National Cancer Institute®
Last Modified: April 1, 2002
UI - 11776488
AU - White RR; Hurwitz HI; Morse MA; Lee C; Anscher MS; Paulson EK; Gottfried
TI - MR; Baillie J; Branch MS; Jowell PS; McGrath KM; Clary BM; Pappas TN; Tyler DS Neoadjuvant chemoradiation for localized adenocarcinoma of the pancreas.
SO - Ann Surg Oncol 2001 Dec;8(10):758-65
AD - Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
BACKGROUND: The use of neoadjuvant (preoperative) chemoradiotherapy (CRT) for pancreatic cancer has been advocated for its potential ability to optimize patient selection for surgical resection and to downstage locally advanced tumors. This article reports our experience with neoadjuvant CRT for localized pancreatic cancer. METHODS: Since 1995, 111 patients with radiographically localized, pathologically confirmed pancreatic adenocarcinoma have received neoadjuvant external beam radiation therapy (EBRT; median, 4500 cGy) with 5-flourouracil-based chemotherapy. Tumors were defined as potentially resectable (PR, n = 53) in the absence of arterial involvement and venous occlusion and locally advanced (LA, n = 58) with arterial involvement or venous occlusion by CT. RESULTS: Five patients (4.5%) were not restaged due to death (n = 3) or intolerance of therapy (n = 2). Twenty-one patients (19%) manifested distant metastatic disease on restaging CT. Twenty-eight patients with initially PR tumors (53%) and 11 patients with initially LA tumors (19%) were resected after CRT. Histologic examination revealed significant fibrosis in all resected specimens and two complete responses. Surgical margins were negative in 72%, and lymph nodes were negative in 70% of resected patients. Median survival in resected patients has not been reached at a median follow-up of 16 months. CONCLUSIONS: Neoadjuvant CRT provided an opportunity for patients with occult metastatic disease to avoid the morbidity of resection and resulted in tumor downstaging in a minority of patients with LA tumors. Survival after neoadjuvant CRT and resection appears to be at least comparable to survival after resection and adjuvant (postoperative) CRT.
UI - 11854545
AU - Wayne JD; Abdalla EK; Wolff RA; Crane CH; Pisters PW; Evans DB
TI - Localized adenocarcinoma of the pancreas: the rationale for preoperative chemoradiation.
SO - Oncologist 2002;7(1):34-45
AD - The Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Pancreatic adenocarcinoma is the fifth leading cause of cancer-related death in the U.S. In spite of advancements in surgical treatment, nearly 80% of patients thought to have localized pancreatic cancer die of recurrent or metastatic disease when treated with surgery alone. Therefore, efforts to alter the patterns of recurrence and improve survival for patients with pancreatic cancer currently focus on the delivery of systemic therapy and irradiation before or after surgery. Postoperative adjuvant therapy appears to improve median survival. However, more than one-fourth of patients do not complete planned adjuvant therapy due to surgical complications or a delay in postoperative recovery of performance status. Utilizing a preoperative (neoadjuvant) approach, overall treatment time is reduced, a greater proportion of patients receive all components of therapy, and patients with rapidly progressive disease are spared the side effects of surgery as metastatic disease may be found at restaging following chemoradiation (prior to surgery). This paper examines the factors pertinent to clinical trial design for resectable pancreatic cancer, and carefully reviews the existing data supporting adjuvant and neoadjuvant therapy for potentially resectable disease.
UI - 11875725
AU - Evans TR; Colston KW; Lofts FJ; Cunningham D; Anthoney DA; Gogas H; de
TI - Bono JS; Hamberg KJ; Skov T; Mansi JL A phase II trial of the vitamin D analogue Seocalcitol (EB1089) in patients with inoperable pancreatic cancer.
