National Cancer Institute®
Last Modified: November 21, 2001
UI - 21417774
AU - Gazdar AF; Minna JD
TI - Targeted therapies for killing tumor cells.
SO - Proc Natl Acad Sci U S A 2001 Aug 28;98(18):10028-30
AD - Hamon Center for Therapeutic Oncology Research and Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
UI - 21271459
AU - Kobayashi S; Asano T; Ochiai T
TI - A proposal of no-touch isolation technique in pancreatoduodenectomy for periampullary carcinomas.
SO - Hepatogastroenterology 2001 Mar-Apr;48(38):372-4
AD - Second Department of Surgery, Chiba University School of Medicine, 1-8-1 Inohana, Chuoh-ku, Chiba 260-8670, Japan. email@example.com
BACKGROUND/AIMS: The procedure of pancreatoduodenectomy for periampullary cancers accompanies a risk to shed cancer cells into a portal vein while handling the pancreas head lesion. This manipulation may subsequently cause a liver metastasis. We devised the no-touch isolation technique for pancreatoduodenectomy without removing a portal vein, for the purpose of preventing the manipulated shedding of cancer cells into a portal vein and liver metastasis. METHODOLOGY: The fundamental procedure of this technique is that isolation of portal vein precedes the handling of tumor mass. Isolation of a portal vein is carried out with the ligature of its surrounding veins after dividing of duodenum and pancreas. We applied the no-touch isolation technique for 10 cases, which consisted of 6 cases of distal bile duct carcinoma and 4 There was neither operative mortality nor liver metastasis cases in these cases. CONCLUSIONS: The no-touch isolation technique without removing a portal vein might be recommended as a safe and reasonable procedure for periampullary cancer patients who have the potential for subsequent liver metastasis.
UI - 21271502
AU - Fujino Y; Suzuki Y; Kamigaki T; Mitsutsuji M; Kuroda Y
TI - Evaluation of gastroenteric bypass for unresectable pancreatic cancer.
SO - Hepatogastroenterology 2001 Mar-Apr;48(38):563-8
AD - Department of Surgery I, Kobe University School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
BACKGROUND/AIMS: It is controversial as to whether gastroenteric bypass is helpful for patients with unresectable pancreatic cancer. This study was designed to evaluate the effects of gastroenteric bypass on dietary intake and the symptoms of gastric outlet obstruction in these patients. METHODOLOGY: We reviewed the cases of 101 patients with unresectable pancreatic cancer surgically treated at the Kobe University Hospital. The effects of gastroenteric bypass were examined by comparing the dietary intake and the symptoms of gastric outlet obstruction on admission, 1 month and 3 months after the operation. RESULTS: The analyses of dietary intake and the symptoms indicated that the gastroenteric bypass operation was not helpful for most of the patients with unresectable pancreatic cancer. Multivariate logistic regression model revealed that dietary intake on admission was the strongest parameter for dietary intake at one month after operation. The patients with a low dietary intake on admission often required a nasogastric tube after the bypass operation, reflecting progression of the disease. CONCLUSIONS: Gastroenteric bypass had no advantage to improve dietary intake and symptoms for almost all the patients with unresectable pancreatic cancer. It was effective only for patients with a high dietary intake without symptoms of gastric outlet obstruction on admission.
UI - 21271503
AU - Kato K; Morita T; Miyasaka Y; Fujita M; Kondo S; Katoh H
TI - Modified Devine exclusion for unresectable pancreatic head carcinoma.
SO - Hepatogastroenterology 2001 Mar-Apr;48(38):569-71
AD - Department of Surgery, Hokkaido Gastroenterological Hospital, Honcho 1-1, Higashiku, Sapporo, 065-0041, Japan.
