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Role of surgery in the treatment of bilio-pancreatic cancer: the European experience.

Pancreatic cancer is the eighth most common cancer in Europe, accounting for 4.1% of cancer deaths in men and 4.8% in women. Standardized pancreatoduodenectomy and left pancreatectomy are the gold standard for routine surgical treatment of pancreatic cancer. Total pancreatectomy should be reserved for positive pancreatic resection margins or severe pancreatic anastomotic leak; mesenterico-portal vein resection should be performed only when it is the only reasonable way to obtain clear margins. Extended lymphadenectomies are recommended only in prospective, randomized studies. Ongoing efforts to standardize surgical procedures will facilitate comparison of selection criteria and trial data among different centers, and will also optimize the study design of ongoing/planned prospective trials using adjuvant and neoadjuvant chemoradiotherapy in pancreatic cancer.

Biliary Tract Neoplasms↗

Expression in normal adult, fetal, and neoplastic tissues of a carbohydrate differentiation antigen recognised by antigranulocyte mouse monoclonal antibodies.

The distribution in paraffin fixed human tissues of a carbohydrate antigen defined by two monoclonal antibodies raised against human granulocytes has been studied by means of an immunoperoxidase technique. In addition to granulocytes, the antigen has been detected in adult tissues on identifiable cell types of the stomach, kidney, adrenal medulla, and brain and on the mucins of the gastrointestinal tract and other secretions. In fetal tissue, epithelial cells of the alimentary tract, lung, brain, and kidney express the antigen. Adenocarcinoma of the colon, stomach, breast, and lung are stained strongly, as are other types of lung cancer. The monoclonal antibodies give a staining pattern similar but not identical to other monoclonal antibodies raised against granulocytes or neoplastic cell lines which recognise the antigen 3-fucosyl N-acetyllactosamine. The use of antibodies against this oncofetal antigen in the study of differentiation and as tumour markers is discussed.

Adrenal Medulla↗

Significance of CA 72.4 serum levels in gastrointestinal diseases.

In order to evaluate the usefulness of Ca 72.4 tumor associated antigen assay in gastrointestinal diseases, we have studied 751 patients suffering from benign (376) and neoplastic (375) digestive diseases and 305 normal controls. The cut-off point was fixed at 6 U/ml. The Ca 72.4 assay, with the proposed method, provides additional information only in gastric cancers; the positivity of the marker in gastric neoplasms is 38.4% and the specificity vs gastric ulcers and atrophic gastritis is 99%. In six patients with gastric cancer, the Ca 72.4 is the only positive test. The most striking observation to be made from the current study is a no good sensitivity of the marker for gastrointestinal cancers (29.6% vs 35.7 and 37.6% for CEA and Ca 19-9 respectively), but rather the excellent specificity of the Ca 72.4 immunoassay with respect to being gastrointestinal diseases (98.7%), vs values of specificity for CEA and Ca 19-9 of 94 and 92%. In conclusion, the high specificity of this marker for gastrointestinal neoplasms may be very interesting in follow-up studies. In fact, an elevation of serum levels of Ca 72.4 should always be taken seriously.

Adult↗

[Cytological characteristics of carcinoid tumors of the respiratory and digestive organs].

The paper discusses the results of a study of 22 primary and metastatic carcinoids which occurred in respiratory and digestive tracts with varying degree of differentiation. They formed the basis of the following cytologic criteria for their diagnosis: monomorphism of small cell elements, among which dark and clear ones can be distinguished; small-lumped chromatin pattern in nuclei of clear cells; and teniform and perivascular structures. Diagnosis was verified in all cases by histological and histochemical methods which were complemented by electron microscopy in 3 cases. On the basis of the said characteristics, tumors with endocrine differentiation can be distinguished from other pulmonary and digestive tract neoplasms.

Biopsy↗

The use of the implantable chemoinfusion pump in the treatment of hepatic metastases of colorectal cancer.

Fifty-five chemoinfusion devices have been implanted in patients with metastasis of colorectal cancer confined to the liver. There were no episodes of pump malfunction or of catheter clotting. Side effects included gastric ulcers in 13 patients and duodenal ulcers in four patients, including one episode of total gastric obstruction. Chemical hepatitis occurred in 13 patients, sclerosing cholangiolitis in one patient, and duodenal dismotility requiring gastroenterostomy in one patient. The response criterion was taken as reduction by at least 50% of the pretreatment carcinoembryonic antigen level; consequently, the response rate was 88%. Median survival of all patients was 19.2 months from the time of diagnosis of hepatic metastases to death, as determined by the Kaplan-Meier method. Median survival from the time of pump implantation to death was 10.1 months.

