Papers by Alessandro Fichera
Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, Jan 22, 2015
The Kono-S (antimesenteric functional end-to-end handsewn) anastomosis has been used for Crohn... more The Kono-S (antimesenteric functional end-to-end handsewn) anastomosis has been used for Crohn's disease in Japan and the USA since 2003 and 2010, respectively. This technique was designed to reduce the risk of anastomotic surgical recurrence. This study reviews the outcomes a decade after the introduction of the Kono-S anastomosis to clinical practice. This study was conducted at five hospitals (four in Japan and one in the USA). A total of 187 patients in Japan (144 patients, group J) and the USA (43 patients, group US) who underwent Kono-S anastomosis for Crohn's disease between September 2003 and September 2011 were included. With a median follow-up of 65 months, two surgical anastomotic recurrences have occurred in group J. Kaplan-Meier analysis showed that 5 and 10 years surgical recurrence-free survival rate was 98.6 % in group J. No surgical anastomotic recurrences have been detected in group US with a median follow-up of 32 months. The Kono-S anastomosis was technic...
Cancer Research, Jun 1, 2006
Aberrant crypt foci (ACF) are collections of abnormal colonic crypts with heterogeneous molecular... more Aberrant crypt foci (ACF) are collections of abnormal colonic crypts with heterogeneous molecular and pathologic characteristics. Large and dysplastic ACF are putative precursors of colon cancer with neoplastic risk related to increased proliferation. In this study, we examined the role of epidermal growth factor receptor (EGFR) signaling in regulating ACF proliferation. Using magnification chromoendoscopy, we collected large ACF with endoscopic features of dysplasia and separately biopsied adjacent mucosa. Transcript levels were measured by real-time PCR, proteins were assessed by Western blotting, and levels were expressed as fold changes of adjacent mucosa. K-ras and B-Raf mutations were assessed by PCR and Ras activation by the ratio Ras-GTP / (Ras-GTP + Ras-GDP). At the RNA level, 38% of ACF were hyperproliferative, with proliferating cell nuclear antigen (PCNA) mRNA z2-fold of adjacent mucosa. Hyperproliferative ACF had significantly increased mRNA levels of EGFR (6.0 F 1.7-fold), transforming growth factor-A (14.4 F 5.0-fold), heparin-binding EGF-like growth factor (4.5 F 1.4fold), cyclin D1 (4.6 F 0.7-fold), and cyclooxygenase-2 (COX-2; 9.3 F 4.2-fold; P < 0.05). At the protein level, 46% of ACF were hyperproliferative (PCNA, 3.2 F 1.2-fold). In hyperproliferative ACF, 44% possessed significant increases in four EGFR signaling components: EGFR (9.5 F 1.3-fold), phosphoactive ErbB2 (2.6 F 0.4-fold), phosphoactive extracellular signal-regulated kinase (3.7 F 1.1-fold), and cyclin D1 (3.4 F 0.8-fold; P < 0.05). Ras was activated in 46% of ACF (3.2 F 0.4-fold; P < 0.05), but K-ras mutations were present in only 7% of ACF. In contrast to COX-2 mRNA, the protein was not increased in hyperproliferative ACF. In summary, we have shown that ACF with up-regulated PCNA possess increased EGFR signaling components that likely contribute to the enhanced proliferative state of
Coloproctology, 2006
Although bowel-sparing techniques have been published for treatment of Crohn&amp;amp;amp;amp;... more Although bowel-sparing techniques have been published for treatment of Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease of the small bowel because of its relentless nature, extent of resection in Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s colitis is still a topic of debate. This study was designed to prospectively evaluate the long-term outcomes of patients with isolated Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s colitis to identify patients that may benefit from initial more aggressive resection. We identified 179 patients with Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease operated on for primary colonic disease. They were divided into segmental colectomy, total abdominal colectomy, and total proctocolectomy groups, based on their initial operation. They were further characterized by extent and location of colonic involvement. Long-term outcome variables evaluated included colonic and small-bowel surgical recurrences, postoperative complications and long-term sequelae, long-term need for medical therapy, and need for permanent fecal diversion. Fifty-five patients underwent segmental colectomy, 49 total abdominal colectomy, and 75 total proctocolectomy. Patients with diffuse colonic involvement were significantly less likely to undergo segmental colectomy than total abdominal colectomy (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) or total proctocolectomy (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Patients with distal involvement or pancolitis were significantly less likely to undergo segmental colectomy than total abdominal colectomy (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) or total proctocolectomy (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Overall there were 31 patients (24.4 percent) with surgical Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s recurrences during follow-up: 19 (38.8 percent) in the segmental colectomy, 8 (22.9 percent) in the total abdominal colectomy, and 4 (9.3 percent) in the total proctocolectomy group. There was a significant difference in time to recurrence between the three groups by log-rank test (P = 0.017). Segmental colectomy patients had a significantly shorter time to first recurrence than total proctocolectomy patients (P = 0.014). After adjusting for extent of disease, the segmental colectomy group had a significantly greater risk of surgical recurrence than the total proctocolectomy group (P = 0.006). Total proctocolectomy patients were significantly less likely to be still taking medications one year after the index operation than total abdominal colectomy patients (P = 0.003) and segmental colectomy patients (P = 0.0003). During follow-up, patients with isolated distal disease were significantly more likely to require a permanent stoma than patients with isolated proximal disease (P = 0.004). A more aggressive approach should be considered in patients with diffuse and distal Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s colitis. Total proctocolectomy in the properly selected patients is associated with low morbidity, lower risk of recurrence, and longer time to recurrence. Patients after total proctocolectomy are more likely to be weaned off all Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s-related medications. Long-term rate of permanent fecal diversion is significantly higher in patients with distal disease.
