Angiogenesis as a prognostic indicator in pancreatic ductal adenocarcinoma.

BACKGROUND: Angiogenesis has gained wide acceptance as a reliable prognostic factor in several solid tumors. However, to date, experience in pancreatic adenocarcinoma is limited. MATERIALS AND METHODS: Specimens from 45 patients radically operated on at our departments from 1988 to 1997 were stained immunohistochemically with the antibodies anti-mutant p53, anti-bcl2, anti Ki67 and anti-CD31. All the slides were reviewed by the same pathologist without knowledge of the patients' outcome. RESULTS: Mutant p53, Ki67 index and vessel count were significantly related to tumoral behaviour and patients' outcome. Among patients with nodal involvement (Stage III), cumulative survival between hypovascular and hypervascular subgroups differed significantly (p = 0.03). Angiogenesis was independent from TNM in assessing the patients'prognosis at COX analysis (p = 0.02). CONCLUSION: In patients with pancreatic adenocarcinoma, angiogenesis is a reliable indicator of tumor extension, lymph node status and survival. Its evaluation as a common procedure may contribute to a further improvement in the management of these patients and to a proper selection of those who could benefit from different follow-up protocols or adjuvant treatment.

[Gastrointestinal stromal tumors: a series of 23 surgically treated cases]. / Tumori stromali gastrointestinali: osservazioni su una serie di 23 casi trattati chirurgicamente.

AIM OF THE STUDY: The recently introduced new nosological category, Gastro Intestinal Stromal Tumors, brought the Authors to a revision of their series and to a critical analysis of surgical behaviour for the treatment of that pathology. MATERIAL AND METHOD: A series of 23 cases of GIST, observed between 1977 and 1999 has been taken into account. In the earlier cases, histopathological classification has been reviewed according to the most used criterions in international scientific literature. RESULTS: 17 of 23 observed tumors were located on the stomach, 4 on the duodenum and 2 on the jejunum. 20 of these cases derived from muscular tissue and 3 cases derived both from muscular and neural tissues. In 7 cases (30%) tumors were accidentally discovered during surgical intervention or diagnostic procedures for other causes. Surgical treatment was performed in all cases and consisted in 6 gastric resections, 14 gastric free-margin excisions, 2 duodenal resections and 1 jejunal resection. The follow-up (performed on 18 patients, with a minimum of 1 year, a maximum of 17 years and a median of 6 years) showed 2 deaths (11%) due to oncological causes, while 2 of the patients (11%) died for other causes. CONCLUSIONS: The only treatment for that group of tumors is, at the moment, surgery. Although that kind of neoplasms has mainly non-aggressive biological behaviour, a radical resection must be performed, due to the absence of macroscopic criterions to help distinguishing, during surgical intervention, aggressive tumors from non-aggressive ones.

Use of autologous blood in general surgery.

BACKGROUND/AIMS: Autologous blood predonation is still not as widespread as it should be in general surgery practice, even if the method is well-known and has benefits established in international literature. Authors describe the impact of an autotransfusion program, in a general surgery university department, focusing on management and cost problems. METHODOLOGY: A description of the efficacy of the program during a yearlong activity period is presented. An analysis has been made about the quantity of predonated blood/plasma units, the quantity actually transfused and use of homologous blood. The problems which occurred and the cost are discussed. RESULTS: The most used autotransfusion method was preoperative predeposit of autologous blood. The analysis of results focused on some organizational problems that need to be avoided in order to show the methods maximum benefits. In a large number of cases (some 50%) predeposit was not made because of several managing/technical problems. In another large number of cases (38%) the quantity of units predonated did not fully supply the needs and several patients received homologous products. In another number of cases predonated blood units were not used at all (61/34%). CONCLUSIONS: Predeposit, preoperative hemodilution and intraoperative recovery, are methods that should all be available in a general surgery department to manage in the best way the single patients blood/plasma needs, reducing post-transfusion complication. To optimize the program and minimize waste some guidelines must be established, with the aim of a rational and correct use of the procedure. Despite the value of the method, and the favor encountered by the patients, we must not forget that the use of autologous blood is not costless.

