US and CT diagnosis of complete cecocolic intussusception caused by an appendiceal mucocele.

Appendiceal mucoceles are found in only 0.2-0.3% of all appendectomy materials. Colocolic intussusception of the appendix is also very uncommon. We report the very rare association of these two entities in a 40-year-old patient presenting with intermittent right abdominal pain accompanied by a palpable mass in the right flank. The full diagnosis was made preoperatively by ultrasound and confirmed by helical CT by means of unequivocal signs of intussusception associated with a very suggestive "cup-and-ball" aspect of the mucocele induced by a global mucinous cystadenoma of the appendix. A brief review of the available literature on mucocele is given.

Autoimmune pancreatitis mimicking cancer of the head of pancreas: report of two cases.

Autoimmune pancreatitis has been characterised in 1995, but only a few cases have been published since then, most of them from Japan. This report describes the cases of two Belgian male patients who presented with isolated obstructive jaundice. Radiological imaging studies were highly suggestive of carcinoma of the head of pancreas and both patients underwent uneventful cephalic pancreaticoduodenectomy with portal vein resection. Pathological analysis of the removed tissues suggested an autoimmune process in both cases. Both patients had hyper-gammaglobulinemia and antinuclear antibodies, but failed to show evidence of any other autoimmune disease or cause of chronic pancreatitis. In both cases final diagnosis was autoimmune pancreatitis. Preoperative clinical suspicion of this diagnosis is mandatory and may avoid unnecessary surgery in future cases.

Impact of carrier solutions on pharmacokinetics of intraperitoneal chemotherapy.

PURPOSE: In the treatment of gastrointestinal malignancies with dissemination to peritoneal surfaces the principal advantage of intraperitoneal chemotherapy over intravenous chemotherapy is the high drug concentration achieved locally with low systemic toxicity. This advantage can be optimized by maintaining a large area of contact between the chemotherapy solution and the surfaces within the abdomen and pelvis over a prolonged time period. Using a rat model we compared the pharmacokinetics of two drugs infused intraperitoneally, 5-fluorouracil and gemcitabine, in five different carrier solutions. METHODS: A total of 120 Sprague Dawley rats were randomized into groups according to the carrier solution and the drug administered. Rats were given a single dose of intraperitoneal 5-fluorouracil (20 mg/kg) or gemcitabine (12.5 mg/kg) in 0.1 ml/g body weight of each carrier solution. The carrier solutions used varied in their tonicity (0.3%, 0.9% or 3% sodium chloride), or were isotonic and varied in molecular weight (0.9% sodium chloride, 4% icodextrin and 6% hetastarch). With the hypotonic, isotonic and hypertonic sodium chloride solutions, only 5-fluorouracil was used. Each group was further randomized according to the intraperitoneal dwell period (1, 3 or 6 h). At the end of the procedure the rats were killed, the peritoneal fluid was withdrawn completely and the blood was sampled using a standardized protocol. The volume of the peritoneal fluid was recorded, and the drug concentrations in the peritoneal fluid and plasma were determined by high-performance liquid chromatography. RESULTS: Measurements of peritoneal fluid volume showed a more rapid clearance of hypotonic and isotonic sodium chloride solutions from the peritoneal cavity as compared to hypertonic sodium chloride and high molecular weight solutions. When comparing the remaining intraperitoneal volumes at 6 h, the differences were statistically significant for both 5-fluorouracil and gemcitabine when hetastarch (P < 0.0001 and P = 0.0004) and icodextrin (P = 0.002 and 0.008) were compared with isotonic sodium chloride solution. Similarly, there was a significant difference in the volumes recorded at 6 h when hypotonic (P < 0.0001) and isotonic sodium chloride solutions (P = 0.0002) were compared with hypertonic sodium chloride solution. The concentrations of chemotherapy in the different carrier solutions varied little. The total amount of drug in the peritoneal cavity decreased with all solutions and more quickly with 5-fluorouracil than with gemcitabine. There was a significant difference in the total intraperitoneal 5-fluorouracil between hypotonic and isotonic sodium chloride solutions at 1 h (P = 0.0003) and 3 h (P = 0.0043), as well as between the isotonic and hypertonic sodium chloride solutions at 1 h (P = 0.03) and 3 h (P < 0.0001). Similarly, there was a significant difference in the total peritoneal gemcitabine at 6 h between icodextrin and isotonic sodium chloride solution (P = 0.01) and between hetastarch and isotonic sodium chloride solution (P = 0.05). There were no significant differences in plasma 5-fluorouracil and plasma gemcitabine concentrations obtained with the five solutions. CONCLUSIONS: These findings show that the clearance of 5-fluorouracil and gemcitabine from the peritoneal cavity can be significantly modified by varying the tonicity or the molecular weight of the carrier solution. Peritoneal fluid clearance was slower with hypertonic sodium chloride and high molecular weight solutions and this resulted in a reduced clearance of chemotherapy. By using a high molecular weight carrier solution the exposure of intraperitoneal cancer cells to gemcitabine was prolonged and drug availability at the peritoneal surface was increased. Similarly, by using a hypertonic carrier solution the exposure to 5-fluorouracil was prolonged and drug availability at the peritoneal surface was also increased.

