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Introduction La proteinose alveolaire pulmonaire (PAP) est caracterisee par l’accumulation de matiere lipoproteique dans les alveoles en raison d’un dysfonctionnement des macrophages alveolaires. Nous decrivons six cas de PAP survenant apres une allogreffe de cellules souches hematopoietiques (CSH). Methodes Enquete aupres des 43 centres francais de greffe de CSH. Six cas de PAP post-allogreffe de CSH ont ete identifies dans cinq centres, diagnostiques entre mai 2016 et avril 2019 (LBA avec coloration PAS 5/6 et biopsie pulmonaire 1/6). Resultats Deux de groupes de PAP etaient distingues selon la date de survenue apres l’allogreffe de CSH : – PAP precoce ( – PAP tardive (> 1 an) : 4 malades. Symptomes d’installation progressive : dyspnee d’exercice croissante jusqu’a dyspnee de repos et fievre chez 2/4 patients. Une infection pulmonaire concomitante a Mycobacterium abscessus. Le role des immunosuppresseurs dans la survenue de la PAP a ete suspecte (rapamune n = 2, ruxolitinib n = 2) ; ils ont ete interrompus et des corticosteroides (0,5 mg/kg/j) ont ete debutes chez un patient. L’atteinte clinique et radiologique s’est amelioree dans les mois suivants l’arret du traitement suspecte. La recherche d’anticorps anti-GM-CSF et de mutation GATA2 etait negative chez 3/3 et 2/2 patients testes respectivement. Le scanner thoracique montrait des opacites en verre depoli, des reticulations et un epaississement des septas interlobulaires dans 6/6 cas, un aspect en crazy paving chez 3/6 patients. Il n’y avait pas de topographie predominante. Aucun patient n’a eu de lavage alveolaire a but therapeutique. Un patient est decede 8 mois apres la greffe de GVH digestive severe. Conclusion Les PAP post-allogreffe peuvent etre distinguees entre PAP precoces pendant la periode d’aplasie et tardives en relation avec des immunosuppresseurs. La prise en charge du facteur favorisant a toujours permis une evolution favorable. La recherche systematique d’une PAP en cas de pneumopathie alveolo-interstitielle post-allogreffe de CSH implique la realisation d’une coloration de PAS sur le liquide de LBA. La recherche d’un traitement pneumotoxique responsable est essentielle.

Introduction La dyspnee chronique, apres avoir contracte la COVID-19, est une plainte frequente des patients. Nous avons du prendre en charge un grand nombre d’entre eux presentant une dyspnee inexpliquee par une premiere ligne d’examens (test fonctionnel respiratoire, electrocardiogramme, tomodensitometrie thoracique, mesure de l’hemoglobine, des D-dimeres et de la troponine). La Societe de pneumologie de langue francaise suggere, dans cette situation, de rechercher notamment un syndrome d’hyperventilation (SHV) [1] . Methodes Nous avons cherche a explorer les mecanismes de la dyspnee de 10 patients, referes au service des maladies respiratoires de l’hopital de Foch, a distance d’une forme legere de COVID-19 (delai median de 46 jours [IQR : 36–60]). Nous avons realise un bilan exhaustif comprenant : un score de Nijmegen, un test d’hyperventilation volontaire, une epreuve d’effort cardiopulmonaire, des gaz du sang arteriels, une scintigraphie pulmonaire de ventilation/perfusion, une IRM cardiaque et cerebrale. Resultats Six patients sur 10 etaient porteurs d’un SHV selon les criteres diagnostics classiques : Nijmegen > 23 et test d’hyperventilation positif. Tous les patients SHV etaient des femmes, avec un âge median de 48 ans [IQR : 46–54] ; la moitie d’entre elles souffraient d’asthme leger. Il existait une hypocapnie au repos a 31,5 mmHg [IQR : 26,5–37,2]. L’aptitude aerobie etait preservee avec une VO2 pic a 108 % [IQR : 93–110]. Tous les patients SHV avaient des stigmates fonctionnels de deconditionnement et 5 d’entre eux avaient un mode ventilatoire disharmonieux a l’effort avec une evolution aleatoire du volume courant et de la frequence respiratoire. Les atteintes cardiovasculaires et cerebrales ont ete exclues par des examens d’imagerie normaux. Conclusion Le SHV semble etre particulierement frequent apres la COVID-19. Il doit etre systematiquement envisage chez les patients affectes par une dyspnee chronique. Une reeducation ventilatoire adaptee pourrait aider a attenuer l’impact respiratoire a long terme de la pandemie.

