Tumor localization in patients by radiolabeled monoclonal antibodies against colon carcinoma.

A radiolabeled monoclonal antibody (MAb) that has been shown to react specifically in vitro and ex vivo to human colorectal carcinoma and to inhibit growth of human carcinomas grafted in nude mice was administered to 52 colorectal carcinoma patients and 15 patients with other types of cancer. Of 63 colorectal carcinoma tumor sites studied, 34 showed significant accumulation of antibody by external photoscanning and tomoscintigraphy, whereas none of the 20 sites of other cancer types gave positive results. One-third of the patients received F(ab')2 fragments of the MAb, which gave a slightly higher percentage (61%) of positive results than did intact MAbs (51%). A few patients scheduled for tumor resection were given injections simultaneously of 131I-labeled MAb and 125I-labeled normal immunoglobulin G. Antibody concentration in resected tumors was 3.6 to 6.3 times higher than the average antibody concentration in adjacent normal tissues (1.5, 3.4, and 9.4 as compared with normal mucosa, serosa, and fat, respectively), and the specificity indices, calculated by differential radioactivity analysis, ranged from 2.1 to 5.1. The results show the potential value and limitations of this particular MAb for tumor detection by immunoscintigraphy.

Increased neuroendocrine cells in resected metastases compared to primary colorectal adenocarcinomas.

Neuroendocrine differentiation has been described in rectal adenocarcinomas receiving neoadjuvant therapy prior to radical surgery, but its clinical relevance is controversial and no data are currently available in colorectal carcinoma metastases as compared to primary tumors. The presence of chromogranin A positive tumor cells was investigated by means of immunohistochemistry on surgical specimens from 54 primary colorectal carcinomas and their corresponding metastases, resected at diagnosis or during tumor progression. In 47 patients, tumor metastases were resected 1 month to 12 years after chemotherapy and/or radiotherapy, while in the remaining seven patients no additional therapy after primary surgery was performed. In primary tumors, neuroendocrine differentiation was found in 12/54 cases (22.2%) as compared to 25/54 metastatic lesions (46.3%; p?=?0.01). The presence of neuroendocrine phenotype was not correlated with any clinical pathological parameter nor with a different proliferation index. However, patients having neuroendocrine cells in the primary tumor had a significantly shorter survival from the time of metastatic spread than those having not (33.3 vs. 55.5 months; p?=?0.04). In summary, our data show that colorectal carcinoma metastases contain a higher percentage of neuroendocrine differentiated cells as compared to their corresponding primaries, a finding possibly related to the influence of chemotherapy in neuroendocrine differentiation during colorectal carcinoma progression.

Utilité et limites du dosage de l'antigène carcinoembryonnaire (CEA) dans la surveillance postopératoire de malades atteints de carcinomes du côlon et du rectu

An attempt is made to define the usefulness and limitations of carcinoembryonic antigen (CEA) radioimmunoassay for evaluation of tumor resection and detection of tumor relapse in patients with large-bowel carcinoma. In 45 patients for whom complete tumor resection was reported, all but 5 showed a drop in CEA to normal values after surgery. The 5 patients whose CEA did not fall to below 5 ng/ml showed a subsequent rise in CEA level and later were all found to have a tumor relapse. The results indicate that an incomplete drop in circulating CEA level one month after surgery is a bad prognostic sign. Twenty-two of these patients were followed up by repeated CEA radioimmunoassay for several months after surgery; 8 showed a progressive increase in CEA levels preceding clinical diagnosis of tumor relapse by 2-10 months. The clinical history of these 8 patients is briefly described. The results demonstrate that relapses of colon and rectum carcinoma can be detected by increased CEA levels months before the appearance of any clinical evidence.

