Tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone initiates and enhances pancreatitis responses.

Clinical studies indicate that cigarette smoking increases the risk for developing acute pancreatitis. The nicotine metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a major cigarette smoke toxin. We hypothesized that NNK could sensitize to pancreatitis and examined its effects in isolated rat pancreatic acini and in vivo. In acini, 100 nM NNK caused three- and fivefold activation of trypsinogen and chymotrypsinogen, respectively, above control. Furthermore, NNK pretreatment in acini enhanced zymogen activation in a cerulein pancreatitis model. The long-term effects of NNK were examined in vivo after intraperitoneal injection of NNK (100 mg/kg body wt) three times weekly for 2 wk. NNK alone caused zymogen activation (6-fold for trypsinogen and 2-fold for chymotrypsinogen vs. control), vacuolization, pyknotic nuclei, and edema. This NNK pretreatment followed by treatment with cerulein (40 µg/kg) for 1 h to induce early pancreatitis responses enhanced trypsinogen and chymotrypsinogen activation, as well as other parameters of pancreatitis, compared with cerulein alone. Potential targets of NNK include nicotinic acetylcholine receptors and ß-adrenergic receptors; mRNA for both receptor types was detected in acinar cell preparations. Studies with pharmacological inhibitors of these receptors indicate that NNK can mediate acinar cell responses through an nonneuronal α(7)-nicotinic acetylcholine receptor (α(7)-nAChR). These studies suggest that prolonged exposure to this tobacco toxin can cause pancreatitis and sensitize to disease. Therapies targeting NNK-mediated pathways may prove useful in treatment of smoking-related pancreatitis.

Experience with instrumental chemolysis for urolithiasis.

PURPOSE: We describe a more efficient solution for calcium magnesium stones, an irrigation technique devised by us, and the indications for and results of our 20-year experience with direct renal or ureteral chemolysis. MATERIALS AND METHODS: Renal and ureteral perfusion is performed with 2 coaxial catheters (where the interspace is 1-way circulation), a normal ureteral catheter to a nephrostomy tube or, if the ureter is impractical, a nephrostomy tube after inserting it in a thin catheter achieving coaxial circulation. The perfusion operates by gravity with continuous flow maintaining a negative pressure in the cavities and keeping the circuits sealed during treatment. All equipment is mounted on a mobile support which the patient can take anywhere in the hospital. RESULTS: During the last 20 years 8 cystine stones and 20 "difficult" stones have been completely dissolved and the volume of 39 staghorn struvite stones has been reduced an average of up to 80% before 1 or 2 final lithotripsy sessions without significant side effects. Small fragments remained in the inferior calices in only 2 cases. CONCLUSIONS: Chemolysis is useful for eliminating cystine stones as well as for cases in which lithotripsy or endourology is considered difficult or risky. Furthermore, chemolysis proved to be a useful method for reducing staghorn stones before performing lithotripsy.

Laparoscopic vs open hemicolectomy for colon cancer.

