Expression of CCL9/MIP-1γ is repressed by BCR/ABL and its restoration suppresses in vivo leukemogenesis of 32D-BCR/ABL cells

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A Small Molecule Inhibitor of PDK1/PLC gamma 1 Interaction Blocks Breast and Melanoma Cancer Cell Invasion

Strong evidence suggests that phospholipase Cγ1 (PLCγ1) is a suitable target to counteract tumourigenesis and metastasis dissemination. We recently identified a novel signalling pathway required for PLCγ1 activation which involves formation of a protein complex with 3-phosphoinositide-dependent protein kinase 1 (PDK1). In an effort to define novel strategies to inhibit PLCγ1-dependent signals we tested here whether a newly identified and highly specific PDK1 inhibitor, 2-O-benzyl-myo-inositol 1,3,4,5,6-pentakisphosphate (2-O-Bn-InsP5), could affect PDK1/PLCγ1 interaction and impair PLCγ1-dependent cellular functions in cancer cells. Here, we demonstrate that 2-O-Bn-InsP5 interacts specifically with the pleckstrin homology domain of PDK1 and impairs formation of a PDK1/PLCγ1 complex. 2-O-Bn-InsP5 is able to inhibit the epidermal growth factor-induced PLCγ1 phosphorylation and activity, ultimately resulting in impaired cancer cell migration and invasion. Importantly, we report that 2-O-Bn-InsP5 inhibits cancer cell dissemination in zebrafish xenotransplants. This work demonstrates that the PDK1/PLCγ1 complex is a potential therapeutic target to prevent metastasis and it identifies 2-O-Bn-InsP5 as a leading compound for development of anti-metastatic drugs

Usefulness of lateral internal sphincterotomy combined with hemorrhoidectomy by the Milligan-Morgan's technique: results of a prospective randomized trial

Pain is invariably experienced after haemorrhoidectomy. Internal anal spasm is considered to be a major factor in the genesis of such pain. This prospective randomized study was designed to compare the effectiveness of two manoeuvres (surgical sphincterotomy and chemical sphincterotomy) in reducing post-haemorrhoidectomy pain. Sixty patients (38 males, 22 females) with grade III and IV haemorrhoids were included in this study. In all cases resting anal pressure was reported in the range of 50-100 mm Hg. Group A patients underwent Milligan-Morgan haemorrhoidectomy plus chemical sphincterotomy; group B patients underwent Milligan-Morgan haemorrhoidectomy plus internal left lateral sphincterotomy (0.8-1 cm in length) and group C patients underwent Milligan-Morgan haemorrhoidectomy alone. The postoperative course was carefully evaluated and was found to be better in group B. None of the patients treated by surgical sphincterotomy developed incontinence. Two patients in group C developed anal strictures. When indicated, internal left lateral sphincterotomy (0.8-1 cm) is a safe procedure and reduces post-haemorrhoidectomy pain and stenosis

Rectal prolapse. Functional results after the Orr-Loygue's rectopexy technique

The aims of surgery in rectal prolapse are various: reducing the prolapse, preventing relapse, clearing up incontinence and avoiding constipation. Among several technical options available, anterior rectopexy would appear to be the most suitable for achieving these aims. A retrospective clinical study was conducted in 32 patients operated on from January 1996 to June 1999. For patient recruitment, the preoperative examinations were clinical evaluation, barium enema, anorectal manometry, and urodynamic tests. Surgical procedures were Orr-Loygue rectopexy in 29 cases and Ripstein rectopexy in 3 cases. A sigmoidectomy was also performed in 9 cases and a Burch cystopexy in 4 cases. Early results are available for all patients; only 29 have been evaluated after a mean follow-up of 47 months (range: 30-72). Rectal tenesmus, faecal incontinence and urinary incontinence improved in all cases. Constipation cleared up in 9 cases after a complementary sigmoidectomy; in 15 of the remaining 20 patients constipation persisted or developed. Indications for surgery for rectal prolapse must be considered with caution. The good results of anterior rectopexy depend on correct surgical technique and prevention of septic and pelvic complications. Sigmoidectomy does not increase the morbility rate. A planned colic resection in patients with delayed transit would prevent postoperative constipation. The good results are stable even over long-term follow-up periods. This procedure is also effective for the treatment of genital prolapses

Spontaneous and postoperative bile peritonitis. Surgical technique

Background. Bile peritonitis has a diversified aetiology that can present in clinical pictures of variable gravity depending on whether the bile is uncontaminated or activated by other secretions (intestinal, pancreatic) or actually infected. The consequent treatment is therefore eclectic. In our opinion, however, the therapeutic strategy proves effective if modulated on the basis of certain priority elements that should be carefully considered. The type of treatment adopted in relation to immediate and long-term results has been evaluated. The investigation was carried out retrospectively on the series of bile peritonitis treated at the Surgical Clinic of the University of Modena from 1980 to 1998. 45 cases of bile peritonitis are reported of which: 32 postoperative, 2 post-traumatic, 2 following transparietohepatic injection, 7 during acute necrotic cholecystitis, 2 following spontaneous perforation of the biliary tree. As regards the type of treatment, in 13 cases (well-drained postoperative forms) a conservative solution was adopted; in another 13 cases (9 septic and 4 with mixed bile supply) surgery was resorted to again, in the remainder transparietohepatic drainage was carried out in association almost always with the application of a transpapillary endoprosthesis. Results. Morbility was 26.6% (12 cases); 4 patients (8.8%) were reoperated for late complications with mortality of 50%. Total mortality was 20% (9 patients). Conclusions. Treatment of bile peritonitis may be eclectic but the complex forms benefit from early surgical or parasurgical treatment for a definitive resolution of this feared complication

