Worse histological grade of proximal colorectal tumors and its relation with stage.

PURPOSE: Accumulated data seem to support the concept that proximal and distal colorectal cancers (CRC) should be considered as different disease entities. We investigated a particular aspect of this assumption by examining variation of stage and grade distribution according to tumor site in a Greek patients' group. METHODS: A total of 200 cases having had undergone surgery for primary CRC was retrospectively analysed. Fifty-seven proximal tumors were compared to 143 distal lesions regarding tumor stage (TNM I-IV) and grade of differentiation (well, moderate and poor). Grade distribution by site was also examined within each particular stage and within additional stage categories (I-II, III-IV, I-III, II-IV, II-III). RESULTS: There was an almost significant trend of distal tumors for earlier stage (I) presentation (p=0.055), whereas proximal cancers were more frequently diagnosed with stages II-III (p=0.08). Poorly differentiated lesions displayed a strong predilection for proximal site (p=0.002), while tumors with moderate differentiation were preferentially found distally (p=0.001). Such segmental differences in grade distribution were also ascertained within most particular stages and all additional stage subsets (especially the last three). Moreover, both the proximal and the poorly differentiated lesions showed a parallel decrease in their incidence during the study period. CONCLUSION: The consistently recorded worse histological pattern of proximal tumors implies a different biological behavior of these lesions possibly due to distinct tumorigenic pathways involved in their development, whereas their tendency for late stage presentation demands further investigation before considered supportive to this concept.

Site impact on colorectal cancer biological behavior in terms of clinicopathological and molecular features.

PURPOSE: We investigated the biological behavior of proximal and distal colorectal adenocarcinomas (CRC), intending to determine specific segmental differences, possibly arising from the distinct genetic pathways involved in their development. METHODS: Thirty-six proximal and 83 distal cancers were comparatively and retrospectively analyzed, regarding tumor stage, grade and Ki-67, p53 and Bcl-2 immunohistochemical expression. RESULTS: Proximal tumors were more likely to be poorly differentiated (p=0.005) and to exhibit low Ki-67 and p53 expression (<20% and ≤ 30% stained nuclei respectively; p=0.026 and 0.0014, respectively). Distal lesions were more likely to be moderately differentiated (p=0.001), to display moderate Ki-67 expression (20-50% stained nuclei, p= 0.013) and p53 staining higher than 30% stained nuclei (p= 0.0014). Such segmental variations regarding mainly p53 and to a lesser extent Ki-67 were seen within most of the specific sub-groups of patients (stratified by stage, grade, gender and age). An association between Bcl-2 expression and distal site was also observed among females (p=0.008). CONCLUSION: Proximal and distal cancers displayed different clinicopathological and molecular patterns, reinforcing the proposal that they are genetically and biologically different entities. Potential clinical applications of these findings should be investigated.

Analysis of 7 immunohistochemical markers in male germ cell tumors demonstrates the prognostic significance of p53 and MIB-1.

BACKGROUND: Various prognostic factors have been investigated in order to predict the minority of male germ cell tumor (GCT) patients who will develop resistant disease. However, no prognostic system has been proven accurate. MATERIALS AND METHODS: Paraffin-embedded tissue specimens, obtained from primary lesions during the initial diagnosis of 83 advanced chemotherapy-treated GCT male patients, were stained for 7 immunohistochemical markers: p53, bax, bcl-2, MIB-1, topoisomerase IIa, c-kit and COX-2. The percentage of positive cells for each marker was measured for each patient. Cox regression was used for the prognostic factor analysis. RESULTS: All patients were followed for a median of 4 years. Nineteen patients had seminoma and 64 non-seminomatous GCT. In univariate analysis, only p53 (hazard ratio (HR) = 4.01, 95% confidence interval (CI) = 1.25-12.84, p = 0.019) and MIB-1 (HR = 3.16, 95% CI = 1.06-9.45, p = 0.039) were found to be prognostic for disease-specific survival. The best prognostic cut-off values of p53 and MIB-1 were 10% and 30% respectively. In multivariate analysis, these two markers obtained independent significance only when considered in combination (HR = 6.63, 95% CI = 1.40-31.41, p = 0.017, for patients with one or both markers above their cut-off), while the International Germ Cell Consensus Cancer Group (IGCCCG) risk was the most significant (HR = 7.99, 95% CI = 1.96-32.52, p = 0.004, for the high-risk group). However, the expression of these markers seemed to be significantly correlated with known prognostic factors. Nevertheless, we identified 34 patients of low IGCCCG risk expressing both markers below their cut-off with excellent survival. CONCLUSION: Among 7 immunohistochemical markers, p53 and MIB-1 demonstrated prognostic significance. Their combination may contribute to improvement of the accuracy of the currently approved prognostic system (IGCCCG).

Reevaluating pancreatic duct ligation in Whipple procedure.

