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J N Vauthey

Publications and source records attributed to J N Vauthey.

At least 19 recordsLinked to original sources
PubMed2002

Limitations of conventional doses of chemoradiation for unresectable biliary cancer.

PURPOSE: To determine, in a retrospective review, the limitations of definitive chemoradiation in the treatment of patients with unresectable extrahepatic cholangiocarcinoma and generate testable hypotheses for future prospective clinical trials. METHODS AND MATERIALS: Between 1957 and 2000, 52 patients with localized, unresectable cholangiocarcinoma were treated with radiotherapy (RT) with or without concurrent chemotherapy. Unresectable disease was defined, by evidence on imaging studies or at surgical exploration, as localized tumor abutting or involving the main portal vein, tumor involvement of secondary biliary radicals, or evidence of nodal metastases. Patients were grouped according to the RT dose: 27 patients received a total dose of 30 Gy (Group 1), 14 patients received 36-50.4 Gy (Group 2), and 11 patients received 54-85 Gy (Group 3). 192Ir intracavitary boosts (median 20 Gy) were delivered in 3 patients, and an intraoperative boost (20 Gy) was used in 1 patient. Of the 52 patients, 38 (73%) received concomitant protracted venous infusion of 5-fluorouracil (200-300 mg/m2 daily, Monday through Friday). Kaplan-Meier analysis was used to calculate the actuarial 1-year and median overall survival (OS), radiographic local progression, symptomatic progression, and distant failure. Treatment-related variables and prognostic factors were evaluated using the log-rank test. RESULTS: The first site of disease progression was local in 72% of cases. The actuarial local progression rate at 12 months for all patients was 59%. The median time to radiographic local progression was 9, 11, and 15 months in Groups 1, 2, and 3, respectively (p = 0.48). Fifteen percent of all patients developed metastatic disease (1-year OS rate 18%). The median survival rate for all patients was 10 months (1-year OS rate 44%). The RT dose, use of concurrent chemotherapy, histologic grade, initial extent of liver involvement, and extent of vascular involvement had no influence on radiographic local progression or OS. Grade 3 or greater toxicity was similar in all dose groups (22% vs. 14% vs. 27%, p = 0.718). CONCLUSION: The primary limitation of definitive chemoradiation was local progression. Although the small patient numbers limited the statistical power of this study, a suggestion of improved local control was found with the use of higher RT doses. To address this pattern of failure, future prospective investigation using high-dose conformal RT with novel cytotoxic and/or biologic agents with radiosensitizing properties is warranted.

Adult↗
PubMed2002

Is the therapeutic index better with gemcitabine-based chemoradiation than with 5-fluorouracil-based chemoradiation in locally advanced pancreatic cancer?

PURPOSE: To retrospectively compare the toxicity and efficacy of concurrent gemcitabine-based chemoradiation with that of concurrent 5-fluorouracil (5-FU)-based chemoradiation in patients with unresectable pancreatic cancer. PATIENTS AND METHODS: Between September 1996 and May 2000, 114 patients with localized unresectable adenocarcinoma of the pancreas were treated with concurrent chemoradiation. Locally advanced unresectable disease was defined as low-density tumor in contact with the superior mesenteric artery (SMA) or celiac artery, or occlusion of the superior mesenteric-portal venous confluence. Fifty-three patients were selected to receive gemcitabine in 7 weekly cycles (250-500 mg/m(2)) with concurrent radiotherapy (median dose 30 Gy, range 30-33 Gy in 10-11 fractions). The remaining 61 patients received continuous-infusion 5-FU (200-300 mg/m(2)) with concurrent radiotherapy (30 Gy in 10 fractions). Radiotherapy was delivered to the primary tumor and regional lymphatics. Patients receiving gemcitabine and those receiving 5-FU had a similar mean Karnofsky performance status (KPS, 89% vs. 86%), distribution of tumor grade (43% vs. 33% poorly differentiated), and percent weight loss (all p = NS). However, patients treated with gemcitabine had a significantly larger median maximum cross-sectional tumor area (TA, 8.8 cm(2) vs. 5.7 cm(2), p = 0.046) and were significantly younger (median age 60 vs. 68 years, p <0.001). Severe acute toxicity (ST) was defined as toxicity requiring a hospital stay of more than 5 days, mucosal ulceration with bleeding, more than 3 dose deletions of gemcitabine or discontinuation of 5-FU, or toxicity resulting in surgical intervention or death. Kaplan-Meier analysis was used to calculate the actuarial rate of local progression on imaging (LP), the rate of distant metastasis (DM), and the overall survival (OS) rate. The imaging was reviewed in resected patients. RESULTS: Patients receiving gemcitabine developed significantly more ST during treatment (23% vs. 2%, p < 0.0001) than did those receiving 5-FU. Patients treated with gemcitabine had a similar 10-month LP rate (62% vs. 61%), 10-month DM rate (55% vs. 47%), 1-year OS rate (42% vs. 28%), and median OS duration (11 months vs. 9 months) to patients treated with 5 FU (all p = NS). Five patients who received gemcitabine and 1 patient who received 5-FU underwent margin-negative pancreaticoduodenectomy after chemoradiation. Three patients had a short segment ( 10 cm(2) (p = 0.03) and poor differentiation (p = 0.07) were associated with a worse survival duration; however, other factors, such as KPS and weight loss >10% and age did not influence OS. CONCLUSION: Despite the selection of healthier patients to receive gemcitabine, there was a significantly higher severe toxicity rate than with 5-FU. The median and 1-year survivals were not significantly different with the use of concurrent gemcitabine; however, the tumors treated were significantly larger. Additionally, a small number of patients with minimal arterial involvement whose disease met our radiographic definition of unresectable disease had margin-negative resections after treatment with gemcitabine-based chemoradiation. These possible benefits and the high rate of severe toxicity define a very narrow therapeutic index for concurrent gemcitabine-based chemoradiation given by this schedule of administration.