[The extempore intraoperative cytology of peritoneal lavage fluid. A study of the reliability of the method]. / Citologia estemporanea intra-operatoria su liquido di lavaggio peritoneale. Studio di attendibilità della metodica.

Data are presented about a 100 cases prospective study, designed to evaluate sensibility/specificity of intra-operative cytology on peritoneal washing in case of cancer of digestive tract. Data analysis showed a very low sensibility of the test (according with most of literature observations) that does not allow to consider it fully reliable. Authors, thus, suggest a critical use of the test and state doubts about his real value in the intra-operative correct managing of therapeutic options.

[The use of autotransfusion in general surgery]. / L'uso dell'autotrasfusione in chirurgia generale.

Authors expose their experience with autotransfusion, made during several years in a general surgery university department. Discussion is made about ethic and economical aspect of the philosophy guiding the most general concept of blood sparing, and different methods of autotransfusion; attention is then focused on practical experience made during two years (1995-1997) when the program worked well. On the whole, in 94 patients, 172 blood units were collected plus 10 plasma units obtained by aferesis. No method-related complications are have been observed. Elements who corresponded to difficulties or obstacles to the fully application of the method have been critically analyzed. Authors propose finally guide-lines which want to be valid proposal to increase method use while respecting at the best ethics, economics, efficacy and efficiency that must guide our work.

[Restoration of digestive continuity after subtotal gastrectomy: comparison of the methods of Billroth I, Billroth II and roux en Y. Randomized prospective study]. / Ripristino della continuità digestiva dopo gastrectomia subtotale: confronto tra la Billroth I, la Billroth II e l'ansa ad Y. Studio prospettico randomizzato.

UNLABELLED: The aim of this study was to evaluate functional results after Billroth I, Billroth II and Roux en Y reconstruction in subtotal gastrectomy. MATERIAL AND METHODS: 45 patients were randomised between 1990 and 1995 and stratified in 3 different groups: 15 BI, 15 BII and 15 Roux. They were investigated by EGDS with multiple biopsies and upper gastro-intestinal scintiscanning, to evaluate gastro-esophageal reflux (GER) and dynamics of gastric emptying. Besides they answered a questionnaire: "Gastrointestinal Quality of Life Index" (GIQLI). RESULTS: A reflux esophagitis was found in 5 BI, in 7 BII and in 2 Roux (p < 0.001). No gastric lesions were found in 6 BI, in 5 BII and in 12 Roux, (BI vs. Y, p < 0.05; BII vs. Y, p < 0.001). Chronic superficial gastritis was present in 9 BI, in 4 BII and in 3 Roux (BI vs. Y, p < 0.05). Dynamic scintiscan demonstrated the presence of GER in 5 BI and gastric emptying was fast (37' < T 1/2 < 86'), but incomplete (60' residual activity: 49-62%). GER was evident in 7 BII with slow (28' < T 1/2 < 143') and incomplete (60' residual activity: 48-72%) gastric emptying. GER was detected in 2 Roux and radioactive bolus progression in the Roux limb was fast (24' < T 1/2 < 53') and complete (60 residual activity: 42-52%) (BI vs. Y; BII vs. Y, p < 0,001). There was not statistical significance between GIQLI score in the 3 groups. CONCLUSION: The authors affirm the Roux en Y is the technique of choice in subtotal gastrectomy, if compared with BI and BII.

[Gastrointestinal stromal tumors: clinical and instrumental diagnosis. Analysis of a review of the literature]. / Tumori stromali gastrointestinali: diagnosi clinica e strumentale. Valutazioni su una revisione di letteratura.