Colo-anal anastomosis represents the only surgical method allowing both resection of the distal third of the rectum and re-establishment of intestinal continuity. Technically similar to a low anterior

Autosomal dominant loss of function mutation of signal transducer and activator of transcription 3 (STAT3) gene (STAT3-deficiency) predisposes to recurrent bacterial pneumonia that are complicated in 67% of patients with bronchiectasis, cavitations and Aspergillus infection or colonization in 22% of patients1. We aimed to report the prevalence, describe clinical, mycological, pathological and radiological presentation and both medical and surgical treatment of mold infections in the National French cohort. Methods Referent physicians of STAT3-deficient patients (n= 74 patients) were contacted to know if patients had evidence of colonization or infection with molds. Clinical and mycological information were collected and imaging was centralized. An expert committee reviewed all charts and classified the cases (EC, SP, CT, AD, FL, OL, MOC). Results Eighteen episodes of filamentous fungal infection in ten (13.5%) STAT3-deficient patients were identified. The median age at first episode was 12 years (IQR 10.2–25). Ninety percent of patients had underlying pulmonary disease, bronchiectasis and cavitations, usually multiple. Mold infections were classified as follow: three aspergillomas, six Chronic Pulmonary Aspergillosis (CPA), five Allergic BronchoPulmonary Aspergillosis (ABPA), two mixed forms ABPA and CPA, one Chronic Allergic Sinus Aspergillosis and one Rasamsonia invasive pulmonary infection. According to EORTC/MSG definitions, no cases of invasive aspergillosis were reported. Aspergillus fumigatus was isolated in 13 cases, Rasamsonia argillocea in one case. Aspergillus precipitins were detectable in 86% of cases (12/14). Two-thirds of fungal episodes (12/18) were breakthrough infections (itraconazole prophylaxis in most cases), and half of the cases (9/18) occurred while on immunoglobulin substitutive therapy. First line antifungal therapy was voriconazole only (8/18) or amphotericin B alone or in association (6/18). Five patients required surgery (4 CPA, 1 aspergilloma). One patient died from respiratory failure at 11 years old. Conclusion Mold infections occurred in 13.5% of STAT3-deficient patients from the French cohort, mostly on anatomical modification of the lung. Notably, patients developed aspergilloma, ABPA or CPA, but no invasive aspergillosis. Despite prolonged antifungal treatment and/or surgery half of the patients (5/10) relapsed.

Introduction Apres transplantation pulmonaire (TP), les cancers bronchiques sont majoritairement developpes sur poumon natif apres transplantation unilaterale et plus rarement transmis par le donneur. Les cellules souches du receveur repeuplent minoritairement le greffon donnant lieu a un troisieme mecanisme rare d’oncogenese dont un cas est rapporte ici. Cas clinique Une patiente non fumeuse de 50 ans atteinte de mucoviscidose developpe de multiples micronodules millimetriques dans les premiers mois suivant une TP bilaterale d’un donneur de sexe masculin tabagique a 35 paquets-annees. Ces lesions regressent sauf une qui evolue vers un adenocarcinome TTF1 + pT1aN0M0 traite par lobectomie 4 ans apres la TP. Le caryotype des cellules tumorales analyse par technique de FISH revele qu’elles proviennent de la receveuse. La patiente est sans rechute a un an. Discussion L’epithelium du greffon pulmonaire est le siege d’un chimerisme dont les modalites d’installation et de regulation sont mal connues. Des cellules souches du receveur repeuplent precocement le greffon et donnent naissance a une composante minoritaire de l’epithelium. On peut imaginer qu’une anomalie des phenomenes de proliferation et de differentiation puisse parfois aboutir a une neoplasie par repopulation non controlee du greffon, illustree par ce cas. Un role de l’immunite dans la regulation de ces phenomenes est possible, amenant a l’hypothese que l’immunosuppression pourrait favoriser cette forme rare de cancer. Conclusion Un desordre de la repopulation du greffon par des cellules souches du receveur peut aboutir a la survenue d’un cancer bronchique apres transplantation pulmonaire.