BACKGROUND/AIMS: Gastrojejunostomy is generally performed for unresectable pancreatic head carcinoma. However, in the case of conventional gastrojejunostomy, the bypass does not always function effectively. METHODOLOGY: For unresectable pancreatic head carcinoma accompanied by severe duodenal stenosis, conventional gastrojejunostomy was performed in 5 cases, and modified Devine exclusion was performed in 7 cases. There were no significant differences between the groups regarding their backgrounds. RESULTS: There were no significant differences between the two groups for the average operation time, the days before peroral ingestion and the hospital stay. The state of peroral ingestion showed better results for modified Devine exclusion. The discharge rates were better for modified Devine exclusion, showing a significant difference (P = 0.028). The 50%-survival periods were 65 days and 159 days, respectively. The bleeding from the tumor occurred in 2 patients from the conventional gastrojejunostomy group, but none in modified Devine exclusion group. CONCLUSIONS: Modified Devine exclusion is a simple and effective technique for unresectable pancreatic head carcinoma.
UI - 21348129
AU - Kawarada Y; Das BC; Naganuma T; Isaji S
TI - Surgical treatment of pancreatic cancer. Does extended lymphadenectomy provide a better outcome?
SO - J Hepatobiliary Pancreat Surg 2001;8(3):224-9
AD - First Department of Surgery, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
The rate of curative resection of pancreatic cancer has increased as a result of extended operations, but this has not led to any significant improvement in postoperative outcome. No definite conclusions were drawn in retrospective studies comparing outcome after standard and extended operations, and there was almost no difference in outcome between the two groups in a recent prospective randomized study. In addition, extended procedures are very stressful operations that, in most instances, impair the patient's quality of life (QOL). As a result, the need for performing extended surgery to treat pancreatic cancer has come into question. The outcome of advanced cancer in patients in whom curative resection cannot be achieved by extended operations is extremely poor, and we believe that, in such patients, priority should be given to QOL, by selecting bypass or limited operations instead. It is hoped that the value of extended surgery will be clarified by a very carefully planned multicenter prospective randomized study in the future.
UI - 21424855
AU - Stanford P
TI - Surgical approaches to pancreatic cancer.
SO - Nurs Clin North Am 2001 Sep;36(3):567-77, xi
AD - Texas A&M University, Corpus Christi, Texas, USA.
Pancreatic cancer continues to be a significant health problem. Recent advances in medical technologies allow patients with pancreatic cancer to undergo diagnosis, staging, treatment, and palliation, and to minimize the traditional use of laparotomy as a method of obtaining information to facilitate treatment planning. Pancreatic surgery, which can impact duration and quality of life, can be reserved for that subset of patients likely to benefit from a surgical approach tailored to the specific needs of the individual patient.
UI - 21381718
AU - Wolff RA; Evans DB; Gravel DM; Lenzi R; Pisters PW; Lee JE; Janjan NA;
TI - Charnsangavej C; Abbruzzese JL Phase I trial of gemcitabine combined with radiation for the treatment of locally advanced pancreatic adenocarcinoma.
SO - Clin Cancer Res 2001 Aug;7(8):2246-53
AD - The Pancreatic Tumor Study Group, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. firstname.lastname@example.org
Gemcitabine has modest activity in the treatment of advanced pancreatic cancer and is a potent radiosensitizer. We conducted a Phase I trial to determine the maximum tolerated dose of weekly gemcitabine delivered concurrently with radiation therapy for the treatment of locally advanced adenocarcinoma of the pancreatic head and to assess the treatment-related toxic effects associated with such a regimen. Eighteen patients with pathologically proven, locally advanced adenocarcinoma of the pancreatic head were enrolled in this study. Patients received seven weekly doses of gemcitabine with 3000 cGy of external beam radiation therapy delivered during the first 2 weeks of therapy. Six patients received gemcitabine at 350 mg/m(2)/week, nine at 400 mg/m(2)/week, and three at 500 mg/m(2)/week. Grade 3-4 hematological toxicity was observed in over half the patients treated. Nonhematological toxicities were significant and included fatigue, anorexia, nausea, vomiting, and dehydration. Forty-four % of the patients required admission to the hospital for management of nausea/vomiting and dehydration. The risk of hospitalization appeared to be dose-related; all of the three patients treated at 500 mg/m(2)/week required hospital admission during treatment. Seventeen patients were evaluated for response, and eight patients (47%) had evidence of a local anticancer effect. Four of these eight patients (24%) had a partial response to therapy. The median survival for the entire group was 6 months. The 1-year survival rate for patients with an objective response to therapy was 66%. The clinical responses observed in this group of patients suggest gemcitabine is a clinically relevant radiosensitizer in patients with pancreatic adenocarcinoma. However, the toxic effects are significant, suggesting that until dose and scheduling issues are explored further, concomitant administration of gemcitabine and radiation therapy should still be considered investigational.