AIM: From a personal experience of 23 treated gastrointestinal stromal tumor (GISTs), this study analyzed both clinical and diagnostic problems of this quite new nosological category. MATERIALS AND METHODS: A this literature review provides a rigid selection of papers (scientific basis, statistic inference, type/quality of the journal, etc.); only numerous series have been included (case reports were excluded) and only those published after 1990. Three-hundred-seventy-five cases have therefore been selected. Starting and late symptoms/signs and diagnostic tests employed were analyzed. RESULTS: Results show 1) a relevant GIST quantity (approx. 30%) is casually discovered, during operations carried out for other pathologies or diagnostic tests for other indications; 2) poor correlation between site of the tumor and clinical manifestations; 3) a positive correlation between tumor diameter and presence of symptoms/signs seems to exists. The accuracy of different diagnostic tests is reported. CONCLUSION: No specific symptoms/signs have been isolated; this kind of tumor is often accidentally found. An analysis of different diagnostic tests available today shows the very important role of endoscopic ultra-sound, together with CT and MRI.

End to side mucomucosal Wirsung jejunostomy after pancreaticoduodenectomy: immediate results and long term follow-up.

BACKGROUND/AIMS: Pancreatico-duodenectomy (PD) is nowadays a widely performed operation which still carries a risk of some morbidity and mortality due to leakage of the Pancreatico-jejunostomy. The aim of the present paper is to describe critically the experience of a surgical team with a large number of consecutive non-selective PDs, where the same surgical procedure was adopted in all cases to manage the pancreatic stump. METHODOLOGY: Sixty six Whipple/Child PDs and 4 Traverso-Longmire (Duodenum Preserving PD) were performed between 1974 and 1993, by the same surgical team in our surgical department. The management of the pancreatic stump was always the same: a hand-made end-to-side mucomucosal Wirsung-jejunostomy, completed by a second layer between pancreatic capsula and jejunal sero-muscular wall. RESULTS: The overall mortality was 7.1% (5 cases). Only one death could be ascribed to pancreatico-jejunostomy related complications (post-operative acute pancreatitis). Specific morbidity was 12.6% (9 cases). Only one complication was related to the Wirsung-jejunostomy (leakage of the anastomosis, treated by a "sleeve" end-to-end pancreato-jejunostomy). Long-term patency of the anastomosis was shown by ERCP. CONCLUSIONS: Even if this anastomotic technique requires a little more time and attention by the surgeon, we think that the low incidence of pancreatico-jejunal anastomosis related complications represents a validation of the method, and a motivation to adopt this anastomotic technique. The long-term patency of the muco-mucosal Wirsung-jejunostomy is another valid argument that supports this kind of management of the pancreatic stump after PD.

Solid cystic tumor of the head of the pancreas in a young woman.

This a case report of a solid papillary tumor of the pancreas in a young woman of 18 years, who was referred to after having suffered for a period of 8 months with a rather vague symptomatology, characterized by dyspepsia, fatigue and, towards the end of the 8 month period, weight loss (approximately 2 kg). In the last week, as a consequence of a modest abdominal trauma, the patient was submitted to abdominal CT that showed a burden at the head of the pancreas, demonstrating a round neoformation about 6 cm in diameter with solid echogenicity slightly hypodense. Subsequently, she underwent an operation with the diagnosis of pseudocystis of the pancreas. During surgery, a big cystic formation of the head of the pancreas, into which a drain was introduced, was revealed. The histological postoperative examination was compatible with pancreatic tumor with a low grade of malignancy, cystic papillary or solid papillary type. Therefore, the patient came under our observation and underwent an operation of pancreatoduodenectomy. Two years after the operation, the patient had completely recovered. In this case, we discussed the problem of performing certain preoperative diagnoses despite the aid of modern diagnostic imaging, this being a very rare illness that almost exclusively plagues young women (median age 19 years). This diagnosis has an uncertain histological origin and is generally accompanied by a modest and vague symptomatology. The surgical procedure, given the low grade of malignancy of the neoplasm and the excellent long-term prognosis, must be, with respect to the oncological radicality, as conservative as possible.

Restorative proctocolectomy: histological assessment and cytometric DNA analysis of ileal pouch biopsies.

