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P H Sugarbaker

Publications and source records attributed to P H Sugarbaker.

At least 19 recordsLinked to original sources
PubMed2001

Patients with pseudomyxoma peritonei associated with disseminated peritoneal adenomucinosis have a significantly more favorable prognosis than patients with peritoneal mucinous carcinomatosis.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a poorly understood condition characterized by disseminated intraperitoneal mucinous tumors, often with mucinous ascites. The term PMP has been applied historically as a pathologic diagnostic term to both benign and malignant mucinous neoplasms that produce abundant extracellular mucin, resulting in a variable and poorly predictable prognosis. A recent study reported a pathologic classification that separated patients into prognostically distinct groups, but the follow-up was relatively short. METHODS: Long-term follow-up data were analyzed for a previously reported series of 109 patients with PMP to examine the prognostic utility of a pathologic classification system that divided patients into three groups: disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and peritoneal mucinous carcinomatosis with intermediate or discordant features (PMCA-I/D). Patients whose tumors were classified 25 DPAM (n = 65 patients) had disease that was characterized by histologically bland to low-grade adenomatous mucinous epithelium associated with abundant extracellular mucin and fibrosis, often with an identifiable appendiceal mucinous adenoma that was the source of the peritoneal lesions. Patients whose tumors were classified 25 PMCA (n = 30 patients) had disease that was characterized by peritoneal lesions that displayed the cytologic and architectural features of mucinous carcinoma associated with extracellular mucin, often with an identifiable invasive mucinous adenocarcinoma of the gastrointestinal tract. Patients whose tumors were classified 25 PMCA-I (n = 11 patients) had peritoneal lesions that combined the features of DPAM and PMCA derived from well differentiated mucinous adenocarcinomas associated with adenomas. Patients whose tumors were classified 25 PMCA-D (n = 3 patients) had markedly atypical appendiceal adenomas associated with peritoneal lesions similar to PMCA. RESULTS: Patients with DPAM had 5-year and 10-year survival rates of 75% and 68%, respectively (mean follow-up, 96 months; median follow-up, 104 months). Patients with PMCA and PMCA-I/D had a significantly worse prognosis, with 5-year and 10-year survival rates, respectively, of 50% and 21% for PMCA-I/D (mean follow-up, 58 months; median follow-up, 51 months) and 14% and 3% for PMCA (mean follow-up, 27 months; median follow-up, 16 months; P = 0.0001). CONCLUSIONS: The term PMP should be used only as a clinical descriptor for patients who have the syndrome of mucinous ascites accompanied by a characteristic distribution of peritoneal mucinous tumors with the pathologic features of DPAM. DPAM should be used as a pathologic diagnostic term for patients with the bland peritoneal mucinous tumors associated with ruptured appendiceal mucinous adenomas and PMP. These patients should not be diagnosed with carcinoma, because they have disease that is distinct pathologically and prognostically from PMCA.

Adenocarcinoma, Mucinous↗
PubMed2001

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.

Animals↗
PubMed2001

Indications for early postoperative intraperitoneal chemotherapy of advanced gastric cancer: results of a prospective randomized trial.

Previous analysis of this prospective randomized trial and meta-analysis of published randomized trials of adjuvant intraperitoneal chemotherapy demonstrated improved survival in patients with advanced gastric cancer. Simple criteria applicable at the time of surgery for patient selection were sought in this analysis. From 1990 to 1995 a series of 248 patients with biopsy-proven gastric cancer were randomized intraoperatively to receive early postoperative intraperitoneal mitomycin C and 5-fluorouracil (125 patients) versus surgery only (123 patients). Gastric resection plus early postoperative intraperitoneal chemotherapy showed improved overall survival compared to surgery only (54% and 38%, respectively; p = 0.0278). There were statistically significant differences in patients with stage III (57% and 23%, respectively; p = 0.0024) and in those with stage IV (28% and 5%, respectively; p = 0.0098) gastric cancer. The improvement in survival rate was statistically significant for the subgroup of patients with gross serosal invasion (52% and 25%, respectively; p = 0.0004) and patients with lymph node metastasis (46% and 22%, respectively; p = 0.0027). The surgeons' impression about lymph node status was unreliable, but assessment of serosal invasion was accurate in 80% of cases. Gross serosal invasion with or without frozen section evaluation of lymph nodes can be used as the major selection criteria for early postoperative intraperitoneal chemotherapy of advanced gastric cancer.

Antibiotics, Antineoplastic↗
PubMed2001

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.

Animals↗
PubMed2001

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.

Adenocarcinoma, Mucinous↗
PubMed2001

Pedunculated peritoneal surface polyps in pseudomyxoma peritonei syndrome.