BACKGROUND: The role of laparoscopic resection in the management of colon cancer is still a subject of debate. In this clinical study, we compared the perioperative results and long-term outcome for two unselected groups of patients undergoing either laparoscopic or open hemicolectomy for colon cancer. METHODS: This prospective nonrandomized study was based on a series of 248 consecutive patients operated on by the same surgical team using the same type of surgical technique for right (RHC) and left (LHC) hemicolectomy, excluding segmental resections; the only difference was the type of access, which was either laparoscopic or open. The choice of type of access was left up to the patient after he or she had read the informed consent form. Operative time, length of stay, complications, and long-term outcome for the two groups were compared. Follow-up time ranged between 12 and 92 months (mean, 42). RESULTS: Between March 1992 and January 2000, 140 patients underwent a laparoscopic hemicolectomy (55 RHC and 86 LHC); at the same time, 107 patients (44 RHC and 63 LHC) were treated via an open approach. There were no conversions to open surgery in the laparoscopic RHC group, but six patients (7%) in the laparoscopic LHC group were converted. The mean operative time for laparoscopic surgery was significantly longer than the time for open surgery (190 vs 140 min for RHC, 240 vs 190 min for LHC,); however, with increasing experience, this time decreased significantly. The mean hospital stay for the patients who underwent laparoscopic procedures was significantly shorter in both the RHC and the LHC groups (9.2 vs 13.2 days for RHC, 10.0 vs 13.2 days for LHC). No statistically significant difference between the two laparoscopic and open groups was observed for the major complication rate (1.9% vs 2.3% for RHC, 7.5% vs 6.3% for LHC). The patient in the laparoscopic RHC group were lost to follow-up. The local recurrence rate was lower after laparoscopic surgery in both arms (5.4% vs 9% for RHC, 1.5% vs 7.5% for LHC), but the differences were not statistically significant. Two port site recurrences were observed in the laparoscopic groups, one after RHC (2.7%) and one after LHC (1.5%). Metachronous metastases rates were similar for the two groups (16.2% vs 15.1% for RHC, 4.4% vs 5.7% for LHC). Cumulative survival probability at 48 months after laparoscopic RHC was 0.865, as compared to 0.818 after open surgery, and 0.971 after laparoscopic LHC, as compared to 0.887 after open surgery. CONCLUSION: These results suggest that laparoscopic hemicolectomy for colonic cancer can be performed safely, with morbidity, mortality, and long-term results comparable to those of open surgery.

ERCP and acute pancreatitis.

Acute biliary pancreatitis (ABP) is a serious complication of biliary stones disease and is associated with significant morbidity and mortality. The role of ERCP in the management of ABP has been the focus of discussion in recent years. In this report, we evaluated a protocol of emergency Endoscopic retrograde Cholangiopancreatography (ERCP) (within 24 hours) and early ERCP (within 72 hours). From July 1997 to July 2000, were observed 45 patients (19 man and 26 women) with acute biliary pancreatitis. Mean age of patients was 63.4 years (range 21-87 years). Diagnosis of ABP was based on anamnesis and clinical assessment and was confirmed by specific laboratory data (hyperamylasemia, hyperlipasemia, total and fractionated bilirubinemia, gamma-GT, transaminase, alkaline phosphatase, hypocalcemia, hyperglycemia, leukocytosis). Ultrasound scanning within 24 h of admission was performed in 45 patients (100%) and it revealed gallbladder stones and muddy bile in 39 patients (87%). Computed tomography (CT) performed in all patients, showed a severe acute pancreatitis in the second or subsequent week following admission. The severity of acute pancreatitis was established by Glasgow's criteria and by clinical details of patients. ERCP and Endoscopic Sphinterotomy (ES) was performed in all 45 patients with acute biliary pancreatitis. Twenty-six patients (57%) were classified as having a severe attack (> 4) 19 as having a mild attack by Glasgow's criteria. ERCP associated with ES was performed within 24 hours in 22 patients (49%), 11 (50%) showed a severe attack and 11 (50%) showed a mild attack. A total of 2 complications (4%) occurred and the mortality was of 2 patients (4%). In 23 patients (51%) ERCP and ES was performed within 72 hours after conservative therapy, 8 (35%) showed a mild attack and 15 (65%) showed a severe attack. A total of 5 complications (9%) occurred and the mortality was of 3 patients (6%). Our study showed that ERCP with endoscopic sphincterotomy can be performed safely by skilled endoscopist, without adverse consequences soon after the onset of acute biliary pancreatitis even within the first 24 hours and it showed that is better than ERCP within 72 hours after conservative therapy.

Evaluation of immune response in patients after open or laparoscopic cholecystectomy.