BACKGROUND/AIMS: The pathological changes and the risk of developing cancer in the ileal pouch mucosa of patients who received restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) were studied. The presence or absence of remaining rectal mucosa below the IPAA in both patients with stapled and handsewn IPAA was also examined. MATERIALS AND METHODS: Endoscopy of the ileal pouch was performed on 38 patients at 4, 12, 18 and 36 months after restorative proctocolectomy with ileal pouch. Mucosal biopsy specimens were taken from the ileal reservoir in order to assess the histological incidence of inflammation. In 23 patients, biopsies were taken to perform cytometric DNA analysis. Clinical symptoms of pouchitis (over six evacuations in 24 hours, night-time evacuations, leakage of feces, bloody diarrhea, abdominal pain and fever) were recorded and correlated with the histological findings. Biopsies were also sampled below the ileo-anal anastomosis (IPAA) in order to identify residual rectal mucosa. RESULTS: Results of histological assessment showed various degrees of chronic inflammation increasing over time (from 42 to 60%) while the presence of both acute and chronic inflammation of the reservoir was less frequent (from 18 to 30%). Villous atrophy was present in 39-68% of patients and the grade of villous atrophy was correlated to the grade of inflammation. Clinical pouchitis was present in 3 to 8% of cases at the different controls and it was always associated with the highest grade of histological inflammation and severe villous atrophy. No significant alteration of the DNA cellular content was observed. Very low incidence of aneuploidy (0.7-1% Ex.R.) has been reported in three cases. However, we found dysplasia in only one patient who underwent surgical treatment for familial polyposis coli. IPAA evaluation showed no residual rectal mucosa in 40% of cases with stapled IPAA; in the remaining 60%, we found a small amount of rectal mucosa (maximum 1 cm). We did not find rectal mucosa after handsewn IPAA with mucosectomy. CONCLUSIONS: Patients treated with restorative proctocolectomy with IPAA showed a higher and increased incidence of inflammation during follow-up. No significant alteration of DNA cellular content nor dysplasia of the pouch mucosa were observed. In this study the chance of leaving rectal mucosa after stapled IPAA was about 60%.

Image analysis in multisample biopsy after ileal pouch-anal anastomosis.

Pouchitis in ileal anal anastomosis represents an important clinical complication after restorative proctocolectomy. Acute and chronic inflammation of the reservoir is a frequent event sometimes associated with villous atrophy and colonic metaplasia. After ileal pouch anastomosis, twenty-one patients affected by ulcerative colitis were studied. An image analyzer CAS 200 (Becton Dickinson) was utilized to evaluate the DNA intranuclear content in every biopsy. In two cases abnormal DNA distribution was observed, and in one case a poliploid pattern was seen. Abnormal DNA distribution was also present in colonic metaplasia. Therefore, image analysis for the detection of DNA aneuploidy may be of additional value together with histologic parameters in follow up, in order to exclude transformation of the ileal mucosa in neoplastic epithelia.

Restorative proctocolectomy: morphological and functional study with coronal CT.

BACKGROUND: Restorative proctocolectomy with ileal pouch has become the surgical treatment of choice for patients with ulcerative colitis (UC) and familial polyposis of the colon. Defecography is the radiological technique commonly employed to obtain detailed information on function and morphology of the ileal pouch; it allows the direct visualization of the ileal pouch and the anal canal, but it does not provide the visualization of the pelvis. METHODS: In all patients, computed tomography (CT) on coronal planes was performed to determine its possibilities as an alternative to defecography; 10 patients with UC submitted to restorative proctocolectomy and were examined. RESULTS: Coronal CT images provided a panoramic vision of the pelvis and demonstrated the morphology of the ileal pouch, the thickness of its walls, and its correlation with the surrounding tissues. Coronal CT also allowed the evaluation of the continence of ileo-anal and ileo-ileal anastomosis and the functional changes of the perineal muscles at rest and during squeezing. CONCLUSION: CT images acquired on coronal planes allows an easy and clear detection of the major postoperative complications, such as stenosis or dehiscences of the anastomosis, pelvic phlogosis, and fistulae.

Aneuploid polyclonality in image analysis.