Histopathologic analysis in 46 patients with pseudomyxoma peritonei syndrome: failure versus success with a second-look operation.

Pseudomyxoma peritonei syndrome is a disease characterized by mucinous ascites and mucinous tumor disseminated on peritoneal surfaces; the disease almost always originates from a perforated appendiceal epithelial tumor. Histopathologic assessment of aggressive versus noninvasive character of the mucinous tumor has been shown to have an impact on survival in patients treated with cytoreductive surgery and intraperitoneal chemotherapy. Out of a database of 312 patients having a complete cytoreduction for pseudomyxoma peritonei syndrome, 46 patients (24 male and 22 female) had at least one second-look surgery. Before this review, all 46 of these patients were clinically uniformly categorized with a diagnosis of pseudomyxoma peritonei. Using the criteria described by Ronnett and colleagues, all specimens from the multiple surgical procedures performed on these patients were reviewed and reclassified as disseminated peritoneal adenomucinosis (adenomucinosis), adenomucinosis/mucinous adenocarcinoma (hybrid), or mucinous adenocarcinoma. The review was performed in a blinded fashion by a single pathologist (HY). To facilitate a critical evaluation of these histopathologic assessments, the patients were separated into two groups: (1) 19 patients who had a second-look surgery that was unsuccessful in that they went on to die of their disease or in that they currently have disease progression and a limited survival and (2) 27 patients who had a successful second look and currently continue disease free with a minimum 3-year follow-up period. As a result of this review, 11 of 19 patients with an unsuccessful second look and originally designated pseudomyxoma peritonei were reclassified as hybrid-type malignancy (four patients) or mucinous adenocarcinoma (seven patients). Only two patients were reclassified in the successful second-look group (P =.0005). Transitions from a less aggressive to a more invasive histology from one cytoreduction to the next occurred on 13 occasions in patients whose second-look surgery failed and in one patient with a successful second-look surgery (P <.0001). Seven patients retained a histologic classification of disseminated peritoneal adenomucinosis but went on to die of an aggressive disease process. Clinical assessments suggested that failure of second-look surgery for pseudomyxoma peritonei was associated with a biologically more aggressive disease. Unsuccessful second-look surgery for patients with a clinical diagnosis of pseudomyxoma peritonei tumor was often related to an inaccurate initial histologic classification of appendiceal mucinous tumor. Also, a transition from less to more aggressive histology was frequently seen in patients dying of this disease. Assessment of tumor histology can predict the outcome if a uniform surgical treatment is used in patients with peritoneal dissemination of mucinous epithelial tumors of the appendix.

Pharmacokinetics of intraperitoneal oxaliplatin: experimental studies.

