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Flow cytometry offers a relatively simple method to determine the DNA content of colorectal cancers. However, the technique can not discover minor changes in karyotype which may characterize near-diploid tumors, nor will it detect very small populations of aneuploid cells. In an attempt to improve the detection of such cells, we incubated biopsy material prior to analysis. This method revealed an aneuploid subpopulation in one of two biopsies studied. This simple protocol may ultimately lead to a more accurate assessment of the ploidy in colon cancer.

We have established 3 new human colorectal cancer cell lines (LS411N, LS513, and LS1034) from clinical biopsy samples. These lines are tumorigenic and grow s.c. as adenocarcinomas in nude mouse xenografts. Specific marker chromosomes are observed in each line. Carcinoembryonic antigen is expressed at the surface of all 3 lines, but with marked quantitative differences. Indeed, less than 10% of the cells from the HT-29 line used as a reference express carcinoembryonic antigen while more than 90% of the LS1034 cells do so. LS513 and LS1034 consistently express HLA class I antigens and intercellular adhesion molecule 1 which are not detected at the surface of the LS411N cells. No expression of HLA class II antigens DR, DQ, and DP has been measured on any of the lines. All three lines grow well in 5% fetal calf serum medium without addition of exogenous growth factors. The LS1034 line has been adapted to growth in serum-free conditions and exhibits increased clonogenicity when cells are seeded in serum-free methylcellulose medium, as compared with medium containing 5% fetal calf serum. The LS513 and LS1034 lines have proved to be of particular interest since they respond to the growth-inhibitory action of TGF-beta 1 and TGF-beta 2 in both liquid and semisolid medium. Both factors were, at pM concentrations, equipotent inhibitors of LS1034 cell proliferation. In contrast, higher concentrations of TGF-beta 1 are inhibitory for proliferation of LS513 cells, whereas TGF-beta 2 has no effect on the growth of these cells in liquid assay. On this basis, using appropriate anti-TGF-beta 1 and anti-TGF-beta 1 IgY, we developed a bioassay for TGF-beta 1 and TGF-beta 2. Two of the three lines have indeed been shown to produce latent-TGF-beta 1 activity.

Rectal leiomyosarcoma is rare, often large and found in the distal third of the rectum. Most symptoms differ from those of an adenocarcinoma. Staging is difficult and should include tumour size, necrosis, cellularity, number of mitoses and anaplasia. Abdominoperineal excision (APE) remains the only effective treatment. A 66 year old asymptomatic female presented with painless rectal bleeding after a fall. Digital examination and proctoscopy revealed a mass on the posterior rectal wall. Pelvic ultrasonography, arteriography and CT-Scan showed a huge retro-rectal lesion. Following APE, histopathology confirmed a leiomyosarcoma. No adjuvant therapy was given; there is no recurrence 4 years later.

Colo-rectal cancer in young patients is a subject of interest for many reasons. Various studies are devoted to this subject but controversies regarding the stages, the evolution and the prognosis still remains. We present intermediate results, of an ongoing study, which is directed to those particular aspects of colon cancer of the patients less than 45 years of age in a region where the global incidence of the disease is one of the highest in the world. In the past five years, we have observed 602 patients with colon cancer. 23 of them (4%) were less than 45 years old. The age at diagnosis was 38 +/- 6 years. Two-thirds of the subjects were male. 13% had had predisposing conditions for colon cancer such as FAP, ulcerative colitis or Turcot syndrome; 50% had a positive familial history for cancer. Symptoms lasted for less than 3 months in two thirds of the patients. 15% had a right sided tumor, 38% were located in the sigmoid and 28.5% in the rectum. At diagnosis, the tumors were classified as follows: 32% Dukes B, 23% Dukes C and 40% were disseminated disease. Most of them were located in the rectum, but 43% of Dukes B lesions were located in ascending or transverse colon. Grading reveal moderately to poorly differentiated tumors in 3/4 of cases. 30% of patients received an adjuvant therapy. After two years, 70% of the patients were alive. None of them with Dukes A or B but one of the patients with Dukes C were dead.(ABSTRACT TRUNCATED AT 250 WORDS)