Based on previous experiments in nude mice, showing that fluoresceinated monoclonal antibodies against carcinoembryonic antigen localized specifically in human carcinoma xenografts and could be detected by laser-induced fluorescence, we performed a feasibility study to determine whether this immunophotodiagnosis method could be applied in the clinic. Six patients, with known primary colorectal carcinoma, received an i.v. injection of 4.5 or 9 mg of mouse-human chimeric anti-carcinoembryonic antigen monoclonal antibody coupled with 0.10-0.28 mg of fluorescein (molar ratio 1/10 to 1/14). The monoclonal antibody was also labeled with 0.2-0.4 mCi of 125I (1 Ci = 37 GBq). Photodetection of the tumor was done ex vivo on surgically resected tissues for the six patients and in vivo by fluorescence rectosigmoidoscopy for the sixth patient. Upon laser irradiation, clearly detectable heterogeneous green fluorescence from the dye-antibody conjugate was visually observed on all six tumors; almost no such fluorescence was detectable on normal mucosa. The yellowish tissue autofluorescence, which was emitted from both tumor and normal mucosa, could be subtracted by real-time image processing. Radioactivity measurements confirmed the specificity of tumor localization by the conjugate; tissue concentrations of up to 0.059% injected dose per g of tumor and 10 times less (0.006%) per g of normal mucosa were found. The overall results demonstrate the feasibility of tumor immunophotodiagnosis at the clinical level.

We have tested growth factor responsiveness of a panel of eight human colorectal carcinoma cell lines. Insulin-like growth factors I and II (IGF-I and IGF-II) stimulated growth of five lines (HT-29, LS411N, LS513, SW480, WiDr). At 30 ng ml-1 both factors enhanced growth up to 3-fold. They induced half-maximal stimulation at 1.9-6.51 ng ml-1. Even after delayed addition IGF-I and II significantly enhanced growth in a short-term proliferation assay. They exerted maximal effects under limiting serum conditions (0.5% FCS) and at low cell density (1.25-5 x 10(4) ml-1). Using these conditions transforming growth factor alpha (TGF alpha) enhanced proliferation of all IGF-responsive cell lines, except SW480. 1.11-3.31 ng ml-1 were required to obtain a half-maximal response. With 10-20 ng ml-1 maximal stimulation occurred at plateau values different from those for IGF-I/II. Proliferation of all cell lines responsive to both IGF-I and TGF alpha was further enhanced by combining both factors, resulting a synergistic response of LS513, while the effects on HT-29, LS411N and WiDr were additive. With HT-29 and LS411N a 24 h exposure to TGF alpha was sufficient to obtain a full response in the co-stimulatory assay. Our results illustrate the importance of IGF-I/II and TGF alpha as stimulators of growth of colorectal carcinomas.

Even though anal incontinence affects a significant proportion of the population, causing a major burden to both patient and society, it still remains "the last closet issue". Less than a third of patients will share this problem with their physician. Consequently, the incidence of anal incontinence is difficult to determine, varying from 2-50%. Since this disabling condition is often associated with urinary incontinence and/or pelvic organ prolapse, a multidisciplinary team approach is required. A wide range of therapeutic options are available. When dietary, medical and rehabilitative treatments have failed, sacral neuromodulation should be considered in selected cases. More invasive surgery is usually undertaken in the presence of major structural defects. The aim of this article is to suggest a comprehensive way of identifying and treating anal incontinence.

