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[Limitations of laparoscopic visceral surgery in oncology].

Controversial discussion focuses on the application of laparoscopic curative resection for cancer due to oncologic radicality,tumor cell dissemination, and port site metastases. Considering the limitations of laparoscopic surgery, it is necessary to objectively evaluate whether laparoscopic surgery is associated with an improved quality of curative treatment. Therefore, controlled studies comparing the results of laparoscopic vs conventional cancer surgery are mandatory. To date, comparable findings on short-term outcome of laparoscopy with open resection can only be shown for colorectal cancer. However, long-term data including recurrence and survival are still missing as randomized studies (phase IIIb) are still to be completed. Consequently, laparoscopic curative resection should only be performed within controlled trials. In terms of the upper GI tract, minimally invasive surgery has proven to be technically feasible in expert centers including limited resections for early gastric cancer, left pancreatectomies, or hepatic resections for malignancy. Finally, laparoscopy has gained acceptance in the field of diagnosis (e.g., staging laparoscopy, laparoscopic ultrasound) and palliative treatment (e.g. gastroenterostomy, thermoablation) without the need for controlled studies.

Colorectal Neoplasms↗

Staging and follow-up of gastrointestinal tumors with PET/CT.

Positron emission tomography (PET) is a functional imaging modality that has been documented to be useful in patient care. Oncologic PET imaging is used for a wide variety of neoplasms, mainly for staging and follow-up, differentiation of equivocal morphologic findings, therapy stratification, and monitoring. Because PET imaging is based on the physiologically mediated distribution of the administered tracer but not on anatomic information, the addition of computed tomography (CT) to PET may improve the interpretation of PET. Combined PET and CT offers several potential advantages over PET alone that may influence the clinical routine. PET/CT was introduced into clinical use only 3 years ago and has found widespread application within only 1 to 2 years. This article summarizes preliminary data of clinical applications for PET/CT in gastrointestinal tumors.

Bile Duct Neoplasms↗

Complications with reconstruction procedures in pylorus-preserving pancreaticoduodenectomy.

This study was conducted retrospectively to examine the efficacy of Traverso reconstruction compared with Billroth I reconstruction after pylorus-preserving pancreaticoduodenectomy, in the prevention of several complications. Pylorus-preserving pancreaticoduodenectomy is an aggressive surgery, and insufficiency of the pancreaticoenterostomy plays an important role in the postoperative progression. However, reports examining the correlation between pancreatic fistula and the type of reconstruction after pylorus-preserving pancreaticoduodenectomy have been limited. Sixty-four patients who underwent pylorus-preserving pancreaticoduodenectomy (33 reconstructed by the Traverso technique and 31 reconstructed by the Billroth I technique) were entered into this study to investigate whether the complications were related to the type of reconstruction procedure employed. Insufficiency of the pancreaticojejunostomy, including major leakage and pancreatic fistula, occurred in 18.2% of the reconstructions by Billroth I and 0% of the reconstructions by Traverso (p < 0.05). In addition, jejunal obstruction by recurrent tumor in the remnant pancreas was observed in 3 patients reconstructed by Billroth I, and required palliative bypass surgery. Reconstruction by the Traverso procedure after pylorus-preserving pancreaticoduodenectomy is a safe surgical method and has an advantage for advanced pancreatic cancer, which has high risk of jejunal obstruction by recurrent tumor in the remnant pancreas.

Aged↗

Role of endoscopic endoprostheses in proximal malignant biliary obstruction.

