Search PubMed⌕ Search

Biomedical subjects

Paul H Sugarbaker

Publications and source records attributed to Paul H Sugarbaker.

At least 19 recordsLinked to original sources
PubMed2007

Perioperative outcomes of cytoreductive surgery and perioperative intraperitoneal chemotherapy for non-appendiceal peritoneal carcinomatosis from a prospective database.

BACKGROUND: Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy has expanded its application in the management of peritoneal carcinomatosis from gastrointestinal and ovarian malignancies. An accurate assessment of perioperative outcomes is crucial for integration of this combined procedure into clinical practice. METHODS: A prospective study of 80 patients undergoing the combined treatment for non-appendiceal peritoneal carcinomatosis was conducted. Forty-seven adverse events by eight organ-systems were rated from Grade I to IV with increasing severity. RESULTS: One patient (1.3%) died postoperatively. Postoperative adverse events affected genitourinary system (38%), hematological system (31%), gastrointestinal system (25%), infection (20%), intravenous catheters status (15%), pulmonary system (14%), cardiovascular system (11%) and neurological system (4%). Thirty-six patients (45%) experienced 49 Grade III adverse events. Six patients (8%) experienced eight Grade IV adverse events. More than four peritonectomy procedures (P = 0.010), and length of hospital stay of more than 21 days (P = 0.007) were strongly associated with Grade III and/or Grade IV morbidity. CONCLUSION: The morbidity and mortality rates after the combined treatment for non-appendiceal peritoneal carcinomatosis were within the acceptable range of surgical treatments for other gastrointestinal cancers. A standardized prospective database is required for an accurate assessment of perioperative outcomes.

Carcinoma↗
PubMed2006

Pharmacokinetic and phase II study of heated intraoperative intraperitoneal melphalan.

BACKGROUND: Peritoneal surface malignancy resulting from local dissemination is a common manifestation of treatment failure of gastrointestinal cancers. Although the management of carcinomatosis has been improved with an aggressive surgical approach of extensive cytoreduction followed by heated intraoperative intraperitoneal chemotherapy, no patients are cured when there is residual disease after surgery. Melphalan (L-phenylalanine mustard) is a well-known antineoplastic alkylating agent which has markedly increased pharmacological activity with heat. The use of heated intraoperative intraperitoneal melphalan may provide a pharmacokinetic and clinical advantage in this group of gastrointestinal cancer patients who cannot be made cancer-free with cytoreductive surgery. METHODS: Thirteen patients with residual disease following cytoreductive surgery for peritoneal carcinomatosis were included in this study. After surgical resection and prior to anastomotic reconstruction, patients received intraperitoneal melphalan (70 mg/m2) in 3 l of 1.5% dextrose peritoneal dialysis solution at 41-42 degrees C for 90 min. Concentrations of melphalan were assessed in the peritoneal fluid, blood, urine and tumor nodules using high-performance liquid chromatography. RESULTS: During the 90 min of treatment 87.2 +/- 4.3% of the drug was absorbed from the perfusate/peritoneal fluid and 11.9 +/- 2.1% was excreted in the urine. The area-under-the-curve ratio of peritoneal fluid to plasma was 33.3 +/- 11.8 with an average peak plasma concentration of 0.82 +/- 0.24 microg/ml occurring at 28.5 +/- 13.1 min. Concentrations of melphalan in tumor nodules on the peritoneal surface were approximately ten times higher than in plasma with an average peak concentration of 7.2 +/- 4.2 microg/gm. The grade III/IV morbidity was 38%; there was no mortality. CONCLUSION: Approximately 90% of the drug was absorbed during the 90-minute procedure with a 30 times greater exposure of drug at the peritoneal surfaces than in the blood. Concentrations of the drug in peritoneal surface tumor nodules were approximately ten times greater than concentrations in the blood. These data demonstrate that heated intraoperative intraperitoneal melphalan could have a significant impact on the treatment of peritoneal surface malignancies.

Adult↗
PubMed2006

Analysis of prognostic factors in seventy patients having a complete cytoreduction plus perioperative intraperitoneal chemotherapy for carcinomatosis from colorectal cancer.