Adenocarcinoma↗
PubMed2001

Elective groin irradiation is not indicated for patients with adenocarcinoma of the rectum extending to the anal canal.

PURPOSE: To evaluate the inguinal nodal failure rate in patients with locally advanced rectal cancer with anal canal involvement (ACI) treated with pelvic chemoradiation without elective inguinal irradiation. METHODS AND MATERIALS: From 1990 and 1998, 536 patients received preoperative or postoperative chemoradiation for rectal cancer with curative intent; 186 patients had ACI (<4 cm from the anal verge on rigid proctoscopy). Two patients had positive inguinal nodes at presentation. Chemoradiation was delivered preoperatively (45 Gy in 25 fraction) or postoperatively (53 Gy in 29 fractions) with concurrent continuous infusion of 5-fluorouracil (300 mg/m2/d). The inguinal region was specifically irradiated in only 2 patients who had documented inguinal nodal disease. RESULTS: The median follow-up was 50 months. Only 6 of 184 ACI patients who had clinically negative inguinal nodes at presentation developed inguinal nodal recurrence (5-year actuarial rate 4%); 4 of the 6 cases were isolated. Two patients underwent successful salvage. Only 1 died of uncontrolled groin disease. Local control was achieved in both patients with inguinal nodal disease at presentation, but both died of metastatic disease. Only 3 patients with tumors >4 cm from the verge developed inguinal recurrence (5-year actuarial rate <1%). CONCLUSIONS: Inguinal nodal failure in rectal cancer patients with ACI treated with neoadjuvant or adjuvant chemoradiation is not high enough to justify routine elective groin irradiation.

Adenocarcinoma↗
PubMed2001

T4 rectal cancer treated with preoperative chemoradiation to the posterior pelvis followed by multivisceral resection: patterns of failure and limitations of treatment.