AIMS: Pseudomyxoma peritonei syndrome is a rare disease that originates from an adenomatous lesion of the appendix that, from pressure, perforates to gain access to the free peritoneal cavity. The relative sparing of the small bowel surfaces allows for complete cytoreduction even though many kilograms of mucinous tumour exist at other sites within the abdomen and pelvis. The purpose of this study was to examine the mechanism whereby the small bowel remains free of gross tumour and peritoneal surface polyps form. METHODS AND RESULTS: Peritoneal surface polyps were harvested and examined grossly and histologically. A hypothesis for their formation on small bowel and small bowel mesentery was proposed. Polyps are known to be associated with repeated motion of enteric contents moving past adenomatous tissue so that, over time, an elongated stalk is created. We have repeatedly observed pedunculated polyps on the peritoneal surface of the small bowel in patients with pseudomyxoma peritonei syndrome. No other site within the peritoneal cavity has had a pseudomyxoma polyp located upon its surface. CONCLUSIONS: The peristaltic motion of the small bowel causes adherent adenomatous tissue to develop a stalk on the peritoneal surface. Motion not only creates polypoid lesions but also repeatedly clears mucinous tumour cells from the small bowel surface. With pseudomyxoma peritonei and with other types of cancerous dissemination, prevention of adherence by motion may interfere with the implantation of malignant cells.

Biomarkers↗
PubMed2001

Pseudomyxoma peritonei in a hernia sac: analysis of 20 patients in whom mucoid fluid was found during a hernia repair.

INTRODUCTION: Pseudomyxoma peritonei syndrome is a rare disease that causes extensive accumulation of non-invasive mucinous tumour and mucinous fluid throughout the abdomen and pelvis. The primary tumour is a perforated appendiceal adenoma or mucinous adenocarcinoma. In patients with an open processus vaginalis or other peritoneal defect, the adenomatous epithelial cells may accumulate within the hernia sac, causing mucoid fluid to be present at the time of hernia repair. MATERIALS AND METHODS: From February 1991 to September 1997, the diagnosis of pseudomyxoma peritonei syndrome was established in 20 patients in whom mucoid material was found in a hernia sac during a hernia repair. Clinical features of these patients were critically evaluated using the completeness of cytoreduction as an endpoint. RESULTS: The treatments delivered at the time of hernia repair had no impact on the outcome. A lack of interim events vs the use of interim treatments between hernia repair and definitive cytoreduction was significant in relation to a complete vs incomplete cytoreduction. Non-aggressive histology and an interval of less than 1 year was statistically significantly associated with a favourable outcome from surgical intervention. CONCLUSION: When mucoid fluid is encountered at the time of a hernia repair, recovery of that fluid and the hernia sac for histologic study is important. When adenomatous epithelial cells are present, a CT scan should be performed to look for the typical distribution of mucinous tumour and fluid that suggests the pseudomyxoma peritonei syndrome. If the diagnosis can be confirmed, referral to a centre experienced in the treatment of this rare disease is suggested.

Adenoma↗
PubMed2001

Cytoreductive surgery and peri-operative intraperitoneal chemotherapy as a curative approach to pseudomyxoma peritonei syndrome.

Peritoneal carcinomatosis, regardless of primary tumour type, has always been a lethal condition. Recently special treatments using cytoreductive surgery with peritonectomy procedures combined with peri-operative intraperitoneal chemotherapy have resulted in long-term survival. Pseudomyxoma peritonei may be especially appropriate for these aggressive local regional treatments. All patients treated prior to 1999 are presented; patients left with gross residual disease after surgery were not given intraperitoneal chemotherapy, but were later treated with intravenous chemotherapy after cytoreduction. The intraperitoneal chemotherapy was given in the peri-operative period, starting with mitomycin C. For patients whose pathology showed adenomucinosis, intraperitoneal chemotherapy was limited to treatment in the operating theatre with heated mitomycin C. Patients with mucinous adenocarcinoma or pseudomyxoma/adenocarcinoma hybrid had, in addition to mitomycin C, 5 consecutive days of intraperitoneal 5-fluorouracil. A complete cytoreduction was defined as tumour nodules <2.5 mm in diameter remaining after surgery. The histopathology categorized the patients as adenomucinosis, intermediate type, or mucinous carcinomatosis. A prior surgical score was used to estimate the extent of previous surgical procedures. The morbidity of treated patients was 27% and the mortality was 2.7%. In a multivariate analysis, prognostic factors for survival included the completeness of cytoreduction (P<0.0001), the histopathological character of the appendix malignancy (P<0.001) and the extent of previous surgical interventions (P=0.001). Patients with a complete cytoreduction and adenomucinosis by pathology had a 5-year survival of 86%; while hybrid pathology survival at 5 years was 50%. Incomplete cytoreduction had a 5-year survival of 20% and 0% at 10 years. Cytoreductive surgery and peri-operative intraperitoneal chemotherapy is the current standard treatment for selected patients with peritoneal surface spread of appendiceal primary tumours. Similar strategies for other patients with peritoneal surface malignancy such as peritoneal carcinomatosis from colon or gastric cancer, peritoneal sarcomatosis, or peritoneal mesothelioma should be pursued.

Adult↗
PubMed2001

Molecular genetic analysis of appendiceal mucinous adenomas in identical twins, including one with pseudomyxoma peritonei.