UI - 21387639
AU - Ianniello GP; Orditura M; Rossi A; De Vita F; Maiorino L; Carrozza F;
TI - Manzione L; Catalano G Gemcitabine plus epirubicin in advanced pancreatic cancer: a phase II multicenter trial.
SO - Oncol Rep 2001 Sep-Oct;8(5):1111-5
AD - Division of Medical Oncology, G. Rummo Hospital, Benevento, Italy. email@example.com
The aim of this phase II multicenter trial was to evaluate the activity of a novel combination of gemcitabine (GEM) and epirubicin (EPI) in advanced pancreatic cancer patients. Clinical benefit and response rate 30 consecutive patients with measurable advanced pancreatic cancer were enrolled. Gemcitabine was administered intravenously in 30 min at a dose of 800 mg/m2 on days 1, 8, 15 followed by i.v. injection of epirubicin 25 mg/m(2); treatment was repeated every 28 days. With regard to clinical benefit response, 8/21 patients (38%) experienced significant palliation of tumor-related symptoms; the median symptom control time was 25 weeks. No complete responses were recorded while 6 patients achieved a partial remission, for an overall response rate of 20%; 10 patients (30%) had a stable disease and 14 (46%) had progressive disease. The median time to progression was 14 weeks. Median survival was 26 weeks, with 6 patients (20%) having long-term survival at 46 weeks. In general, chemotherapy was well tolerated; 9 patients (30%) suffered from WHO grade 3-4 haematological toxicity and 5 patients (16.6%) suffered from grade 3 non-haematological toxicity. In conclusion, the GEM plus EPI regimen represent a feasible approach for improvement of clinical benefit in advanced pancreatic cancer patients, but confirmatory investigations are required.
UI - 98333945
AU - Brown NK; Thompson DJ; Prentice RL
TI - Nontreatment and aggressive narcotic therapy among hospitalized pancreatic cancer patients.
SO - J Am Geriatr Soc 1998 Jul;46(7):839-48
AD - Department of Medicine, University of Washington School of Medicine, USA.