BACKGROUND/AIMS: Laparoscopic cholecystectomy is a so called mini-invasive surgical procedure, and on this basis, we investigated whether and how the immune response is modified in patients after laparoscopic cholecystectomy compared to patients who underwent open cholecystectomy. METHODOLOGY: In a prospective, nonrandomized trial, 35 patients underwent laparoscopic cholecystectomy and 31 open cholecystectomy. Immune activity (neutrophils, total lymphocytes, lymphocyte subpopulations, human leukocyte antigen (HLA-DR), interleukin 6, skin Multitest) was evaluated before surgery and respectively, 1, 3, and 6 days postoperatively. RESULTS: One day after surgery, an increase in interleukin 6 (P < 0.01) was noted in patients who had undergone open cholecystectomy, while this parameter was almost unchanged in patients with laparoscopic cholecystectomy. Moreover, skin tests showed a hypo or anergic response in the majority (81.8%) of open cholecystectomy patients compared to laparoscopic cholecystectomy patients (10.5%), (P < 0.01). Finally, monocyte antigen HLA-DR was also reduced in open cholecystectomy patients (P < 0.05). In this group, we noted 2 cases (6.45%) of respiratory tract infection. CONCLUSIONS: Even though laparoscopic cholecystectomy requires a longer surgery, it reduces postoperative pain, and hospitalization. It also facilitates rapid recovery, a return to normal activity, avoids postoperative immunosuppression and shows a better postoperative morbidity compared to open surgery.

[Fistulectomy with closure by first intention in the treatment of perianal fistulae]. / La fistulectomia con chiusura per prima intenzione nel trattamento delle fistole perianali.

The authors report in a retrospective study their experience in the treatment of anal fistulas suggesting the total exercises of the fistula with primary closure of external and internal anal sphincters and rectal mucosa. In our department of surgery between 1987 and 1993, 36 patients (22 males and 14 females) with anal fistulas (17 intersphincteric, 15 trans-sphincteric and suprasphincteric) were treated with this technique. Postoperative in-hospital stay ranged between 2 and 5 days (mean 3.1) and surgical healing needed 12-15 days. A dehiscence of distal tract was observed in 3 cases (8.2%). in these cases secondary closure of the wound needed 24-28 days. All the patients controlled at follow-up (it lasted at least 1 year) did not show rectal incontinence for gas or stools. The authors conclude that total exeresis with primary closure is a safe procedure indicated in the treatment of anal fistula not associated to inflammatory bowel disease in consideration of earlier healing and minor costs.

[Anorectal functional study. The state of the art]. / Studio della funzione anorettale. Orientamenti attuali.

Disturbances of anal continence and evacuation are frequent. Numerous techniques are now available to measure anorectal function. There is also a better understanding of the anatomy and physiology of the pelvic floor which has a major role in anorectal function. ANORECTAL MANOMETRY. Manometry of the anal canal is an index of the resistance of sphincters to the passage of faeces. Resting pressure is due mainly to the internal anal sphincter whereas voluntary contraction is due mainly to the external anal sphincter. Anorectal manometry is essential in measuring the length of the anal canal and in establishing the presence of the rectoanal inhibitory reflex. Several techniques are employed to evaluate anorectal manometry which is useful in the investigation of patients with faecal incontinence and constipation. PUDENDAL LATENCIES: Pudendal latencies are valuable in the study of the innervation of the external anal sphincter. Pudendal latencies are measured thanks to the stimulation of the S2-S4 nerves lying in the proximity of the ischial spine through the use of a special glove (St Mark's glove). Prolonged pudendal latencies are typical of neurogenic faecal incontinence but it can be brought about by childbirth, rectal prolapse, obstructed defecation and old age. ELECTROMYOGRAPHY. Electromyography is useful in the study of the function of the pelvic floor. This technique can be performed with single fibre needles which make it possible to measure the action potentials and the fibre density of the muscular fibres. Fibre density is raised in neurogenic faecal incontinence and the action potentials are polyphasic in this condition. Concentric needles are employed to map the anal sphincters and this is useful for evaluating the extent of the damage caused by traumatic events like a third degree tear. ANAL ENDOSONOGRAPHY. Anal ultrasound is very effective in the study of the morphology of the anal sphincters and it requires a rectal probe fitted with a 7-MHz transducer. It is as accurate as electromyography in evaluating the damage to the anal sphincters but it is not painful and it is more acceptable to the patient. DEFECOGRAPHY. This radiological test is a dynamic study of the pelvic floor during defecation. It is very useful for investigating the function and the morphology of the rectum and the pelvic floor during defecation. Important parameters like: the anorectal angle, the opening of the anal canal, the position of the pelvic floor and the descent of the perineum can be evaluated with this test. Defecography is useful in the study of patients with rectal prolapse and constipation. CONCLUSION. All these tests provide extremely useful information on the pelvic floor and are reproducible. They can be of great help in evaluating patients with pelvic floor disorders but they are no substitute for clinical judgement.