BACKGROUND AND OBJECTIVES: Oxaliplatin is an antineoplastic platinum-based compound which has shown significant activity against advanced colon cancer. For cancers occurring within the abdominal cavity, the advantage of intraperitoneal chemotherapy is the high drug concentration that can be achieved locally with low systemic toxicity. Using a rat model, this study was designed to compare the pharmacokinetics and tissue absorption of intraperitoneal versus intravenous oxaliplatin. METHODS: In the first phase of this study, fifteen Sprague Dawley rats were given a single dose of oxaliplatin then randomized into three groups according to dose and route of delivery (5 mg/kg intravenously, 5 mg/kg intraperitoneally, or 25 mg/kg intraperitoneally). In the second phase, 10 Sprague Dawley rats were given a continuous intraperitoneal perfusion of oxaliplatin (15 mg/kg) and randomized into two groups according to the temperature of the peritoneal perfusate (normothermic vs. hyperthermic). In both phases, peritoneal fluid and blood were sampled using a standardized protocol. At the end of each procedure the animals were sacrificed. Selected tissue samples were taken in the second phase only. For all samples, platinum levels were measured by direct current (d-c) plasma emission spectroscopy. RESULTS: When oxaliplatin was delivered at 5 mg/kg the area under the curve (AUC) of the peritoneal fluid was 15-fold higher with intraperitoneal administration as compared to intravenous administration (P < 0.0001). The AUC ratio (AUC peritoneal fluid/AUC plasma) was 16 (+/- 5):1 for intraperitoneal delivery as opposed to 1:5 (+/- 2) for intravenous delivery (P = 0.0059). The AUC ratio for intraperitoneal oxaliplatin at 25 mg/kg was 17 (+/- 8):1. With the exception of the kidneys and the mesenteric nodes, tissue samples in the hyperthermic group exhibited increased oxaliplatin concentrations. These differences were not significant. For both groups colon tissues had the highest oxaliplatin concentrations. CONCLUSIONS: These experiments demonstrated that the exposure of peritoneal surfaces to oxaliplatin was significantly increased with intraperitoneal administration. Although the differences were not statistically significant, hyperthermia did show a trend toward the enhancement of tissue absorption of oxaliplatin. The high concentration of drug observed in colonic tissues suggests the need for clinical studies to evaluate intraperitoneal oxaliplatin for microscopic residual tumor after surgical resection of colon malignancies.

Multi-targeted antifolate (MTA): pharmacokinetics of intraperitoneal administration in a rat model.

AIMS: LY 231514 or MTA is a multi-targeted antifolate which has been used as an anticancer drug. It is an analogue of folic acid which has shown antitumour activity against various malignancies, particularly mesothelioma and colon cancer. For cancers with peritoneal surfaces extension, the advantage of intraperitoneal chemotherapy over intravenous chemotherapy administration is the high drug concentration that can be achieved locally. Using a rat model, this study was designed to compare the pharmacokinetics and tissue adsorption of intraperitoneal vs intravenous MTA. METHODS: Sprague-Dawley rats were randomized into three groups according to dose and route of delivery of chemotherapy (10 mg/kg: intravenous; 10 mg/kg: intraperitoneal; 100 mg/kg: intraperitoneal). During the course of the experiment, peritoneal fluid and blood were sampled using a standardized protocol. At the end of the 3 hour procedure the rats were sacrificed, all urine was extracted and selected tissue samples were taken. One additional rat was studied over a 6 hour period for each group. The concentration of MTA in all samples was determined by high performance liquid chromatography (HPLC). RESULTS: When MTA was delivered at 10 mg/kg the area under the curve (AUC) of the peritoneal fluid was significantly higher with intraperitoneal administration (10 778 microg/mlxmin) compared to intravenous administration (454 microg/mlxmin) (P<0.0001). This represents a 24-fold increase in exposure for tissues at peritoneal surfaces after intraperitoneal administration. The AUC ratio (AUC peritoneal fluid/AUC plasma) was 40.8 for intraperitoneal delivery as opposed to 0.014 for intravenous delivery (P=0.0063). The AUC ratio for intraperitoneal MTA at 100 mg/kg was 19.2. The half-life of MTA in the peritoneal fluid after intraperitoneal infusion was approximately 2 hours. There was a significant difference in MTA concentration in the mesenteric nodes and the abdominal wall (P=0. 0036 and 0.0017) and in the kidneys (P=0.0122) when intraperitoneal and intravenous administration were compared. Other tissue samples did not demonstrate any difference in drug concentration. CONCLUSION: These experiments demonstrated that the exposure of peritoneal surfaces to MTA is significantly increased with intraperitoneal MTA administration. Due to the high likelihood of microscopic residual disease after resection of intra-abdominal malignancies, clinical studies to evaluate intraperitoneal MTA may be indicated.

