Current management of incidental gallbladder cancer: A review.

Early-stage gallbladder cancer (GBC) is mostly discovered incidentally by the pathologist after cholecystectomy for a presumed benign disease. It is the most common malignancy of the biliary tract with a variable incidence rate all over the World. The majority of patients with GBC remain asymptomatic for a long time and diagnosis is usually late when the disease is at an advanced stage. Radical surgery consisting in resection of the gallbladder liver bed and regional lymph nodes seems to be the best treatment option for incidental GBC. However, recurrence rates after salvage surgery are still high and the addition of neoadjuvant/adjuvant chemotherapy may improve outcomes. The aim of the present review is to evaluate current literature for advances in management of incidental GBC, with particular focus on staging techniques and surgical options.

Perianal mucinous adenocarcinoma with dysplastic polyps of the colon: A case report.

INTRODUCTION: Perianal mucinous adenocarcinoma is rarely encountered in the setting of anal neoplasms. The rarity of the disease and the paucity of publications on this topic are responsible for a lack of diagnostic and therapeutic guidelines. PRESENTATION OF CASE: An 80-year-old man with mucinous adenocarcinoma of the anal canal associated with dysplastic polyps of the colon was treated by multiple endoscopic polypectomies and abdomino-perineal resection of the rectum. We discuss the management of this rare case from the diagnosis up to one-year follow-up. DISCUSSION: Perianal mucinous adenocarcinoma is a very rare entity frequently combined with chronic fistulas. Inflammatory symptoms may mislead its diagnosis, which is often delayed. The unique association between perianal mucinous adenocarcinoma and dysplastic polyps of the colon, that we have reported, may suggest a secondary etiology. High clinical suspicion is important for early and correct diagnosis, which should be based on endoanal ultrasound and/or magnetic resonance imaging followed by deep tissue biopsies. CONCLUSION: We stress the importance of accumulating such cases in the literature. The understanding of the etiopathogenic mechanisms may lead to the development of novel diagnostic and therapeutic protocols.

Multiple Signatures of the JC Polyomavirus in Paired Normal and Altered Colorectal Mucosa Indicate a Link with Human Colorectal Cancer, but Not with Cancer Progression.

The JC polyomavirus (JCV) has been repeatedly but discordantly detected in healthy colonic mucosa, adenomatous polyps, and colorectal cancer (CRC), and proposed to contribute to oncogenesis. The controversies may derive from differences in JCV targets, patient's cohorts, and methods. Studies of simultaneous detection, quantification, and characterization of JCV presence/expression in paired samples of normal/altered tissues of the same patient are lacking. Therefore, we simultaneously quantified JCV presence (DNA) and expression (mRNA and protein) of T-antigen (T-Ag), Viral Protein 1 (Vp1), and miR-J1-5p in paired normal/altered tissues of CRC or polyps, and from controls. JCV signatures were found in most samples. They increased in patients, but were higher in normal mucosa than in corresponding polyp or CRC lesions. JCV non-coding control region (NCCR) DNA rearrangements increased in CRC patients, also in normal mucosa, thus before the onset of the lesion. A new ∆98bp NCCR DNA rearrangement was detected. T-Ag levels were higher in normal mucosa than in adenoma and adenocarcinoma lesions, but decreased to levels of controls in established CRC lesions. In CRC, miR-J1-5p expression decreased with CRC progression. Vp1 expression was not detected. The data indicate a JCV link with the disease, but possible JCV contributes to oncogenesis should occur at pre-polyp stages.

Mastectomy patterns, but not rates, are changing in the treatment of early breast cancer. Experience of a single European institution on 2315 consecutive patients.