The Magnet Tracking System (MTS) is a minimally-invasive technique of continuous evaluation of gastrointestinal motility. In this study, MTS was used to analyse colonic propulsive dynamics and compare the transit of a magnetic pill with that of standard radio-opaque markers. MTS monitors the progress in real time of a magnetic pill through the gut. Ten men and 10 women with regular daily bowel movements swallowed this pill and 10 radio-opaque markers at 8 pm. Five hours of recordings were conducted during 2 following mornings. Origin, direction, amplitude and velocity of movements were analysed relative to space–time plots of the pill trajectory. Abdominal radiographs were taken to compare the progress of both pill and markers. The magnetic pill lay idle for 90% of its sojourn in the colon; its total retrograde displacement accounted for only 20% of its overall movement. Analysis of these movements showed a bimodal distribution of velocities: around 1.5 and 50 cm min–1, the latter being responsible for 2/3 of distance traversed. There were more movements overall and more mass movements in males. Net hourly forward progress was greater in the left than right colon, and greater in males. The position of the magnetic pill correlated well with the advancement of markers. MTS showed patterns and propulsion dynamics of colonic segments with as yet unmet precision. Detailed analysis of slow and fast patterns of colonic progress makes it possible to specify the motility of colonic segments, and any variability in gender. Such analysis opens up promising avenues in studies of motility disorders.

Background Direct colonic electrical stimulation may prove to be a treatment option for specific motility disorders such as chronic constipation. The aim of this study was to provoke colonic contractions using electrical stimulation delivered from a battery-operated device. Methods Electrodes were inserted into the caecal seromuscular layer of eight anaesthetized pigs. Contractions were induced by a neurostimulator (Medtronic 3625). Caecal motility was measured simultaneously by video image analysis, manometry and a technique assessing colonic transit. Results Caecal contractions were generated using 8–10 V amplitude, 1000 µs pulse width, 120 Hz frequency for 10–30 s, with an intensity of 7–15 mA. The maximal contraction strength was observed after 20–25 s. Electrical stimulation was followed by a relaxation phase of 1·5–2 min during which contractions propagated orally and aborally over at least 10 cm. Spontaneous and stimulated caecal motility values were significantly different for both intraluminal pressure (mean(s.d.) 332(124) and 463(187) mmHg respectively; P < 0·001, 42 experiments) and movement of contents (1·6(0·9) and 3·9(2·8) mm; P < 0·001, 40 experiments). Conclusion Electrical stimulation modulated caecal motility, and provoked localized and propagated colonic contractions.

In a prospective study, the DNA content of Feulgen-stained nuclei obtained from fresh samples of 211 colorectal adenocarcinomas was evaluated by means of image analysis. The DNA histogram classification took into account aneuploidy and S-phase fraction for diploid cases. No significant relationship was found between ploidy and sex, age, preoperative carcinoembryonic antigen (CEA), size of the tumor, histologic differentiation, or Dukes' stage. Aneuploidy was more frequently encountered in distal tumors. Preoperative CEA, histologic differentiation, Dukes' stage, and ploidy were individually associated with overall survival. In Dukes' A, B, and C tumors, patients with normal and elevated CEA had no significant difference in overall survival. A relationship was apparent between disease-free survival and site, histologic differentiation, Dukes' stage, and ploidy. Multivariate overall survival analysis did not reveal independent prognostic significance of ploidy when all Dukes' stages were considered. In contrast, Dukes' stage, differentiation, and ploidy were good indicators of higher risk of colorectal cancer-related death in patients undergoing curative surgery. Dukes' stage and ploidy were also indicators for recurrence. Thus, routine histopathologic characteristics should be used in combination with quantitative cytologic features for the definition of a relevant prognostic index in colorectal cancer.

The evolution of visceral surgery is characterized by defining with ever increasing precision the real role of new techniques. Hernia repair, abdominal compartment syndrome, pancreatic and colorectal cancers, as well as haemorrhoids, confirm this reality. Although laparoscopy has clear indications in hernia repairs, many still prefer open approach. The abdominal compartment syndrome, now better understood thanks to laparoscopy, is increasingly important in intensive care. The role of laparoscopy for pancreatic and colorectal cancers is still limited. The development of minimally invasive techniques has led to a reduced morbidity of surgery for haemorrhoids and better results. The economic impact of new technologies must remain a primary concern.

We present a new graphical tool to investigate the time evolution of phase-synchronization clusters and apply it to a computer model of the intestine consisting of coupled oscillators. The method estimates the synchronized zones using a covariance analysis of the electrical activity to detect any linear relationship between segments of the intestine. Synchronization expresses itself by the formation, merging and destruction of clusters, which are groups of oscillators with a related dynamics. Specific patterns of cluster evolution were generated with different frequency gradients, reflecting the different properties of segments of the intestine. This tool allowed us to identify characteristic patterns for the small and the large intestine.