Carcinoembryonic Antigen↗

A randomized study of two different schedules of methyl CCNU, 5-FU and vincristine for metastatic colorectal carcinoma.

Sixty-seven patients with measurable colorectal carcinoma were randomized to receive two different schedules of Methyl CCNU, 5-FU and Vincristine (MOF). The treatment schedule consisted of Methyl CCNU 150 mg/m2 po q 70 days, 5-FU 300 mg/m2 iv for 5 consecutive days q 35 days, and Vincristine 1 mg/m2 IV q 35 days. The same total dose was used in each arm; in MOF A, the Methyl CCNU was given on day 1, while in MOF B, the Methyl CCNU was divided and given over 5 consecutive days. In MOF A, there was a 10% partial response rate and a 10% minor response rate. In MOF B, the partial response rate was 12% and the minor response rate was 21%. This difference is not statistically significant, but the patients in MOF B experienced less gastrointestinal toxicity (p less than .001).

Adult↗

Isolation of a sulfated glycopeptidic antigen from human gastric tumors: its localization in normal and cancerous gastrointestinal tissues.

A sulfated glycopeptidic antigen (SGA) was purified from papain-digested cancerous human gastric mucosa. The amino acid composition of this antigen was characterized by a high percentage of threonine and proline. Serine was present in small quantities and aromatic amino acids were absent. The amount of sulfate present was evaluated at 7.5%. Fucose, galactose, N-acetyl glucosamine, N-acetyl galactosamine and sialic acid were found to be present in the molar ratio 1:4.6:3.0:6.2:5.0. With immunofluorescence techniques, a rabbit antiserum against the sulfated glycopeptide stained adult gastric mucosa when this tissue had intestinal metaplasia and stained the goblet cells of the intestinal tract (small and large intestines). About 50% of colonic carcinomas and some gastric carcinomas contained SGA. This sulfated antigen was present in well-differentiated tumors and there was a good correlation between tumoral acid mucous secretory activity and the SGA positivity.

Amino Acids↗

Current pancreatogastrointestinal anastomotic methods: results of a Japanese survey of 3109 patients.

BACKGROUND: Pancreatogastrointestinal anastomosis is the most important anastomotic method of reconstructing the digestive tract following pancreaticoduodenectomy. METHODS: We therefore conducted a survey on pancreatogastrointestinal anastomosis at the 28th Japan Pancreatic Surgery Club in 2001. RESULTS: Results revealed that of the methods of pancreatogastrointestinal anastomosis, pancreatojejunostomy (82.9%) was overwhelmingly more popular than pancreatogastrostomy (17.1%). Anastomotic leakage occurred in 12.8% of cases, and 13.0% of these patients died. The incidence of anastomotic leakage was 11.0% with pancreatogastrostomy, and 13.3% with pancreatojejunostomy. There was no significant difference in the development of anastomotic leakage among the anastomotic organ used with the pancreas, the pancreas resection method, and the pancreatic juice drainage method. Investigation of intra-abdominal hemorrhage and abscess, which are serious complications that result from anastomotic leakage, revealed that intra-abdominal hemorrhage occurred in 1.1% of all cases, and intra-abdominal abscess was seen in 3.3% of all cases. However, there were no significant differences between pancreatogastrostomy and pancreatojejunostomy with respect to incidence rates of intra-abdominal hemorrhage and abscess or mortality. CONCLUSIONS: The method of pancreatogastrointestinal anastomosis should be chosen according to each individual case.

Adolescent↗

Stents or open operation for palliation of colorectal cancer: a retrospective, cohort study of perioperative outcome and long-term survival.