PURPOSE: To analyze the overall pattern of treatment failure and sites of pelvic disease recurrence relative to the radiation fields used in treating patients with clinically staged T4 rectal cancer with preoperative chemoradiation followed by multivisceral resection. METHODS AND MATERIALS: Between 1990 and 1998, 45 patients with T4 rectal cancer were treated with preoperative chemoradiation. Clinical staging was according to the system of the American Joint Cancer Committee and was based on endoscopic ultrasonography, chemotherapy (CT), and physical examination. A diagnosis of T4 disease required evidence of invasion of a contiguous structure on CT (n = 31) or endorectal ultrasonography (n = 6), vaginal mucosal involvement on pelvic examination (n = 6), or a combination of these findings (n = 2). Chemoradiation was delivered with 18 MV photons using a 3-field belly-board technique. The median total dose was 45 Gy in all patients (range 45-63). Nine patients received a boost with external beam radiotherapy (EBRT) (n = 5, 1.8-18 Gy), intraoperative RT (n = 3, 10-20 Gy), or interstitial brachytherapy (n = 1, 20 Gy). All patients received concurrent chemotherapy consisting of protracted venous infusion 5-fluorouracil (300 mg/m(2), 5 d/wk). Resection was not performed in 13 (29%) of the 45 patients because of metastases detected before resection or patient refusal. Multivisceral resection and pelvic exenteration was required in 21 (66%) and 11 (34%) of 32 patients, respectively. We compared the location of pelvic disease recurrence with the RT simulation films. The Kaplan-Meier method was used to calculate the 4-year actuarial pelvic and distant recurrent rates and the overall survival rate. RESULTS: The median length of follow-up was 31.0 months for all patients and 40.0 months for patients alive at last follow-up. When only the resected cases were considered, the local recurrence rate was 20%. Distant metastases occurred in 44% of cases; the overall survival rate was 69%. When all patients were considered, the local recurrence rate was similar (24%), but the rate of distant recurrence (51%) was higher and the overall survival rate lower (50%). Pelvic disease was controlled in all 8 patients whose disease responded well to chemoradiation (either a histologically complete response or microscopic residual disease). Three of 4 patients with close or positive margins had pelvic recurrences despite intraoperative RT and brachytherapy. Nine of the 10 pelvic recurrences occurred in the radiation field. Elective external iliac nodal irradiation was not used, and nodal metastases were not seen in that region. In 1 case, marginal recurrence occurred in a common iliac node at the superior edge of the treatment field. CONCLUSIONS: Despite aggressive multimodality therapy including multivisceral resection, a high rate of pelvic and distant disease recurrence occurred in patients with clinically staged T4 disease. Regional disease recurred almost exclusively in the radiation field. The intraoperative RT and interstitial brachytherapy doses used did not prevent pelvic disease recurrence in patients with close or positive margins. Novel strategies such as higher preoperative doses of RT with or without altered fractionation or more effective radiosensitizers are needed to improve locoregional control in patients with T4 disease. Future strategies must also include more effective systemic therapy.

Adult↗
PubMed2001

Biallelic inactivation of the APC gene is associated with hepatocellular carcinoma in familial adenomatous polyposis coli.

BACKGROUND: Certain primary hepatic tumors have been associated with familial adenomatous polyposis (FAP), a condition caused by germline mutations of the adenomatous polyposis coli (APC) gene. However, a genetic association between FAP and hepatocellular carcinoma (HCC) has not been shown. This study tested the hypothesis that biallelic inactivation of the APC gene contributed to the development of HCC in a patient with FAP and a known germline mutation of the APC gene at codon 208, but no other risk factors for HCC. METHODS: Total RNA and genomic DNA were isolated from the tumor, and in vitro synthesized protein assay and DNA sequencing analysis were used to screen for a somatic mutation in the APC gene. RESULTS: A somatic one-base pair deletion at codon 568 was identified in the wild-type allele of the APC gene. CONCLUSIONS: To the authors' knowledge, this study provides the first evidence that biallelic inactivation of the APC gene may contribute to the development of HCC in patients with FAP.

Adenomatous Polyposis Coli↗
PubMed2001

Underlying liver disease, not tumor factors, predicts long-term survival after resection of hepatocellular carcinoma.

HYPOTHESIS: A subset of patients can be identified who will survive without recurrence beyond 5 years after hepatic resection for hepatocellular carcinoma (HCC). DESIGN: A retrospective review of a multi-institutional database of 591 patients who had undergone hepatic resection for HCC and on-site reviews of clinical records and pathology slides. SETTING: All patients had been treated in academic referral centers within university-based hospitals. PATIENTS: We identified 145 patients who had survived for 5 years or longer after hepatic resection for HCC. MAIN OUTCOME MEASURES: Clinical and pathologic factors, as well as scoring of hepatitis and fibrosis in the surrounding liver parenchyma, were assessed for possible association with survival beyond 5 years and cause of death among the 145 five-year survivors. RESULTS: Median additional survival duration longer than 5 years was 4.1 years. Women had significantly longer median additional survival durations than did men (81 months vs 38 months, respectively, after the 5-year mark) (P =.008). Surgical margins, type of resection, an elevated preoperative alpha-fetoprotein level, and the presence of multiple tumors or microscopic vascular invasion had no bearing on survival longer than 5 years. However, patients who survived for 5 years who also had normal underlying liver or minimal fibrosis (score, 0-2) at surgery had significantly longer additional survival than did patients with moderate fibrosis (score, 3-4) or severe fibrosis/cirrhosis (score, 5-6) (P<.001). CONCLUSIONS: Death caused by HCC is rare beyond 5 years after resection of HCC in the absence of fibrosis or cirrhosis. The data suggest that chronic liver disease acts as a field of cancerization contributing to new HCC. These patients may benefit from therapies directed at the underlying liver disease.