BACKGROUND: Although lymph node and liver metastases are recognized as indications for resection of metastatic disease from colorectal cancer, carcinomatosis has not traditionally been regarded as having surgical treatment options. Reports have suggested that complete surgical removal of carcinomatosis combined with thorough irrigation of the peritoneal cavity with chemotherapy could result in longterm survival in selected patients. Proper selection factors are important because palliative surgery in these patients has not proved beneficial. STUDY DESIGN: From a database of 156 patients with carcinomatosis from colorectal cancer, a retrospective analysis of data prospectively recorded in 70 patients with complete cytoreduction was performed. Eleven clinical and treatment factors were studied in univariate and multivariable analyses using survival as an end point. RESULTS: By univariate analysis, patients with peritoneal cancer index (PCI) of<20 had a median survival of 41 months compared with 16 months for patients with PCI>20 (p=0.004). The difference in negative versus positive lymph nodes was also significant; differences in survival that were improved but not significant were present for age greater than 30 years, mucinous histology, location within the colon versus rectum, and absence of an adverse factor such as cancer perforation or obstruction present at the time of primary cancer resection. Only PCI<20 versus PCI>20 and lymph node status were significant in the multivariable analysis. CONCLUSIONS: Favorable longterm results of complete cytoreduction in patients treated for carcinomatosis are associated with a limited volume of carcinomatosis observed at the time of cytoreduction and in patients with negative lymph nodes at the time of primary operation.

Adenocarcinoma↗
PubMed2006

Prognostic indicators for patients undergoing cytoreductive surgery and perioperative intraperitoneal chemotherapy for diffuse malignant peritoneal mesothelioma.

BACKGROUND: This study evaluates clinical, radiological and histopathological prognostic indicators for survival of patients undergoing cytoreductive surgery and perioperative intraperitoneal chemotherapy for diffuse malignant peritoneal mesothelioma (DMPM). METHODS: Sixty-two consecutive patients with DMPM underwent cytoreduction and perioperative intraperitoneal chemotherapy at the Washington Cancer Institute. Twenty-six clinical, radiological and histopathological parameters were analyzed in univariate and multivariate analyses using overall survival as an endpoint. RESULTS: The overall survival was 79 months (range 1-143 months), with 1-, 3- and 5-year survival rates of 84%, 58% and 50%, respectively. The following 14 prognostic variables were significant for survival in the univariate analysis: gender (P = .045), peritoneal cancer index (P = .038), completeness of cytoreduction score (P = .010), interpretive CT findings of the small bowel and mesentery (P = .001), mesothelioma cell type (P < .001), mesothelioma nuclear size (P < .001), nuclear/cytoplasmic ratio (P < .001), mitotic count (P < .001), atypical mitosis (P < .001), chromatin pattern (P < .001), cellular necrosis (P < .001), perineural invasion (P = .037), stroma pattern (P < .001) and depth of invasion (P = .014). In the multivariate analysis, the only factor that was independently associated with an improved survival after cytoreduction and perioperative intraperitoneal chemotherapy was mesothelioma nuclear size. CONCLUSIONS: Mesothelioma nuclear size was the dominant factor determining overall survival in patients with DMPM. A histopathological staging system based on measurement of the nuclear size was proposed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

A systematic review on the efficacy of cytoreductive surgery and perioperative intraperitoneal chemotherapy for pseudomyxoma peritonei.