PURPOSE: Expandable, metallic stents provide a new modality of palliation for patients with noncurable metastatic colorectal adenocarcinoma. This study was designed to compare the use of expandable metallic stents as a palliative measure to traditional open surgical management, with particular reference to length of stay, and survival. METHODS: Patients admitted between 1997 and 2002 with left-sided (splenic flexure and distal), colorectal adenocarcinoma and nonresectable metastatic disease (Stage 4) were treated with expandable metal stents or open surgery (resection, bypass, or stoma). The group of patients having stents inserted were compared with regard to perioperative outcome and survival to those having open surgical procedures. RESULTS: Twenty-two of 25 patients had colonic stents successfully inserted and 19 patients underwent open surgery. The two groups were comparable: stent: median age, 66 (range, 37-88) years; 13 males; and open operation: median age, 68 (range, 51-85) years; 12 males. The tumors were primary in 22 stents procedures and 18 open operations. The site of obstruction was: splenic flexure, 2 stent vs. 0 open operation; descending colon, 2 stent vs. 2 open operation; sigmoid colon, 12 stent vs. 6 open operation; rectum, 9 stent vs. 11 open operation. The American Society of Anesthesiologists (ASA) class was: ASA 1, 0 stent vs. 0 open operation; ASA 2, 6 stent vs. 9 open operation; ASA 3, 15 stent vs. 7 open operation; ASA 4, 4 stent vs. 3 open operation. The open operations were laparotomy only (n = 2), bypass (n = 1), stoma (n = 7), resection with anastomosis (n = 4), resection without anastomosis (n = 5). The complications after open operation were urinary (n = 2), stroke (n = 1), cardiac (n = 2), respiratory (n = 2), deep vein thrombosis (n = 1), anastomotic leak (n = 1). There were no stent-related complications. The mean length of stay was significantly shorter in the stent group (4 vs. 10.4 days; P < 0.0001). There was no difference in survival between the two groups (median survival: stent group, 7.5 months; open operation, 3.9 months; log-rank P value = 0.2156). CONCLUSIONS: Patients treated with stents are discharged earlier than after open surgery. Stents do not affect survival. Expandable metal stents provide an acceptable alternative and may be better than traditional open surgical techniques.

Adenocarcinoma↗

Immunohistochemical diagnosis of alimentary lymphomas and severe intestinal inflammation in cats.

Intestinal tissue samples were examined from 32 cats in which a histopathological diagnosis of alimentary lymphoma or multicentric lymphoma affecting the gastrointestinal tract had been made. These samples were re-evaluated histopathologically and serial sections were examined immunohistochemically with antisera specific for the lymphoid markers CD3, CD79a and BLA-36 and for class II molecules of the major histocompatability complex. The cats ranged in age from 4-16 years (median 10.5 years). The main presenting clinical signs were vomiting, diarrhoea and weight loss. The majority of alimentary lymphomas were of the B-cell type (n=15), whereas cases of T-cell lymphoma were fewer in number (n=8). Four cats had lymphoma of a mixed T-and B-cell phenotype. In five of the cats, immunohistochemistry suggested an inflammatory process, in contradiction to the original histopathological diagnosis of lymphoma. Immunolabelling would appear to be a useful adjunct to histopathology in classifying cases of feline alimentary lymphoma, and may help in distinguishing lymphoma from severe intestinal inflammation.

Animals↗

Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer.

Prostate stem cell antigen (PSCA) is a recently defined homologue of the Thy-1/Ly-6 family of glycosylphosphatidylinositol (GPI)-anchored cell surface antigens. PSCA mRNA is expressed in the basal cells of normal prostate and in more than 80% of prostate cancers. The purpose of the present study was to examine PSCA protein expression in clinical specimens of human prostate cancer. Five monoclonal antibodies were raised against a PSCA-GST fusion protein and screened for their ability to recognize PSCA on the cell surface of human prostate cancer cells. Immunohistochemical analysis of PSCA expression was performed on paraffin-embedded sections from 25 normal tissues, 112 primary prostate cancers and nine prostate cancers metastatic to bone. The level of PSCA expression in prostate tumors was quantified and compared with expression in adjacent normal glands. The antibodies detect PSCA expression on the cell surface of normal and malignant prostate cells and distinguish three extracellular epitopes on PSCA. Prostate and transitional epithelium reacted strongly with PSCA. PSCA staining was also seen in placental trophoblasts, renal collecting ducts and neuroendocrine cells in the stomach and colon. All other normal tissues tested were negative. PSCA protein expression was identified in 105/112 (94%) primary prostate tumors and 9/9 (100%) bone metastases. The level of PSCA expression increased with higher Gleason score (P=0.016), higher tumor stage (P=0.010) and progression to androgen-independence (P=0. 021). Intense, homogeneous staining was seen in all nine bone metastases. PSCA is a cell surface protein with limited expression in extraprostatic normal tissues. PSCA expression correlates with tumor stage, grade and androgen independence and may have prognostic utility. Because expression on the surface of prostate cancer cells increases with tumor progression, PSCA may be a useful molecular target in advanced prostate cancer.