Adult↗
PubMed2001

Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: treatment variables and survival duration.

BACKGROUND: For patients with potentially resectable pancreatic cancer, the poor outcome associated with resection alone and the survival advantage demonstrated for combined-modality therapy have stimulated interest in preoperative chemoradiotherapy. The goal of this study was to analyze the effects of different preoperative chemoradiotherapy schedules, intraoperative radiation therapy, patient factors. and histopathologic variables on survival duration and patterns of treatment failure in patients who underwent pancreaticoduodenectomy for adenocarcinoma of the pancreatic head. METHODS: Data on 132 consecutive patients who received preoperative chemoradiation followed by pancreaticoduodenectomy for adenocarcinoma of the pancreatic head between June 1990 and June 1999 were retrieved from a prospective pancreatic tumor database. Patients received either 45.0 or 50.4 Gy radiation at 1.8 Gy per fraction in 28 fractions or 30.0 Gy at 3.0 Gy per fraction in 10 fractions with concomitant infusional chemotherapy (5-fluorouracil, paclitaxel, or gemcitabine). If restaging studies demonstrated no evidence of disease progression, patients underwent pancreaticoduodenectomy. All patients were evaluated with serial postoperative computed tomography scans to document first sites of tumor recurrence. RESULTS: The overall median survival from the time of tissue diagnosis was 21 months (range 19-26, 95%CI). At last follow-up, 41 patients (31%) were alive with no clinical or radiographic evidence of disease. The survival duration was superior for women (P = .04) and for patients with no evidence of lymph node metastasis (P = .03). There was no difference in survival duration associated with patient age, dose of preoperative radiation therapy, the delivery of intraoperative radiotherapy, tumor grade, tumor size, retroperitoneal margin status, or the histologic grade of chemoradiation treatment effect. CONCLUSION: This analysis supports prior studies which suggest that the survival duration of patients with potentially resectable pancreatic cancer is maximized by the combination of chemoradiation and pancreaticoduodenectomy. Furthermore, there was no difference in survival duration between patients who received the less toxic rapid-fractionation chemoradiotherapy schedule (30 Gy, 2 weeks) and those who received standard-fractionation chemoradiotherapy (50.4 Gy, 5.5 weeks). Short-course rapid-fractionation preoperative chemoradiotherapy combined with pancreaticoduodenectomy, when performed on accurately staged patients, maximizes survival duration and is associated with a low incidence of local tumor recurrence.

Adenocarcinoma↗
PubMed2001

A caution regarding lymphatic mapping in patients with colon cancer.

BACKGROUND: The value of lymphatic mapping and sentinel lymph node biopsy in the treatment of colon cancer is controversial. The purpose of this study was to determine the accuracy of lymphatic mapping in patients with colon cancer. METHODS: Forty-eight patients with colon cancer underwent lymphatic mapping and sentinel lymph node biopsy using isosulfan blue dye followed by standard surgical resection. The sentinel lymph nodes underwent thin sectioning as will as immunohistochemical staining for cytokeratin, in addition to standard hematoxylin and eosin staining. RESULTS: In 47 (98%) patients, a sentinel lymph node was identified. Sixteen patients had lymph nodes containing metastatic disease, and in 6 patients the sentinel lymph node was positive for disease. In no patient was the sentinel lymph node the only site of metastatic disease. In 10 patients the sentinel lymph node was negative for disease, whereas the nonsentinel lymph nodes contained metastatic disease (false negative rate = 38%). CONCLUSIONS: The role of lymphatic mapping and sentinel lymph node biopsy in colon cancer is not as clear as its role in other tumors. Further large prospective studies are needed to evaluate the accuracy and potential benefit of this procedure in patients with colon cancer.

Aged↗
PubMed2001

Portal vein embolization: rationale, technique and future prospects.

