Review article: anti-fibrotic agents for the treatment of Crohn's disease - lessons learnt from other diseases.

BACKGROUND: The current therapies for Crohn's disease (CD) are mainly focused on blockade of inflammation. Fibrosis remains one of the major complications of CD often leading to surgery, affecting patients' quality-of-life. AIM: To summarize the published data regarding the potential anti-fibrotic role of drugs commonly used in CD and the most effective anti-fibrotic drugs used in other diseases evaluating their potential use to treat intestinal fibrosis in CD. METHODS: A literature search was performed in the PubMed, Medline, Cochrane and EMBASE databases, considering in vitro, animal and human studies on fibrosis in inflammatory bowel disease and other similar chronic pathologies. RESULTS: Treatment of fibrosis in CD is limited to surgery or endoscopic dilatation, although some of the drugs currently used may have anti-fibrotic activity. In other diseases, anti-fibrotic agents are already used or are in preclinical or clinical trials. ACE inhibitors, Angiotensin Receptor Blockers, and HMG-CoA inhibitors merit further investigation in CD because of their role in preventing fibrosis in cardiovascular and renal diseases. CONCLUSIONS: Anti-fibrotic drugs are under evaluation or already used in clinical practice in other chronic inflammatory diseases. In CD, there is a great need for investigation into agents that may prevent, reduce or reverse intestinal fibrosis.

[Can Helicobacter pylori infection be a risk factor for the severity of rheumatoid arthritis?]. / L'infezione da Helicobacter pylori può essere un fattore di rischio per la severità dell'artrite reumatoide?

AIM: In this study we assessed the effect of Helicobacter pylori eradication in patients with established rheumatoid arthritis (RA) in order to show a possible pathogenetic role of the infection in this disease. METHODS: We recruited 31 patients with variable RA activity. Of them, 15 were Hp-positive (12 F and 3 M, mean age 55 +/- 10.6 years) and 16 Hp-negative (13 F and 3 M, mean age 54.2 +/- 9.1 years) on the basis of the concomitant positive or negative findings of both CLO-test and histology performed on both antral and corpus biopsies. The infected group was treated and the bacterium was considered eradicated when both tests were negative a month after therapy. We have evaluated the disease activity at baseline and during a total follow-up period of 16 months with check-points every 4-months and compared clinical and laboratory findings between the Hp-negative and the eradicated groups. Both groups were being treated with NSAIDs and prednisolone (< or = 7.5 mg/die) or its equivalents. RESULTS: Hp-eradicated RA patients showed a progressive improvement overtime (p = 0.0009) of all clinical indices compared with baseline, while Hp-negative RA patients did not. At the 16-month checkpoint, the eradicated RA patients differed significantly (p < 0.006) from patients without Hp infection by all indices, except grip strength of the hands. Also all laboratory data improved significantly from baseline to the 16 month checkpoint (p < 0.03) within the Hp-eradicated group and between the two groups of eradicated and Hp-negative RA patients (p < 0.0007) except for Hb, aCL IgM and gamma-globulins. CONCLUSIONS: Our data suggest that Hp infection is implicated in the pathogenesis of RA. On the basis of our data, the eradication of Hp should be recommended in infected RA patients.

Is intensive follow-up really able to improve prognosis of patients with local recurrence after curative surgery for rectal cancer?

BACKGROUND: Because more than 90% of local recurrences after curative surgery for rectal cancer appear within the first 36 months after surgery, an intensive and strict follow-up program during this period could improve early diagnosis and, thus, prognosis of patients. METHODS: Of the 216 patients who underwent surgery for rectal cancer, 127 entered an intensive follow-up program (median follow-up: 42 months); the clinical outcome of the remaining 89 patients was reconstructed with the help of their general practitioners. RESULTS: Fifty eight (26.8%) of the 216 patients who were treated with curative surgery alone developed a local recurrence; pelvic recurrences were prevalent. Eleven (30.5%) of the 36 patients who had recurrence during follow-up, and 6 of the 22 who had not undergone follow-up, had a reoperation with curative intent; the median survival was 19 months vs. 8 months, respectively (P = ns). Four (44.4%) curative reoperations were performed on the 9 asymptomatic patients and in 13 (26.5%) of the 49 cases with symptomatic local recurrences. Median survival was 15 months vs. 14 months, respectively (P = n.s). All patients except one (living after 42 months from reoperation) died within 48 months. CONCLUSIONS: In our study, adherence to a strict follow-up program unfortunately proved to be ineffective for improving long-term survival for patients who underwent reoperation with curative intent.