[Computerized tomography and magnetic resonance in the evaluation of patients with Crohn disease. Their role in the identification, assessment of extent and management of the disease]. / Valutazione con tomografia computerizzata e risonanza magnetica dei pazienti con morbo di Crohn. Ruolo nella identificazione, nel bilancio di estensione e nella gestione della malattia.

In this study we evaluated the role of barium examinations and above all computed tomography and magnetic resonance imaging in the study of Crohn's disease. CT is most often requested for patients with suspected or known intraabdominal or pelvic abscesses. MR plays a very important role in the localization of perirectal and perianal abscesses.

[Treatment of symptomatic bone metastases of prostatic carcinoma using strontium chloride (Sr-89)]. / Trattamento delle metastasi ossee sintomatiche da carcinoma prostatico con Cloruro di Stronzio (Sr-89).

Until now, patients with a progressive prostatic cancer, in whom all therapies failed and the disease spread locally and distally, was considered "a lost patient"; because it did not exist an effective therapy easily to be used. The skeletal pain control is a serious problem and it is a great responsibility also for the Urologists especially if the patient has not a short survival time and the quality of life is very poor. Physicians feel the need for a systemic, well tolerated and effective therapy also for a long time, uniform and repeatable, able to be efficient for these patients. Strontium 89 chloride seems to offer all these possibilities and to be the best procedure for Urologist, Radiotherapists and Nuclear Specialists in order to satisfy the patients requirements. International research has shown Sr-849 Chloride is a powerful new therapy. Sr-89 Chloride is a radiopharmaceutical product for the treatment of painful metastases from prostatic cancer. It is a new treatment but its effectiveness is well documented and results are reported in the most important international literature. In our Department a clinical research has started and our purpose is to produce more data for a clinical and biological evaluation of the results, hoping that a similar research will extend as a multicenter study.

[Adjuvant interferon alpha in renal carcinoma with a high risk of recurrence. Multicenter pilot study]. / Alfa-interferone adiuvante nel carcinoma renale ad alto rischio di ricaduta. Studio pilota multicentrico.

Twenty-eight consecutive patients submitted to radical nephrectomy for Robson's stage II-III renal cell carcinoma underwent adjuvant recombinant a-2b interferon, 5 MUI s.c. 3 times a week, for 6 consecutive months. Home-feasibility of this therapy resulted easy. The most frequent acute (flu-like syndrome) and late (myalgia, fatigue, anorexia) side effects did not affect normal daily life of patients. Eight (28.5%) patients had WHO grade < or = 2 biochemical and hematological toxicity, that normalized after a reduction or a temporarily suspension of therapy. Twenty-seven patients were evaluable for response. Out of these, 7 (26%) relapsed after a 16 months median follow-up.

[Treatment of symptomatic bone metastases of prostatic carcinoma with strontium (Sr-89) chloride: initial experience]. / Trattamento delle metastasi ossee sintomatiche da carcinoma prostatico con Cloruro di Stronzio (Sr-89), esperienza iniziale.