BACKGROUND: The efficacy of cytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) for patients with pseudomyxoma peritonei (PMP) remains to be established. METHODS: Searches for all relevant studies prior to March 2006 were performed on six databases. Two reviewers independently appraised each study using a predetermined protocol. The quality of each study was assessed. Clinical effectiveness was synthesized through a narrative review with full tabulation of results of all included studies. RESULTS: Ten most recent updates from each institution were included for appraisal and data extraction. There were no randomized controlled trials or comparative studies. All included articles were observational studies without control groups. Five studies were relatively large series (n>or=100). Two studies had relatively long-term follow-up (48 months and 52 months). The median follow-up in the remaining eight studies was shorter than 3 years (range 19-35 months). The median survival ranged from 51 to 156 months. The 1-, 2-, 3- and 5-year survival rates varied from 80 to 100%, 76 to 96%, 59 to 96% and 52 to 96%, respectively. The overall morbidity rate varied from 33 to 56%. The overall mortality rates ranged from 0 to 18%. CONCLUSIONS: This study reviewed current evidence on CRS and PIC for PMP. Only observational studies were available for evaluation, which demonstrated some promising long-term results, as compared to historical controls. Due to the rarity of this disease, a well-designed prospective multi-institutional study would be meaningful.

Antineoplastic Agents↗
PubMed2006

Morbidity and mortality assessment of cytoreductive surgery and perioperative intraperitoneal chemotherapy for diffuse malignant peritoneal mesothelioma--a prospective study of 70 consecutive cases.

BACKGROUND: Although many reports regarding morbidity and mortality of cytoreductive surgery plus perioperative intraperitoneal chemotherapy are available, there are no prospective data on morbidity and mortality limited to patients with diffuse malignant peritoneal mesothelioma (DMPM). METHODS: This prospective morbidity and mortality assessment was performed on 70 consecutive cytoreductive procedures with perioperative intraperitoneal chemotherapy for DMPM. Forty-seven adverse events by eight categories were rated from grades I to IV with increasing severity. Grade I morbidity was self-limiting; grade II required medical treatments; grade III required an invasive intervention; grade IV required returning to the operating room or intensive care management. Risk factors for grades III and IV morbidity were determined. RESULTS: The perioperative mortality rate was 3%. The grades III and IV morbidity rates were 27 and 14%, respectively. Primary colonic anastomosis (P = 0.028), more than four peritonectomy procedures (P = 0.015), duration of the operation of more than 7 h (P = 0.027) were the risk factors for grade IV morbidity. Survival analysis of these 70 patients was provided. CONCLUSIONS: The morbidity and mortality results for cytoreductive surgery and perioperative intraperitoneal chemotherapy for patients with DMPM were within the acceptable range for major gastrointestinal surgery. Grade IV morbidity was associated with more extensive cytoreduction.

Adult↗
PubMed2006

Systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal carcinoma.

PURPOSE: The efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for patients with peritoneal carcinomatosis from colorectal carcinoma remains to be established. METHODS: A systematic review of relevant studies before March 2006 was performed. Two reviewers independently appraised each study using a predetermined protocol. The quality of studies was assessed. Clinical effectiveness was synthesized through a narrative review with full tabulation of results of all included studies. RESULTS: Two randomized controlled trials, one comparative study, one multi-institutional registry study, and 10 most recent case-series studies were evaluated. The level of evidence was low in 13 of the 14 eligible studies. The median survival varied from 13 to 29 months, and 5-year survival rates ranged from 11% to 19%. Patients who received complete cytoreduction benefited most, with median survival varying from 28 to 60 months and 5-year survival ranging from 22% to 49%. The overall morbidity rate varied from 23% to 44%, and the mortality rate ranged from 0% to 12%. CONCLUSION: The current evidence suggests that cytoreductive surgery combined with perioperative intraperitoneal chemotherapy is associated with an improved survival, as compared with systemic chemotherapy for peritoneal carcinomatosis from colorectal carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Optimizing the factors which modify thermal enhancement of melphalan in a spontaneous murine tumor.