BACKGROUND: Advances in surgery have reduced the mortality rate after major liver resection, but complications resulting from inadequate postresection hepatic size and function remain. Portal vein embolization (PVE) was proposed to induce hypertrophy of the anticipated liver remnant in order to reduce such complications. The techniques, measurement methods and indications for this treatment remain controversial. METHODS: A Medline search was performed to identify papers reporting the use of PVE before hepatic resection. Techniques, complications and results are reviewed. RESULTS: Complications of PVE typically occur in less than 5 per cent of patients. No specific substance (cyanoacrylate, thrombin, coils or absolute alcohol) emerged as superior. The increase in remnant liver volume averages 12 per cent of the total liver. The morbidity rate of resection after treatment is less than 15 per cent and the mortality rate is 6-7 per cent with cirrhosis and 0-6.5 per cent without cirrhosis. Embolization is currently used for patients with a normal liver when the anticipated liver remnant volume is 25 per cent or less of the total liver volume, and for patients with compromised liver function when the liver remnant volume is 40 per cent or less. CONCLUSION: This treatment does not increase the risks associated with major liver resection. It may be indicated in selected patients before major resection. Future prospective studies are needed to define more clearly the indications for this evolving technique.

Blood Loss, Surgical↗
PubMed2001

Laparoscopy in the staging of pancreatic cancer.

BACKGROUND: Over the past decade, laparoscopy has emerged as a popular method of detecting extrapancreatic metastatic disease in patients presumed to have localized pancreatic cancer. METHODS AND RESULTS: The English language literature on laparoscopic staging of pancreatic cancer was reviewed. Interpretation of this literature on staging laparoscopy is difficult because (1) there has been inconsistent use of high-quality computed tomography (CT) in prospective studies, (2) many studies have included patients with locally advanced disease, and (3) the R0/R1/R2 resection rates among patients staged by laparoscopy have not been reported, making it impossible to correlate laparoscopic findings with the R0 resection rate. Laparoscopy may prevent unnecessary laparotomy in a proportion of CT-staged patients presumed to have resectable pancreatic cancer. However, routine laparoscopy is performed on patients judged to have resectable disease by high-quality CT, this fraction of patients is between 4 and 13 per cent. CONCLUSION: When state-of-the-art CT is available, the routine use of staging laparoscopy may not be easily justified from the data in the recent literature. Selective use of laparoscopy may be more appropriate and will probably be a more cost-effective staging approach. Criteria are presented for the selective use of laparoscopy in the staging of patients with localized pancreatic cancer.

Cost-Benefit Analysis↗
PubMed2001

Combining gemcitabine with radiation in pancreatic cancer: understanding important variables influencing the therapeutic index.

We compared and evaluated available laboratory and clinical data on the use of concurrent gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) and radiation in pancreatic cancer to provide guidance for subsequent prospective research initiatives. Preclinical data suggest that the timing of administration of gemcitabine with respect to radiotherapy is important, but this issue has not yet been confirmed by clinical data. Phase I clinical data indicate that the amount of acute toxicity from the combination of gemcitabine and radiotherapy is strongly related to the dose and schedule of administration of gemcitabine, as well as to the radiation field size. There also appears to be an inverse linear relationship between the maximum tolerated gemcitabine dose and radiation dose. Also important, but less clear, is the infusion rate of gemcitabine as it relates to the systemic efficacy of the drug. The combination of additional agents with gemcitabine and radiation appears to be feasible. Finally, the addition of radioprotectors may enable chemotherapy dose escalation, but safe escalation of the radiotherapy dose with newer techniques has not been established. Semin Oncol 28 (suppl 10):25-33.

Antimetabolites, Antineoplastic↗
PubMed2001

Nonfunctioning islet cell carcinoma of the pancreas: survival results in a contemporary series of 163 patients.