Nat Rev Gastroenterol Hepatol, 2009
Considerable advances in tools for the diagnosis and management of Crohn&amp;amp;amp;amp;amp;... more Considerable advances in tools for the diagnosis and management of Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease have been made. Despite technological progress, a new study reports that more than one-third of patients with Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease are still diagnosed with fistulizing disease intraoperatively and that the surgical management of these patients is not well characterized.
JAMA Surgery, 2016
Despite professional recommendations to delay elective colon resection for patients with uncompli... more Despite professional recommendations to delay elective colon resection for patients with uncomplicated diverticulitis, early surgery (after &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;3 preceding episodes) appears to be common. Several factors have been suggested to contribute to early surgery, including increasing numbers of younger patients, a lower threshold to operate laparoscopically, and growing recognition of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;smoldering&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; (or nonrecovering) diverticulitis episodes. However, the relevance of these factors in early surgery has not been well tested, and most prior studies have focused on hospitalizations, missing outpatient events and making it difficult to assess guideline adherence in earlier interventions. To describe patterns of episodes of diverticulitis before surgery and factors associated with earlier interventions using inpatient, outpatient, and antibiotic prescription claims. This investigation was a nationwide retrospective cohort study from January 1, 2009, to December 31, 2012. The dates of the analysis were July 2014 to May 2015. Participants were immunocompetent adult patients (age range, 18-64 years) with incident, uncomplicated diverticulitis. Elective colectomy for diverticulitis. Inpatient, outpatient, and antibiotic prescription claims for diverticulitis captured in the MarketScan (Truven Health Analytics) databases. Of 87 461 immunocompetent patients having at least 1 claim for diverticulitis, 6.4% (n = 5604) underwent a resection. The final study cohort comprised 3054 nonimmunocompromised patients who underwent elective resection for uncomplicated diverticulitis, of whom 55.6% (n = 1699) were male. Before elective surgery, they had a mean (SD) of 1.0 (0.9) inpatient claims, 1.5 (1.5) outpatient claims, and 0.5 (1.2) antibiotic prescription claims related to diverticulitis. Resection occurred after fewer than 3 episodes in 94.9% (2897 of 3054) of patients if counting inpatient claims only, in 80.5% (2459 of 3054) if counting inpatient and outpatient claims only, and in 56.3% (1720 of 3054) if counting all types of claims. Based on all types of claims, patients having surgery after fewer than 3 episodes were of similar mean age compared with patients having delayed surgery (both 47.7 years, P = .91), were less likely to undergo laparoscopy (65.1% [1120 of 1720] vs 70.8% [944 of 1334], P = .001), and had more time between the last 2 episodes preceding surgery (157 vs 96 days, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). Patients with health maintenance organization or capitated insurance plans had lower rates of early surgery (50.1% [247 of 493] vs 57.4% [1429 of 2490], P = .01) than those with other insurance plan types. After considering all types of diverticulitis claims, 56.3% (1720 of 3054) of elective resections for uncomplicated diverticulitis occurred after fewer than 3 episodes. Earlier surgery was not explained by younger age, laparoscopy, time between the last 2 episodes preceding surgery, or financial risk-bearing for patients. In delivering value-added surgical care, factors driving early, elective resection for diverticulitis need to be determined.