OBJECTIVES: Strong feelings about patient autonomy as expressed in living wills, polls, and legislative referenda have been challenging the medical establishment to increase nontreatment, defined as foregoing a life-prolonging treatment, and even to provide treatments having life-shortening potential to selected patients. Because there are little data about the actual practice of these procedures, including aggressive narcotic therapy as defined herein, we studied the terminal management of 417 pancreatic cancer patients. DESIGN AND PARTICIPANTS: The medical records of 417 residents of King County, Washington, who died of pancreatic cancer in the time periods 1959-1962, 1969-1972, and 1985-1990, were reviewed to study the frequency of, and risk factors for, end-of-life nontreatment decisions and aggressive narcotic therapy decisions, defined here as the decision to administer treatment doses of narcotics or major sedatives to already comatose patients within 4 hours of death. RESULTS: Antibiotics were not provided to 71% of the 70 febrile patients (two readings >38.33-38.83 degrees C or one reading of 38.88 degrees C), intravenous fluid was not provided to 43% of 294 dehydrated patients (oral intake <500 mL/24 hours), transfusions were not provided to 39% of 57 severely anemic patients (hematocrit <20%), and laparotomy was not performed for 86% of 36 patients with abdominal emergencies (obstruction, bleeding, dehiscence). Also, 46% of the 118 patients who were comatose for at least 24 hours before death received aggressive narcotic therapy, as defined above. A total of 335 of the 417 patients had documentation of at least one of the above life-threatening conditions or were comatose for at least 24 hours before death, and 289 (86%) of these patients experienced nontreatment of one or more of these conditions or received aggressive narcotic therapy. Nontreatment decisions for febrile, dehydrated, or anemic patients tended to be more frequent if the patient was comatose (P=.004, .010, and .065, respectively), if there was a nontreatment statement in the medical record (P=.009, .035, and .001, respectively), or if the patient was described as terminal (P=.262, .029, and .002, respectively). Aggressive narcotic therapy in comatose patients was more common among patients who had regular visitors (P=.002), who had pre-coma pain (P=.006), who had nontreatment statements in their charts (P=.031), whose in-charge physician was an oncologist (P < .001), who were treated in a community nonprofit hospital compared with a Catholic hospital (P=.007), or who were treated in recent years (P=.011). CONCLUSION: Both nontreatment and aggressive narcotic therapy forms of medical management have been occurring commonly in terminal pancreatic cancer patients in King County, Washington, during the past 3 decades, the latter with greater frequency in recent years.
UI - 21323881
AU - Evans DB; Wolff RA; Crane CH
TI - Neoadjuvant strategies for pancreatic cancer.
SO - Oncology (Huntingt) 2001 Jun;15(6):727-37; discussion 741-4, 747
AD - University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
Recent prospective and retrospective data suggest that the use of multimodality therapy combining pancreaticoduodenectomy with postoperative adjuvant chemotherapy (fluorouracil) and external-beam radiation therapy maximizes local tumor control and improves the length of survival in pancreatic cancer patients, compared with surgery alone. Since postoperative chemoradiation is often delayed in these patients due to the morbidity and prolonged recovery time associated with surgery, investigators are assessing the efficacy of administering chemoradiation before pancreaticoduodenectomy in patients with potentially resectable pancreatic adenocarcinoma. When given prior to surgery, chemoradiation is not delayed and patients found to have disease progression after chemoradiation are not subjected to an unnecessary laparotomy.
UI - 21523827
AU - Carrio M; Mazo A; Lopez-Iglesias C; Estivill X; Fillat C
TI - Retrovirus-mediated transfer of the herpes simplex virus thymidine kinase and connexin26 genes in pancreatic cells results in variable efficiency on the bystander killing: implications for gene therapy.
SO - Int J Cancer 2001 Oct 1;94(1):81-8
AD - Centre de Genetica Medica i Molecular, Institut de Recerca Oncologica (IRO), L'Hospitalet de Llobregat, 08907-Barcelona, Spain.
Currently, there is no effective treatment for pancreatic cancer and prodrug-activating gene therapy with the herpes simplex virus thymidine kinase gene (HSV-tk) in combination with ganciclovir (GCV) has been suggested as a candidate approach against this disease. In the present study, we have evaluated the efficacy of the HSV-tk/GCV treatment in a panel of pancreatic tumor cells (NP-9, NP-18, NP-31) and the potentiation of the cytotoxic effect in combination with the overexpression of the connexin 26 gene (Cx26). Pancreatic cells transduced with a retrovirus containing the HSV-tk gene showed different sensitivities to GCV that seemed to be independent of HSV-tk expression levels. The extent of the bystander effect also varied among the pancreatic tumor cells and correlated with the level of gap junction intercellular communication (GJIC). Transduction of the pancreatic tumor cells with a retrovirus carrying the connexin 26 gene resulted in high levels of connexin 26 expression and in an increase in the GJIC that correlated to an extent in the bystander effect in both NP-9Cx26 and NP-18Cx26 cells. Neither an increment in GJIC nor an increase in the bystander killing was detected in NP-31Cx26. The bystander effect in NP-18 Cx26 cells was also prevented by the long term inhibitor of GJIC, 18-alpha-glycyrrhetinic acid (AGA). Together, these results demonstrate that pancreatic tumor cells are highly different as regards the susceptibility to HSV-tk/GCV treatment. Moreover, they indicate that overexpression of the Cx26 gene does not always correspond to an increase in GJIC although they clearly suggest the role of GJIC in mediating the bystander effect. Copyright 2001 Wiley-Liss, Inc.