Aims: The purpose of this study was to evaluate excision and open granulation versus excision and primary closure as treatments for pilonidal sinus. Subjects and methods: We evaluated a group of 141 patients operated on for a pilonidal sinus between 1991 and 1995. Ninety patients were treated by excision and open granulation, 34 patients by excision and primary closure and 17 patients by incision and drainage, as a unique treatment of an infected pilonidal sinus. Results: The first group, receiving treatment of excision and open granulation, experienced the following outcomes: average length of hospital stay, four days; average healing time; 72 days; average number of post-operative ambulatory visits, 40; average off-work delay, 38 days; and average follow-up time, 43 months. There were five recurrences (6%) in this group during the follow-up period. For the second group treated by excision and primary closure, the corresponding outcome measurements were as follows: average length of hospital stay, four days; average healing time, 23 days; primary healing failure rate, 9%; average number of post-operative ambulatory visits, 6; average off-work delay, 21 days. The average follow-up time was 34 months, and two recurrences (6%) were observed during the follow-up period. In the third group, seventeen patients benefited from an incision and drainage as unique treatment. The mean follow-up was 37 months. Five recurrences (29%) were noticed, requiring a new operation in all the cases. Discussion and conclusion: This series of 141 patients is too limited to permit final conclusions to be drawn concerning significant advantages of one form of treatment compared to the other. Nevertheless, primary closure offers the advantages of quicker healing time, fewer post-operative visits and shorter time off work. When a primary closure can be carried out, it should be routinely considered for socio-economical and comfort reasons.

Mutations of the TP53 and Ki- ras genes have been reported to be of prognostic importance in colorectal carcinomas. An increased intracellular concentration of the p53 protein, although not identical to, is sometimes seen in tumours with TP53 mutation and has been correlated with poor prognosis in some tumour types. Previous colorectal cancer studies, addressing the prognostic importance of Ki- ras mutation and TP53 aberrations, yielded contradictory results. The aim of this study was to determine in a clinically and therapeutically homogeneous group of 122 sporadic Dukes' B colorectal carcinomas with a median follow-up of 67 months (3–144 months) whether or not p53 protein expression, TP53 mutation and K- ras mutation correlated with prognosis. p53 staining was performed by immunohistochemistry, using the monoclonal antibody DO7 on paraffin-embedded tissue. Mutations in exons 5–8 of the TP53 gene and in codons 12 and 13 of the K- ras gene were assayed in paraffin-embedded tissue by the single-strand conformation polymorphism (SSCP) assay. Nuclear p53 staining was found in 57 (47%) tumours. Aberrant migration patterns indicating mutation of the TP53 gene were found in 39 (32%) tumours. Forty-six carcinomas (38%) showed a mutation of the Ki- ras codons 12 or 13. In a univariate analysis, patients with wild-type TP53 status showed a trend towards better survival, compared with those with mutated TP53 (log-rank test, P =0.051). Likewise, tumours immunohistochemically positive for p53 showed a worse prognosis than p53-negative tumours ( P =0.010). The presence or absence of mutations in Ki- ras did not correlate with prognosis ( P =0.703). In multivariate analysis, only p53 immunoreactivity emerged as an independent marker for prognosis hazard ratio (HR)=2.16, 95% confidence interval (CI) 1.12–4.11, P =0.02). Assessment of p53 protein expression is more discriminative than TP53 mutation to predict the outcome of Dukes' stage B tumours and could be a useful tool to identify patients who might benefit from adjuvant therapy.

Prognosis of patients after colorectal cancer resection is predominantly influenced by the extent of local tumour growth and the presence or absence of nodal or distant metastasis. However, many factors have been used to generate numerous classification systems, leading to some debate and confusion. The effects on survival of 7 clinical and pathological parameters were reviewed in 801 consecutive patients operated upon with locally curative intent for colorectal cancer over a ten-year period. Age less than 50 or more than 70 years, poor cellular differentiation, high mucous secretion by tumour cells and Dukes' staging were the parameters significantly correlated to poor overall survival (p