Management of postoperative peritonitis due to gastric and duodenal fistulas

Background. A leak from the anastomosis or gastroduodenal suture or the duodenal fistula after endoscopic sphincterotomy are a very serious complication of supramesocolonic surgery and at this regard multifocal or disseminated peritonitis is a much more serious situation than a possible gastroduodenocutaneous fistula. Methods. The treatment of 21 cases of postoperative supramesocolonic peritonitis is discussed. It is proposed a procedure of diluition, neutralization and aspiration of digestive secretions with an intraluminal three routes drainage associated to a system of perivisceral drainage. A Witzel jejunostomy is performed in order to provide continous high energy enteral support. Results. Mortality rate has been 28.6% (6 patients: 1 case of pulmonary embolism, 1 case of massive haemorrhage and 4 cases of MOF). The external fistula created by this technique healed spontaneously in an average time of 32 days (range 16-46); in two cases a late surgical procedure was required. The late complications involve only the abdominal wall (13 patients out of 21). Conclusions. This procedure prevents the recurrence of intrabdominal sepsis and local complications due to enzymatic action of digestive secretions

Postoperative peritonitis. Policy for reoperation

Background. Postoperative peritonitis is a pathologic condition with a sometime nuclear clinical occurence and therefore with an uncertain timing for reoperation. Aim of this paper is to identify the type and frequency of the digestive and systemic symptoms in relation to the anatomo-pathologic peroperative picture. Methods. Between 1980 and 1996, 119 patients were reoperated for a postoperative peritonitis (PPO) in the Surgical Department of Modena University. PPO was due to a lesion situated above the mesocolon in 33 patients, from the small bowel in 18, postappendicectomy in 25 and from the colon in 40. The first operation (for benign disease in 66.4%, for malignancy in 33.6%) was performed in emergency in 47 cases (39.5%) and as elective surgery in 72 (60.5%). Results. The global mortality was of 33.6% (40 patients). An attempt is made to identify, the earlier and the most important bioclinical parameters for a correct indication to surgery. Twenty symptoms have been identified that, with different frequency, are strictly related with the onset of a PPO (in average 5 symptoms were positive). A research of these parameters, each 4-6 hours, allow to identify a subclinic PPO. Conclusions. During the decisional timing, it is important to check these general and digestive symptoms, apparently not serious, in order to avoid the onset appearance of an abdominal tenderness or a multiorgan failure that make the prognosis more severe

The role of surgery in severe acute pancreatitis. Indications and timing from a prospective study

Background. From January 1991 to December 1995 in the General Surgery Unit of the University of Modena, 119 consecutive patients with acute pancreatitis have been included in a prospective study; postoperative pancreatitis has been excluded. Methods. The severity of the disease has been evaluated by means of Ranson's and Imrie's scores, by contrast enhanced computed tomography and by a computer-assisted method elaborated on the bases of a retrospective series which considers 11 parameters taken into account no later than 8-12 hours from hospitalization. Results. The computer-assisted classification failed only in 8 cases (6.7%) with an attitudinal understaging in comparison with the pathological pictures. The computer-assisted method may be actually considered reliable for the assessment of therapeutical policy Conclusions. In severe acute pancreatitis with extensive necrosis and early lethal outcome despite intensive care, surgical treatment (long active drainage according to Levy) in the acute phase, represents the only hope to reduce early mortality rate. In severe acute pancreatitis with a milder clinical pattern, in the early stage of the disease, 30-40% shows late infectious contamination of necrotic collections. In these cases the computer-assisted method has been particularly useful in picking up, in an early phase, the cases with septic complications with a formal indication to surgery in order to avoid a condition of septic shock. This policy has reduced the mortality rate of acute pancreatitis to 19.4%

The treatment of iatrogenic injuries of CBD: Surgery vs endoprostheses

Analysis of the long-term results of 83 Roux-en-Y bilio-enteric anastomosis and 25 endoscopic stentings for iatrogenic biliary strictures, has allowed, in spite of drawbacks of a retrospective study, the identification of good indications for treatment. The good long-term results of surgical treatment (84.3%) after a mean follow-up of 8.5 years, have a favorable relationship with an intrahepatic preexisting dilatation of the biliary tree in the absence of chronic rough inflammation of the biliary wall. Otherwise, endoscopic stenting can be a good indication both as definitive treatment and complementary to surgery. On the contrary, the Hutson-Russell loop cutaneous choledochojejunostomy can represent a viable access to intrahepatic biliary tree for endoscopic instrumentation in case of recurrent anastomotic stricture. The long-term results are roughly similar after endoscopic (mean follow-up 23.6 months) and surgical treatment. The cases with unsatisfactory evolution after endoscopic management are the long strictures with late treatment with long-standing biliary infections. Nevertheless follow-ups of endoscopic series are too short to say that long-term results are really definitive. Short and incomplete strictures with bilio-cutaneous fistula have to be thought a good indication to endoscopic treatment. In our opinion self-expanding metallic stents have not to be used in benign strictures