The management of hilar strictures is dependent upon their resectability and may therefore require a multidisciplinary approach. However, resectability rates for such tumors are reported to be in the region of 15%-20%, and, therefore, palliative therapy will be the mainstay of treatment for most patients. With the presenting symptoms being those of obstructive jaundice and the consequences of cholestasis, a significant improvement in morbidity can be obtained by achieving biliary drainage. A number of options are available, including the placement of Teflon or expandable metallic endoprostheses by either the endoscopic or percutaneous route. Some considerable debate exists as to which route of stent placement is best, and in many circumstances the decision will depend on the availability of local services. Some have suggested that success rates with percutaneous stenting are superior to those for endoscopic placement, but the latter technique may be associated with fewer complications. In competent hands, endoscopic placement does achieve a high rate of success and it should be remembered that a combined approach may further improve success rates. The debate over the use of plastic versus metallic stents is centered around the higher rates of stent occlusion/migration for plastic stents seen in some studies, although a stent change is usually possible. An additional advantage of metallic stents is that they may provide drainage of the side branches of the biliary tree through the mesh. However, possible drawbacks may be a greater difficulty in placement of a second stent where a first provides inadequate drainage, and cost issues often have to be taken into consideration. Considerable debate exists over the optimum number of stents required to achieve adequate drainage and minimize the risks of cholangitis. There is good evidence that if overfilling of the biliary tree with contrast is avoided with only the segments to be drained visualized, a single stent may be all that is required, while others argue that placement of more than one stent may improve survival. In the following review we discuss these issues, and conclude by considering success rates and complications following endoprosthesis insertion; we also discuss the prognosis of patients treated in this way.

Cholestasis, Extrahepatic↗

Risk of second cancers in patients with colorectal carcinoids.

INTRODUCTION: It is often stated that patients with colorectal carcinoid tumors have an increased risk of developing other malignancies. However, this risk has not been conclusively documented. A comprehensive evaluation is needed to more thoroughly assess the risk of second cancers in patients with colorectal carcinoids. METHODS: A search of the National Cancer Institute Surveillance, Epidemiology, and End Result database from 1973 to 1996 revealed 2,086 patients with colorectal carcinoids. This subset of patients was examined for occurrence of second cancers. The observed incidence of cancer for each site was compared with the expected incidence based on the gender-adjusted and age-adjusted cancer rates in the remaining Surveillance, Epidemiology, and End Result file. A Poisson distribution probability was used to determine the significance of these comparisons. RESULTS: Patients with colorectal carcinoids had an increased rate of cancer in the colon and rectum (P < 0.001), small bowel (P < 0.001), esophagus/stomach (P = 0.02), lung/bronchus (P < 0.001), urinary tract (P = 0.005), and prostate (P < 0.001), when compared with a control population. Most of the gastrointestinal tract cancers were synchronous cancers, whereas lesions outside the gastrointestinal tract were most commonly metachronous tumors. CONCLUSIONS: A significantly increased risk of synchronous colorectal, small-bowel, gastric, and esophageal cancers and metachronous lung, prostate, and urinary tract neoplasms is clearly demonstrated. After the diagnosis of colorectal carcinoid tumors, patients should undergo appropriate screening and surveillance for cancer at these sites.

Age Distribution↗

Pyloric and gastric preservation with pancreatoduodenectomy.

Pyloric and gastric-preserving pancreatic resection was performed in 35 patients with no mortality. Twenty-seven patients were followed for at least 8 months postoperatively and are reported herein in detail. This variation in the Whipple procedure is associated with a satisfactory weight gain after operation for benign disease, does not produce the usual postgastrectomy digestive symptoms, and so far jejunal or anastomotic ulceration has not been a problem. We believe this variation of the Whipple procedure is the operation of choice for benign disease and for certain types of periampullary malignant growth.

Ampulla of Vater↗

Indications of endoscopic ultrasonography of the digestive tract.

Endoscopic ultrasonography of the digestive tract provides for a precise ultrasonic study of the accessible gastrointestinal walls (esophagus, stomach, duodenum, rectum) and through the walls, of the adjacent organs (lymph node clusters, posterior mediastinum, pancreas, extrahepatic biliary ducts and perirectal environment). This method is more efficient than computerized tomography to evaluate the local and regional extension of esophageal, gastric and rectal carcinomas, producing little or no stenosis. It is the examination of choice to detect a perianastomotic recurrence of these cancers in the aetiological diagnosis of obstacles in the biliary tract and in the diagnosis and the pretherapeutic assessment of pancreatic cancers.

Cholestasis, Extrahepatic↗

Prospective study of serum cholesterol and site-specific cancers.