Lymph node status is pivotal to the staging of colorectal carcinoma. The diagnosis of a lymph node negative tumor should imply a good prognosis; however, the outcomes for Dukes' B (TNM Stage II) patients remain variable, possibly in part due to understaging. The aim of this study was to determine whether examining a specified minimum number of lymph nodes using conventional techniques would eliminate the risk of understaging and thus have an effect on prognosis.Data on patients who underwent surgery for colorectal carcinoma at a single institution between 1985 and 1990 were reviewed. Patients with Dukes' B (TNM Stage II) or C (TNM Stage III) tumors and histologically confirmed disease-free resection margins who were treated with curative intent were included. Correlations among variables were assessed using the chi-square test, and survival comparisons were made using Kaplan-Meier curves and the log rank test. Multivariate analysis was performed using a Cox regression model.Dukes' B (TNM Stage II) patients withor =6 lymph nodes examined had significantly poorer overall survival than those withor =7 lymph nodes examined (P = 0.0014). Such a significant difference was not observed among Dukes' C (TNM Stage III) patients (P = 0.7). Survival of Dukes' C patients was significantly worse compared with that of Dukes' B patients overall and Dukes' B patients withor =7 lymph nodes examined (P0.0001). There was no significant difference in survival between Dukes' C and Dukes' B patients withor =6 lymph nodes examined (P = 0.02). The number of examined lymph nodes was the only significant parameter correlated with survival in the multivariate analysis (P = 0.002).Because Dukes' B patients withor =6 examined lymph nodes have poorer outcomes than those with a higher number examined (probably due to understaging), the total number of examined lymph nodes should always be reported.

Patients suffering from disorders of the colon, rectum, and anus often complain of vague symptoms. A detailed description of them must therefore be obtained, so that they may be associated with a precise anatomic location to provide a basis for appropriate examinations and a reliable diagnosis. Even without a specific association with a particular location, numerous symptoms nevertheless suggest a probable site of origin. As in all fields of medicine, the assessment of the patient’s history is the single most important piece of data that the physician can obtain. The circumstances in which a symptom appears, its localization, its development, the appearance of secondary associated complaints, and their exact characteristics should all be ascertained in detail.

We have investigated the secretion of interferon alpha (IFN-alpha), IFN-gamma, interleukin-1alpha (IL-1alpha), IL-1beta, IL-2 and tumour necrosis factor alpha (TNF-alpha) in whole blood cell cultures (WBCCs) of colorectal cancer patients upon mitogen stimulation. Whereas the values for IL-1beta and TNF-alpha remained virtually unchanged in comparison with healthy control subjects, WBCCs of colorectal cancer patients secreted significantly lower amounts of IFN-alpha (P < 0.005), IFN-gamma (P < 0.0001), IL-1alpha (P < 0.0001) and IL-2 (P < 0.05). This reduction correlated with the progression of the disease. The total leucocyte and monocyte population were almost identical in both groups. In contrast, a dramatic depletion of lymphocytes was observed in colorectal cancer patients, which affected both lymphocyte counts (P < 0.0005) and their distribution (P < 0.0001). Our results suggest a selective suppression of cytokines in colorectal cancer patients that is related to tumour burden. Several mechanisms might account for this phenomenon, one of which might be lymphocyte depletion.

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal, dominantly inherited disease leading to a marked increase in cancer susceptibility, notably colorectal cancer, affecting up to one in 400 individuals in the Western world. Four genes responsible for the majority of cases have been identified. Colorectal cancer in affected people tends to be right sided, occur at an earlier age, and there is a propensity for synchronous or metachronous lesions. Extra-colonic tumours may occur with an elevated frequency, most importantly cancer of the endometrium, but also stomach, hepatobiliary system, small bowel, proximal ureter and renal pelvis, and ovary. On account of these features, management guidelines for members of HNPCC kindreds require modification from those generally advised for patients with sporadic tumours. The cardinal feature for the identification of affected families is the family history. All clinicians have a duty to identify such patients under their care as appropriate screening and surgery should lead to an improved prognosis for such patients and their families.