BACKGROUND: Hyperthermia enhances the cytotoxicity of some chemotherapeutic agents. Both clinical and laboratory studies suggest melphalan may be an important drug when hyperthermia is added to chemotherapy treatments. Factors that may modify the thermal enhancement of melphalan were studied to optimize its clinical use with hyperthermia. METHODS: The tumor studied was an early-generation isotransplant of a spontaneous C3Hf/Sed mouse fibrosarcoma, Fsa-II. All studies were performed under supervision of the Animal Care and Use Committee. Hyperthermia was administered by immersing the tumor-bearing foot into a constant temperature water bath. Four factors were studied: duration of hyperthermia, sequencing of hyperthermia and melphalan, intensity of hyperthermia, and tumor size. To study duration of hyperthermia tumors were treated at 41.5 degrees C for 30 or 90 min immediately after intraperitoneal administration of melphalan. For sequencing of hyperthermia and melphalan, animals received hyperthermia treatment of tumors for 30 min at 41.5 degrees C immediately after drug administration, both immediately and 3 h after administration of drug or only at 3 h after administration of drug. Intensity of hyperthermia was studied using heat treatment of tumors for 30 min at 41.5 or 43.5 degrees C immediately following drug administration. Effect of tumor size was studied by delaying experiments until three times the tumor volume (113 mm3) was observed. Treatment of tumors was for 30 min at 41.5 degrees C immediately following drug administration. Tumor response was studied by the mean tumor growth time. RESULTS: Hyperthermia in the absence of melphalan had a small but significant effect on tumor growth time at 43.5 degrees C but not at 41.5 degrees C. Hyperthermia at 41.5 degrees C immediately after melphalan administration doubled mean tumor growth time at 30 min and caused a threefold increase at 90 min (P=0.0002) when compared to tumors treated with melphalan alone at room temperature. Application of hyperthermia for one-half hour immediately following drug administration was the most effective in delaying tumor growth. No significant difference in mean tumor growth time was observed with an increase in temperature from 41.5 to 43.5 degrees C. For large tumors heat alone and melphalan alone caused a moderate increase in tumor growth delay. These effects in large tumors were greatly increased by a combination of chemotherapy and hyperthermia. CONCLUSIONS: From our data it would appear that the administration of intraperitoneal melphalan immediately prior to 90 min of heat at 41.5 degrees C may optimize anti-neoplastic activity. These data may be useful in formulating clinical protocols in which melphalan and heat are combined.

Animals↗
PubMed2006

Perioperative intraperitoneal chemotherapy for peritoneal surface malignancy.

The treatment of peritoneal surface malignancy mainly focuses on diffuse malignant peritoneal mesothelioma, pseudomyxoma peritonei from appendiceal cancer, and peritoneal dissemination from gastrointestinal and ovarian cancers. Cancer progression causes peritoneal implants to be distributed throughout the abdominopelvic cavity. These nodules plus the ascitic fluid result in abdominal distension. As the disease progresses, these tumors cause intestinal obstruction leading to debilitating symptoms and a greatly impaired quality of life. In the past, the prognosis of patients with peritoneal surface malignancy was regarded dismal and cure was not an option. Recently, cytoreductive surgery combined with perioperative intraperitoneal chemotherapy has shown an improved survival in selected patients with this disease. To date, multiple different treatment regimens of perioperative intraperitoneal chemotherapy have been used. This review focuses on the perioperative intraperitoneal chemotherapy currently in use in conjunction with cytoreductive surgery for the treatment of peritoneal surface malignancy at the Washington Cancer Institute.

Journal Article↗
PubMed2006

Prospective morbidity and mortality assessment of cytoreductive surgery plus perioperative intraperitoneal chemotherapy to treat peritoneal dissemination of appendiceal mucinous malignancy.

BACKGROUND: Appendiceal mucinous neoplasms present, in most patients, with peritoneal dissemination at the time of initial diagnosis. Patients may have a borderline tumor showing disseminated peritoneal adenomucinosis or an aggressive malignancy identified as peritoneal mucinous adenocarcinoma. Patients with these diagnoses were treated by cytoreductive surgery and perioperative intraperitoneal chemotherapy. METHODS: A database was established in 1998 that prospectively evaluated the morbidity and mortality of this group of patients. By using common toxicity grading criteria, 8 categories were scored on a grade of I to V. Grade IV indicated that the adverse event required urgent and definitive intervention: often a return to the operating room or to the surgical intensive care unit. Grade V indicated that the adverse events resulted in the patient's death. Adverse events were tabulated for each cytoreduction performed in these appendiceal malignancy patients. RESULTS: There were 356 procedures in patients taken to the operating room who received cytoreductive surgery with peritonectomy procedures plus heated intraoperative intraperitoneal chemotherapy. Only patients who had this combined treatment at our institution were included in the analysis. The total 30-day or in-hospital mortality was 2.0%. Nineteen percent of procedures were accompanied by at least one grade IV adverse event, and 11.1% of patients returned to the operating room. The most common category of grade IV complications was hematological (28%), followed by gastrointestinal (26%). CONCLUSIONS: The mortality of 2.0% and the overall grade IV morbidity of 19% in these patients may be acceptable in light of modern standards for the management of gastrointestinal cancer.