Patienten, die an anorektalen Erkrankungen leiden, geben haufig nur unbestimmte Symptome an. Daher mus eine genaue Beschreibung dieser Krankheitszeichen erfolgen, damit sie einer genauen anatomischen Lokalisation zugeordnet werden konnen. Dies liefert letztlich die Basis fur geeignete Untersuchungen und eine zuverlassige Diagnose. Bei einer Vielzahl von Symptomen last sich der wahrscheinliche Ursprungsort vermuten, auch wenn eine spezielle Zuordnung zu einer besonderen Lokalisation nicht moglich ist. Die proktologische Anamnese ist daher von groser Wichtigkeit (s. Kap. 3). Die Umstande, unter denen ein Symptom auftritt, seine Lokalisation, Entwicklung und das Auftreten sekundarer Beschwerden sowie deren charakteristische Merkmale sollten detailliert ermittelt werden.

Fluoropyrimidines are commonly used in clinical oncology, but their strong dose-dependent toxicity limits therapeutic application. The synthetic derivative 5′-deoxy-5-fluorouridine (5′-dFUrd) [1] has raised marked interest due to a higher therapeutic index as compared with 5-fluorouracil (5-FUra) or other related compounds [2–4]. It is also a less potent leukopenia inducer [2, 5] and is not as strongly immunosuppressive as other fluoropyrimidines [6, 7]. The biological activity of this pro-drug is dependent upon its enzymatic cleavage to 5-FUra by a pyrimidine Phosphorylase [8–10] which is found in much higher levels in human and animal tumours than in normal tissues, except in the intestinal tract [3, 4, 10–12].

„Es wird mehr versaumt durch Nicht-Schauen als durch Nicht-Wissen. “ Diese Feststellung von Thomas McCrae (1870–1935) unterstreicht die uberragende Wichtigkeit der klinischen Untersuchung fur die proktologische Diagnosestellung. Obwohl die proktologische Konsultation fur den Arzt eine routinemasige Tatigkeit sein kann, ist sie fur den Patienten doch etwas vollig anderes. Dieser kann haufig mit einem Eingriff dieser Art schwer umgehen, besonders wenn es der erste dieser Art ist. Es gibt verschiedene personliche, psychologische und soziale Ursachen fur die — gelegentlich recht lange — Zeitspanne zwischen dem Auftreten der ersten Symptome und der proktologischen Konsultation. Ebenso ist es auch heutzutage nicht ungewohnlich, das Patienten wegen eines proktologischen Beschwerdebilds langere Zeit behandelt werden, ohne das zuvor irgendeine lokale Untersuchung durchgefuhrt worden ist. Daher werden fortgeschrittene Lasionen gelegentlich erst bei der ersten Konsultation beim Spezialisten entdeckt.

In an attempt to improve the prognostic accuracy for colon carcinoma, numerous alternative classifications have been proposed [1–13].

The biological activity of 5'-deoxy-5-fluorouridine (5'-dFUrd) depends upon intracellular enzymatic cleavage by pyrimidine phosphorylase to form 5-fluorouracil (5-FU). Interferon-alpha 2a (IFN-alpha) effect was analysed alone and combined with 5-FU or 5'-dFUrd, on proliferation inhibition of eight human colorectal cancer cell lines. The toxicity of 5-FU was enhanced by IFN-alpha in only one line (SW-480). In contrast, interactive enhancement of IFN-alpha was observed with 5'-dFUrd in five lines (WiDr, HT-29, 513, SW-480 and Co-115). In each of the lines showing potentiation by IFN/5'dFUrd but not by IFN/5-FU, cytoplasmic pyrimidine phosphorylase activity was increased after 5 days' incubation with IFN-alpha in a dose-dependent manner. Two lines (LISP-1 and SW-620) showed no potentiation of either 5-FU or 5'-dFUrd toxicity by IFN-alpha, and no change in pyrimidine phosphorylase activity. Potentiation of 5'-dFUrd effect by IFN-alpha may thus be explained by an enhancement of its conversion to 5-FU through stimulation of pyrimidine phosphorylase activity.

Familial adenomatous polyposis (FAP) is an autosomal-dominant disease with delayed expression, in which multiple polyps develop throughout the colon with a malignant potential of 100%. Genetic counselling and follow-up of patients at risk is essential for presymptomatic diagnosis. Prophylaxis of cancer arising from this condition would greatly improve if a genetic or a congenital phenotypic marker of gene carriers were available.