BACKGROUND: The natural history of nonfunctioning islet cell carcinoma of the pancreas is poorly defined. We therefore reviewed our institutional experience during a period of 12 years to define more clearly the natural history of this disease as a basis for individual therapeutic recommendations. METHODS: The records of all patients who had histologically or cytologically confirmed nonfunctioning islet cell carcinoma of the pancreas were retrospectively reviewed. Patients were grouped by extent of disease at diagnosis and by initial treatment. Survival distributions were estimated by Kaplan-Meier analysis. RESULTS: One hundred sixty-three patients with nonfunctioning islet cell carcinoma of the pancreas were identified. The overall median survival duration was 3.2 years. The median survival was 7.1 years in patients with localized disease who underwent a potentially curative resection and 5.2 years in those with locally advanced, unresectable, nonmetastatic disease (P = .04). Patients with metastatic disease that could not be resected had a median survival of 2.1 years. CONCLUSIONS: Patients with completely resected localized disease had a long median survival. Patients with nonmetastatic but unresectable locally advanced disease also had a surprisingly long median survival; major treatment-related morbidity may be hard to justify in this subgroup. The short median survival in patients with metastatic disease suggests that the frequent practice of observation in this patient subgroup needs to be reexamined and that continued investigation of regional and systemic therapies with novel agents is warranted.

Adult↗
PubMed2001

Improved overall survival among responders to preoperative chemoradiation for locally advanced rectal cancer.

The aim of this study was to determine if the response to preoperative radiation and chemotherapy with continuous infusion 5-fluorouracil (5-FU) was predictive for survival among patients with locally advanced rectal cancer. Preoperative chemoradiation (CTX/XRT) that delivered 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-FU (300 mg/m2/day) was given to 117 patients. The pretreatment stage distribution, as determined by endorectal ultrasound (u), included uT2N0 in 2%, uT3N0 in 47%, uT3N1 in 49%, and uT4N0 in 2% of cases; endorectal ultrasound was not performed in 13% of cases (15 patients). Approximately 6 weeks after completion of CTX/XRT, surgery was performed. Adjuvant chemotherapy, consisting of 400 to 425 mg/m2 of 5-FU plus 20 mg/m2 leucovorin for 5 days, was administered every 28 days for 4 to 6 cycles after surgical resection. Among the 74 patients treated with adjuvant chemotherapy, the preoperative stage of disease was 31 with T3N0 and 43 T3N1. Median follow-up was 46 months (range 2 to 89 months). The pathologic tumor stages were Tis-2N0 in 26%, T2N1 in 5%, T3N0 in 21%, T3N1 in 15%, T4N0 in 5%, and T4N1 in 1%; a complete response (CR) to preoperative CTX/XRT was pathologically confirmed in 32 (27%) of patients. Tumor down-staging occurred in 72 (62%) cases. A sphincter-saving procedure (SP) was possible in 59% of patients. The median DFS and overall survival rates for responders were 46 months and 47 months, respectively; for non-responders these outcome measures were 38 months and 41 months, respectively. Log-rank analysis showed that the distant metastatic-free survival rates improved with any response to CTX/XRT (p < 0.00001), CR to CTX/XRT (p < 0.009) and SP (p < 0.012). Likewise, these parameters also significantly influenced DFS rates (CTX/XRT p < 0.00001; CR p < 0.006; and SP p < 0.008). Control of pelvic disease was influenced by clinical size (p < 0.002) and SP (p < 0.016) on univariate analysis. On multivariate analysis only clinical size (p < 0.002) continued to be a significant factor for local control. Factors on multivariate analysis that resulted in significant improvements in cancer-specific survival included any response to preoperative CTX/XRT (p < 0.017) and administration of adjuvant chemotherapy (p < 0.034). Any response to preoperative CTX/XRT improved distant metastatic-free and disease-free survival rates. Multivariate analysis confirmed that a response to preoperative CTX/XRT predicted for improvements in overall survival among patients with locally advanced rectal cancer. Patients who fail to respond to preoperative 5-FU based chemotherapy given concomitantly with radiation have higher rates of distant metastases with adjuvant 5-FU therapy.

Adult↗
PubMed2001

Effect of preoperative biliary decompression on pancreaticoduodenectomy-associated morbidity in 300 consecutive patients.