BACKGROUND: Recent literature reports that rates of mastectomy are increasing in early breast cancer. However, data from European institutions are limited and revealed conflicting results. We report on 15-year trends of mastectomy, mastectomy plus immediate reconstruction and contralateral prophylactic mastectomy (CPM) at an academic institution. METHODS: We identified women diagnosed with unilateral early breast cancer at stage 0-IIa, with tumour size ≤ 4 cm, between 2002 and 2016. Trends were assessed using the Cochrane-Armitage test. Multivariable logistic regression was used to identify factors associated with receipt of mastectomy plus immediate reconstruction. RESULTS: A total of 2315 patients were identified. Of them, 65.7% underwent breast conserving surgery (BCS), while 34.3% underwent mastectomy as upfront surgery. Two point four per cent also received CPM. Immediate reconstruction was performed in 36.0% of patients receiving mastectomy. There was no change in trends of mastectomy over the 15 years studied (p = 0.69), as well as in trends of patients undergoing CPM (p = 0.44). In contrast, rates of immediate reconstruction rose significantly over the study period (from 12.2% in 2002 to 62.7% in 2016, p < 0.0001). Women were more likely to receive mastectomy plus immediate reconstruction if they were aged 50 years or younger, or had tumours larger than 2 cm, or had non-invasive carcinoma. CONCLUSIONS: Our study suggests that rates of both mastectomy and CPM in early breast cancer are not increasing, while use of immediate reconstruction is on the rise.

Cost and morbidity analysis of chest port insertion in adults: Outpatient clinic versus operating room placement.

BACKGROUND: Totally implantable venous access devices (TIVADs) represent a convenient way for the administration of medications or nutrients. Traditionally, chest ports have been positioned by surgeons in the operating room, however there has been a transition over the years to port insertion by interventional radiologists in the radiology suite. The optimal method for chest port placement is still under debate. MATERIALS AND METHODS: Data on all adult patients undergoing isolated chest port placement at our institution in a 12-year period were retrospectively reviewed. The aim of this cohort study was to compare cost and morbidity for chest port insertion in two different settings: outpatient clinic and operating room. RESULTS: Between 2003 and 2015 a total of 527 chest ports were placed in adult patients. Of them, 262 procedures were performed in the operating room and 265 procedures were undertaken in the outpatient clinic. Patient characteristics were similar and there was no significant difference in early (<30 days, p = 0.54) and late complications (30-120 days, p = 0.53). The average charge for placement of a chest port was 1270 Euros in the operating room versus 620 Euros in the outpatient clinic. CONCLUSION: Our results suggest that chest ports can be safely placed in most patients under local anesthesia in the office setting without fluoroscopy or ultrasound guidance. Future randomized controlled studies may evaluate if surgeons or interventional radiologists should routinely perform these procedures in a dedicated office setting and reserve more sophisticated facilities only for patients at high risk of technical failure.

Molecular identification of Mycobacterium avium subspecies paratuberculosis in oral biopsies of Crohn's disease patients.

Oral lesions may be found in patients with Crohn's disease (CD), in a percentage up to 20%. The aim of this study was to investigate a possible relationship between Mycobacterium avium subsp. paratuberculosis (MAP) and oral lesions in CD patients. 23 oral biopsies were examined performing IS900 Nested PCR; 9 of them were positive: 8 from CD patients and 1 from a control. Our purpose is to go on with this study, amplifying the number of subjects examined and testing subjects with oral lesions related to diseases other than CD to verify the specific association between MAP and oral lesions in CD patients.

Interaction between Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium avium subspecies paratuberculosis with the enteric glia and microglial cells.

BACKGROUND: We investigated the interaction of Mycobacterium avium subspecies paratuberculosis, M. bovis and M. tuberculosis and different glial cells (enteric glial and microglial cells) in order to evaluate the infecting ability of these microorganisms and the effects produced on these cells, such as the evaluation of cytokines expression. RESULTS: Our experiments demonstrated the adhesion of M. paratuberculosis to the enteroglial cells and the induction of IL-1A and IL-6 expression; M. tuberculosis and M. bovis showed a good adhesive capability to the enteric cell line with the expression of the following cytokines: IL-1A and IL-1B, TNF-α, G-CSF and GM-CSF; M. bovis induced the expression of IL-6 too.The experiment performed with the microglial cells confirmed the results obtained with the enteroglial cells after the infection with M. tuberculosis and M. bovis, whereas M. paratuberculosis stimulated the production of IL-1A and IL-1B. CONCLUSION: Enteroglial and microglial cells, could be the target of pathogenic mycobacteria and, even if present in different locations (Enteric Nervous System and Central Nervous System), show to have similar mechanism of immunomodulation.