Treatment of primary colon cancer with peritoneal carcinomatosis: comparison of concomitant vs. delayed management.

PURPOSE: The initial dissemination of colon cancer occurs through three routes: the lymphatics, the portal blood, and the peritoneal surfaces. Although lymphatic and hematogenous metastases indicate an aggressive disease process, it is possible that dissemination to peritoneal surfaces may be only superficial contamination of the parietal and visceral peritoneum that may be treatable for cure. Unfortunately, surgery may have an adverse impact on peritoneal surface dissemination. Surgical interventions may convert a superficial process into an invasive condition with a greatly reduced prognosis. This study was conducted to test this hypothesis by the use of data prospectively recorded from patients treated for peritoneal carcinomatosis concomitant with resection of the primary colon cancer or treated for carcinomatosis after disease recurrence prompted referral. METHODS: Our first group of patients had definitive treatment of carcinomatosis simultaneous with resection of the primary colon cancer. They had cytoreductive surgery including peritonectomy procedures followed by heated intraoperative intraperitoneal chemotherapy with mitomycin C plus early postoperative intraperitoneal 5-fluorouracil. The comparison group was treated with a colon resection at an outside hospital and then later referred to us with progressive disease for treatment. The major difference between the groups is the timing of the definitive treatment of carcinomatosis. These patients were also studied by use of the completeness of the cytoreduction score and the peritoneal cancer index as prognostic indicators. Survival was the end point for all the analysis. RESULTS: Of 104 patients with peritoneal carcinomatosis from colon or rectal adenocarcinoma, five patients (4.8 percent) had definitive treatment of the peritoneal surface spread of the cancer concomitant with resection of the primary lesion. Median survival for these patients has not been reached and their five-year survival rate is 100 percent. The remainder of the patients (n = 99) were referred for local and regional recurrence after their primary cancer had been removed and there was progression of carcinomatosis. Forty-four patients (42.3 percent) had a complete cytoreduction resulting in a 24-month median survival and a 30 percent five-year survival (P < 0.0001). The other 55 patients (52.9 percent) had an incomplete cytoreduction resulting in a 12-month median survival and a 0 percent five-year survival (P < 0.0001). Patients with a peritoneal cancer index of 10 or less had a 48-month median survival and a 50 percent five-year survival rate. Patients with a peritoneal cancer index between 11 and 20 had a 24-month median survival and a 20 percent five-year survival rate (P < 0.0001). Patients with a peritoneal cancer index of more than 20 had a 12-month median survival and a 0 percent five-year survival (P < 0.0001). CONCLUSIONS: In patients with peritoneal seeding occurring at the time of resection of the primary malignancy, peritonectomy procedures and perioperative intraperitoneal chemotherapy should be performed concomitantly. By use of a quantitative scoring system, the mass of cancer present in the abdomen and pelvis at the time of treatment of carcinomatosis correlated directly with survival. Aggressive treatment of patients with peritoneal carcinomatosis requires consideration in the management of colorectal cancer.

CT in the selection of patients with abdominal or pelvic sarcoma for reoperative surgery.