OBJECTIVE: To examine the relationship between preoperative biliary drainage and the morbidity and mortality associated with pancreaticoduodenectomy. SUMMARY BACKGROUND DATA: Recent reports have suggested that preoperative biliary drainage increases the perioperative morbidity and mortality rates of pancreaticoduodenectomy. METHODS: Peri-operative morbidity and mortality were evaluated in 300 consecutive patients who underwent pancreaticoduodenectomy. Univariate and multivariate logistic regression analyses were done to evaluate the relationship between preoperative biliary decompression and the following end points: any complication, any major complication, infectious complications, intraabdominal abscess, pancreaticojejunal anastomotic leak, wound infection, and postoperative death. RESULTS: Preoperative prosthetic biliary drainage was performed in 172 patients (57%) (stent group), 35 patients (12%) underwent surgical biliary bypass performed during prereferral laparotomy, and the remaining 93 patients (31%) (no-stent group) did not undergo any form of preoperative biliary decompression. The overall surgical death rate was 1% (four patients); the number of deaths was too small for multivariate analysis. By multivariate logistic regression, no differences were found between the stent and no-stent groups in the incidence of all complications, major complications, infectious complications, intraabdominal abscess, or pancreaticojejunal anastomotic leak. Wound infections were more common in the stent group than the no-stent group. CONCLUSIONS: Preoperative biliary decompression increases the risk for postoperative wound infections after pancreaticoduodenectomy. However, there was no increase in the risk of major postoperative complications or death associated with preoperative stent placement. Patients with extrahepatic biliary obstruction do not necessarily require immediate laparotomy to undergo pancreaticoduodenectomy with acceptable morbidity and mortality rates; such patients can be treated by endoscopic biliary drainage without concern for increased major complications and death associated with subsequent pancreaticoduodenectomy.

Adolescent↗
PubMed2001

Biliary tract cancer.

Advances in cellular and molecular biology of extrahepatic cholangiocarcinoma and gallbladder adenocarcinoma are providing innovative means for the diagnosis and treatment of biliary tract cancer. Similarly, refinements in noninvasive studies--including helical computed tomography, magnetic resonance cholangiopancreatography, and endoscopic ultrasonography--are enabling more accurate diagnosis, staging, and treatment planning for these tumors. Complete resection remains the only means for cure, and recent reports from major hepatobiliary centers support aggressive wide resection for bile duct and gallbladder cancer. Palliation of malignant strictures has improved with advanced endoscopic techniques, newer polyurethane-covered stents, endoscopic microwave coagulation therapy, and radiofrequency intraluminal endohyperthermia. The preliminary data on such minimally invasive techniques suggest an improvement in quality of life and survival for selected patients.

Journal Article↗
PubMed2001

Toxicity and efficacy of concurrent gemcitabine and radiotherapy for locally advanced pancreatic cancer.

BACKGROUND: Gemcitabine and radiotherapy are a potent combination. A clinical assessment of the therapeutic ratio for locally advanced pancreatic cancer patients has not yet been reported. AIM OF STUDY: To assess the toxicity, survival, and pattern of failure of locally advanced pancreatic cancer patients treated with concurrent gemcitabine-based chemoradiation. Patients and Methods. Between the dates of December 1996 and August 2000 51 patients with locally advanced unresectable adenocarcinoma of the pancreas were treated with concurrent gemcitabine and radiotherapy at MDACC. Patients received 250-500 mg/m2 of gemcitabine weekly x7 over 30 min and 30-33 Gy in 10-11 fractions over two weeks to the primary tumor and regional lymphatics. Severe toxicity was defined as admission > 5 d, mucosal ulceration, > 3 dose deletions of gemcitabine or toxicity resulting in surgical intervention or that resulted in death. RESULTS: The median survival was 11 mo. Overall, 37 of 51 patients had objective evidence of local progression. The actuarial rate of local progression rate at 9 mo was 70%. The 9-mo distant metastasis rate was 52%. Tumors > or = 10 cm2 had worse local control, distant control, and overall survival. Six patients underwent pancreaticoduodenectomy after therapy. After review of the imaging, only four of these patients had minimal arterial involvement, one was incorrectly staged, and one had initial inflammatory change on CT that resolved. Twelve of 51 (24%) patients suffered severe acute toxicity, and 17 of 51 (33%) patients were admitted for supportive care. CONCLUSION: Concurrent gemcitabine and radiotherapy can be a very difficult combination to administer safely. Our results do not suggest a prolongation of median survival for patients with localized pancreatic cancer treated with this therapy. It is possible that gemcitabine-based chemoradiation contributes to the margin-negative resectability of a small number of patients with minimal arterial involvement, but this benefit is obscured by the frequent toxicity encountered in most patients. Locally advanced pancreatic cancer patients should continue to be enrolled on prospective studies investigating novel combinations of cytotoxic and/or biologic agents with concurrent radiotherapy.

Adenocarcinoma↗