Digestive fistulae have a quite variable clinical presentation, depending on their origin and topography. Even when very small, they can cause considerable mechanical or metabolic derangement. Surgical correction often implies an operation with important consequences. The injection of an occlusive emulsion can, in a certain number of cases, close off the fistulous tract with minimal inconvenience. We have injected several invalidating fistulae between the digestive or respiratory tract and the skin with Ethibloc. Total occlusion of the fistulae was accomplished after one or more injections. The emulsion is resorbed after around 10 days, leaving a scar. The inclusion of radio-opaque material allows intraoperative control of injection. This technique widens the therapeutic modalities applicable to a difficult medical condition. When confronted with advanced inflammatory or neoplastic disease, for example, Ethnibloc injection can be considered if the tissue quality is sufficient. Gross infection or tissue necrosis are, in our experience, relative contraindications; the occlusive emulsion cannot adhere and is rapidly evacuated by the fistula.

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.

Stenosis of the rectum after surgery is a rare complication of low anastomosis. Infection, ischemia, foreign body reaction, technical faults or recurrence of neoplasms are the most important causes. Dilatation is attempted either manually or by instrument, if the stenosis causes discomfort and in particular if diarrhea results. Rarely resection of the stenosed segment is necessary. Stenosis in conjunction with incontinence is the most feared complication of anorectal surgery. It develops exceptionally after scarring of a large mucocutaneous defect after hemorrhoidectomy, correction of an anal fistula, a mucosal prolapse, electro-resection, infection or trauma. Anal stenosis leads to increasing constipation, a reduction of stool volume, abdominal cramps and rectal bleeding.

Reconstructive surgery of the aortoiliac junction often requires interruption of the inferior mesenteric artery. Ischaemic colitis following this type of surgery occurs in 15-20% of cases, most often in the splenic flexure and the sigmoid colon. It is caused by general haemodynamic factors and/or atherosclerotic changes in the intestinal arteries. Clinical symptoms are often subtle or atypical and the diagnosis is difficult. However intestinal ischaemia causes considerable morbidity and mortality. Around 1000 aortoiliac reconstructive procedures were performed, with a 2.8% incidence of post-operative colonic ischaemia. The two most important risk factors were hypovolemia and ligation of the inferior mesenteric artery.

Patients suffering from anorectal disorders often complain of vague symptoms. A detailed description of these symptoms 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. The proctologic history is therefore of great importance (see Chapter 3). The circumstances in which a symptom appears, its localisation, its development, the appearance of secondary associated complaints, and their exact characteristics should all be ascertained in detail.

“More is missed by not looking than by not knowing. ” This statement by Thomas McCrae (1870–1935) underlines the paramount importance of clinical examination in protological diagnosis. Although a proctological consultation may well represent a routine professional activity for the doctor, it is quite otherwise for the patient. He or she often finds a procedure of this kind difficult to cope with, particularly if it is the first time. There are various personal, psychological, and social reasons for the interval of time, which may be quite long, elapsing between the appearance of the first symptoms and the proctological consultation. Likewise it is not uncommon, even at the present time, for patients to be subjected to a prolonged treatment for a proctological complaint without any prior local examination being made. This is why advanced lesions may sometimes be discovered at the specialist’s initial consultation.

Although intrahepatic infusion therapy with 5-fluorouracil for unresectable colorectal liver metastases may lead to improved overall survival for some patients, it is not clear why a response is not observed in others. Gene alterations in oncogenes or tumor-suppressor genes are critical events in tumor formation, and some of them could play a role in the process of drug resistance. The tumor-suppressor gene p53, which is known to trigger cell arrest or apoptosis in response to DNA damage, is found to be mutated in a wide range of human tumors. The aim of this work is to establish whether a relationship is found between p53 mutations and survival in patients undergoing adjuvant chemotherapy for advanced Dukes' D colorectal cancers. Seventeen tumors from patients treated with 5-fluorouracil regimen via intrahepatic infusion for unresectable colorectal hepatic metastasis were considered. p53 mutations from tumor DNA were detected, after amplification by PCR of exons 5 to 8, by non-radioactive single-strand conformation polymorphism and direct DNA sequencing. Patients with mutated p53 colorectal tumors had short survival, whereas prolonged survival was associated with the presence of wild-type p53 (p = 0.0 19). Our data suggest that mutated p53 colorectal tumors had a weak response, or even no response, to chemotherapeutic treatment. Routine assessment of p53 status would be helpful in selecting patients with only wild-type p53 gene who have a predictably better response to chemotherapy. o 1996 Wilq-Liss, Inc. The outcome of patients with unresectable liver metastasis from colorectal cancer is poor. The median survival time for patients without treatment is estimated to be 6 to 9 months

