappa=0.38±0.12). US seems inferior to MRI for the identification of mural nodules < 5 mm (CR=97.2 %, kappa=0). CONCLUSIONS: In a cohort of low-risk BD-IPMN, US presented high agreement rate with MRI regarding location, number, and size. There was a good agreement for MPD dilatation and thickened septa, while US underperform for detection of mural nodules < 5 mm.

Primary duodenal adenocarcinoma.

AIMS AND BACKGROUND: Primary duodenal adenocarcinoma is a rare tumor with a poorly defined natural history and prognostic factors. It presents with nonspecific symptoms, and for this reason the diagnosis is often delayed. It is a serious problem for the surgeon because of the difficulty in obtaining an early diagnosis and standardizing basic tenets for an appropriate surgical approach. The aim of this work was to conduct a review of the literature analyzing the points most frequently debated about this pathology. METHODS AND STUDY DESIGN: A bibliographic search was carried out on the main search engines to find studies regarding duodenal adenocarcinoma, published in English, from January 1992 to January 2007. RESULTS: A total of 19 articles was selected. Results concerning symptoms, location of the tumor, diagnostic examinations, surgical treatment, histopathology of the tumor, survival and follow-up were obtained and discussed. CONCLUSIONS: All patients who are medically fit to undergo surgery should be given the option of aggressive resection regardless of tumor size, tumor invasion or appearance of positive lymph nodes. Hopefully, an early diagnosis will correlate with improved long-term survival.

T1 adenocarcinoma of the rectum: transanal excision or radical surgery?

Although local excision for rectal cancer has been practiced for more than 120 years, its proper use for the cure of localized rectal cancers is still incompletely understood. The studies on this topic are heterogeneous in terms of selection criteria, surgical approaches and study design. The stage of the disease at the time of diagnosis is the main prognostic factor in rectal cancer. Today the commonly utilized criteria for local excision of rectal cancer are stage T1N0M0, histological grade G1 or G2, and size 3 to 4 cm. Total recurrence rates have been reported to be as low as 0%-4% and as high as 17%-31%. Notwithstanding the differences among the various case series, the risk of recurrence after local excision is real. The evidence seems to point to occult unresected locoregional tumor spread as the major risk factor. We speculate that the combination of unresected occult nodal disease and inadequate adjuvant therapy are two factors that can explain the higher rates of local and distant recurrences. Even radical surgery after the appearance of a recurrence may not be sufficient. When high-risk features are found, patients who return to the operating room immediately for radical surgery have an improved disease-free survival compared to patients who have radical surgery at the time of local recurrence. We conclude that today there is a preference for local excision in older patients in whom radical surgery may be associated with a high risk of complications and death. Local excision in younger and fit patients should be reserved for low-risk cancers in patients who will accept an increased risk of tumor recurrence.

Locally advanced breast cancer in the elderly: curettage mastectomy.

AIMS AND BACKGROUND: Locally advanced breast tumor represents 5-20% of new cases diagnosed every year. The purpose of this study was to report our experience and to compare it with the literature. METHODS: From 1998 to 2003 at the Molinette Hospital in the Turin University Third Division of General Surgery, there were 34 cases of breast cancer in older women (between 70 and 94 years of age), 14 of which (41.18%) were locally advanced breast tumor. We evaluated the type of surgical intervention and anesthesia used, muscular invasion, the presence of receptors positive to estrogens and progesterone, the operative mortality, the percentage of local-regional recurrence, and relapses after a period of time. RESULTS: Among the patients with locally advanced breast tumor, 21.43% (3/14) were at stage IIIA and 78.57% (11/14) at stage IIIB. In 14.29% (2/14) of the cases, Patey's radical mastectomy was performed, in 57.14% (8/14) Halsted's radical mastectomy, and in 28.57% (4/14) a simple mastectomy with the removal of the fascia of the major pectoral muscle. Three (21.43%) patients underwent a second intervention for local-regional disease. None of the patients had distant metastasis in the first 2 years after the operation. Mortality after 2 years was 23.1% (3/13). None of the patients who underwent surgery had adjuvant therapy, usually because it was refused by the patients themselves or their families. All the negative and positive hormone receptor patients received tamoxifen. CONCLUSIONS: Locally advanced breast tumors are frequent in elderly women. In the past, there has been a tendency to surgical under-treatment. As regards locally advanced breast tumor, curettage operations represent the only possibility to improve the quality of life of the elderly. These should be performed after carefully evaluating a series of variables in the general and local condition of the patient, the aggressiveness of the intervention and the life expectancy.

[Results of extended lymphadenectomy in the surgical treatment of gastric carcinoma. Considerations on data from the literature]. / I risultati della linfadenectomia estesa nella chirurgia del carcinoma gastrico. Considerazioni sui dati della letteratura.

In the surgical response to gastric carcinoma the use of extensive lymphadenectomy (D2) is still being debated. In Japan D2 is the operation of choice and the numerous selected case studies emphasize better long term survival at all stages with this operation. In the West D2 has not obtained the same approval, besides which it is burdened by higher postoperative morbidity and mortality. The important prospective non-selective trials have not shown differences in the general rates of survival between D1 and D2: the analysis of subgroups, instead, shows better results for stages II and IIIA. The distal splenopancreasectomy and the lack of experience of the surgeons worsen the results of D2. Therefore, when reanalyzing the results of the trials in the light of this information a difference is obtained in the rates of survival in favour of D2 for a wider category of patients. The age of the patient necessitates strict preoperative selection. In some selected cases D2 may be performed; for the majority of older patients the operation of choice is D1 extended to the celiac lymph nodes.