Amongst family members at risk of developing familial adenomatous polyposis (FAP) to distinguish between those who are affected by the disease and those who are not, in order to provide optimal treatment to those requiring it whilst excluding those without the disease from the endoscopic surveillance programme.A programme of endoscopy, ophthalmologic examination for retinal pigment lesions associated with FAP and genetic analysis was proposed to a patient suffering from FAP and 3 of his children considered to be at risk.One person at risk eventually proved to have the disease. He had diffuse recto-colic polyposis as well as the typical retinal lesions found in his father and was treated by prophylactic proctocolectomy. He had inherited the mutated paternal allele. The other 2 children had neither polyposis nor retinal lesions and had inherited the normal allele from their father.Retinal lesions seen at fundoscopy allowed the diagnosis of FAP to be made before endoscopic confirmation in one patient at risk for FAP, but their absence did not exclude the diagnosis in the other 2. In these patients genetic analysis revealed that they had inherited the normal paternal allele and hence would not develop FAP.Systematic investigation of a family suffering from FAP allowed the members at risk to be identified. Two subjects at risk were able to be excluded from further follow-up and the remaining patient was able to be treated in an optimal fashion. An algorithm is proposed for the screening of patients at risk.

We have recently shown that immunophotodetection of human colon carcinomas in nude mice and in patients is possible by using anti-carcinoembryonic antigen (CEA) monoclonal antibodies (MAb) coupled to fluorescein. Here we show, by using a new fluorescent dye, indocyanin, coupled to either anti-CEA or anti-squamous cell carcinoma MAbs, that the efficiency of tumor immunophotodetection in nude mice bearing either human colon carcinoma or squamous cell carcinoma xenografts, can be markedly improved. This improvement is due to the higher absorption and emission wavelengths of indocyanin (652 – 667 nm) as compared to fluorescein (488–515 nm), which give a deeper tissue penetration and lower tissue autofluorescence. Preliminary clinical studies in patients with SCC, however, showed that the tumor to normal tissue ratios obtained after injection of 125I-MAb E48-indocyanin conjugates were not sufficient to allow satisfactory immunophotodiagnosis. In contrast, when we used our chimeric anti-CEA antibody coupled to indocyanin in patients with colon carcinomas, we obtained very elegant and specific tumor immunophotodetection. The overall results demonstrate the feasibility of a new form of in vivo tumor diagnosis called immunophotodetection, which may open the way to the development of a more specific approach to phototherapy of early carcinomas.

Stem cell factor (SCF) is a cytokine which plays an important role in the development of precursor cells. We have investigated the expression of SCF and its receptor, the c-kit proto-oncogene, in human colorectal carcinoma cell lines. Using reverse transcription-PCR, we confirmed the expression of c-kit in two lines (LS174T and LS1034) and of SCF in 9 of 11 cell lines tested. In a Northern blot, a single transcript of 6.6 kb was detected for SCF mRNA. In addition, two lines (LS174T and HT29) synthesized SCF protein, as detected by Western blot analysis. SCF stimulated proliferation and colony formation of LS174T in a dose-dependent manner up to 160%. A half-maximal effect was obtained with about 5.5 ng/ml of SCF under both growth conditions. LS174T cells expressed the M(r) 145,000 c-kit protein on the cell surface and a neutralizing anti-c-kit mAb inhibited colony formation of LS174T by 40%. Interleukin 4 (IL-4) completely inhibited SCF-induced proliferation of LS174T cells. Interestingly, IL-4 induced an almost complete down-regulation of both c-kit and SCF expression in LS174T. Our findings suggest that in LS174T cells, an SCF-mediated autocrine loop is functional and that IL-4 down-regulates the expression of both the receptor and the ligand of this circuit.

Numerous acquired genetical mutations are now well described by molecular biology and seem to be related to tumour progression. K-RAS mutation is of interest in colorectal cancer where it could be correlated to an aggressive tumoral behaviour leading to a high risk of recurrence or metastasis.

Secretion of several cytokines by colorectal carcinoma cells has been substantiated. These do not include granulocyte-macrophage colony-stimulating factor (GM-CSF) thus far. We show that the supernatant of two human colorectal carcinoma cell lines, LS1034 and SW480, stimulates proliferation of GM-CSF-dependent M07e cells. The activity was constitutively secreted by LS1034 cells and could be induced by serum-free culture conditions in SW480 cells. Addition of a neutralizing anti-GM-CSF antibody completely inhibited this activity. Preabsorption with anti-GM-CSF antibody removed all M07e growth-stimulating activity from LS1034 and SW480 supernatant. Western blot analysis revealed the presence of GM-CSF in LS1034 supernatant. Our results indicate that human colorectal carcinoma cells secrete indeed biologically active GM-CSF.