Solid tumors such as colorectal adenocarcinomas consist of biologically diverse cell subpopulations. Nuclear DNA content of tumor cells in colorectal carcinomas may be studied with different techniques of intranuclear DNA quantification. In the current study, the DNA ploidy of samples obtained from 68 patients with colorectal carcinoma (age ranging from 46 to 86 years, mean age 66 years), treated with radical surgery, between the years 1992 and 1995 was analyzed. DNA ploidy was assessed using a CAS 200 image analyzer and was evaluated on neoplastic tissue and undamaged healthy mucosa obtained from the edges of the surgical resection. Approximately 150-300 cells were analyzed for each sample. The aim of this study was to evaluate the prognostic significance of the polyclonal cases correlated with lymph node infiltration and disease free-survival. The pathological stage according to the TNM classification was compared to ploidy: an increase in multiple stemlines was observed in stage III cases, i.e., a progression towards aneuploidy and multiple stemlines was significantly associated with lymphatic metastasis (p<0.0003). Concerning distant metastasis, we found a correlation between stage IV and polyclonality. A significant correlation was observed between disease-free survival and aneuploid and polyclonal cases (p<0.0053). In polyclonal cases a nine fold greater relapse risk compared to the non-polyclonal cases was observed (p<0.0004). In two cases, the adeno-carcinoma of the sigma was polyclonal and its hepatic metastasis contained the predominant aneuploid clone with the same cytometric characteristics (DNA index) of the original lesion.

[Restorative proctocolectomy. A morphological-functional study by computed tomography with coronal scans]. / Proctocolectomia ricostruttiva. Studio morfologico-funzionale con Tomografia Computerizzata con scansioni coronali.

Restorative proctocolectomy with ileal pouch has become the surgical treatment of choice for patients with ulcerative colitis and familial polyposis of the colon. Defecography is the radiologic technique commonly used to obtain detailed information on function and morphology of the ileal pouch, but it fails to depict the pelvis. Computed Tomography (CT), with coronal images only was used to examine 10 patients with ulcerative colitis, submitted to restorative proctocolectomy. Coronal CT, yielding a panoramic view of the pelvis, represent an effective alternative technique to defecography. In fact, the two techniques provide comparable information relative to the ileal pouch; coronal CT also depicts the possible thickening of pouch walls and of pelvic fat tissue. Coronal CT also depicts the continence of ileo-anal and ileo-ileal anastomoses and the functional changes of the perineal muscles at rest and during squeezing. Coronal CT images allow easy and clear detection of such major postoperative complications as pelvic inflammation and fistulae (less frequently stenosis or dehiscences of the anastomosis).

Efficacy of octreotide in the prevention of pancreatic fistula after elective pancreatic resections: a prospective, controlled, randomized clinical trial.

BACKGROUND: A prospective, randomized controlled clinical trial was conducted in 33 Italian surgical departments with the aim of evaluating the efficacy of octreotide in the prevention of pancreatic fistula after elective pancreatic resections. METHODS: Between July 1990 and May 1992, 278 patients were enrolled in the study. Fifty-four dropped out because of unresectable disease and six were excluded because of protocol violation; the remaining 218 were randomly assigned to the octreotide group (n = 111) or to the placebo group (n = 107). There were 131 men and 87 women with a mean age of 58.2 +/- 11.7 yrs. Pancreaticoduodenectomy was the most common operation performed (n = 143), sixty-four percent of patients had a pancreatic or periampullary cancer; chronic pancreatitis accounted for 8.2% of cases. RESULTS: Mortality rate was 6.9%. A pancreatic fistula occurred in 31 patients (14.2%), 9% in the octreotide group and 19.6% in the placebo group (p < 0.05). Morbidity rate was significantly lower in the octreotide (21.6%) than in the placebo group (36.4%) (p < 0.05). When specific pancreatic complications were grouped together and evaluated, they occurred less frequently in the treated (15.3%) than in the placebo group (29.9%) (p < 0.05). CONCLUSIONS: Octreotide was able to reduce significantly the incidence of pancreatic fistula after elective pancreatic resections.

Perendoscopic manometry of the distal ileum and ileocecal junction: technique, normal patterns, and comparison with transileostomy manometry.