SO - Br J Cancer 2002 Mar 4;86(5):680-5
AD - CRC Department of Medical Oncology, Beatson Oncology Centre, Western Infirmary, Dumbarton Road, Glasgow G11 6NT, UK. J.Evans@beatson.gla.ac.uk
Inoperable cancer of the exocrine pancreas responds poorly to most conventional anti-cancer agents, and new agents are required to palliate this disease. Seocalcitol (EB1089), a vitamin D analogue, can inhibit growth, induce differentiation and induce apoptosis of cancer cell lines in vitro and can also inhibit growth of pancreatic cancer xenografts in vivo. Thirty-six patients with advanced pancreatic cancer received once daily oral treatment with seocalcitol with dose escalation every 2 weeks until hypercalcaemia occurred, following which patients continued with maintenance therapy. The most frequent toxicity was the anticipated dose-dependent hypercalcaemia, with most patients tolerating a dose of 10-15 microg per day in chronic administration. Fourteen patients completed at least 8 weeks of treatment and were evaluable for efficacy, whereas 22 patients were withdrawn prior to completing 8 weeks' treatment and in 20 of these patients withdrawal was due to clinical deterioration as a result of disease progression. No objective responses were observed, with five of 14 patients having stable disease in whom the duration of stable disease was 82-532 days (median=168 days). The time to treatment failure (n=36) ranged from 22 to 847 days, and with a median survival of approximately 100 days. Seocalcitol is well tolerated in pancreatic cancer but has no objective anti-tumour activity in advanced disease. Further studies are necessary to determine if this agent has any cytostatic activity in this malignancy in minimal disease states. Copyright 2002 Cancer Research UK
UI - 11915724
AU - Ishikawa O; Ohigashi H; Yokoyama S; Yamada T; Sasaki Y; Imaoka S
TI - [Present and future in the surgical treatment of pancreatic cancer]
SO - Gan To Kagaku Ryoho 2002 Mar;29(3):364-9
AD - Dept. of Surgery, Osaka Medical Center for Cancer and Cardiovascular Disease, 1-3-3 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan.
Owing to the recent advances in surgical techniques and postoperative care, the operative indication for adenocarcinoma of the pancreas has been widened in Japan. In our institution, we have extended lymphatic and connective tissue clearance during surgical resection of this cancer. As a result, the 5-year survival rate has increased from 8% to 25% due to a significant decrease in the incidence of locoregional recurrence. The prognostic benefit gained by this procedure is seen mainly in those patients with stage III cancer or in whom no positive nodes were detected beyond the pancreatic head region. Thus, our extended surgery seems to have been useful due to eradicating the microinvasion in the peripancreatic connective tissues, rather than dissecting the positive lymph nodes. More advanced cancers should be treated by effectively combining chemo- and/or radiation-therapies with surgery. In order to cure the patients more easily with less-invasive surgery in the future, we should develop both an early diagnosis system and sensitive examinations of micrometastases or microinvasions.
UI - 11915725
AU - Doi R; Fujimoto K; Wada M; Imamura M
TI - [Current status of adjuvant therapy for pancreatic cancer]
SO - Gan To Kagaku Ryoho 2002 Mar;29(3):370-5
AD - Dept. of Surgery & Surgical Basic Science, Kyoto University Graduate School of Medicine, 54 Shogoinkawara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Pancreatic cancer is considered to be one of the malignancies most resistant to therapy. It is characterized by early local invasion and distant spread. Therefore, resection with curative intent is limited to a very small proportion of patients. Even in these selected patients, long-term survival remains very poor because of liver and local recurrence. Therefore, control of occult liver metastasis and local residual tumor with perioperative radiotherapy and chemotherapy may provide some palliative benefits, and should have some impact on overall survival. However, none of the studies to date are considered definitive. Japanese pancreatic surgeons have developed a number of adjuvant therapies which theoretically could be good enough to prolong long term survival, however, they have not been tested in randomized controlled trials. Planning co-operative studies on this important issue in pancreatic cancer therapy is urgently needed.