BACKGROUND: Retroperitoneal or visceral sarcoma may recur with disease limited to the abdomen and pelvis. In this clinical situation, further surgical treatments in an attempt to control the disease may be appropriate. CT is used to help select patients for additional surgical interventions. STUDY DESIGN: Preoperative abdominal and pelvic CT scans of 33 patients with recurrent sarcoma were reviewed retrospectively. All patients underwent reoperative surgery and, when appropriate, perioperative intraperitoneal chemotherapy. Patients were divided into two groups according to survival and disease status: alive with no evidence of disease (n = 7) and alive with disease or dead of disease (n = 26). Twenty-two CT indices were studied retrospectively for each patient and evaluated statistically. RESULTS: The presence of large (greater than 5 cm) tumor volume in 3 of the 13 abdominopelvic regions resulted in a significant difference in the prognosis between the groups of patients. These findings included tumor in the left lower quadrant (p = 0.032), tumor in the pelvis (p = 0.008), and tumor in the distal jejunum (p = 0.032). Two other CT indices that showed a significant difference in survival between the groups were involvement of five abdominopelvic regions or fewer (p = 0.008) and a peritoneal cancer index of 15 or less (p = 0.03). A statistical approach using a tree-structured diagram showed that patients with tumor diameter greater than 5 cm in the pelvis accompanied by tumor involvement of more than one segment of small bowel had a 0% probability of postoperative disease-free survival. In contrast, patients with tumor diameter less than 5 cm in the pelvis on CT had an 86% probability of disease-free survival. CONCLUSIONS: For patients with recurrent sarcoma, selection criteria were generated by a preoperative CT of the abdomen and pelvis. In this disease, CT was a reliable diagnostic test for predicting benefit from further surgical interventions and should be used in the future to help select patients for an aggressive versus a palliative approach.

Pleural extension of mucinous tumor in patients with pseudomyxoma peritonei syndrome.

BACKGROUND: Pseudomyxoma peritonei syndrome is a rare disease arising from perforation of an adenoma of the appendix. The syndrome is characterized by progressive accumulation of mucinous fluid and tumor within the abdomen and pelvis. Although this tumor is only superficially invasive and does not metastasize, it is a fatal disease. Extra-abdominal spread of pseudomyxoma peritonei is a rare occurrence, with few reports in the medical literature. This review focuses on pleural extension of mucinous tumor in patients with pseudomyxoma peritonei syndrome. METHODS: From December 1983 to April 1999, all patients who underwent cytoreductive surgery for pseudomyxoma peritonei syndrome were assessed for pleural involvement at the time of the presentation or follow-up. Clinical information on these patients, including chest computed tomographic scan, was retrospectively reviewed. The mechanisms of extension of mucinous tumor from peritoneal cavity to pleural surface and the results of treatment were of special interest. RESULTS: Twenty-three of 426 patients (5.4%) showed pleural extension of pseudomyxoma peritonei syndrome. In four patients (17%), extension into the chest occurred before cytoreductive surgery. In 18 patients, the pleural space was entered during a subdiaphragmatic peritonectomy; and, in 12 patients, extension of disease from peritoneal to pleural space occurred. In six patients (26%), surgical interventions were required to excise tumor that had invaded the hemidiaphragm; and, in the six other patients (26%), there was a minor penetration during subphrenic peritonectomy, which was closed immediately. Finally, in seven patients (30%), the mechanism of spread was unknown. Twelve patients were treated for pleural thoracotomy. Eight patients had an attempt to completely eradicate pleural mucinous tumor, and five patients are currently disease free in the chest (22%); four of these five had intrapleural cytoreduction plus intrapleural chemotherapy. The median survival for all 23 patients is 55 months. CONCLUSION: Pleural spread of pseudomyxoma peritonei syndrome may be a direct result of cytoreductive surgery and the subphrenic peritonectomy procedure. In some patients, dissecting mucinous tumor may infiltrate through the diaphragm and result in pleural extension. Pleural extension of pseudomyxoma peritonei syndrome carries a poor prognosis. Intrapleural chemotherapy combined with cytoreductive surgery may be of considerable value in treatment and prevention of disease dissemination; it should be considered when pleural extension of mucinous tumor is feared or confirmed at the time of cytoreductive surgery.