UI - 21451485
AU - Ahmad NA; Lewis JD; Ginsberg GG; Haller DG; Morris JB; Williams NN;
TI - Rosato EF; Kochman ML Long term survival after pancreatic resection for pancreatic adenocarcinoma.
SO - Am J Gastroenterol 2001 Sep;96(9):2609-15
AD - Department of Medicine, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Cancer Center, Philadelphia, Pennsylvania, USA.
OBJECTIVE: The aim of this study was to determine the long term survival of patients with pancreatic adenocarcinoma who underwent surgical resection and to assess the association of clinical, pathological, and treatment features with survival. METHODS: Between January, 1990, and December, 1998, 125 patients underwent a pancreaticoduodenal or partial pancreatic resection for pancreatic ductal adenocarcinoma at our institution. The records of these patients were reviewed for demographics, tumor characteristics including size, histological grade, margin status, lymph node status, surgical TNM staging, and postoperative adjuvant therapy. The primary outcome variable analyzed was survival. RESULTS: A total of 116 patients had complete follow-up and were included in the final analysis. The median survival after surgery was 16 months. The 1-, 3-, 5-, and 7-yr survival rates for all 116 patients were 60%, 23%, 19%, and 11%, respectively. The 1-, 3-, 5-, and 7-yr survival rates for patients who received adjuvant therapy were 69%, 28%, 23%, and 18% compared with 20% and 0% in patients who did not receive adjuvant therapy (p < 0.0001). The 1-, 3-, 5-, and 7-yr survival rates for patients with negative lymph nodes were 73%, 38%, 26%, and 22% compared with survival rates of 52%, 14%, 14%, and 9% in patients with positive lymph nodes (p = 0.01). In multivariate analyses, adjuvant therapy was the only feature found to be strongly associated with survival (hazards ratio = 0.26, 95% CI = 0.15-0.44). CONCLUSIONS: The overall 5- and 7-yr survival rates of 19% and 11% in our study further validate that surgical resection in patients with pancreatic adenocarcinoma can result in long term survival, particularly when performed in association with adjuvant chemoradiation.
UI - 21523853
AU - Xu Z; Friess H; Solioz M; Aebi S; Korc M; Kleeff J; Buchler MW
TI - Bcl-x(L) antisense oligonucleotides induce apoptosis and increase sensitivity of pancreatic cancer cells to gemcitabine.
SO - Int J Cancer 2001 Oct 15;94(2):268-74
AD - Department of Visceral and Transplantation Surgery, University of Berne, Inselspital, Berne, Switzerland.
