Francesco Cantarella

Epigenetic Modulation by Methionine Deficiency Attenuates the Potential for Gastric Cancer Cell Dissemination

IntroductionMethionine dependency occurs frequently in tumor cells. Here we have investigated the effect of methionine deficiency on metastatic potential of gastric cancer cells in vitro and in vivo.Materials and MethodsModel of peritoneal carcinomatosis and xenograft was generated by intraperitoneal or subcutaneous implantation of gastric cancer cells in NOD-SCID mice. In comparison to control medium, 3-day culture of MKN45, MKN74, and KATOIII cells in a methionine-deficient medium inhibited cell proliferation, increased the rate of cell apoptosis, and reduced cell adhesion and migration. In the xenograft model induced by implantation of MNK45 and MNK74 cells, two cycles of methionine-deficient diet reduced the tumor growth. Further on, a 10-day cycle of methionine-deficient diet reduced the number of peritoneal nodules in the model of peritoneal carcinomatosis induced by MKN45 cells injection. Finally, a microarray analysis of the methylation of promoter CpG islets demonstrated that methionine deficiency reduced the promoter methylation of E-cadherin whose expression was markedly increased in vivo and in vitro.ResultsIn summary, we have provided evidence that a methionine-deficient diet modulates the growth of gastric tumor cells and in vitro deficiency of methionine increased apoptosis and decreased cellular adhesion and migration associated to epigenetic change of E-cadherin gene, in vivo and in vitro.

Indications for the laparoscopic approach to acute small bowel obstruction: A retrospective review of 50 cases, a literature review, and a single hospital's preliminary experience

Small bowel obstruction (SBO) is mainly caused by postoperative adhesions, but a broad spectrum of diseases may cause this pathogenetic condition. Laparoscopic treatment represents an efficient approach to SBO. The aim of this paper was to review a single centers experience with a minimally invasive approach to multiple pathologic scenarios causing SBO. From January 2010 to December 2012, 50 consecutive patients underwent laparoscopic surgery for mechanical SBO. In 90% of patients, the surgical procedure was totally laparoscopic, while 10% required conversion to midline laparotomy. In‐hospital morbidity was 15% among totally laparoscopic patients and 40% among those who underwent conversion to midline laparotomy. Thirty‐day mortality was zero. One patient died 4 months postoperatively from neoplastic disease progression; the remaining patients were free from occlusive symptoms at follow‐up. The minimally invasive technique applies to a broad spectrum of cases. A larger cohort of patients seems necessary to reproduce our results and confirm the effectiveness of a laparoscopic approach to SBO.

Sepsis from Spontaneous Vesicocutaneous Fistula

Giant bladder calculi (GBC) are uncommon; they are attributable primarily to bladder outlet obstruction, vesical diverticula, benign prostatic hyperplasia, and neurogenic bladder [1]. Another known risk factor is the presence of an orthotopic neobladder [2]. Symptoms include mild lowerabdominal discomfort, urinary obstruction, recurrent urinary tract infections (UTI), and fever; in some cases, GBC can lead to acute complications such as bladder rupture [3], visceral perforation, and rectal or colonic compression with bowel obstruction [4]. An 80-year-old man presented to our department with sepsis (hypotension, hypoxia, metabolic disorder, acidosis, leukocytosis, acute kidney injury, and congestive heart disease). No recent history of recurrent UTI was reported, although his history was suggestive of a single episode of left kidney stones at the age of 40, which resolved spontaneously. Severe prostate hyperplasia was present. The patient complained of lower abdominal pain, purulent urethral discharge, and hypogastric cutaneous ulceration with spontaneous serous–purulent discharge. Physical examination revealed hypogastric tenderness with diffuse subcutaneous emphysema. A hard hypogastric mass was palpable, causing acute pain and urethral passage of purulent material. A computed tomography (CT) scan showed multiple GBC, free air in the bladder, and a vesicocutaneous fistula with multiple abdominal wall abscesses (Fig. 1). Antibiotic therapy (ciprofloxacin 400 mg bid) was given, and a cystolithotomy was performed with drainage of multiple abdominal-wall abscesses. Surgery allowed the removal of three giant stones with a maximum dimension of 11 · 8 · 7 cm and a total weight of 1,580 g. A double-lumen catheter was left in the bladder through the suprapubic incision to perform continuous transcurrent bladder lavage during the post-operative course, favoring the resolution of local infection and avoiding the development of blood clots in the vesical lumen. The abscesses were drained with closed suction drains. The post-operative period was uneventful. The sepsis abated rapidly with no residual purulent discharge after postoperative day 2. An intra-operative vesical swab yielded Escherichia coli and Proteus mirabilis, both susceptible to ciprofloxacin, which was continued until 10 days after surgery, whereas lavage was stopped on day 6. The doubleFIG. 1. Computed tomography scans showing multiple giant vesical stones causing a spontaneous vesicocutaneous fistula, confirmed by the presence of air and liquid in the abdominal wall and soft tissues (A, B). Vesicolithotomy and abscess drainage with transcurrent bladder lavage were performed, with complete healing of the fistula. The underlying infection caused by Escherichia coli and Proteus mirabilis responded to ciprofloxacin 400 mg bid. The online Image Data Repository can be found at http://www.sisna.org in the Members Only area.