The discovery of synchronous hepatic metastases from colorectal cancer poses a tactical problem ticklish to resolve. What are favourable circumstances for curative excision of hepatic metastases? When and how to operate them? To try to respond, we analysed a collective of 36 patients between 10. 1. 1985 and 30. 12. 1986. Of the patients staged Dukes B presenting synchronous hepatic metastases (less than 4, less than 50% of hepatic involvement by the tumour) without systemic involvement, excision at the first attempt is realizable and will be a benefit for the patient. For the others, excision is to be considered in the near future after having analysed (tumour grading and staging, CEA, ploidy of primary tumour). Patients presenting extrahepatic metastases will not benefit from hepatic resection. Surgery, associated or not to regional infusion chemotherapy is discussed.

The assessment and management of fistulae complicating Crohn’s disease present many problems. In order to draw up some guidelines, we have reviewed our recent experience of this problem.

Fifty-seven patients with suspected CEA-producing tumors were studied prospectively by radioimmunoscintigraphy (RIS) using a 123I-labeled anti-CEA monoclonal antibody (MAb) (essentially the F(ab')2 or Fab fragments) and emission computed tomography (ECT). Results of RIS were compared to those of a comprehensive diagnostic study. Final diagnosis was based on surgery, biopsy and autopsy (n = 39) or follow-up findings (n = 18). Three groups of patients were defined: Group A with suspected primary tumors (n = 11), Group B with probable (n = 19) and Group C with questionable (n = 27) tumor relapse. Eighty-eight per cent, 93% and 71% of the anatomic regions studied were correctly identified as being involved, and 97%, 97%, and 87% as being free from tumor in Groups A, B, and C, respectively. In the 27 patients from Group C with no definite diagnosis of relapse, and in whom diagnosis was most difficult, 38 tumor sites were involved. Of these, 21 were detected by both prospective RIS and repeated comprehensive study, six by RIS only and seven by conventional methods only. Four sites remained undetected by both approaches. Ten of the 21 lesions were detected by RIS more than 1 mo earlier than by any other method. Among the seven tumor sites detected by other diagnostic modalities only, three were identified at the time of RIS and four became positive more than 6 mo later. Overall diagnosis was entirely correct in 30, partially correct in 16 and incorrect in six patients studied. RIS with ECT and 123I-labeled anti-CEA MAb allows early detection of recurrence or metastasis of colorectal cancer. It thus contributes to reduced delay between diagnosis and treatment.

A severe or lengthy disturbance of immunity favors the development of malignant tumors. The increased incidence of lymphomas, leukemias and certain carcinomas in cases of congenital immunodeficiency, as well as of Kaposi's sarcoma and certain lymphomas in the acquired immunodeficiency syndrome (AIDS) are well known. In transplantees, patients undergoing immunosuppressive treatment for autoimmune disorders and cancer patients receiving chemotherapy, the occurrence of secondary neoplasias represents a phenomenon with a specific profile. We have seen 14 solid tumors in patients who were immunosuppressed for one of the 3 above-mentioned reasons. It is a heterogeneous group, both in terms of patient profile and tumor localisation. However, there are certain characteristics of these tumors which distinguish them from similar ones arising in the general population. The advent of more aggressive immunosuppressive therapies, the constant increase in organ transplants and the development of new cancer treatment modalities which influence the patients immune systems explain the importance of this phenomenon. Thus one must constantly be wary of these unusual tumors which occur independently of age and usual risk factors.