From 1965 to 1968, 7716 Japanese-American men were examined and tested for serum cholesterol. After 22 years, 1380 incident cancer cases were identified. Of the site-specific cancers, only colon cancer cases had a significantly lower mean serum cholesterol value than that of noncases (213.0 mg/dl vs 219.0 mg/dl). When the study subjects were separated into either a low, middle or high group, based on their serum cholesterol values, there was a significant inverse trend for cases of oral/pharyngeal/esophageal cancer combined. The association was present for cases diagnosed within 10 years of examination (p = 0.012), but not for cases diagnosed after 10 years. This suggests that the inverse association is due to the metabolic effects of undiagnosed oral/pharyngeal/esophageal cancer upon serum cholesterol levels. These results are discussed in relation to other studies on serum cholesterol.

Aged↗

A role for dihydropyrimidine dehydrogenase and thymidylate synthase in tumour sensitivity to fluorouracil.

Despite being one of the oldest anti-cancer drugs, fluorouracil (FU) is still being increasingly used in cancer chemotherapy. The source of variability for FU sensitivity in patients may be complex, although an overproduction of thymidylate synthase (TS) was the only mechanism of resistance identified in tumours from FU-resistant patients. Dihydropyrimidine dehydrogenase (DPD) is the first and rate-limiting enzyme of FU catabolism. Thus, DPD activity may be a potential factor for controlling FU responsiveness. A panel of 19 human tumour cell lines, including digestive tract, breast and head and neck cancer cells, were investigated. Both TS and DPD activities were measured in parallel to FU responsiveness. None of the cell lines had been previously exposed to FU, and thus expressed a spontaneous sensitivity to FU. Sensitivity between cell lines showed marked differences, with IC50 values ranging from 45 ng/ml (colon cell line) to 5063 ng/ml (head and neck cell line). TS activity was measurable in all cell lines and varied within a 46-fold range. DPD activity was detected in all but four cell lines, showing a 100-fold range of variation. Cell lines most sensitive to FU exhibited the lowest DPD and TS activities and vice versa. Simple linear regression analysis showed that both TS (r2 = 0.22, P = 0.042) and DPD (r2 = 0.27, P = 0.022) activities were significantly correlated to FU effectiveness (log 10 IC50): the greater the enzyme activities, the higher the FU IC50. TS and DPD were demonstrated to be independent variables. A multiple regression analysis showed that the combination of TS and DPD activities explained 36% of the variability in FU IC50 (r2 = 0.36, P = 0.01). Two groups of cell lines could be identified, one group with both low TS and low DPD activities (G1), and the other with either high TS and/or high DPD activities (G2). Mean FU IC50 values were 193 and 930 ng/ml in G1 and G2, respectively, and this difference in FU sensitivity was highly significant (P = 0.009). The present study shows, for the first time, that DPD activity in tumour cells is an independent factor significantly related to FU sensitivity. These results should encourage DPD and TS coupled measurements in tumours of patients before FU treatment in order to establish their prognostic relevance. DPD and TS measurements could also be used during the treatment course to determine the implication of these enzymes in the development of tumour resistance to FU.

Breast Neoplasms↗

Randomised phase II study of epirubicin-vindesine versus mitoxantrone-vindesine in metastatic breast cancer.

The purpose of this study was to compare the activity and toxicity of epirubicin-vindesine (EV) with mitoxantrone-vindesine (MV) in patients with metastatic breast cancer. A total of 295 patients was randomly allocated to treatment with vindesine 3 mg/m2 combined with either epirubicin 40 mg/m2 or mitoxantrone 10 mg/m2. All drugs were given by intravenous push, treatment cycles were repeated at 3-4 week intervals. 255 patients were available for response, and 283 for toxicity. EV and MV yielded similar objective response rates (34 and 26%, respectively), response durations, times to progression and survival. Median time to remission was 1.8 and 3.1 months (P = 0.006) with EV and MV, respectively. In patients with visceral metastases, response rate was higher with EV than MV (40 versus 23%; P = 0.03). Patients receiving MV had less nausea/vomiting (P = 0.007) and alopecia (P = < 0.001) of WHO grade > or = 2. Bone marrow, cardiac and other toxicities were mild with both treatments. The observed differences in activity and toxicity between the two regimens appear to have clinical relevance. EV proved to be more active in visceral disease and to be able to induce remissions more rapidly. Accordingly, patients with visceral metastases or severe tumour-related symptoms may benefit from epirubicin-based treatment. Subjective toxicities, i.e. nausea/vomiting and alopecia, were less frequent and severe with MV. Thus, MV may prove useful in patients with more indolent disease and appears to warrant phase III evaluation in such patients.