A rare variant of gallstone ileus: Bouveret's syndrome.

INTRODUCTION: Bouveret's syndrome (gastric outlet obstruction due to impaction of a stone) is a rare variant of gallstone ileus. A recently observed case led us to review the literature, with the aim to discuss the recent advances in the management of this rare syndrome. DISCUSSION: A 69-year-old woman was admitted with symptoms of high intestinal obstruction. Computed tomography scan of the abdomen showed a large gallstone impacted in the duodenum. One-stage surgery, consisting in enterolithotomy, cholecystectomy, and fistula repair, was carried out. Although several surgical and nonoperative procedures have been used, the optimal treatment of Bouveret's syndrome remains controversial. Surgery still maintains a prominent position, even though nonoperative procedures have an increasing role especially in high risk patients with important comorbidities. The decision should be taken on an individual basis, after evaluating patient's general condition and age, stone size, comorbidities influencing the operative risk, and expertise of surgical and endoscopic teams. One-stage surgery may offer definitive management in selected patients.

Contrast-enhanced ultrasonographic evaluation of inflammatory activity in Crohn's disease.

BACKGROUND & AIMS: We sought to test the diagnostic accuracy of ultrasound (US), color Doppler US (CD-US), and contrast-enhanced US (CE-US) in the evaluation of inflammatory activity in patients with Crohn's disease (CD), and to correlate the findings of these sonographic studies with inflammatory activity, as scored by the CD activity index (CDAI). METHODS: Patients with CD were enrolled in the study. Radiologists performing the scans were blinded to clinical status. Baseline US, CD-US, and CE-US examinations were conducted with high-frequency probes (8-14 and 5-7 MHz) before and after injection of sulfur hexafluoride-filled microbubbles. The diagnostic accuracy of baseline US, CD-US, and CE-US were calculated by using the endoscopic and histologic findings as reference standards and correlated with the CDAIs by using the Pearson linear correlation coefficient. RESULTS: Forty-seven patients (20 men; 27 women; mean age +/- SD, 38 +/- 14 years) with a CDAI > 150 (n = 30) or < 150 (n = 17), were recruited. CE-US showed the highest performance, with 93.5% sensitivity, 93.7% specificity, and 93.6% overall accuracy. CE-US revealed 3 bowel wall perfusion patterns after microbubble injection: submucosal enhancement and inward and outward transparietal enhancement. The linear correlation coefficient for CE-US versus CDAI was 0.74 (P < .0001); for baseline US (assessing thickness, length, and multilayer appearance of the diseased bowel) versus the CDAI, the coefficients were 0.68 (P < .0001), 0.47 (P = .0009), and 0.60 (P < .0001), respectively; and for CD-US versus CDAI the coefficient was 0.73 (P < .0001). CONCLUSIONS: CE-US has a high sensitivity and specificity in detecting inflammatory activity and a strong correlation with the CDAI.

Primary appendiceal tumors: report on 10 cases.

We report our experience on 10 patients with primary tumors of the appendix treated at our institution from 1998 to 2005. There were 5 women and 5 men, with a mean age of 59.1 years. Laparotomy was performed in 4 cases; whereas, the other 6 patients underwent laparoscopic exploration: Three operations were completed laparoscopically, and 3 were converted to laparotomy. Six tumors were malignant, and the remaining were benign. Proportions of perioperative and late mortality were both 10%. Two of the four patients with benign tumors died from causes unrelated to the appendiceal neoplasm. The 6 patients with malignant tumors and the other 2 with benign disease were alive and disease free after a mean follow-up of 43 months. Despite the rarity of appendiceal primary tumors, surgeons should be aware of these neoplasms for making correct treatment decisions. We stress the importance of laparoscopic exploration in the management of appendiceal masses.

Effective management of intrathoracic anastomotic leak with covered self-expandable metal stents. Report on three cases.