Transvaginal bone-anchored synthetic sling for the treatment of stress urinary incontinence: an outcomes analysis.

OBJECTIVES: To evaluate the results and complications of a new transvaginal minimally invasive procedure for the treatment of stress urinary incontinence. METHODS: Sixty-seven women aged 37 to 77 years underwent a pervaginal bone-anchoring synthetic sling procedure between April 1997 and February 1999. Sixty-three patients had a defect of the anatomic support, and 4 had iatrogenic intrinsic sphincteric deficiency (ISD). Patients were assessed at least 1 year postoperatively, underwent physical examination, and filled in the self-assessment questionnaire with the help of a nonpartisan health care provider. The questionnaire inquired about urine leakage, obstructive and irritative symptoms, quality of life, and satisfaction with the treatment received. The physician and questioner had no knowledge of each other. RESULTS: Mean follow-up was 17 months. Perfect dryness was seen in 82% of patients with improvement in 9% and failure in 9%. Patients reporting a failed outcome were significantly older than those reporting improvement or cure (P = 0.01). All patients with ISD failed. Moderate obstructive symptom scores have been noticed in 31% of patients. Irritative voiding symptoms have been recorded in 22% of cured patients and 83% and 80% of improved and failed patients, respectively (P <0.001). Three percent of patients experienced pain during intercourse. Mild pelvic pain was found in 8% of patients. The only main complication of the operation was the vaginal erosion and sling removal in 16% of patients. Seventy-two percent of patients were completely satisfied with the treatment received. CONCLUSIONS: This procedure allows a high cure rate in patients with urinary incontinence due to a defect of anatomic support, and it is unsuitable when incontinence is due to ISD. The only main complication came from the use of the gelatin-coated Dacron sling that resulted in vaginal erosion, often necessitating the sling removal. The use of different synthetic or nonsynthetic materials may be advisable.

Role of impression cytology during hypovitaminosis A.

AIMS: Evaluation of the morphological damage to the ocular surface of patients operated for biliopancreatic diversion for pathological obesity and the correlation of impression cytology with vitamin A plasma levels, adaptometry, and other general variables. METHODS: 48 patients (15 males, 33 females, age range 21-73) and 34 normal subjects were examined with fluorescein and rose bengal, a plasma dose of vitamin A, and adaptometry. The results of the various tests were subdivided into three levels (0 = normal, 1 = moderately altered, 2 = seriously altered). The impression cytology and adaptometry results were correlated with vitamin A levels and other patient data (age, nutritional condition, time since operation, percentage weight loss). All the examinations were repeated after intramuscular therapy with vitamin A. RESULTS: Corneoconjunctival alterations visible with fluorescein and rose bengal staining were present in 67.7% of cases, impression cytology alterations in 93.7%, adaptometric alterations in 82.2%; vitamin A plasma levels were below normal in 95.8% of cases. After the therapy with vitamin A a significant reduction was found for every examination. The correlation between impression cytology and adaptometry and vitamin A plasma levels and between corneoconjunctival alterations and vitamin A plasma levels was significant. There was no significant correlation between impression cytology and nutritional condition, age time since operation, and percentage weight loss. CONCLUSION: These results show impression cytology is a specific indicator for hypovitaminosis A because it is not influenced by other factors related to the general condition of the patient. Many patients with hypovitaminosis A not demonstrating ocular symptoms of changes visible with fluorescein and rose bengal showed alterations with impression cytology.

[Detection of Helicobacter pylori in 201 stomach biopsies using the polymerase chain reaction, histological staining (H&E/Giemsa) and immunohistochemistry]. / Evidenziazione degli Helicobacter Pylori in 201 biopsie gastriche mediante Polymerase Chain Reaction, colorazioni istologiche (EE/giemsa) e di immunoistochimica.