Congenital pleuroperitoneal communication in a patient with pseudomyxoma peritonei.

BACKGROUND AND OBJECTIVES: Pseudomyxoma peritonei syndrome is a rare disease arising from a perforated appendiceal adenoma. The syndrome is characterized by progressive accumulation of mucinous ascites and tumor within the peritoneal cavity. Direct extension of pseudomyxoma peritonei to the pleural cavity is uncommon and has been associated with surgical penetration of the diaphragm at the time of cytoreduction. METHODS: We review the case of a patient who presented with mucoid peritoneal and pleural fluid consistent with spontaneous pleural spread of pseudomyxoma peritonei. RESULTS: Surgical exploration confirmed direct pleuroperitoneal communication by macroscopic diaphragmatic fenestration. CONCLUSIONS: This is a rare phenomenon. We outline a therapeutic approach to be applied when pleural involvement is suspected in patients with pseudomyxoma peritonei syndrome.

Pharmacokinetics of intraperitoneal gemcitabine in a rat model.

BACKGROUND: Gemcitabine (2'-2' difluorodeoxycytidine) has been shown to possess a broad spectrum of antitumor activity against various malignancies, particularly pancreatic carcinoma. For cancers occurring within the abdominal cavity, the advantage of intraperitoneal (i.p.) chemotherapy over intravenous (i.v.) chemotherapy is the high drug concentration that can be achieved locally. In addition, the cytotoxic effect of several anticancer agents can be enhanced by hyperthermia. Using a rat model, this study was designed to compare i.p. vs i.v. gemcitabine and to evaluate the effect of hyperthermia on i.p. gemcitabine. METHODS: In the first phase of this study, 18 Sprague Dawley rats were given a single dose of gemcitabine then randomized into three groups according to dose and route of delivery of chemotherapy (12.5 mg/kg--i.v., 12.5 mg/kg--i.p. or 125 mg/kg--i.p.). In a separate experiment (phase 2), 12 Sprague Dawley rats were given a continuous i.p. perfusion of gemcitabine (12.5 mg/kg in 150 mL total perfusate) and randomized into two groups according to the temperature of the peritoneal perfusate (normothermic or hyperthermic). During the course of both experiments, peritoneal fluid and blood were sampled using a standardized protocol. At the end of the procedure the rats were sacrificed and all urine was extracted. Selected tissue samples were taken from rats in the second phase of the study. The concentration of gemcitabine in all samples was determined by high performance liquid chromatography (HPLC). RESULTS: When gemcitabine was delivered at 12.5 mg/kg (phase 1) the area under the curve (AUC) was significantly higher with i.p. administration as compared to i.v. administration (P = 0.001). The AUC ratio (AUC peritoneal fluid/AUC plasma) was 12.5+/-3.2 for i.p. delivery as opposed to 0.2+/-0.2 for i.v. delivery (P = 0.0002). The AUC ratio for i.p. gemcitabine at 125 mg/kg was 26.8+/-5.8. Although there was no significant difference in drug concentrations between samples from the normothermic and hyperthermic groups, all tissue samples (except stomach) in the hyperthermic group exhibited increased gemcitabine concentrations. CONCLUSION: These experiments demonstrated that the exposure of peritoneal surfaces to gemcitabine is significantly increased with i.p. gemcitabine. Intraabdominal hyperthermia had no significant effect on the pharmacokinetics of i.p. gemcitabine but there was evidence of increased absorption of gemcitabine in most intraabdominal tissues. Due to the likelihood of a high incidence of microscopic residual disease after resection of a pancreatic carcinoma, clinical studies to evaluate i.p. hyperthermic gemcitabine may be indicated.