Antibodies, Monoclonal↗

Multimodal CME for surgeons and pathologists improves colon cancer staging.

BACKGROUND: Optimal treatment of localized colorectal cancer (CRC) depends on accurate retrieval and assessment of lymph nodes (LN) in the resected specimen. METHODS: Formal CE, informal opinion leadership and reinforcing strategies aimed at pathologists and surgeons to improve LN assessment were implemented. RESULTS: In the pre-intervention period a median of 8 lymph nodes were assessed in making a designation of Stage II CRC (n = 115). Thirty months later (post-intervention period) the median number of LN reported in Stage II CRC increased to 18 (n = 41), p < 0.001. CONCLUSION: A durable improvement in staging was realized through a multipronged change initiative aimed at both surgeons and pathologists.

Aged↗

The effect of clustering of outcomes on the association of procedure volume and surgical outcomes.

BACKGROUND: A large body of literature documents associations between the volume of cases a hospital or surgeon treats and clinical outcomes. Most of these studies have used conventional statistical methods that do not recognize the fact that hospitals or surgeons with similar volumes may have very different outcomes because of systematic differences in processes of care, a phenomenon that exaggerates the true statistical significance of the effect of volume on outcome. OBJECTIVE: To describe methods to assess the degree of this "clustering" of outcomes and to explore the impact of available statistical techniques that correct for clustering. DESIGN: Reanalysis of 3 previously published volume-outcome studies. SETTING: Medicare beneficiaries 65 years of age or older undergoing surgery for colon, prostate, or rectal cancer in the population defined by the Surveillance, Epidemiology, and End Results cancer registries during 1992 to 1996. PATIENTS: 3 data sets were analyzed to assess the impact of surgeon volume on outcomes: 1) 24 166 colectomies performed by 2682 surgeons, 2) 10 737 prostatectomies performed by 999 surgeons, and 3) 2603 rectal resections performed by 1141 surgeons. MEASUREMENTS: Volume-outcome trends were analyzed by a conventional method (logistic regression) and corrected for clustering. Two widely used statistical methods for analyzing clustered data, a random-effects model and generalized estimating equations, were used and compared, and the degree of clustering was presented graphically. RESULTS: Substantial clustering was observed in the analyses involving morbidity end points. The 2 statistical techniques produced noticeably different results in some analyses. CONCLUSIONS: The presence of clustering represents variations in outcomes among providers with similar volumes. Thus, in volume-outcome studies, the degree of clustering of outcomes should be characterized because it may provide insight into variations in quality of care.

Clinical Competence↗

Peritonectomy combined with intraperitoneal chemohyperthermia in abdominal cancer with peritoneal carcinomatosis: phase I-II study.

OBJECTIVE: To evaluate the feasibility and the tolerance of Peritonectomy Procedure (PP) combined with Intraperitoneal Chemohyperthermia (IPCH) in patients with peritoneal carcinomatosis, a phase I-II study has been realised from January 1997 to September 1998. METHODS: Eighteen patients were included for peritoneal carcinomatosis from colorectal cancer (13), ovarian cancer (2), gallbladder cancer (1), gastric cancer (1) and peritoneal mesothelioma (1). Peritoneal carcinomatosis were mainly advanced disease (16 stage 3 and 4, 2 stage 2). All the patients underwent surgical resection of their primary tumor with PP as described by Sugarbaker and IPCH (with Mitomycin C, Cisplatinum or both). IPCH used in this study was a "closed sterile circuit" device with inflow temperatures ranging from 46 to 48 degrees C. IPCH was performed on the same day as PP (8118) or delayed (10/18). RESULTS: Significant down-staging of peritoneal carcinomatosis was achieved for 16 patients. One patient died postoperatively, while the morbidity rate was 6/18 (long postoperative ileus, grade 3 leucopenia and anastomotic leakage). CONCLUSIONS: Combination of PP and IPCH could achieve significant tumoral volume reduction in peritoneal carcinomatosis. This aggressive treatment must be employed selectively because of its morbidity. Larger phase III studies are now needed.

Abdominal Neoplasms↗