UI - 11915726
AU - Okada S
TI - [Radiotherapy and chemotherapy for unresectable pancreatic cancer]
SO - Gan To Kagaku Ryoho 2002 Mar;29(3):376-82
AD - Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Despite many advances in the diagnosis of pancreatic cancer (PC), only a small minority of patients are candidates for surgical resection with curative intent. Moreover, even for these selected patients, the prognosis remains unfavorable because of postoperative recurrence. Accordingly, to improve the prognosis of PC, there is an urgent need to develop effective non-surgical treatments for this disease. Radiotherapy (RT) alone does not have a significant clinical impact in PC, but when combined with chemotherapy (CHT), it provides a survival benefit in locally unresectable PC. However, to establish optimal methods of combining RT with CHT, newer approaches such as specialized RT techniques and new CHT agents are actively being pursued. At present CHT for PC has only limited value in clinical practice due to the lack of any individual agent with a truly high level of activity. The strategies for effective CHT in PC include biochemical modulation of anticancer agents, multi-agent CHT, and new agents with different mechanisms of action. Among these strategies, the identification of more effective new agents is a high priority in developing a truly effective CHT for PC. The novel nucleoside analog gemcitabine has the potential to produce better results than those achieved with 5-FU, and has been accepted as first-line CHT for patients with advanced PC. Moreover, increased understanding of the biology of PC should facilitate the development of entirely novel treatment options. We must continue to actively search for more effective non-surgical treatments for PC.
UI - 11915727
AU - Homma H; Niitsu Y
TI - [A new regional arterial infusion chemotherapy for patients with advanced pancreatic cancer]
SO - Gan To Kagaku Ryoho 2002 Mar;29(3):383-9
AD - Gastroenterology Center, Tokeidai Hospital, 2-3 North 1 East 1, Chuo-ku, Sapporo 060-0031, Japan.
Various arterial infusion chemotherapies have been tried for the purpose of local control of advanced pancreatic carcinoma. However, these treatments were not effective against the primary lesion because of its special anatomical position and the complex hemodynamics, although they were effective against the liver metastases. Therefore, the vascular supply distribution was altered by superselective embolization to control the primary legion in the pancreas, after transcatheter peripancreatic arterial embolization toward the primary site. Furthermore, bilateral (hepatic and splenic) arterial infusion chemotherapy was applied to both the primary site and liver metastasis. As a result, the response rate was 73.9%, with a mean survival period 18.26 +/- 10.06 months. We believe that the current chemotherapy was an effective treatment for unresectable pancreatic cancer since it was possible to treat patients with little harm to their quality of life.
UI - 11915728
AU - Yahara N; Oka M
TI - [Immunotherapy for unresectable pancreatic cancer]
SO - Gan To Kagaku Ryoho 2002 Mar;29(3):390-7
AD - Dept. of Digestive Surgery and Surgical Oncology (Surgery II), Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
To treat unresectable pancreatic cancer, we have performed cell therapies using lymphokine-activated killer cell, cytotoxic T lymphocytes (CTLs) induced by mixed lymphocyte culture (MLC) with autologous tumor cells, and CTL recognizing MUC1 induced by MLC with an allogeneic pancreatic tumor cells line, YPK-1. CTL therapy was effective in some cases. We also performed cell therapy using MUC1 peptide-pulsed dendritic cells (MUC1-DCs) and MUC1-CTLs. This therapy was effective in one of three cases so far. Cancer peptide vaccine therapy trials for unresectable pancreatic cancer are also ongoing. Cell therapy and peptide vaccine therapy may be promising approaches for unresectable pancreatic cancer.
UI - 11900219
AU - Shojamanesh H; Gibril F; Louie A; Ojeaburu JV; Bashir S; Abou-Saif A;
TI - Jensen RT Prospective study of the antitumor efficacy of long-term octreotide treatment in patients with progressive metastatic gastrinoma.
SO - Cancer 2002 Jan 15;94(2):331-43
AD - Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1804, USA.