Helicobacter Pylori is believed to be an essential etiologic agent of type B chronic gastritis and peptic ulcer disease in humans. Recent reports have also suggested a role for these organisms in the development of gastric carcinoma and MALT-Lymphoma. A variety of diagnostic procedures are used for the identification of Helicobacter Pylori in clinical samples. 201 gastric biopsy (164 antral and 37 body biopsy specimens) were obtained from 164 patients with endoscopic abnormalities. These samples were studied for the detection of the presence of Helicobacter Pylori by histological staining (EE/Giemsa), immunohistochemistry and PCR by using a primer pair derived from the nucleotide sequence of the Urease A gene of Helicobacter Pylori. Specific amplification of a 411 base pair DNA fragment from all strain of Helicobacter Pylori tested was achieved. Of the 201 gastric biopsy analyzed, 63 (31%) were infected with Helicobacter Pylori on the basis of both histological and immunohistochemical staining, and 81 (41%) were positive with PCR (P < 0.001). Our results support a role for PCR in the rapid and highly sensitive and specific identification of Helicobacter Pylori in gastric biopsy specimens.

[Critical review of treatment outcome in 54 patients with synchronous liver metastasis of colorectal cancer]. / Revisione critica dei risultati del trattamento di 54 pazienti portatori di metastasi epatiche sincrone da cancro colorettale.

Short- and long-term results of the treatment of 54 patients (12.5%) with synchronous hepatic metastases were critically reviewed by means of retrospective analysis of 431 colorectal cancer patients surgically treated over a period ranging from January 1980 to December 1989. Incidence and stage of hepatic metastases (Gennari Classification, 1984) are not significantly correlated to stage (T3), grade (G2-G3) and mucinous colorectal tumours; but they are significantly correlated to metastatic lymph nodes (p < 0.01). Actuarial survival is significantly influenced by surgery (p < 0.01) and stage of liver metastases (p < 0.05). The restriction of preoperative exclusion criteria and the simultaneous surgical treatment of primary colorectal and secondary hepatic metastases seem to be responsible for the high rates of operative mortality.

Upper abdominal surgery: does a lung function test exist to predict early severe postoperative respiratory complications?

We evaluated the capacity to predict severe respiratory complications (SRCs) following upper abdominal surgery (UAS) by using the results of a respiratory questionnaire and preoperative pulmonary function tests. Lung volumes, flows and transfer factor of the lung for carbon monoxide (TL,CO,sb) were assessed in 361 consecutive adult patients (248 males and 113 females). SRCs were diagnosed 24 h after UAS by clinical examination and chest radiography. Univariate and stepwise multiple logistic regression analyses were performed to estimate the odds ratio (OR) and 95% confidence interval (95% CI) of each single input variable, and to determine which indices best predicted outcome. These patients had a 1% mortality rate and 14% incidence of SRCs, with a male:female ratio of 0.86. The best predictors for SRCs by multiple analysis were: preoperative current hypersecretion of mucus (OR=133; p<0.0001); an increase in residual volume (RV) (OR=3.11; p=0.01); and, to a lesser extent, low percentage of predicted values both of forced expiratory volume in one second (FEV1 % pred) and TL,CO,sb. The algorithm thus obtained (logit theta) was extremely sensitive (84%), specific (99%), and accurate (95%) for preoperative prediction of SRCs. We have found that preoperative current hypersecretion of mucus and pulmonary hyperinflation, and to a lesser extent percentage predicted values both of forced expiratory volume in one second and transfer factor of the lung for carbon monoxide, have a significant predictive capacity for severe respiratory complications following upper abdominal surgery.

Radical nephrectomy for renal cell carcinoma: long-term results and prognostic factors on a series of 328 cases.