In an effort to avoid the morbidity and mortality related to pancreaticojejunal anastomosis after pancreaticoduodenectomy (PPD), we report on the treatment of the pancreatic stump by pancreatic duct ligation (PDL) following Whipple procedure. We studied a series of 9 consecutive unselected patients (8 with pancreatic cancer and 1 with chronic pancreatitis). Of those, pancreatic fistula occurred in 4 patients and persisted for 14 to 58 days (mean 35.4 days). Two patients died within 30 days after surgery from causes not related to PDL. None of our patients developed diabetes mellitus following PDL surgery, nor any of the other frequently mentioned postoperative complications such as acute pancreatitis or pancreatic insufficiency. In conclusion, PDL may occasionally lead to a controlled pancreaticocutaneous fistula with fading inactive contents over time not causing further metabolic complications but is a safe, simple and fast alternative to pancreaticojejunostomy.

Kit expression in male germ cell tumors.

OBJECTIVE: KIT functions as the receptor for stem cell factor (SCF) and this interaction is essential for regulation of proliferation and survival, particularly for germ cells since it regulates oogenesis, folliculogenesis and spermatogenesis. Up-regulation of KIT signalling has been associated with oncogenic transformation in cells expressing the molecule. Our objective was to investigate the expression of KIT in germ cell tumor patients and correlate it with the patients' clinical characteristics. PATIENTS AND METHODS: One hundred and seventy-three archival blocks of formalin fixed, paraffin-embedded tumor samples from histologically confirmed germ cell tumor (GCT) patients were included in the study. Immunohistochemical staining for KIT was performed and the percentage of positive cells was calculated by an independent pathologist. KIT expression was considered as positive if > 10% of tumor cells displayed membranous or cytoplasmic staining. RESULTS: Sixty-one patients with seminomatous (49 pure, 11 anaplastic, 1 spermocytic) and 112 with non-seminomatous GCTs (36 malignant teratoma undifferentiated (MTU), 15 malignant teratoma trophoblastic (MTT), 20 malignant teratoma intermediate (MTI), 35 malignant teratoma combined (MTC) and six others) were identified. Among pure seminoma patients, 38 (77.5%) revealed a positive staining for KIT, while only two out of eleven (18.2%) anaplastic seminoma patients were identified as positive. This difference was statistically significant (p < 0.001). Among 35 patients with an MTC, 48.6% had a positive KIT staining while only two of the remaining patients with a non-seminomatous GCT had a positive staining. Although KIT was strongly correlated with seminomatous histology (p < 0.001), it failed to correlate with stage (p = 0.19) or treatment response (p = 0.11) in these patients. Overall, four (one seminoma, three MTC) out of 22 chemoresistant patients showed a positive staining for KIT. CONCLUSION: KIT is expressed in the majority of seminomas and in seminomatous components of the combined tumors, but only in a minority of anaplastic seminomas and rarely in non-seminomatous GCTs. The recent development of tyrosine kinase inhibitors may offer a possibility of cure in chemoresistant patients overexpressing KIT.

[Primary linitis plastica of the rectum]. / La linite plastique primitive du rectum.

One case of primary linitis plastica of the rectum is presented, it is a rare entity presentation in younger patients. The diagnosis was made by excluding the stomach as a primary source by peroperative palpation and fibroscopy examination. Because of potential for local invasion and infiltration, linitis is often detected only at the equivalent of stage C (Astler-Cller). The prognosis is poor, the mean survival time is about 9 months.

[Stromal tumor of the stomach with exo-gastric growth]. / Les tumeurs stromales du tube digestif. Réflexions à propos d'un cas à développement exo-gastrique.

A 60 year-old male patient presented with a giant stromal tumor of the stomach that showed predominant extragastric growth. Surgery consisted of total tumor resection with partial gastrectomy. The stromal origin of the tumor was established by immunohistochemistry. In spite of its large size and the presence of necrotic foci, the tumor was considered to be of low grade in view of the low mitosis index. The patient was maintained on careful surveillance. The histological features which characterize these tumors and their implications for prognosis and therapy are briefly discussed.

p53 protein accumulation and colonic adenoma recurrence.