Pancreatic cancer is one of the leading causes of cancer-related death in Western countries. Bcl-x(L) is an anti-apoptotic factor of the Bcl-2 family, which is overexpressed in pancreatic cancer and its presence correlates with shorter patient survival. In this study, sequence-specific antisense oligonucleotides targeting the coding region of Bcl-x(L) were designed to examine whether apoptosis could be induced and chemosensitivity could be increased in pancreatic cancer cells. Five pancreatic cancer cell lines, Panc-1, MIA-PaCa-2, Capan-1, ASPC-1 and T3M4, were treated with Bcl-x(L) sense or antisense oligonucleotides and gemcitabine and the cell viability was examined by the SRB method. Apoptosis was determined using DAPI staining. In all examined pancreatic cancer cells, Bcl-x(L) expression was reduced after transfection of the antisense oligonucleotides. Cell death analysis using DAPI staining revealed that antisense, but not sense oligonucleotides caused apoptotic cell death. Furthermore, Bcl-x(L) antisense oligonucleotides enhanced the cytotoxic effects of gemcitabine in pancreatic cancer cells. Our results indicate that Bcl-x(L) antisense oligonucleotides effectively inhibited pancreatic cancer cell growth and caused apoptosis by reducing Bcl-x(L) protein levels. Bcl-x(L) antisense oligonucleotides also increased the chemosensitivity of pancreatic cancer cells, suggesting that Bcl-x(L) antisense therapy might be a potential future approach in this disease. Copyright 2001 Wiley-Liss, Inc.
UI - 21473283
AU - Yamaguchi K; Yokohata K; Ohkido M; Watanabe M; Ogawa Y; Chijiiwa K;
TI - Tanaka M Which is less invasive--distal pancreatectomy or segmental resection?
SO - Int Surg 2000 Oct-Dec;85(4):297-302
AD - Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
BACKGROUND: For a pancreatic body tumor, distal pancreatectomy (DP) has been a standard operation. Segmental resection (SR) of the pancreas has been introduced as a less invasive procedure in consideration of preservation of the pancreatic functions and postoperative quality of life. Surgical stress and exocrine and endocrine functions of the residual pancreas were compared between DP and SR. METHODS: Clinical findings including serum levels of C reactive protein (CRP), fasting blood sugar, a 120 min value of the 75 g oral glucose tolerance test, and N-benzol-L-tyrosyl-p-aminobenzoic acid excretion value (a pancreatic exocrine function test) were compared between 47 patients with DP and 10 with SR performed for benign pancreatic diseases. RESULTS: Operation time was longer in SR (356 min) than in DP (272 min; P = 0.0123). Operative blood loss and peri-operative blood transfusion were not different between the two groups. Serum levels of CRP increased after the operation, reaching the peak on postoperative day 2 or 3, and decreased thereafter The peak of serum CRP level was similar between the two groups (13.4+/-1.8 mg/dl in SR and 14.8+/-1.1 mg/dl in DP). Postoperative hospital stay in 10 patients with SR (65 days) was significantly longer than that in 47 with DP (33 days; P = 0.0001). When postoperative complications were compared between the two groups, the incidence of pancreatic fistula was significantly higher in SR (4/10 [40%]) than in DP (4/46 [9%]; P = 0.0103). Abdominal abscess was seen in 30% of SR and in 11% of DP. Postoperative intra-abdominal hemorrhage was seen only in one patient with SR After DP, glucose tolerance deteriorated at short-term in nine of 24 patients examined and at long-term in two of five patients examined. Only one patient showed improvement of glucose intolerance at short-term after the operation. On the other hand, SR showed no alteration of the pancreatic endocrine and exocrine functions in eight patients examined. CONCLUSIONS: SR is superior to DP from the view-point of preservation of the pancreatic functions, although SR has a longer operation time, a longer hospital stay and a higher incidence of postoperative complications.
UI - 21538334
AU - Tsukagoshi S
TI - [Results of gemcitabine hydrochloride in the treatment for pancreatic cancer]
SO - Gan To Kagaku Ryoho 2001 Oct;28(10):1461-7
AD - Cancer Institute, Japan Foundation Cancer Research.
Pancreatic cancer has extremely poor prognosis. However no satisfactory effective chemotherapy for this cancer has been established. Gemcitabine hydrochloride, a novel anti-tumor agent, had shown the remarkable for pancreatic cancer of this agent has been approved in Japan and it is expected to be widely and increasingly introduced for clinical use. This review summarizes the study results of gemcitabine mono-therapy for pancreatic cancer and discusses other possibility of the treatment by Gemcitabine with the reported data about its combination therapy with other anti-cancer drug or radiation.
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