Intrathoracic anastomotic leakage is one of the major complications of esophageal surgery that can lead to high mortality rate. Depending on the clinical presentation, therapeutic options include surgical reintervention and conservative management with or without external drainage or stenting. In this paper, we report a series of three patients, two men and one woman, mean age of 55.6 years (range 34-68 years), having intrathoracic anastomotic leak after esophagogastrectomy treated by insertion of four covered self-expandable metal stents performed exclusively under fluoroscopic view. Complete resolution of the leakage was obtained in all patients. Despite the limited number of patients, conservative management of intrathoracic anastomotic leaks with covered self-expandable metal stents performed under fluoroscopic guidance has proved to be rapid, safe, and effective in all cases of this series.

Mycobacterium avium subspecies paratuberculosis infection in cases of irritable bowel syndrome and comparison with Crohn's disease and Johne's disease: common neural and immune pathogenicities.

Mycobacterium avium subsp. paratuberculosis causes Johne's disease, a systemic infection and chronic inflammation of the intestine that affects many species, including primates. Infection is widespread in livestock, and human populations are exposed. Johne's disease is associated with immune dysregulation, with involvement of the enteric nervous system overlapping with features of irritable bowel syndrome in humans. The present study was designed to look for an association between Mycobacterium avium subsp. paratuberculosis infection and irritable bowel syndrome. Mucosal biopsy specimens from the ileum and the ascending and descending colon were obtained from patients with irritable bowel syndrome attending the University of Sassari, Sassari, Sardinia, Italy. Crohn's disease and healthy control groups were also included. Mycobacterium avium subsp. paratuberculosis was detected by IS900 PCR with amplicon sequencing. Data on the potential risk factors for human exposure to these pathogens and on isolates from Sardinian dairy sheep were also obtained. Mycobacterium avium subsp. paratuberculosis was detected in 15 of 20 (75%) patients with irritable bowel syndrome, 3 of 20 (15%) healthy controls, and 20 of 23 (87%) people with Crohn's disease (P = 0.0003 for irritable bowel syndrome patients versus healthy controls and P = 0.0000 for Crohn's disease patients versus healthy controls). One subject in each group had a conserved single-nucleotide polymorphism at position 247 of IS900 that was also found in isolates from seven of eight dairy sheep. There was a significant association (P = 0.0018) between Mycobacterium avium subsp. paratuberculosis infection and the consumption of hand-made cheese. Mycobacterium avium subsp. paratuberculosis is a candidate pathogen in the causation of a proportion of cases of irritable bowel syndrome as well as in Crohn's disease.

Relationship between Crohn's disease, infection with Mycobacterium avium subspecies paratuberculosis and SLC11A1 gene polymorphisms in Sardinian patients.

AIM: To study the association between Crohn's disease (CD), Mycobacterium avium subspecies paratuberculosis (MAP), and genetic factors by examining the role of natural resistance-associated macrophage protein 1 (NRAMP1) gene polymorphisms (now SLC11A1) in Sardinian patients with CD and controls. METHODS: Thirty-seven CD patients and 34 controls with no inflammatory bowel disease (IBD) were recruited at the University of Sassari after giving written consent. Six SCL11A1 polymorphisms previously reported to be the most significantly associated with IBD were searched. M. paratuberculosis was identified by IS900 PCR and sequencing. Logistic regression was used to calculate odds ratios (OR) for the associations among CD, presence of MAP, and 6 loci described above. RESULTS: For the first time, a strong association was observed between polymorphisms at NRAMP1 locus 823C/T and CD. While CD was strongly associated with both NRAMP1 and MAP, NRAMP1 polymorphisms and MAP themselves were not correlated. CONCLUSION: Combined with previous work on the NOD2/CARD15 gene, it is clear that the interplay of genetic, infectious, and immunologic factors in the etiology of CD is complex.

Mycobacterium avium subsp. paratuberculosis, genetic susceptibility to Crohn's disease, and Sardinians: the way ahead.