Until now, patients with a progressive prostatic cancer, in whom all therapies failed and the disease spread locally and distally, was considered "a lost patient"; because it did not exist an effective therapy easily to be used. The skeletal pain control is a serious problem and it is a great responsibility also for the Urologists especially if the patient has not a short survival time and the quality of life very poor. Physicians feel the need for a systemic, well tolerated and effective therapy also for a long time, uniform and repeatable, able to be efficient for these patients. Strontium 89 chloride seems to offer all those possibilities and to be the best procedure for Urologist, Radiotherapists and Nuclear Specialists in order to satisfy the patients requirements. International research has shown Sr-89 Chloride is a powerful new therapy. Sr-90 Chloride is a radiopharmaceutical product for the treatment of painful metastases from prostatic cancer. It is a new treatment but its effectiveness is well documented and results are reported in the most important international literature. In our Department a clinical research has started and our purpose is to produce more data for a clinical and biological evaluation of the results hoping that a similar research will extend as a multicenter study.

[Postoperative esophageal-visceral fistulae: their prevention and treatment]. / Fistole esofago-viscerali postoperatorie: prevenzione e trattamento.

A series of 12 cases of esophageal anastomotic leakage following esophageal surgery observed from 1969 to 1989 is retrospectively analyzed. In the period 1969-1975 6 patients were treated in emergency and the mortality rate was 66.6%, while the remaining 6 patients observed from 1975 to 1989 were treated conservatively with total parenteral nutrition (sometimes associating adequate surgical drainage): the mortality rate was 16.6%. In conclusion, not only in the treatment of anastomotic leakage, but also in its prevention, artificial nutrition has a crucial role. The outcome of thoracic and abdominal fistulas depends mainly on adequate drainage, not necessarily surgical. Cervical fistulas heal in 2-4 weeks, but strictures arise frequently and respond to endoscopic dilatation.

[Limitations and complications of the use of the basket]. / Limiti e complicanze nell'uso del basket.

During the last 15 years the Dormia stone dislodger has been used in 352 cases (80%) out of 435 of ureteral stones: 318 were at ileo pelvic, 34 at lumbar level. 303 ileo pelvic and 21 lumbar stones have been successfully removed (92%). Considering that the probability of stone removal is directly proportional to the ureteral expansibility and indirectly proportional to the volume of the stone, the Basket technique isn't indicated: When the stone is more than 1 cm.; When the ureter is widely stiff (as in Ormond d. or post-radiotherapy stiffness); When stenosis is present. The impossibility of bypassing the stone, the insufficient expansion of the Basket, the stone irremovability and the difficult extraction through the meatus, my limit the successes of this technique while iperating. The immediate complications have been: 4 sectoral rips of the mucosa surrounding the ureteral end, cured by catheterisation without aftereffects (1.2%); 1 sliding of the ureter through the trigone up to urethral meatus (in a woman), which has been repaired, without aftereffects, by direct catheterisation of the ureter, out of the urethra, after removal of the Basket and stone from the ureteral extremity. (0.3%) Strictures occurred in 5 cases (1.5%) and vescicoureteral reflux in 6 (1.8%). These results of the sole Basket technique (performed according to the well-known directions) seem to be much better than those (which have been illustrated) obtained with the endoscopic lithotripsy.

Early complications after surgery for Crohn's disease.

A group of 212 patients operated upon for Crohn's disease were studied and the early postoperative complications with related problems were assessed. The morbidity was 28.3 per cent, 60 patients had at least one complication, mainly of septic nature. The mortality was 3.3 per cent (7 patients), sepsis and deep vein thrombosis with pulmonary embolism were the most common causes of death. Postoperative complications were significantly higher (39.7%) (p less than 0.001) in patients with a pre-operative nutritional deficit and in those who had urgent surgery (44.4%) (p less than 0.001). Among patients with pre-operative sepsis, the morbidity was also higher (34.6%), but was not significant. Peri-anastomotic complications (dehiscence, abscess, fistula, bleeding) were apparently more frequent (45.4%) in patients with histological residual Crohn's disease at macroscopically free resection margins although this contrasts with previous series. A proper pre-operative diagnostic approach, adequate peri-operative protein-caloric repletion, antibiotic therapy, prevention of thromboembolism and elective surgery, are still the primary tools in reducing the morbidity and mortality after surgery for Crohn's disease.