Percutaneous drainage and surgery for splenic abscess: a case report.

Splenic abscess is a rare clinical entity; however, thanks to the refinement of diagnostic techniques and to the increase of population at risk its presence is discovered more frequently. In our ward we evaluated a patient by ematochimical and bacteriological exams and abdomen CT. After antibiotical therapy and percutaneous drainage the patient was discharged on the fifteenth day. One month later the patient returned to our emergency room: for the presence of two intrasplenic lesions; he underwent splenectomy. Six month after the operation, the patient was healty. The two methods (surgery and radiological drainage) cannot be compared because the indications are different. Therefore a progressively invasive therapeutic approach would appear to be indicated. If this not successful, splenectomy performed whit laparoscopic or laparotomic techniques should follow.

Endorectal ultrasound in the diagnosis of rectal cancer: accuracy and criticies.

INTRODUCTION: Endorectal ultrasound (ERU) is used for locoregional staging of rectal cancer. Our work compares the data in the literature regarding diagnostic accuracy of the technique and results of routine use of the technique in two centers in Piedmont. MATERIAL AND METHODS: 77 reports ultrasound with the final diagnosis of rectal cancer from the period 2008-2012 were examined. The echographies were performed by two experienced operators, using two ultrasound device with the same technical characteristics. RESULTS: Sensitivity levels are high, with the exception of stage T3. Specificity is always high. The relationships of verisimilitude, both negative and positive, showing that the accuracy of the test is still high. The risk of overstaging is higher for pT1, while most important the risk of understaging concerns the stage T3 (23.5%); on the contrary the ERU is able to exclude infiltration of perirectal organs with a good accuracy (NPV of 99.3%). CONCLUSION: Although our study was a retrospective study, likewise some literature's reports, the interpretation of our analysis results shows a significant risk of downstaging T3 and N+ tumors. ERU represents in our experience a very important radiological staging methods to evaluate T1 and T2 rectal cancer.

Vascular anatomy of the rectal stump after total mesorectal excision.

PURPOSE: For many years, poor vascularization of the short rectal stump has been considered the main cause of leakage. The purpose of this study was to evaluate the vascularization of the rectal stump after total mesorectal excision. METHODS: We studied the iliac vascularization on 28 volunteers with healthy rectum to have an anatomic basis. Then, we studied the vascularization of the rectal stumps after total mesorectal excision by using angio computed tomography at seven and three months after operating on 22 patients; we validated this technique by studying the vascularization using angio computed tomography in 18 rectal specimens from cadavers. RESULTS: Both in healthy rectums and in rectal stumps after total mesorectal excision, there is good vascularization sustained by middle and inferior rectal arteries. The former is more important and frequent as described in previous literature. CONCLUSIONS: The vascularization of the short rectal stump is generally well represented even after total mesorectal excision.

Ligation of the inferior mesenteric artery in the surgery of rectal cancer: anatomical considerations.

BACKGROUND: No agreement has been found in the literature concerning the safest point of ligation of the inferior mesenteric artery (ima) in order to avoid nerve damage during the surgery of rectal cancer. STUDY DESIGN: The distance between the origin of the ima and the left paraortic trunk was measured, as was the distance between the left paraortic trunk and the origin of the left colic artery (lca). The measurements were carried out on 20 cadavers and during 22 operations for rectal cancer. RESULTS: The left paraortic trunk always runs posterior to the ima: its distance from the origin of the ima is on average 1.2 cm; the distance of the left paraortic trunk from the origin of the lca is on average 0.4 cm. The point at which the ima and the left paraortic trunk cross varies greatly, but it is never near the origin of the ima. CONCLUSIONS: From an anatomical point of view the safest point of ligation of the ima is at its origin. At this point, the left paraortic trunk never runs; so there isn't any risk to damage the nerve involving it during the ligation of the artery.

Decreased expression of stem cell factor in esophageal and gastric mucosa after esophagogastric anastomosis for cancer: potential relevance to motility.

BACKGROUND: Esophageal replacement with gastric tube is a well-established reconstruction of the alimentary tract after esophagectomy in cancer patients. The resulting molecular events in the transposed gastric tube and residual esophagus have yet to be investigated. Stem cell factor (SCF) was recently shown to be critical for signaling in gastrointestinal motility. SCF expression is here correlated with changes in mucosal morphology, acid and biliary reflux, and motility in the residual esophagus and gastric tube. METHODS: Thirteen patients surgically resected for squamous esophageal carcinoma with gastric tube replaced by esophagogastric anastomosis underwent upper endoscopy, esophageal manometry, 24-hour pH monitoring, and bile reflux detection. Esophageal and gastric mucosa samples were examined for SCF expression by immunohistochemical and semiquantitative reverse transcriptase-polymerase chain reaction analysis and for SCF serum levels by enzyme-linked immunosorbent assay. RESULTS: All patients showed severe residual esophagus hypoperistalsis and no gastric tube motor activity. The 24-hour pH monitoring was positive in most; 24-hour bile detection was mostly negative. SCF levels in the residual esophageal and gastric tube mucosa were dramatically decreased compared with those of normal subjects. The correlation between SCF and slow-wave activity was positive. CONCLUSIONS: Hypomotility of the residual esophagus and gastric tube seems closely associated with disruption of the SCF/c-kit signaling pathway. However, the absence of notable relations between mucosal changes after chronic exposure to acid, biliary gastric content, and SCF expression indicates that this analysis cannot be considered part of endoscopic follow-up.