Clin Cancer Res, 2009
Colon cancer is a major cause of cancer deaths. Dietary factors contribute substantially to the r... more Colon cancer is a major cause of cancer deaths. Dietary factors contribute substantially to the risk of this malignancy. Western-style diets promote development of azoxymethane-induced colon cancer. Although we showed that epidermal growth factor receptors (EGFR) controlled azoxymethane tumorigenesis in standard fat conditions, the role of EGFR in tumor promotion by high dietary fat has not been examined. A/J x C57BL6/J mice with wild-type Egfr (Egfr(wt)) or loss-of-function waved-2 Egfr (Egfr(wa2)) received azoxymethane followed by standard (5% fat) or western-style (20% fat) diet. As F(1) mice were resistant to azoxymethane, we treated mice with azoxymethane followed by one cycle of inflammation-inducing dextran sulfate sodium to induce tumorigenesis. Mice were sacrificed 12 weeks after dextran sulfate sodium. Tumors were graded for histology and assessed for EGFR ligands and proto-oncogenes by immunostaining, Western blotting, and real-time PCR. Egfr(wt) mice gained significantly more weight and had exaggerated insulin resistance compared with Egfr(wa2) mice on high-fat diet. Dietary fat promoted tumor incidence (71.2% versus 36.7%; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) and cancer incidence (43.9% versus 16.7%; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) only in Egfr(wt) mice. The lipid-rich diet also significantly increased tumor and cancer multiplicity only in Egfr(wt) mice. In tumors, dietary fat and Egfr(wt) upregulated transforming growth factor-alpha, amphiregulin, CTNNB1, MYC, and CCND1, whereas PTGS2 was only increased in Egfr(wt) mice and further upregulated by dietary fat. Notably, dietary fat increased transforming growth factor-alpha in normal colon. EGFR is required for dietary fat-induced weight gain and tumor promotion. EGFR-dependent increases in receptor ligands and PTGS2 likely drive diet-related tumor promotion.
Archives of Surgery, Jan 16, 2012
Gastroenterology, 2009
length was 5 (3-8) cm. Overall wound infection and incisional hernia rates were 11.2% and 5.5%, r... more length was 5 (3-8) cm. Overall wound infection and incisional hernia rates were 11.2% and 5.5%, respectively, with a median follow-up of 12.1 (1.2-58.4) months. There was no significant differences in wound infection rates among the extraction sites, however incisional hernia rates for midline, transverse and Pfannenstiel incisions were 8.2% (28/339), 2.7% (2/74) and 1.6% (3/185), respectively (P<0.01). Obesity (P=0.02) was the only independent risk factor associated with wound infection. The extraction-site location (P=0.3), use of wound protector (P=0.4) or HAL port (P=0.7) were not associated with wound infection. Risk factors independently associated with incisional hernia were obesity (P<0.01), midline extraction site (P=0.04), and postoperative wound infection (P=0.01). Conclusion: During laparoscopic colectomy, different extraction sites may be associated with differing complications. While different extraction site locations have similar rates of wound infection, midline incisions are associated with an increased rate of incisional hernia.
Digestive Diseases and Sciences, May 30, 2008
Current therapies offer scant benefit to patients with advanced esophageal adenocarcinoma. We inv... more Current therapies offer scant benefit to patients with advanced esophageal adenocarcinoma. We investigated the effects of Sorafenib, a multifunctional kinase inhibitor, on several growth regulatory pathways that control cell growth and survival in SEG-1 cells derived from Barrett&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s adenocarcinoma. SEG-1 cells were exposed to acidified medium or taurocholic acid, with and without pre-incubation with Sorafenib. Cyclin D1 and E, c-Myc, and Bcl-2 expression levels as well as STAT3 activations were determined by Western blotting. Cyclin D1 mRNA was measured by real-time PCR. Apoptosis was assessed by TUNEL assay. Sorafenib significantly inhibited SEG-1 cell proliferation stimulated by acid or bile acid treatments and reduced cell survival. This drug significantly reduced the up-regulations of cyclin D1, cyclin E, c-Myc, and Bcl-2 as well as the activation of STAT3 in SEG-1 cells. These results support a rational basis for future clinical studies to assess the therapeutic benefit of Sorafenib in esophageal adenocarcinoma.
Gastroenterology, 2011
Introduction Total abdominal colectomy is the procedure of choice for debilitated patients with a... more Introduction Total abdominal colectomy is the procedure of choice for debilitated patients with acute, medical refractory ulcerative colitis in our practice. A laparoscopic approach has been previously shown to be safe and effective, and has become our preferred strategy. This study illustrates the laparoscopic evolution towards a truly minimally invasive approach comparing three phases of a single colorectal surgeon experience. Material and methods In May 2010 single incision laparoscopy was introduced in our practice and has become our preferred approach. Ten consecutive ulcerative colitis patients were case matched and compared with 10 previous laparoscopic-assisted () total abdominal colectomies. Patient, disease and surgery-related factors were analyzed and short-term outcomes were compared. Results Given the study design, there were no differences in demographics, smoking history, disease duration and severity, nutritional and inflammatory parameters, and indication for surgery between groups. Single incision patients were more likely to have received immunosuppressive therapy within 30 days of the surgery (p=0.016). In the single incision group we noticed significantly shorter duration of surgery (p<0.001) and faster resumption of solid diet (p=0.019) compared to the other groups. Other short-term outcomes did not differ between groups. Conclusion Single incision laparoscopy offers a safe alternative to other laparoscopic approaches. Despite the higher technical complexity, the duration of surgery is shorter with faster resumption of oral intake. Studies with larger sample size and longer follow-up will be required to confirm the benefits of this approach.