BACKGROUND: Malignant pancreatic endocrine tumors (PETs) have a poor prognosis and existing antitumor treatments are unsatisfactory. Recent studies have shown somatostatin analogues to have antitumor growth effects in patients with malignant PETs; however, to the authors' knowledge, little information exists regarding their efficacy or effect on survival in patients with progressive malignant gastrinoma, the most common symptomatic malignant PET. The purpose of the current study was to study prospectively the efficacy, safety, and effect on survival of long-term treatment with octreotide in consecutive patients with progressive malignant gastrinoma. METHODS: Fifteen consecutive patients with malignant gastrinoma with progressive hepatic metastases were studied. All patients underwent conventional imaging studies (computed tomography scan, magnetic resonance imaging, ultrasound, and, if needed, selective angiography) and somatostatin receptor scintigraphy prior to treatment and at 3-6-month intervals while receiving treatment. The patients all were treated initially with octreotide, 200 microg every 12 hours, and at last follow-up were being maintained on long-acting release octreotide, 20-30 mg every month. Tumor size and/or number were used to classify patient responses as either no tumor response or tumor response (stabilization or decrease in size). Treatment response was correlated with tumor and clinical characteristics. RESULTS: Tumors in 8 of the 15 patients studied (53%) responded at 3 months, with 47% (7 of 15 patients) demonstrating tumor stabilization and 6% (1 of 15 patients) demonstrating a decrease in tumor size. The mean duration of response was 25.0+/-6.1 months (range, 5.5-54.1 months). Six of the eight responders were continuing to respond at the time of last follow-up. Tumor response did not correlate with any clinical parameter (e.g., tumor extent, fasting gastrin, or acid secretory rates). However, slow-growing tumors were more likely to respond prior to treatment (86% vs. 0%) (P < 0.0014). During follow-up (range, 4-8 years), 25% of the responders died compared with 71% of the nonresponders, a difference that approached statistical significance (P = 0.10). Two patients (13%) developed serious side effects that required the withdrawal of octreotide. CONCLUSIONS: Octreotide is an effective antitumor treatment in patients with progressive malignant gastrinoma. In approximately 50% of these patients octreotide has an antigrowth effect; treatment is associated with a low incidence of serious side effects compared with other antitumor treatments commonly used and, in contrast to many studies, the growth response is long-lasting. The results of the current study suggest that octreotide treatment should replace chemotherapy as the standard treatment for these patients, especially those patients with slow-growing tumors. Additional studies involving larger numbers of patients will be needed to determine a convincing effect on survival.
UI - 11865376
AU - Jang JY; Kim SW; Park SJ; Park YH
TI - Comparison of the functional outcome after pylorus-preserving pancreatoduodenectomy: pancreatogastrostomy and pancreatojejunostomy.
SO - World J Surg 2002 Mar;26(3):366-71
AD - Department of Surgery, Seoul National University College of Medicine, 28 Yongon-dong Chongno-ku, Seoul 110-744, Korea.
To determine if there is any difference in pancreatic function after pylorus-preserving pancreatoduodenectomy(PPPD) according to the type of pancreatoenterostomy [pancreatojejunostomy (P-J) or pancreatogastrostomy (P-G)], we evaluated the long-term functional status of 34 patients who underwent PPPD and survived for more than 1 year without clinical evidence of recurrence. Altogether 20 patients underwent P-J and 14 P-G. To compare the two groups, we analyzed the (1) general nutritional status; (2) quality of life using three scoring systems; (3) gastrointestinal symptoms; and (4) pancreatic exocrine function by the stool elastase I test and endocrine function by oral glucose tolerance test (GTT). After PPPD, body weight decreased in both groups, with no difference between the two groups. No statistical differences were found in triceps skinfold thickness or serum protein/albumin. Regarding the quality of life and postoperative gastrointestinal symptoms, there were no differences between the two groups except steatorrhea. There were 4 mild and 15 severe cases of pancreatic exocrine insufficiency among those who underwent P-J, whereas all of the patients who underwent P-G showed severe pancreatic insufficiency. On GTT, excluding preoperative diabetes patients, 43.8% (7/16) of the P-J group had abnormal results after surgery, whereas 75.0% (9/12) of the PG group had an abnormal postoperative GTT (p = 0.11). Severe exocrine and endocrine pancreatic insufficiency developed after PPPD in both the P-J and P-G groups, but there was more functional deterioration in the P-G group than in the P-J group. General nutritional status and quality of life were not affected by the pancreatoenterostomy method in either group.
UI - 11870159
AU - Rocha Lima CM; Savarese D; Bruckner H; Dudek A; Eckardt J; Hainsworth J;
TI - Yunus F; Lester E; Miller W; Saville W; Elfring GL; Locker PK; Compton LD; Miller LL; Green MR Irinotecan plus gemcitabine induces both radiographic and CA 19-9 tumor marker responses in patients with previously untreated advanced pancreatic cancer.