Pseudomyxoma peritonei (PMP) is a clinical syndrome characterized by mucinous ascites and peritoneal lesions composed of histologically bland to low-grade adenomatous mucinous epithelium within pools of extracellular mucin, often with an associated mucinous adenoma of the appendix. There is evidence that the peritoneal lesions in PMP are clonally derived from the associated appendiceal adenoma. Little is known about the molecular genetic alterations or hereditary factors involved in the development of appendiceal mucinous tumors and PMP. We report the only known example of appendiceal mucinous adenomas in identical twin brothers, one of whom developed PMP. We analyzed the status of the K-RAS and APC genes in these tumors using digital polymerase chain reaction and digital single nucleotide polymorphism (SNP) assay. Identical K-RAS mutations were detected in the appendiceal adenoma and peritoneal tumor from the twin with PMP, whereas the adenoma from the other twin harbored a different mutation. Digital SNP analysis demonstrated loss of heterozygosity of APC only in the adenoma from the twin without PMP but not from the appendiceal or peritoneal tumors of the twin with PMP. The adjacent normal tissue in each case retained both APC alleles. The K-RAS mutational analysis supports the view that PMP is clonally derived from the associated appendiceal mucinous adenoma. The lack of loss of heterozygosity of APC in the adenoma and peritoneal tumor from the twin with PMP suggests that loss of heterozygosity of APC is not necessarily involved in the development of all appendiceal adenomas or PMP. The different types of mutations in K-RAS and the different allelic status of the APC locus in the tumors from both twins suggest that mutation in K-RAS and loss of heterozygosity of APC occurs somatically in adenomas and is independent of the identical genetic background of the twins.

Adult↗
PubMed2001

Second-look surgery in patients with peritoneal dissemination from appendiceal malignancy: analysis of prognostic factors in 98 patients.

OBJECTIVE: To establish selection criteria for reoperation in patients with peritoneal dissemination from appendiceal malignancy. SUMMARY BACKGROUND DATA: The outcome of patients with mucinous appendiceal neoplasms with peritoneal surface dissemination has changed as a result of a better understanding of the clinical and pathologic features of this disease. This knowledge, combined with aggressive strategies for the use of perioperative intraperitoneal chemotherapy and peritonectomy procedures, has resulted in long-term disease-free survival in many of these patients. However, some of the patients develop progressive disease, and a question regarding additional surgery is appropriate. A critical analysis of the results of second-look surgery should assist in the management of patients with recurrent peritoneal surface dissemination of an appendiceal neoplasm. METHODS: Three hundred twenty-one patients with epithelial peritoneal surface malignancy of appendiceal origin underwent surgery during a 12-year period. Ninety-eight of these patients (30.5%) underwent a second-look procedure. A database of selected clinical features regarding these 98 patients was gathered from the clinical records. A critical statistical analysis of these clinical features and their prognostic impact was performed using survival as an endpoint. All patients were managed by a treatment regimen that used cytoreductive surgery and intraperitoneal chemotherapy. RESULTS: The overall 5-year survival rate of these 98 patients was 73.6%. This compared favorably with a 68% survival rate of 223 patients who did not undergo reoperation. Survival based on the number of cytoreductive surgeries and the free interval between them showed no significant difference. Patients who had second-look surgery with bowel obstruction as a symptom and those in whom the amount of tumor was increased or minimally decreased at the first and second cytoreductions had a significantly inferior 5-year survival rate. A complete second cytoreduction was associated with an improved 5-year survival rate. CONCLUSIONS: Follow-up of patients treated for peritoneal dissemination from neoplasms of appendiceal origin is indicated. Selected patients in whom recurrence develops are candidates for repeat cytoreductive surgery plus intraperitoneal chemotherapy with curative intent.

Adenocarcinoma, Mucinous↗
PubMed2000

Early localized peritoneal mesothelioma as an incidental finding at laparoscopy. Report of a case and implications regarding natural history of the disease.

BACKGROUND: Peritoneal mesothelioma is regarded as a fatal disease that presents with progressive ascites in a relatively late stage of its natural history. To the authors' knowledge, prior published articles have not described the early manifestations of this cancer. METHODS: A 30-year-old asymptomatic woman underwent laparoscopy for an infertility workup. Nodules noted in the pelvis were biopsied and determined to be mesothelioma. Standard immunohistochemical studies were performed. Cytoreductive surgery and heated intraoperative intraperitoneal chemotherapy were used for treatment. RESULTS: Multiple (approximately 30) tumor nodules up to 2 mm in dimension and limited to the pelvis were observed and resected. No primary tumor focus was evident. These tumor nodules stained positive for Calretinin and negative for carcinoembryonic antigen immunohistochemically. CONCLUSIONS: In this patient, no incidence for transcoelomic dissemination of mesothelioma from a single primary site was observed. Rather, this patient's clinical presentation suggested that mesothelioma may be multifocal in origin within a limited region of the peritoneal cavity. This hypothesis may support a rationale for aggressive local-regional management of selected patients in whom peritoneal mesothelioma is of limited distribution and mass.

Adult↗
PubMed2000

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.

Female↗