Surgery for Hirschsprung's disease: comparison between the Duhamel method and the transanal endorectal pull-through based on 59 patients and a review of the literature

Background:¦Hirschsprung's disease (HSCR) is a congenital malformation of the enteric nervous system due to the¦arrest of migration of neural crest cells to form the myenteric and submucosal plexuses. It leads to an anganglionic intestinal segment, which is permanently contracted causing intestinal obstruction. Its incidence is approximately 1/5000 birth, and males are more frequently affected with a male/female ratio of 4/1. The diagnosis is in most cases made within the first year of life. The rectal biopsy of the mucosa and sub-mucosa is the diagnostic gold standard.¦Purpose:¦The aim of this study was to compare two surgical approaches for HSCR, the Duhamel technique and the transanal endorectal pull-through (TEPT) in term of indications, duration of surgery, duration of hospital stay, postoperative treatment, complications, frequency of enterocolitis and functional outcomes.¦Methods:¦Fifty-nine patients were treated for HSCR by one of the two methods in our department of pediatric¦surgery between 1994 and 2010. These patients were separated into two groups (I: Duhamel, II: TEPT), which were compared on the basis of medical records. Statistics were made to compare the two groups (ANOVA test). The first group includes 43 patients and the second 16 patients. It is noteworthy that twenty-four patients (about 41% of all¦patients) were referred from abroad (Western Africa). Continence was evaluated with the Krickenbeck's score.¦Results:¦Statistically, this study showed that operation duration, hospital stay, postoperative fasting and duration of postoperative antibiotics were significantly shorter (p value < 0.05) in group II (TEPT). But age at operation and length of aganglionic segment showed no significant difference between the two groups. The continence follow-up showed generally good results (Krickenbeck's scores 1; 2.1; 3.1) in both groups with a slight tendency to constipation in group I and soiling in group II.¦Conclusion:¦We found two indications for the Duhamel method that are being referred from a country without¦careful postoperative surveillance and/or having a previous colostomy. Even if the Duhamel technique tends to be replaced by the TEPT, it remains the best operative approach for some selected patients. TEPT has also proved some advantages but must be followed carefully because, among other points, of the postoperative dilatations. Our postoperative standards, like digital rectal examination and anal dilatations seem to reduce the occurrence of complications like rectal spur and anal/anastomosis stenosis, respectively in the Duhamel method and the TEPT technique.

Anal mucosectomy for haemorrhoids: should we start to speak Chinese?

AIM: Circular stapled mucosectomy is the standard therapy for the treatment of symptomatic third-degree haemorrhoids and mucosal prolapse. Recently, new staplers made in China have entered the market offering an alternative to the PPH stapling devices. The aim of this prospective randomized study was to compare the safety and efficacy of these new devices. METHODS: Fifty patients with symptomatic third-degree haemorrhoids were randomized to mucosectomy either by using stapler A (CPH32; Frankenman International Ltd, Hong Kong, China; n = 25) or stapler B (PPH03; Ethicon Endo-Surgery, Spreitenbach, Switzerland; n = 25). All procedures were performed by two experienced surgeons. After the stapler was fired by one surgeon, the other surgeon, who was blinded for stapler type, evaluated the stapler line. Postoperative outcome including pain, complications and patient satisfaction were analysed. RESULTS: Demographic and clinical features were no different between the groups. There was no significant difference regarding venous bleeding (P = 0.55), but arterial bleeding was significantly more frequent when stapler B was used (P < 0.001). This led to significantly more suture ligations (P = 0.002). However, no differences regarding operation time (P = 0.99), weight of the resected mucosa (P = 0.81) and height of the stapler line (anterior, P = 0.18; posterior, P = 0.65) were detected. Postoperative pain scores (visual analogue scale) and patient satisfaction were no different either (P = 0.91 and P = 0.78, respectively). No recurrence or incontinence occurred during follow-up. CONCLUSIONS: CPH32 required significantly fewer sutures for bleeding control along the stapler line after circular mucosectomy. However, operation time, rate of postoperative complications and patient satisfaction were similar in both groups.

Gastrointestinal complications of post-diarrheal hemolytic uremic syndrome.