Adult↗

EO9 phase II study in advanced breast, gastric, pancreatic and colorectal carcinoma by the EORTC Early Clinical Studies Group.

In a phase II trial, the activity of EO9, a new bioreductive alkylating agent, was assessed. EO9 was used as second-line chemotherapy in breast cancer patients and as first-line chemotherapy for patients with gastric, pancreatic and colorectal cancer. EO9 was given as a 5 min i.v. infusion at a weekly dose of 12 mg/m2. 92 patients were entered; 22 with breast cancer, 26 with colon cancer, 24 with pancreatic cancer and 20 with gastric cancer. In general, the drug was well tolerated with nausea and vomiting occurring in 26.42 and 13.3% of courses, respectively. Reversible proteinuria was the main toxicity occurring in 45% of courses. Antitumour activity was not observed. At this dose and schedule, EO9 is not an active drug in the type of tumour studied.

Adult↗

Epidemiology and treatment of extramammary Paget disease in the Netherlands.

AIM: To determine the incidence of EMPD and to describe its epidemiology, treatment, survival and the risk of developing other malignancies. METHOD: All cases of EMPD, diagnosed between 1989 and 2001, were selected from the Netherlands Cancer Registry. RESULTS: In total, 178 cases of invasive and 48 cases of in situ EMPD had been registered. The overall relative 5-year survival for invasive tumours was 72%. Most patients with invasive as well as in situ cancer underwent surgery. Other malignancies were found in 32% of patients with invasive EMPD and 35% of patients with in situ EMPD. Patients had an increased risk of developing a second primary cancer (standardized incidence ratio: 1.7; 95% confidence interval 1.2-2.4). The most frequent localizations of the other cancers were the colorectum, the prostate, the breast and the extragenital skin. CONCLUSIONS: For EMPD, which is a rare disease in the Netherlands, there are no clear diagnostic and treatment guidelines. The prognosis is fairly good. A thorough search for other tumours is recommended for these patients.

Adult↗

Resected periampullary adenocarcinoma: 5-year survivors and their 6- to 10-year follow-up.

BACKGROUND: Many studies have reported 5-year survival data after pancreaticoduodenectomy for periampullary adenocarcinoma. This study evaluates 10-year survival in patients surviving 5 years after initial surgery. METHODS: We reviewed all patients undergoing pancreaticoduodenectomy for periampullary adenocarcinoma from April 1970 to July 1999 at a single institution. All 5-year survivors were identified, and their subsequent 5-year survival was compared with the actuarial survival of the general population starting at 70 years of age. RESULTS: Nine hundred fifteen patients underwent pancreaticoduodenectomy for periampullary adenocarcinoma. Follow-up was complete on 890 patients. There were 201 (23%) 5-year survivors with a median age of 65 years at initial surgery; 51% were male and 92% were Caucasian. For the 5-year survivors, the carcinoma origin was pancreatic in 46%, ampullary in 25%, distal bile duct in 17%, and duodenal in 12%. For all 5-year survivors, the subsequent 5-year actuarial survival rate was 65%, with a median survival after achieving the 5-year landmark of 7.9 additional years. The subsequent 5-year survival by site of tumor origin was 55% for pancreatic, 66% for ampullary, 74% for bile duct, and 85% for duodenal cancer. For the age-matched population, the 5-year survival rate was 87% (P<.001 when compared with those with all periampullary cancers). CONCLUSIONS: While the 5-year survival rate for all patients with resected periampullary adenocarcinoma is only 23%, these data imply that attainment of the 5-year survival landmark carries with it an improved survival for the subsequent 5 years. While the survival rate was less than that of the age-matched population, 65% of 5-year survivors survived 5 more years, bringing them to the 10-year postresection landmark.

Adenocarcinoma↗

Prognostic factors for survival after pancreaticoduodenectomy for malignant disease.

Forty patients underwent pancreaticoduodenectomy for malignant disease in a 25-year review of 6 Portland-area hospitals. After resection, 10 patients survived for greater than 5 years. Characteristics of survivors included a short prodrome of symptoms, minimal weight loss, tumor in the periampullary region, and female sex. Factors that did not influence survival included degree of jaundice, primary tumor size, and initial abnormal liver function studies.

Adult↗