Journal of Gastroenterology, Mar 1, 2005
Apoptosis, Feb 1, 2008
Patients with mutations in the death receptor CD95 (Fas/APO-1) frequently develop B-cell lymphoma... more Patients with mutations in the death receptor CD95 (Fas/APO-1) frequently develop B-cell lymphoma. However, solid tumors have not been found in the context of defective CD95. This could be due to the fatal autoimmune proliferative disease that develops in the absence of functional CD95 or to a difference in CD95 signaling in lymphoid versus nonlymphoid tissues. To test this we reconstituted mice that harbor a point mutation in the death domain of CD95 (lpr(cg) mice), either in one or in both alleles, with bone marrow from wild-type (wt) mice. After a year one third of the lpr(cg)/lpr(cg) mice developed spontaneous hepatic neoplasms. In contrast only one of the wt/lpr(cg) mice and none of the wt mice developed liver cancer. The agonistic anti-CD95 antibody Jo2 induced massive apoptosis in the liver of wt mice but not in the livers of either wt/lpr(cg) or lpr(cg)/lpr(cg) mice. The susceptibility of lpr(cg)/lpr(cg) mice to liver cancer cannot solely be due to impaired CD95 mediated apoptosis because there was no clear correlation between apoptosis resistance and tumor formation. A gene chip analysis identified genes selectively upregulated in the liver of wt and wt/lpr(cg) mice which may protect these mice from developing liver cancer. Our data represent the first case of CD95 protecting from developing a solid cancer.
Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, Jan 22, 2015
Fistulae-in-ano represent one of the more challenging anorectal diseases faced by surgeons, as ap... more Fistulae-in-ano represent one of the more challenging anorectal diseases faced by surgeons, as appropriate management requires careful balance between the need for local sepsis control and patients' desire to maintain fecal continence. The ligation of intersphincteric fistula tract (LIFT) procedure, first described by Rojanasakul and colleagues in 2007, represents a sphincter-sparing technique for fistula management which has become our method of choice for transsphincteric fistulas. With this technique, patients frequently enjoy successful fistula healing., or, at worst, conversion to a less complex fistula tract. Here, we describe and illustrate our surgical approach and review success and recurrence rates presented in the published literature.
Journal of the American College of Surgeons, 2015
Journal of the American College of Surgeons, 2015
Minerva dietologica e gastroenterologica
Impairment of esophageal motor function is well recognized in connective tissue disease. We have ... more Impairment of esophageal motor function is well recognized in connective tissue disease. We have investigated esophageal function, by manometric studies, presence of symptoms of esophageal involvement and antibodies pattern, in 18 female patients affected by systemic lupus erythematosus (SLE). Esophageal manometry showed motor abnormalities in 72.3% of the patients, especially hypokinetic abnormalities (hypotony of lower esophageal sphincter pressure, low amplitude or alterations of peristaltic waves) or, rarely, an increase of amplitude of peristaltic contractions. No significant correlation were found between antinuclear antibodies, esophageal symptoms and manometric findings. Hypoperistalsis or aperistalsis, may be due to an inflammatory reaction in the esophageal muscles or to an ischemic vasculitic damage of Auerbach plexus. High amplitude of peristaltic esophageal waves may be due to an early stage of reflux esophagitis: we have found gastro-esophageal reflux symptoms in more than half of our patients.
Gastroenterology
INTRODUCTION: Eicosanoids have been implicated in colon carcinogenesis. We observed that in human... more INTRODUCTION: Eicosanoids have been implicated in colon carcinogenesis. We observed that in human colon cancer tissue the levels of PGF~ are elevated comp;ired to normal colon tissue (J Lab Clin Med 122:518) and that the expression of MHC class I and II ant|gens is profoundly reduced in human colon cancer (Cancer Res 53:2374-2378. Theerefore, we investigated the effect of PGE2, PGF2~ and LTB4 on the regulation of class I MHC genes in HT29 human adenocarcinoma cells and in colonocytes of mice treated with 16,16 dimethyI-PGE~. METHODS: Cell
Journal of WOCN
Obesity has become the number one health problem in the United States. The patients who is obese ... more Obesity has become the number one health problem in the United States. The patients who is obese and undergoing a surgical procedure that results in the formation of fecal or urinary diversion requires advanced skills of a multidisciplinary healthcare team. Patients who are obese carry a high risk of wound and cardiopulmonary complications and often present a serious challenge in terms of stoma creation and management. The purpose of this article is to examine the risk factors that face the patient who is obese and undergoing stoma surgery, the challenges of stoma creation, and the resultant stoma management problems.
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Papers by Alessandro Fichera