The technique of perendoscopic manometry was used to study the motor patterns of the ileocecal junction and distal ileum. An expert endoscopist cannulated the distal ileum of 20 unsedated subjects in 260 +/- 252 (mean +/- SD) seconds, causing no discomfort beyond that of an ordinary colonoscopic examination. No sphincter-like motor activity was detected at the ileocecal junction, and four distinct motility patterns were identified in the distal ileum: (1) tone variations, (2) slow phasic contractions, (3) regular rapid phasic contractions, and (4) prolonged rapid phasic contractions. Previous appendectomy and insertion of the colonoscope into the distal ileum to position the manometric catheter did not affect the manometric recordings. Perendoscopic manometry of the distal ileum was compared with transileostomy manometry in 9 subjects. Perendoscopic and transileostomy manometric recordings showed the same motor patterns except for a longer occurrence of tone variations with perendoscopic manometry. In conclusion, this study shows that perendoscopic manometry of the distal ileum and ileocecal junction is feasible; recorded motor patterns are not affected.

Critical evaluation of the anastomoses in large bowel surgery: experience gained in 533 cases.

We critically examined the morbidity and mortality of manual and stapled colorectal anastomosis in a retrospective study of 533 patients who underwent colorectal resection for neoplastic and non-neoplastic disease. The clinically detected anastomotic dehiscence rate was 4.5%, and the mortality rate 1.8%. The extraperitoneal site of the anastomosis after rectal anterior resection with stapled anastomosis and surgery for cancer showed a statistically significant predisposition to anastomotic dehiscence. Age, emergency surgical intervention, curative versus palliative resection, the location of the anastomosed intestinal segments, type of anastomosis and presence of a protective colostomy did not appear to be statistically significant factors for anastomotic dehiscence. While the stapler may offer an advantage in the individual case, the low incidence of morbidity and mortality for manual anastomosis in this study reaffirms the soundness and importance of the manual colorectal anastomosis in the surgeon's technical armamentarium.

[Use of surgical staplers in proctocolectomy with ileal pouch. Effects on immediate results]. / L'impiego delle suturatrici meccaniche nella proctocolectomia con pouch ileale. Influenza sui risultati immediati.

The immediate results of 37 restorative proctocolectomies are reported comparing morbidity of stapled vs manual procedures. The stapled technique is easier and faster but does not reduce the incidence of leakages and pelvic sepsis related to the ileal pouch. It seems, though, to be more useful in reducing the morbidity related to the ileoanal anastomosis.

[VIPoma: surgical treatment]. / VIPoma: trattamento chirurgico.

This paper reports a case of pancreatic VIPoma with widespread hepatic metastasis which was treated for approximately 2 years with a synthetic somatostatin analog (SMS 201/995). The treatment of choice in cases in which the tumour was fully removable is surgical resection. This occurred rarely since approximately 80% of VIPomas are malignant and are operated late when local infiltration is already widespread; in addition, 50% of cases are already metastasised at diagnosis. In this case, due to the infiltration of the superior mesenteric artery by the primary tumour it was necessary to carry out a left pancreasectomy which included two-thirds of the neoplastic mass. This was justified by slow tumour growth and also facilitated control of diarrhea and ensured a greater efficacy of possible postoperative chemotherapy. The use of synthetic somatostatin analog (SMS 201/995) enabled diarrhea to be satisfactorily controlled and is therefore specifically indicated for this type of tumour. NSE serum assay (neuron specific enolase) allowed the evolution of disease to be monitored during follow-up.

Extended resection in the treatment of colorectal cancer.

Between 1975 and 1990, 525 patients underwent resection of colorectal cancer in our unit. Of these, 38 had tumour invading adjacent structures and underwent an extended resection. Overall, there were 67 cases treated palliatively. Of these, three were in the group of 38 having an extended resection. When the groups of radical not extended (n = 423) and radical extended resections (n = 35) were compared, respective values for mortality (1.9% vs 0) and morbidity (12.8% vs 11.3%) were not different. Respective local recurrence rates (13% vs 26%) were significantly greater after extended resection. Five-year survival after extended resection was 30%, no different from the general survival rate for standard resections for T2-3 node-positive tumours. Extended resection is thus a safe and important approach for locally advanced tumours.