OBJECTIVES: The prognostic value of p53 protein accumulation in colonic adenomas is still controversial. The aim of the present study was to determine whether the evaluation of p53 protein accumulation in newly diagnosed colonic adenomas could predict the development of metachronous adenomas. DESIGN/METHODS: Fifty-five patients who underwent prior endoscopic polypectomy for colonic adenomas were colonoscopically re-evaluated at 24-38 months after index colonoscopy. In cases with more than one adenoma, the one with the greatest diameter and the most serious histology was taken into account. p53 protein expression was immunohistochemically examined using specific monoclonal antibody. RESULTS: p53 protein was detected in 41.8% of the 55 index adenomas. Recurrent adenomas were present in 21 patients (38.2%). Metachronous adenomas were present in 56.5% of patients with p53-positive index adenomas and in 25% of those with p53-negative index adenomas (odds ratio 3.90, P = 0.018). Among patients with 1 or 2 index adenomas, metachronous adenomas were found in 50% of those with p53-positive index adenomas and in 22.6% of those with p53-negative index adenomas (odds ratio 3.43, P= 0.042). Multivariate stepwise logistic regression analysis revealed that number of index adenomas per patient (1 or 2 versus > 2) and p53 expression (positive versus negative) in index adenomas contain independent prognostic information for adenoma recurrence (chi2 = 8.2, P= 0.004 and chi2 = 4.08, P = 0.04 respectively). Patients aged < 60 years developed recurrent adenomas relatively more frequently if they had a p53-positive index adenoma (P= 0.068). In the subgroup of patients aged < 60 years with 1 or 2 index adenomas, the recurrence of adenomas was more frequent in those with a p53-positive index adenoma but the difference did not reach statistical significance (P= 0.13). CONCLUSIONS: Our data suggest that p53 expression in index adenomas is associated with recurrent colonic adenomas.

Proliferative patterns of rectal mucosa as predictors of advanced colonic neoplasms in routinely processed rectal biopsies.

OBJECTIVES: We sought to determine whether the evaluation of rectal cell proliferation in routinely processed rectal biopsies of apparently normal mucosa can predict the presence of advanced colonic neoplasms. METHODS: Fifty consecutive patients, who did not meet any of the following exclusion criteria, underwent total colonoscopy. Patients with nonadvanced adenomas, inflammatory bowel disease, hereditary predisposition to colonic cancer, or a history of colonic neoplasms were excluded. Patients with neoplasms in the distal 40 cm of the large bowel were also excluded. An adenoma was considered advanced if it had a diameter > 1 cm, or villous or severe dysplasia histology were present. In 26 of the 50 patients (Group A: 16 men, 10 women; mean age, 65 yr) advanced colonic neoplasms (advanced adenomas or cancer) were detected; in the remaining 24 (Group B: 13 men, 11 women; mean age, 66 yr) the large bowel was free of neoplasms. In all patients the proliferative patterns of apparently normal rectal mucosa were evaluated using the monoclonal antibody MIB-1 to assess the expression of Ki-67 antigen in routinely processed tissues. Proliferation index for the entire crypt, as well as proliferation indices for each of the five equal compartments, into which the crypt had been divided longitudinally, were calculated for each patient. RESULTS: The mean proliferation indices were similar between the two groups compared. The mean proliferation index for the upper crypt compartments (4 + 5) in the Group A patients was significantly higher than for those of the Group B patients (p < 0.01). Multivariate stepwise logistic regression analysis revealed that among gender, age, and proliferative parameters, the pattern of cell proliferation in the upper rectal crypt (4 + 5) compartment was the only predictor of advanced colonic neoplasms (beta = 11.01, p < 0.001). CONCLUSIONS: Our data suggest that the evaluation of the upward expansion of the rectal crypt proliferative zone in routinely processed rectal biopsies of apparently normal mucosa appears to predict the presence of advanced colonic neoplasms. These preliminary results should be confirmed in larger studies.

[Apropos of a case of gas gangrene of the abdominal wall after cholecystectomy]. / A propos d'une observation de gangrène gazeuse de la paroi abdominale après cholécystectomie.

The authors report a new case of gas gangrene following cholecystectomy with a fatal outcome. Mode of infection and principles of diagnosis and therapy are discussed together with a review of the literature.

Proliferative activity in colonic adenomas as a predictor of metachronous adenomas as assessed by proliferating cell nuclear antigen immunohistochemistry.

OBJECTIVES: The aim of this study was to determine whether cell proliferation in colonic adenomas, as estimated by proliferating cell nuclear antigen (PCNA), predicts the development of metachronous colonic adenomas. METHODS: Forty patients who underwent prior endoscopic polypectomy for colonic adenomas were reevaluated by colonoscopy 2 yr later. The expression of PCNA was studied in all adenomas that were removed. A five-point semiquantitative scale of 1-5 was used to estimate the PCNA score by the percentage of positively stained cells. RESULTS: Among the 40 patients studied, 16 developed recurrent adenomas (group A) and 24 were free of adenomas (group B). At initial colonoscopy, a total number of 51 adenomas (25 in group A and 26 in group B), were found. The median PCNA score in group A and group B index adenomas was 4 (interquartile range, 3-5) and 2 (interquartile range, 1-3), respectively (p < 0.01, Mann-Whitney U-test). A stepwise logistic regression analysis showed that PCNA score is a significant risk factor (p = 0.007, odds ratio 15.8, 95% confidence interval 2.2-112.4) in predicting adenoma recurrence. The median PCNA score in metachronous adenomas was 2 (interquartile range, 1-3). The difference in the PCNA score between group A index and metachronous adenomas was again statistically significant (p < 0.01, Mann-Whitney U-test). CONCLUSIONS: We conclude that the increased expression of PCNA in colonic adenomas may be a predictor for metachronous adenomas.