PURPOSE: Whereas gastrointestinal symptoms such as vomiting, diarrhea and abdominal pain are common in children suffering from the so-called post-diarrheal form (D+) of hemolytic uremic syndrome (HUS), more serious gastrointestinal complications are rare. We tried to define factors predictive of the severity of gastrointestinal complications post D+ HUS. METHODS: We reviewed the files of all children admitted to our hospital for D+ HUS between 1988 and 2000. We retained those cases with gastrointestinal complications and analyzed the consequences of these complications on the evolution of the children's conditions. RESULTS: Sixty-five children with D+ HUS were admitted to our hospital during this period. Sixteen children developed gastrointestinal complications involving one or more digestive organs: necrosis of the colon or ileum, hemorrhagic colitis, pancreatitis, transient diabetes, hepatic cytolysis and cholestasis, peritonitis and prolapse of the rectum. One child died. CONCLUSION: Gastrointestinal complications of D+ HUS are rare, but they can be lethal, and early surgery may sometimes prove necessary. However, we were not able to demonstrate a correlation between the severity of the gastrointestinal manifestations and the clinical or biological signs accompanying D+ HUS.

Is it worth treating fever in intensive care unit patients? Preliminary results from a randomized trial of the effect of external cooling.

BACKGROUND: Antipyresis is a common clinical practice in intensive care, although it is unknown if fever is harmful, beneficial, or a negligible adverse effect of infection and inflammation. METHODS: In a randomized study, rectal temperature and discomfort were assessed in 38 surgical intensive care unit patients without neurotrauma or severe hypoxemia and with fever (temperature >/=38.5 degrees C) and systemic inflammatory response syndrome. Eighteen patients received external cooling while 20 received no antipyretic treatment. RESULTS: Temperature and discomfort decreased similarly in both groups after 24 hours. No significant differences in recurrence of fever, incidence of infection, antibiotic therapy, intensive care unit and hospital length of stay, or mortality were noted between the groups. CONCLUSIONS: These results suggest that the systematic suppression of fever may not be useful in patients without severe cranial trauma or significant hypoxemia. Letting fever take its natural course does not seem to harm patients with systemic inflammatory response syndrome or influence the discomfort level and may save costs.

Endocarditis prophylaxis revisited: experimental evidence of efficacy and new Swiss recommendations. Swiss Working Group for Endocarditis Prophylaxis.

Because of its severity, it is agreed that infectious endocarditis should be prevented whenever possible. Determining adequate prophylactic measures involves establishing (a) the patients at risk, (b) the procedures that might provoke bacteraemia, (c) the most effective prophylactic regimen, and (d) a balance between the risks of side effects from prophylaxis and of developing infectious endocarditis. Patients at risk and procedures inducing bacteraemia have been identified by clinical studies. On the other hand, the efficacy of prophylactic antibiotics has been based on animal studies. Randomised, placebo-controlled studies do not exist in humans because they would require large patient numbers and would raise ethical issues due to the severity of the disease. Case-control studies have indicated that infectious endocarditis prophylaxis is effective, but prevents only a limited number of cases. Animal experiments have revealed several key issues for human application. First, antibiotics do not prevent the early stages of valve colonisation, but rather kill the microorganisms after their attachment to the cardiac lesions. Second, the duration of antibiotic presence in the serum is critical. Under experimental conditions, the drugs must remain above their minimal inhibitory concentration for the organisms for > or = 10 h, to allow time for bacterial clearance from the valves. Third, antibiotic-induced killing is not the only mechanism allowing bacterial clearance. Other factors, such as platelet microbicidal proteins, may act in concert with the drugs to sterilise the lesions. Recommendations for prophylaxis have recently been revised in Europe and the USA. New information has improved the definition of groups at risk. Since most cases of infectious endocarditis are not preceded by medical procedures, primary prevention of infectious endocarditis should target infected foci responsible for spontaneous bacteraemia (e.g. poor dental hygiene). The purpose of this article is to update the existing recommendations in Switzerland, under the perspective of changing epidemiology, the availability of new drugs, and harmonisation with recommendations in other countries.

Anorectal Malformations: Finding the Pathway out of the Labyrinth.

Anorectal malformations (ARMs) are a complex group of congenital anomalies involving the distal anus and rectum, as well as the urinary and genital tracts in a significant number of cases. Most ARMs result from abnormal development of the urorectal septum in early fetal life. In most cases, the anus is not perforated and the distal enteric component ends blindly (atresia) or as a fistula into the urinary tract, genital tract, or perineum. ARMs are also present in a great number of syndromes and associations of congenital anomalies. The classification of ARMs is mainly based on the position of the rectal pouch relative to the puborectal sling, the presence or absence of fistulas, and the types and locations of the fistulas. All of this information is crucial in determining the most appropriate surgical approach for each case. Imaging studies play a key role in evaluation and classification of ARMs. In neonates, clinical and radiologic examinations in the first 3 days of life help determine the type of ARM and the need for early colostomy. In older children, preoperative pelvic magnetic resonance imaging is the most efficient diagnostic method for evaluating the size, morphology, and grade of development of the sphincteric musculature.