The present study was performed to determine what proportion of people in Sardinia with or without Crohn's disease were infected with Mycobacterium avium subspecies paratuberculosis and had a preponderance of allelic variants of Nod 2, an intracellular protein involved in Crohn's disease susceptibility. Genetic analysis of the alleles of the NOD 2/CARD 15 gene (ins C 3020, G 908 R, and R 702 W alleles), linked to susceptibility or genetic predisposition to Crohn's disease in humans, was carried out on specimens from 37 Crohn's disease patients and 34 patients without Crohn's disease. Our results show that more than 70 percent of people in Sardinia with Crohn's disease carry at least one of the susceptibility-associated NOD 2/CARD 15 alleles and were infected with Mycobacterium avium subspecies paratuberculosis.

Detection and Isolation of Mycobacterium avium subspecies paratuberculosis from intestinal mucosal biopsies of patients with and without Crohn's disease in Sardinia.

OBJECTIVES: Sardinia is an island community of 1.6 million people. There are also about 3.5 million sheep and one hundred thousand cattle in which Johne's disease and Mycobacterium avium subspecies paratuberculosis infection are endemic. The present study was designed to determine what proportion of people in Sardinia attending for ileocolonoscopy with or without Crohn's disease were infected with this pathogen. METHODS: Mycobacterium avium subspecies paratuberculosis was detected by IS900 PCR on DNA extracts of fresh intestinal mucosal biopsies as well as by isolation in culture using supplemented MGIT media followed by PCR with amplicon sequencing. RESULTS: Twenty five patients (83.3%) with Crohn's disease and 3 control patients (10.3%) were IS900 PCR positive (p = 0.000001; Odds ratio 43.3). Mycobacterium avium subspecies paratuberculosis grew in cultures from 19 Crohn's patients (63.3%) and from 3 control patients (10.3%) (p = 0.00001; Odds ratio 14.9). All patients positive by culture had previously been positive by PCR. Mycobacterium avium subspecies paratuberculosis first appeared in the liquid cultures in a Ziehl Neelsen (ZN) staining negative form and partially reverted through a rhodamine-auramine positive staining form to the classical ZN positive form. This resulted in a stable mixed culture of all 3 forms illustrating the phenotypic versatility of these complex chronic enteric pathogens. CONCLUSIONS: Mycobacterium avium subspecies paratuberculosis was detected in the majority of Sardinian Crohn's disease patients. The finding of the organism colonizing a proportion of people without Crohn's disease is consistent with what occurs in other conditions caused by a primary bacterial pathogen in susceptible hosts.

Spontaneous regression of hepatocellular carcinoma: report of a case.

The widespread use of ultrasound in screening programmes for chronic liver disease has led to early diagnosis of hepatocellular carcinoma (HCC), and to the observation of some cases of tumour spontaneous regression. This is a rare event whose underlying mechanism is still unclear. We present here a case of spontaneous regression of HCC in a 71-year-old woman with chronic hepatitis and discuss possible aetiologies. None of the causative mechanisms proposed for spontaneous regression of HCC is completely satisfactory, so further studies are necessary to improve understanding of this unusual biological event. Therefore, we stress the importance of accumulating all such cases in the literature, because the clarification of aetio-pathogenic mechanisms may lead to the development of new treatment strategies for HCC.

Correction of congenital chordee penis by 'ventral separation and outward rotation of corpora'.

BACKGROUND/PURPOSE: The formation of congenital chordee penis in patients with or without hypospadias is multifactorial and not completely clear. In most cases, after release of all known causes of chordee, "residual" penile curvature can persist. The authors discuss the etiopathogenetic mechanisms of congenital chordee penis and describe their experience in surgical correction of "residual" penile curvature by "ventral separation and outward rotation of corpora." METHODS: In 22 patients with congenital chordee penis with or without hypospadias, "residual" penile curvature was corrected by "ventral separation and outward rotation of corpora." RESULTS: Ventral separation and outward rotation of corpora resulted in satisfactory correction of penile curvature. In only 2 cases of chordee penis without hypospadias was further intervention necessary: a Nesbit's plication was carried out in one and a neourethra placed in the other. At follow-up no residual penile curvature was observed. CONCLUSIONS: An arrest of development of the penis caused by failure of outward ventral rotation of the corpora, may contribute to the formation of chordee penis. When "residual" penile curvature persists, "ventral separation and outward rotation of corpora" can be used to correct this complex malformation.