Immunolocalization of transitional cell carcinoma of the bladder with intravesically administered technetium-99m labelled HMFG1 monoclonal antibody.

The aim of this study was the immunolocalization of transitional cell carcinoma of the bladder with a radiolabelled murine tumour-associated monoclonal antibody and the measurement of the absolute uptake of the antibody by the tumour. Fourteen patients with transitional cell carcinoma of the bladder received 3-6 mCi (111-222 MBq) of technetium-99m labelled HMFG1 monoclonal antibody intravesically and one patient, 2 mCi (74 MBq) of iodine-131 labelled 11.4.1, which is a non-tumour-specific monoclonal antibody. Four of the 15 patients were evaluated with single-photon emission tomography (SPET) 1 1/2 to 2 h post administration. All patients underwent transurethral resection of the bladder tumour within 12-20 h following intravesical administration of the radiolabelled antibody. The radioactivity of biopsy specimens from normal urothelium and tumour areas were counted in a gamma counter. The mean uptake of the radiolabelled antibodies from normal and tumour sites was expressed as a percentage of the administered dose per kilogram of tissue. Conventional histology and immunohistochemistry using HMFG1 monoclonal antibody were performed on paraffin sections of the biopsy specimens. Although our results are preliminary, it can be concluded that: (a) bladder tumours are well imaged by SPET when using 99mTc-HMFG1; (b) intravesically administered radiolabelled antibody remains on the bladder tissue and does not escape into the systemic circulation; (c) the wide range of tumour uptake values (0%-9.3% administered dose/kg) observed probably can be attributed to heterogeneity of the antigenic expression of the tumour; (d) values of 99mTc-HMFG1 monoclonal antibody uptake by the tumour do not justify future attempts at radioimmunotherapy.

Expression of a cell surface antigen recognized by the monoclonal antibody AUA1 in bladder carcinoma: an immunohistochemical study.

The expression of a cell surface antigen recognized by the epithelium-specific, tumor-associated monoclonal antibody (Moab) AUA1 has been studied in 22 cases of normal urothelium, 7 cases of dysplastic urothelium and 86 cases of transitional cell carcinoma. Tissue specimens were stained with the conventional hematoxylin-eosin technique as well as with the indirect immunoperoxidase technique using Moab AUA1. Results showed that: (a) Moab AUA1 reacts mainly with cells of high or intermediate grade transitional cell carcinoma and with a restricted number of normal urothelial cells, and (b) antigenic heterogeneity exists between tumors of the same grade and within the same tumor.

Immunoscintigraphy with iodine-131-labelled monoclonal antibody AUA1 in patients with transitional cell carcinoma of the bladder.

The monoclonal antibody AUA1, labelled with 2 or 3 mCi iodine-131, was administered intravesically to 11 patients with known or suspected bladder carcinoma and was kept in the bladder for 1 h. All patients underwent immunoscintigraphy of the bladder at 2 h and three patients also at 20 h after instillation. Conventional histological and immunohistochemical examinations were performed on tissue samples from tumour and normal areas taken during cystoscopy, carried out 24-h after the instillation. Transitional cell carcinoma of the bladder was present in nine patients whereas dysplastic and normal urothelium was found in the remaining two patients, respectively. Six out of nine tumours were successfully imaged at the 2-h scan. Normal urothelium showed no uptake while dysplastic urothelium was positive on imaging. Successful detection was correlated with size and grade of tumour in almost all cases. Tumors with a diameter of 1 cm or less were not detected. Four out of five grade II tumours and two out of three grade III tumours were detected with this method. The method is a promising one although further studies using more suitable isotopes and/or monoclonal antibodies are required to increase its sensitivity.

A case of gonadoblastoma in a normal woman with tubal pregnancy.

Gonadoblastoma is a rare tumor arising usually in a dysgenetic gonad. The commonest karyotypes seen in patients with this neoplasm are 46XY and 46XY/45XO mosaicism. The occurrence of gonadoblastoma in pregnant or normal (46XX karyotype) women is extremely rare. A case of gonadoblastoma in a pregnant eukaryotic (46XX) woman is reported.

[Ileo-cecal tuberculosis. A difficult diagnosis]. / La tuberculose iléo-caecale. Un diagnostic difficile.

An ileocaecal tuberculosis suspected in an Algerian girl was confirmed only by operative findings and by the presence of caseum at histological examination. Mycobacterium tuberculosis could not be cultured from the lesions. Diagnostic problems between tuberculous enteritis and Crohn's disease are discussed.