Colon-specific deletion of epithelial sodium channel causes sodium loss and aldosterone resistance.

Aldosterone promotes electrogenic sodium reabsorption through the amiloride-sensitive epithelial sodium channel (ENaC). Here, we investigated the importance of ENaC and its positive regulator channel-activating protease 1 (CAP1/Prss8) in colon. Mice lacking the αENaC subunit in colonic superficial cells (Scnn1a(KO)) were viable, without fetal or perinatal lethality. Control mice fed a regular or low-salt diet had a significantly higher amiloride-sensitive rectal potential difference (∆PDamil) than control mice fed a high-salt diet. In Scnn1a(KO) mice, however, this salt restriction-induced increase in ∆PDamil did not occur, and the circadian rhythm of ∆PDamil was blunted. Plasma and urinary sodium and potassium did not change with regular or high-salt diets or potassium loading in control or Scnn1a(KO) mice. However, Scnn1a(KO) mice fed a low-salt diet lost significant amounts of sodium in their feces and exhibited high plasma aldosterone and increased urinary sodium retention. Mice lacking the CAP1/Prss8 in colonic superficial cells (Prss8(KO)) were viable, without fetal or perinatal lethality. Compared with controls, Prss8(KO) mice fed regular or low-salt diets exhibited significantly reduced ∆PDamil in the afternoon, but the circadian rhythm was maintained. Prss8(KO) mice fed a low-salt diet also exhibited sodium loss through feces and higher plasma aldosterone levels. Thus, we identified CAP1/Prss8 as an in vivo regulator of ENaC in colon. We conclude that, under salt restriction, activation of the renin-angiotensin-aldosterone system in the kidney compensated for the absence of ENaC in colonic surface epithelium, leading to colon-specific pseudohypoaldosteronism type 1 with mineralocorticoid resistance without evidence of impaired potassium balance.

Monoclonal antibodies against carcinoembryonic antigen (CEA) used in a solid-phase enzyme immunoassay. First clinical results.

A solid-phase enzyme immunoassay using both mouse monoclonal and goat polyclonal antibodies against carcinoembryonic antigen (CEA) was developed. The assay detects 0.6 to 1.2 ng of CEA per ml of serum and has 3 incubation steps which can be performed in 1 day. Polystyrene balls coated with polyclonal goat anti-CEA antibodies are first incubated with heat-extracted serum samples. Bound CEA is then detected by addition of mouse monoclonal antibodies, followed by goat IgG anti-mouse IgG1 coupled to alkaline phosphatase. Results with this enzyme immunoassay using monoclonal antibodies (M-EIA) have been compared with those obtained by the conventional inhibition radioimmunoassay (RIA) using goat antiserum. Three hundred and eighty serum samples from 167 patients with malignant or non-malignant diseases and from 134 normal individuals with or without heavy smoking habits were analyzed by the 2 assays. Excellent correlation between the results of the 2 assays was obtained, but the M-EIA, using monoclonal antibodies from a single hybridoma, did not discriminate better than the conventional RIA between CEA produced by different types of carcinoma and between CEA associated with malignant or non-malignant diseases. Follow-up studies of several patients by sequential CEA determinations with the 2 assays showed that the M-EIA was as accurate as the RIA for the detection of tumor recurrences.

Home and hospital treatment of acute seizures in children with nasal midazolam.