OBJECTIVES: A series of 328 evaluable patients with renal cell carcinoma operated by radical transabdominal nephrectomy with regional lymphadenectomy was reviewed to assess the prognostic significance of various pathologic parameters (pT, N, M, G and venous involvement) and the value of lymphadenectomy and of surgery of venous tumor thrombus. PATIENTS AND METHODS: The complete charts of 328 patients with renal cell carcinoma available to follow-up, who were operated between 1970 and 1993, were reviewed. All patients underwent transabdominal extrafascial nephrosurrenalectomy and in all but 14 metastatic ones a regional retroperitoneal lymphadenectomy was performed. Surgery of venous tumor thrombus was performed in 79 patients. Life expectancy according to pT stage, pN stage, M stage, nuclear grade and venous involvement was calculated by means of the life tables method and differences in survival were evaluated by means of the log rank test. Correlation analysis and multivariate data analysis according to the Cox model were also performed. RESULTS: Overall survival of the 328 patients was 50.70% at 5 years, 35.10% at 10 years and 29% at 15 years. At multivariate data analysis the most important prognostic factors is the presence of metastases (8% survival at 5 years and no patient surviving more than 7 years after surgery), tumor grade was the second prognostic factor and statistically significant differences were also found at life tables analysis among G1, G2 and G3 tumors. Local tumor stage was the third leading prognostic factor at multivariate data analysis and statistically significant differences were also found at life tables analysis. Nodal and venous involvement had only minor importance at multivariate data analysis although statistically significant differences were found at life tables analysis between the pN+ and the pN0 patients, also in the absence of venous involvement and distant metastases. Anyway survival of the pN + M0V0 patients was satisfactorily high (53.20% at 5 years, 39.10% at 10 years and 16% at 15 and 20 years). In patients with venous involvement no differences in survival were observed depending on the level reached by the tumor thrombus; differences in survival were observed between patients with venous involvement alone (38% surviving at 5 and 10 years) and patients who also had nodal or distant metastases (5.20% at 5 years and 0% at 10 years). CONCLUSIONS: From the review of our series it seems that the most important prognostic factors are synchronous metastases, tumor grading and the completeness of tumor exeresis. In fact, the low impact on survival of nodal involvement by itself is probably due to the completeness of lymphadenectomy. The value of regional lymphadenectomy is sustained by the high long term survival of N + M0V0 patients. Regarding venous involvement, it seems that V+ patients free from nodal and distant metastases may benefit from radical surgery, which on the contrary has only minimal impact on survival of V+M+/N+ patients.

Comparative DNA analysis of breast cancer by flow cytometry and image analysis.

Measurement of DNA ploidy can be performed either with Flow Cytometry (FCM) and Image-Analysis (IA); both methods provide prognostic information in primary breast cancer. We compared the results of quantitative DNA analysis of formalin fixed, paraffin embedded tissue from 62 invasive ductal breast cancers. For FCM nuclear suspensions from disaggregated tumor were stained with Propidium Iodide and analyzed by means of Ortho Cytoron Absolute. For IA nuclear suspensions were stained by the Feulgen method and analyzed by means of Vidas system. We found a good correlation between flow cytometry DNA Index and Histogram Type, according to Auer classification (rs = 0.65, p < 0.001) and between DNA Index and Grading of Malignancy (MG) which had been measured by Bocking's algorithm (rs = 0.38, p < 0.05). Concerning to disease free survival (DFS), flow cytometric DNA Index showed a better correlation (rs = 0.56, p < 0.001). We concluded that the two methods provide comparable results, but offer individual advantages and are complementary for analyzing DNA ploidy in breast cancer.

Human breast cancer: prognostic significance of DNA ploidy compared with c-erbB2 expression, Cathepsin D and silver-binding nucleolar organizer regions (AgNORs).

We evaluated breast cancer specimens from 150 patients after a follow-up more than 10 years, by means of DNA flow cytometry, immunohistochemistry (cerbB2 and Cathepsin D) and argyrophilic (AgNORs) methods. In univariate analysis all indexes studied provide prognostic information about the disease free survival, whereas in the multivariate Cox model the DNA Index is the most important prognostic factor. We conclude that the data obtained from DNA flow cytometry, associated with other parameters, can be of greatest importance for the decision an the level of aggressiveness of adjuvant therapy for the decision an the level of aggressiveness of adjuvant therapy for a individual patients.

[Medical students and psychiatry. A survey of students' opinion]. / Studenti di medicina e psichiatria. Osservazioni da un sondaggio di opinione.