SO - J Clin Oncol 2002 Mar 1;20(5):1182-91
AD - H. Lee Moffitt Cancer Center, University of South Florida, Gastrointestinal Program Office, Tampa, FL 33612, USA. firstname.lastname@example.org
PURPOSE: This phase II, multicenter, open-label, single-arm study evaluated the efficacy and safety of irinotecan and gemcitabine as combination chemotherapy for previously untreated patients with unresectable or metastatic pancreatic cancer. PATIENTS AND METHODS: Patients received repeated 21-day cycles at starting doses of gemcitabine 1,000 mg/m(2) over 30 minutes followed immediately by irinotecan 100 mg/m(2) over 90 minutes, both given intravenously on days 1 and 8. Patients were evaluated for objective tumor response, changes in the serum tumor marker CA 19-9, time to tumor progression (TTP), survival, and safety. RESULTS: Forty-five patients were treated. Eleven patients (24%) had 50% or greater reductions in tumor area. These were confirmed one cycle later in nine patients (response rate, 20%; 95% confidence interval, 8% to 32%). Among 44 patients with baseline CA 19-9 determinations, CA 19-9 decreased during therapy in 22 patients (50%) and was reduced by 50% or more in 13 patients (30%). Median TTP was 2.8 months (range, 0.3 to 10.8 months). There were significant (P <.001) correlations between proportional changes in CA 19-9 and radiographic changes in tumor area with regard to extent of change (r =.67), timing of minimum on-study values (r =.85), and tumor progression (r =.89). Median survival was 5.7 months (range, 0.4 to 19.4+ months), and the 1-year survival rate was 27%. Severe toxicities were uncommon and primarily limited to grade 4 neutropenia (2%), grade 4 vomiting (2%), and grade 3 diarrhea (7%). CONCLUSION: Irinotecan/gemcitabine is a new combination that offers encouraging activity in terms of radiographic and CA 19-9 response and notable 1-year survival in pancreatic cancer. The regimen was well tolerated, with minimal grade 3 and 4 toxicities and excellent maintenance of planned dose-intensity.
UI - 11753801
AU - Hohenberger W; Schoolmann S; Kastl S
TI - [Quality management in surgery: treatment of pancreatic carcinoma--What is evidence-based?]
SO - Zentralbl Chir 2001 Nov;126(11):901-7
AD - Chirurgische Universitatsklinik Erlangen, Germany.
Summary.The term "evidence-based medicine" (EBM) - an Anglicism in common use in modern medicine - has of the nature of a catchword, the actual meaning of which is not always clear to all who use it. Generally speaking it is taken to mean that decision-making in the areas of diagnosis and treatment is based on data obtained from randomized, preferably double-blind and controlled, studies involving sufficient numbers of cases. This, however, is not always automatically equatable with arriving at a decision at the highest level of confirmed scientific knowledge, including the most recently acquired facts. Taking account of the current literature, the present article attempts an analysis of the following four aspects of surgical treatment of pancreatic carcinoma: the required extent of lymph node dissection, the relevance of multimodal treatment concepts, the significance of pylorus-preserving partial duodenopancreatectomy and the relevance of portal vein resection.
UI - 11753802
AU - Adam U; Makowiec F; Riediger H; Trzeczak S; Benz S; Hopt UT
TI - [Distal pancreatic resection--indications, techniques and complications]
SO - Zentralbl Chir 2001 Nov;126(11):908-12
AD - Chirurgische Universitatskliniken Rostock und Freiburg, Germany.