Rectal diazepam is widely used in the treatment of acute seizures in children but has some disadvantages. Nasal/sublingual midazolam administration has been recently investigated for this purpose but never at home or in a general paediatric hospital. The aim of this open study was to determine the efficacy, the tolerance and the applicability of nasal midazolam during acute seizures in children both in hospital and at home. We included known epileptic children for treatment at home and all children with acute seizures in the hospital. In all, 26 children were enrolled, 11 at home and 17 in the hospital (including two treated in both locations); only one had simple febrile seizure. They had a total of 125 seizures; 122 seizures (98%) stopped within 10 minutes (average 3.6 minutes). Two patients in the hospital did not respond and in three, seizures recurred within 3 hours. None had serious adverse effects. Parents had no difficulties administering the drug at home. Most of those who were using rectal diazepam found that nasal midazolam was easier to use and that postictal recovery was faster. Among 15 children who received the drug under electroencephalogram monitoring (six without clinical seizures), the paroxysmal activity disappeared in ten and decreased in three. Nasal midazolam is efficient in the treatment of acute seizures. It appears to be safe and most useful outside the hospital in severe epilepsies, particularly in older children because it is easy for parents to use. These data should be confirmed in a larger sample of children. Its usefulness in febrile convulsions also remains to be evaluated.

Utilisation en tomoscintigraphie d'anticorps monoclonaux radio-marqués pour la détection chez l'homme des cancers digestifs et des cancers médullaires de la thyroïde

Two 131-Iodine radiolabelled monoclonal antibodies were used to perform tomoscintigraphy in 42 patients: 11 patients bearing medullary thyroid cancers and 19 patients bearing gastrointestinal cancers received an antibody directed against carcino-embryonic antigen; 12 patients bearing gastro-intestinal cancers received an antibody directed against a non circulating antigen expressed by human colorectal cancers cell lines. Tomoscintigraphy is particularly useful for analysing the complex biodistribution of radiolabelled antibodies and the low contrast images encountered in immunoscintigraphy; the problems related to the true positive rate and to the clinical specificity of the method are discussed.

Red meat and cancer risk in a network of case-control studies focusing on cooking practices.

BACKGROUND: Consumption of red meat has been related to increased risk of several cancers. Cooking methods could modify the magnitude of this association, as production of chemicals depends on the temperature and duration of cooking. METHODS: We analyzed data from a network of case-control studies conducted in Italy and Switzerland between 1991 and 2009. The studies included 1465 oral and pharyngeal, 198 nasopharyngeal, 851 laryngeal, 505 esophageal, 230 stomach, 1463 colon, 927 rectal, 326 pancreatic, 3034 breast, 454 endometrial, 1031 ovarian, 1294 prostate and 767 renal cancer cases. Controls included 11 656 patients admitted for acute, non-neoplastic conditions. Odds ratios (ORs) and confidence intervals (CIs) were estimated by multiple logistic regression models, adjusted for known confounding factors. RESULTS: Daily intake of red meat was significantly associated with the risk of cancer of the oral cavity and pharynx (OR for increase of 50 g/day = 1.38; 95% CI: 1.26-1.52), nasopharynx (OR = 1.29; 95% CI: 1.04-1.60), larynx (OR = 1.46; 95% CI: 1.30-1.64), esophagus (OR = 1.46; 95% CI: 1.23-1.72), colon (OR = 1.17; 95% CI: 1.08-1.26), rectum (OR = 1.22; 95% CI:1.11-1.33), pancreas (OR = 1.51; 95% CI: 1.25-1.82), breast (OR = 1.12; 95% CI: 1.04-1.19), endometrium (OR = 1.30; 95% CI: 1.10-1.55) and ovary (OR = 1.29; 95% CI: 1.16-1.43). Fried meat was associated with a higher risk of cancer of oral cavity and pharynx (OR = 2.80; 95% CI: 2.02-3.89) and esophagus (OR = 4.52; 95% CI: 2.50-8.18). Risk of prostate cancer increased for meat cooked by roasting/grilling (OR = 1.31; 95% CI: 1.12-1.54). No heterogeneity according to cooking methods emerged for other cancers. Nonetheless, significant associations with boiled/stewed meat also emerged for cancer of the nasopharynx (OR = 1.97; 95% CI: 1.30-3.00) and stomach (OR = 1.86; 95% CI: 1.20-2.87). CONCLUSIONS: Our analysis confirmed red meat consumption as a risk factor for several cancer sites, with a limited impact of cooking methods. These findings, thus, call for a limitation of its consumption in populations of Western countries.