In the last years research on the didactics of Psychiatry and opinions of medical students on Psychiatry has gained great interest. The authors think that this research could be useful for the improvement of didactics, for better understanding the meanings of professional choice, the identity of psychiatrist and their relationship with colleagues in other medical field. The goal of this research work was a preliminary survey of Genoese University Medical Student's opinions about psychiatry didactics, and choice of specialization. A questionnaire was submitted to all the students who passed Clinical Psychiatry examination in the period from November 1987 to December 1988. The students were divided in two randomized groups: the first group of students (224) was submitted to the questionnaire immediately after Clinical Psychiatry examination; while to the second group of students (66) the questionnaire was mailed. The aim of the questions was to assess the student's opinions on psychiatry, psychoanalysis, psychotherapy, the career they wanted to take up, and the difficulties of studying psychiatry: 69% of the students of the first group and 42% of the students of the second group answered the questionnaire. Female students answered that they preferred psychiatric specialization more than their male colleagues did, but the difference has no statistical importance. In most cases, the students who answered that they have taken into account psychiatry as a choice of specialisation, are more interested in medical specialties (primary care, etc.) than in surgical specialties. Most of the medical students declare some emotional troubles (anxiety, sleeplessness, problem in social relations).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of aging on some specific and nonspecific mechanisms of the host defense system in 146 healthy subjects.

The influence of aging on some parameters of systemic host defense mechanisms, i.e. white cell counts, lymphocyte subpopulations, delayed-type hypersensitivity (DTH), polymorphonuclear and mononuclear leukocyte functions, was evaluated. One hundred and forty-six healthy volunteers (60 men and 86 women), aged 25-100 years, were enrolled. None of the subjects had taken any drug in the month before the study. Subjects were divided into three age groups: 25-45, 46-65 and 66-100 years. Groups were comparable in size, and sex distribution was similar throughout all age groups. Elderly people were 51 healthy volunteers between the ages of 66 and 100 years (mean age 79.2). Younger people were 41 subjects between the ages of 46 and 65 years (mean age 54.3) and 53 between the ages of 25 and 45 years (mean age 32.7). As for the comparison between sexes, no significant differences in the values of the studied parameters were found between males and females (p > 0.05). Only quantitative DTH data, i.e. the number of antigens producing positive reactions and the score (sum of positive reaction diameters), were significantly (p < 0.05) reduced in responsive females when compared to males. Aging did not affect white cell counts, lymphocyte subsets and many phagocytic functions, i.e. phagocytosis frequency and index, nitroblue tetrazolium reduction, superoxide production, microbicidal activity against bacteria and yeasts. A significant decrease (p < 0.05) in the chemotactic response to serum-derived chemotactic factors was observed in aged people in comparison to younger subjects. Anergy was more frequent in older (about 29%) than in younger (5-9.4%) healthy volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)

Multiple tumour markers for diagnosis, management and follow-up of potentially resectable lung cancer.

The present prospective study has been carried out to evaluate the role of tumour markers in the preoperative assessment and follow-up of patients with potentially resectable lung cancer. The carcinoembryonic antigen (CEA), neuron specific enolase (NSE), and tissue polypeptide antigen (TPA) have been preoperatively measured in 133 lung cancer patients and in 75 healthy smokers. The same tumour markers have been serially determined during the 12 to 30 month-follow-up of 53 subjects who had a complete resection. In screening for localized lung cancer, TPA determination was the single most accurate diagnostic test. The combined measurement of several tumour markers did not result in a greater diagnostic accuracy of the assay. In predicting lung cancer unresectability, CEA, though being the most suitable test, allowed preoperative detection of only one third of patients with unremovable tumours. In monitoring the postresectional course of subjects who had a complete resection, the combined measurement of TPA and NSE proved to be a very reliable predictor of disease recurrence.

[Expression of P53 protein in cutaneous melanoma]. / Espressione della proteina P53 nel melanoma cutaneo.

P53 protein in cutaneous melanoma. We report the results of an immunohistochemical analysis about the nuclear phosphoprotein P53 expression performed on 48 primary and 10 metastatic cutaneous melanoma in order to assess the prevalence of the expression of mutant P53 protein (m-P53) in this skin tumour. In our study m-P53 was found in about 46% of primary tumours without any significant relationship with the corresponding metastatic lesions. Therefore the P53 count in cutaneous melanoma is not a prognostic marker of tumour spread and aggressiveness.

Nucleolar organizer regions: a prognostic factor in infiltrating ductal carcinoma in the breast.