Adenocarcinoma, Mucinous↗
PubMed2006

Hybrid ileostomy.

Explore the source record for details and available documents.

Anastomosis, Surgical↗
PubMed2006

New standard of care for appendiceal epithelial neoplasms and pseudomyxoma peritonei syndrome?

Appendiceal mucinous neoplasms sometimes present with peritoneal dissemination, which was previously a lethal condition with a median survival of about 3 years. Traditionally, surgical treatment consisted of debulking that was repeated until no further benefit could be achieved; systemic chemotherapy was sometimes used as a palliative option. Now, visible disease tends to be removed through visceral resections and peritonectomy. To avoid entrapment of tumour cells at operative sites and to destroy small residual mucinous tumour nodules, cytoreductive surgery is combined with intraperitoneal chemotherapy with mitomycin at 42 degrees C. Fluorouracil is then given postoperatively for 5 days. If the mucinous neoplasm is minimally invasive and cytoreduction complete, these treatments result in a 20-year survival of 70%. In the absence of a phase III study, this new combined treatment should be regarded as the standard of care for epithelial appendiceal neoplasms and pseudomyxoma peritonei syndrome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Prognostic significance of histomorphologic parameters in diffuse malignant peritoneal mesothelioma.

CONTEXT: Diffuse malignant peritoneal mesothelioma is currently regarded as a rare and lethal primary tumor arising from the peritoneal membrane. In the past, treatment plans with variable combinations of surgery and systemic chemotherapy were associated with a median survival of approximately 1 year. Standardized treatments using cytoreductive surgery and perioperative intraperitoneal chemotherapy have extended this survival. OBJECTIVE: To critically analyze the prognostic significance of histomorphologic parameters as a determinant of survival. DESIGN: Sixty-two consecutive patients with diffuse malignant peritoneal mesothelioma in whom data were prospectively accumulated were retrospectively analyzed by 14 different histomorphologic parameters. The influences of these pathologic characteristics on survival were critically statistically evaluated. RESULTS: In a univariate analysis, histologic type, nuclear/nucleolar size, stroma, depth of invasion into the bowel, atypical mitoses, mitotic index, necrosis, lymph node involvement, and chromatin patterns were found to be significant. In the multivariate analysis, histologic type and nuclear/nucleolar size remained as determinant histomorphologic characteristics. Use of biphasic/sarcomatoid histologic type as a poor prognostic characteristic was limited in that only 8% of patients showed this histology. CONCLUSIONS: Histomorphologic parameters carry prognostic significance in predicting the survival of patients with diffuse malignant peritoneal mesothelioma when treated in a standardized fashion using cytoreductive surgery and perioperative intraperitoneal chemotherapy. Nuclear/nucleolar size was found to be a reliable histomorphologic assessment available to assess prognosis in these patients.

Cell Nucleolus↗
PubMed2006

[The results of surgical treatment for pseudomyxoma peritonei].

The surgical results of 37 patients with pseudomyxoma pertonei are reported. Twenty eight patients received laparotomy and complete cytoreduction (CC-0) could be done in 6 patients. However, 13 patients received incomplete cytoreduction, and 9 patients underwent drainage of ascites and peritoneal washing. The Peritoneal Carcinomatosis Index (PCI) was less than 20 in CC-0 patients. CC-0 patients survived significantly better than patients with residual disease. Accordingly, peritoneal washing to remove free cancer cells should be aimed for complete cytoreduction of the solid mucinous nodules.

Adult↗