We report 30 cases of non-Hodgkin's gastric lymphomas (according to the Rappaport classification): 1 nodular lymphocytic lymphoma well differentiated, 7 diffuse lymphocytic lymphomas poorly differentiated, 2 diffuse mixed cellularity lymphomas, 20 diffuse histiocytic lymphomas and 4 pseudolymphomas, over a period of 21 years at the CHUV, in Lausanne (1958-1979). There are 56% of advanced stages (IIIE and IVE) according to Ann Arbor. Survival to 5 years is of 27%. The mean survival of patients who died from their lymphomas is of 5 months only. Lymph node invasion worsens considerably the prognosis (75% of survival to 5 years for stage IE against 25% for stage IIE). This phenomenon is particular to non-ganglionary lymphomas. We do not observe good remission for the diffuse histiocytic forms at an advanced stage, remission being characteristic of the ganglionary lymphomas only. Treatment is poorly codified. Surgery along seems possible for the localised forms (IE): triple therapy (surgery, radiotherapy and chemotherapy) is necessary for advanced stages and histological unfavorable forms.

Aneurysms of the cervical internal carotid artery are not rare lesions although they often remain symptomless. The authors describe the case of an eighteen-year-old boy presenting bilateral cervical internal carotid artery aneurysms of probable traumatic origin and treated conservatively. Etiology, pathogenesis, difficulties in diagnosis and choice of treatment are discussed.

In the treatment of acute pyogenic soft-tissue abscess incision, curettage, and primary suture was compared with incision and drainage alone in a randomised prospective trial. Operations were performed under antibiotic cover by casualty officers, and patients were reviewed by an independent observer in a septic dressing clinic. Altogether 114 patients were studied, of whom 54 were treated by curettage and primary suture and 60 by simple drainage. The mean healing time was 8.9 days in those treated by primary suture and 7.8 days in those treated by simple drainage (p less than 0.05). Primary healing failed to occur in 19 (35%) of the sutured wounds, but there were no other complications in either group. It is concluded that incision and drainage alone is adequate treatment for acute soft-tissue abscess.

The analysis of ploidy provides valuable information allowing a more precise diagnosis, a more dependable prognostic and the choice of appropriate therapy. With ploidy analysis one can assess the aggressiveness of a given tumor. Aneuploidy of tumors clearly indicates a significantly lower patient survival index. Ploidy analysis of tissue sections yields a clear overall indication of the proportion of cells exhibiting hyperploidy within the tumor mass. The application of this approach is amenable to diverse types of tumors including colo-rectal neoplasias. Additionally, it provides a correlation with the histological presentation of each tumor. The study includes DNA ploidy analysis of 212 patients with primary adenocarcinoma. Sixty-four of the cases examined had follow-ups of a least 2 years. Eighteen of this group had diploid non-proliferating tumors, of which 2 (11%) subsequently died. Nineteen of the 64 had proliferating diploid tumors, 11 (58%) of whom died within the follow-up periods. Twenty-seven patients had tumors which were clearly aneuploid, 12 (45%) of whom later died. Our study demonstrates the prognostic value of ploidy analysis. The preliminary results indicate that mortality of patients with proliferating tumors is approximately 50% after 2 years. This prognostic is independent of other more classical criteria of tumor staging, namely Dukes' classification, histological differentiation and size of tumor. In the near future, ploidy analysis should be introduced as a standard part of tumor assessment. It clearly provides a valuable prognostic allowing the selection of patients requiring a careful follow-up.

Our experience in the management of 16 enterovaginal fistulas complicating Crohn's disease leads us to believe that such fistulas usually arise from active rectal disease and, despite being evident clinically, are difficult to confirm endoscopically or radiologically. Patients with few symptoms can be managed conservatively. Surgical repair protected by diversion may have a place in management, but most with severe symptoms will require excision of the intestine from which the fistula is arising.

Homeobox genes are a network of genes encoding nuclear proteins functioning as transcriptional regulators. Human and murine homeobox genes of the HOX family are organised in four clusters on different chromosomes. Gene order within each cluster is highly conserved, perhaps in direct relation to their expression. Homeobox genes have recently been involved in normal development and oncogenesis. We have analysed HOX gene expression in normal human colon and in primary and metastatic colorectal carcinomas. The majority of HOX genes are active in normal adult colon and their overall expression pattern is characteristic of this organ. Furthermore, the expression of some HOX genes is identical in normal and neoplastic colon indicating that these genes may exert an organ-specific function. In contrast, other HOX genes exhibit altered expression in primary colon cancers and their hepatic metastases which may suggest an association with colon cancer progression.