By means of an AgNOR technique, the authors have carried out a retrospective study on proliferative activity in 170 cases of infiltrating ductal breast carcinoma (so-called carcinoma NOS). The follow-up period was 138 months. A statistically significant correlation was found between AgNOR score and outcome of the disease ("vital status"), clinical stage and OS respectively. By means of discriminant analysis a threshold value of AgNOR score was identified (= 9.5) which distinguished two risk groups among the cases under examination. Those cases with an average AgNOR score below the threshold value showed a favourable prognosis. The cases with an AgNOR score greater than 9.5 had an unfavourable outcome. The authors suggest that AgNOR score may be used as a prognostic parameter in breast carcinoma.

Extension of lymph node dissection and survival in primary gastric cancer.

The histories of 429 patients who underwent surgery for primary gastric cancer at our ward from January 1970 to December 1985, were reviewed. All patients underwent surgery: potentially curative surgery, 54.8%, non-curative resection, 18.2%; palliative surgery, 27%. Nodal status was as follows: N0, 28%; N1, 17.7%; N2, 44.5%; N3, 9.8%. The incidence of N0 cases was significantly increased in Stage T1 and T2 disease compared to Stage T3 and T4 lesions (p < 0.001). In Stage T3 and T4 patients the incidence of distant metastases increased if lymph node involvement was also present (p < 0.005). In patients without nodal metastases 5-year survival was 70% (median survival: 60+ months) whereas, in patients with lymph node involvement survival was 32% (median survival: 24 months) (p < 0.001). Our data suggest that elective extensive lymph node dissection (R2) is indicated in all patients because survival is improved by this procedure. We recommend R3 lymph node dissection only in macroscopic N3 node involvement patients.

[The use of different suture materials in thyroid surgery. A statistical evaluation of the immediate and long-term results]. / Utilizzo di differenti materiali di sutura in chirurgia della tiroide. Valutazione statistica dei risultati immediati e a distanza.

Six groups of patients for a total of 120 cases were examined for cervical wound suture results. Different synthetic absorbable sutures and different suture techniques were employed. Good aesthetic results were always obtained in long-term follow-up. The patients sutured with Polydioxanone, a monofilament with prolonged breaking strength retention, had a lower incidence of local complications.

Counting the nucleolar organizer region-associated proteins is a prognostic clue of malignant melanoma.

BACKGROUND AND DESIGN: The nucleolar organizer regions (NORs) are chromosomal loops of DNA to which acidic proteins are associated that are seen by silver staining as black dots within the nucleoli (hereafter, these silver-staining NORs will be referred to as AgNORs). As their size and number reflect cell and nuclear activity, their counting in paraffin sections is regarded as a useful tool for diagnosing and prognosing malignant tumors. We counted AgNORs in 98 patients with stage I melanoma, followed up to an average of 73 months, to verify whether the number of AgNORs is of prognostic value. RESULTS: The number of AgNORs averaged 2.792 +/- 0.901 in the 64 patients without metastases and 4.889 +/- 1.403 in the 34 with metastases. In patients with counts higher than 3.62, there was an 82% probability of metastases developing. CONCLUSION: The technique is fast, simple, and reproducible with easily available reagents and standard light microscopy. In our population, AgNOR counts constituted a more accurate prognostic indicator than Clark's level and Breslow's thickness. Confirmation in a new population is needed.

Glutaraldehyde-tanned mandril-grown grafts as venous substitutes.

The present study was performed to evaluate the potential of glutaraldehyde-tanned mandril-grown grafts as caval substitutes. Short-term experiments consisted of 30 tubular grafts (35 x 8 mm), either of tanned collagen or polytetrafluoroethylene, that were sutured in the infrarenal inferior vena cava of pigs and removed 1 hour after implantation. There was no significant difference between the extent of the thrombus-lined graft surface in the biologic group and that in the polytetrafluoroethylene group. The amount of inner thrombus on tanned collagen grafts was significantly correlated to platelet activity. Long-term experiments involved 30 similar segments of both materials, which were sutured in the inferior vena cava and harvested 7, 14, 28, 56, and 112 days after operation. The 112-day patency rate of collagen grafts was 67%. The 56-day patency rate of polytetrafluoroethylene grafts was 16%. The difference was statistically significant (p less than 0.01). Collagen grafts were lined by a thin neointima (200 micron) in all but two cases. The neointima was completely endothelialized within 4 weeks from implantation. In conclusion, tanned collagen grafts may represent a suitable material for venous replacement.