Interferon-alpha (IFN-alpha) enhances the activity of the 5-fluorouracil (5-FU) prodrug 5'-deoxy-5-fluorouridine (5'-dFUrd) in colorectal cancer cells in vitro by upregulating the enzyme pyrimidine nucleoside phosphorylase (PNPase), which is responsible for converting 5'-dFUrd to 5-FU. We examined whether such enhancement also occurs in vivo using human colorectal xenografts in nude mice. The Co-115 line has high basal levels of PNPase and the enzyme level was increased in tumours from mice treated for 3 weeks with 50,000 IU/day (5 days/week) of IFN-alpha A/D. The prodrug 5'-dFUrd (200 mg/day, 5 days/week) had a much greater antitumour activity than 5-FU had when it was used at an approximately equitoxic dose (20 mg/day, 5 days/week). However, because of the high activity of 5'/dFUrd as a single agent, no enhancement by IFN-alpha A/D was observed. Studies on xenografts of WiDr cells indicated that this line is much less sensitive to 5'-dFUrd. However, treatment of animals with IFN-alpha A/D at doses of 75,000 IU/day or 150,000 IU/day resulted in significant inhibition of WiDr tumour growth. Combination treatment with 75 mg/kg/day or 150 mg/kg/day of 5'-dFUrd resulted in enhanced antitumour activity, particularly at the higher dose of IFN-alpha A/D. Synergy of this drug combination was confirmed by isobologram analysis. Analysis of PNPase levels in WiDr tumours, excised from mice treated with IFN-alpha A/D, demonstrated that the enzyme activity was increased by IFN-alpha in a dose-dependent manner. Slight increases were also seen in normal liver and intestine from the same animals. Our results indicate that modulation of converting enzymes for anticancer prodrugs by cytokines could be a novel therapeutic strategy for combination therapy of colorectal cancer.

Cancer of unknown primary site is a common clinical entity, accounting for 5% of all cancer patients. The diagnostic evaluation of these patients must permit to exclude treatable tumors. We reviewed the charts of 85 patients admitted with this diagnostic. We propose an algorithm for investigation of these patients.

Malrotation is a rare aetiological factor of intestinal occlusion in adult. We report our experience of 16 cases collected from 1976 to 1991. The incidence is about 0.2-0.5% with two peaks, at 25 and 55 years respectively. Mean age is of 41 years. The symptoms were occlusion in more than 90%. A contrast enema was performed in acute as well as in chronic situations. The surgical treatment whatever it is, is the treatment of choice but has to be put in balance with age.

Described in Switzerland in the early '60, the major features of hereditary non-polyposis colon cancer syndrome (HNPCCS) were established 20 years ago by H. T. Lynch. HNPCCS accounts for at least 60% of the colon cancer etiology. Cancer family syndrome is defined by the presence of extracolonic primary tumors in addition to colon cancer. Both syndromes are transmitted by an autosomic dominant pattern. None of the known biomarkers are specific and/or sensitive enough to rely on their predictive values of patient's risks. A typical Swiss family was investigated on the basis of the cancer-prone family history. 21% of the family members observed over 5 generations presented one or more (30% of the cases) colo-rectal neoplasms at the age of 50. 55% of the tumors were right sided. Histologically, half of the tumors were mucinous. 30% of metachronous cancer appeared within 10 years. Polyps (1-3) and flat adenomas were associated to the lesion in 57%. Extra-colonic tumors appeared in 18% of family members and in half of the colon cancer patients. The sites of these tumors were the urinary tract, ovary, small bowel, breast and stomach. Two fibroblast strains of affected individuals were established. No increased tetraploidy was noted. Preliminary results suggest that this two strains are rather sensitive to ionising radiation. Often neglected, family history of colon cancer remains the major diagnostic and decision-making tool of a such syndrome. It will necessitate special treatment of affected subjects and early screening of the relatives.(ABSTRACT TRUNCATED AT 250 WORDS)