AIM: Description of the indications, surgical technique and postoperative complications of distal pancreatic resection. METHODS: We analyzed the prospectively documented perioperative data of 41 patients undergoing distal pancreatectomy between 1994 and 2001. Indications for resection were chronic pancreatitis (n = 21), malignant or benign tumors (n = 19) and others (n = 1). RESULTS: Median operation time was 4.5 hours, a Y-Roux-pancreaticojejunostomy was performed in 66 %. Further organs were resected in 93 %, most frequently in form of splenectomy. A malignant vascular invasion led to positive resection margins in three patients. Mortality was 2 %. Postoperative complications occurred in 41 % with 15 % revealing pancreatic leakage. A relaparotomy was carried out in 20 %. Pancreatic leakage was more frequently seen in the first part of the study period and after oversewing of the pancreatic stump. A new onset diabetes occurred postoperatively in 6 % of the patients. CONCLUSIONS: Distal pancreatectomy can be carried out with low mortality, despite a high complication rate. The probability of postoperative diabetes is low. The frequency of pancreatic leakage may be reduced significantly by increasing hospital experience. The management of the pancreatic stump by pancreatojejunostomy should be considered in patients with a high risk of pancreatic leakage.
UI - 11753803
AU - Stumpf M; Kasperk R; Bertram P; Truong S; Schumpelick V
TI - [Role of surgical biliary bypass for palliation of pancreatic cancer - a retrospective study of 107 cases]
SO - Zentralbl Chir 2001 Nov;126(11):913-6
AD - Chirurgische Klinik und Poliklinik, Medizinische Fakultat, Rheinisch-Westfalische Technische Hochschule, Aachen, Germany.
BACKGROUNDS AND STUDY AIMS: At the time of diagnosis most patients with pancreatic cancer are still irresectable for cure. The aim of this study was to evaluate surgical palliation, in particular against the background of endoscopic stent placement. PATIENTS AND METHODS: This retrospective study analyses the therapeutic results in 107 patients with an irresectable pancreatic carcinoma operated on between 1990 and 1998. RESULTS: 104 patients showed primary therapeutic success with adequate bile drainage. In 97 % a simultaneous gastrojejunostomy was performed. The overall complication rate was 24 % and the hospital mortality 3.7 %. Median survival after surgical treatment was 201 days. CONCLUSIONS: Because of a decrease in perioperative morbidity and mortality, surgical palliation of irresectable pancreatic carcinoma still remains an effective therapy, especially for patients expected to survive 6 months or more. The surgical procedure offers the better chance for long-term palliation of obstructive jaundice and duodenal obstruction compared to the endoscopic approach. However, to consider both, the surgical and the endoscopic treatment, complementing each other, seems to be important to guarantee optimal palliation for the individual patient.
UI - 11762810
AU - Halford S; Yip D; Karapetis CS; Strickland AH; Steger A; Khawaja HT;
TI - Harper PG A phase II study evaluating the tolerability and efficacy of CAELYX (liposomal doxorubicin, Doxil) in the treatment of unresectable pancreatic carcinoma.
SO - Ann Oncol 2001 Oct;12(10):1399-402
AD - Department of Medical Oncology, Guy's Hospital, London, UK.
BACKGROUND: Preclinical studies of liposomal doxorubicin (CAELYX) have demonstrated significant inhibition of growth of human pancreatic cancer explants in nude mice. This study evaluated the efficacy of CAELYX in chemotherapy-naive patients with unresectable, histologically confirmed pancreatic carcinoma. Secondary endpoints were quality of life (QOL). time to progression and overall survival. PATIENTS AND METHODS: Twenty-two patients (median age 65) were enrolled. CAELYX was administered to the first five patients at a dose of 30 mg/m2 three-weekly. Two of these patients were dose escalated to 50 mg/m2 four-weekly. Subsequent patients were all treated on the latter schedule. RESULTS: Two patients died after consenting to enter the study but before treatment was commenced and are not included in the analysis. Sixteen patients were evaluable for response. No objective responses were seen. Six patients had stable disease. One patient experienced grade 4 toxicity with palmar plantar dysaesthesia (PPE), but continued treatment after dose reduction and delay. Four patients experienced grade 3 stomatitis and two grade 3 nausea. Median survival from time of starting chemotherapy was 3.2 months (range 21 days to 19 months) and one year survival was 10%. Eight patients completed at least two EORTC QLQ C-30 questionnaires. There was no significant change in either global QOL or in any functional or symptom subscale score. CONCLUSION: No objective responses were seen with CAELYX in this study. CAELYX was however associated with stable disease, but data were inconclusive with regard to clinical benefit. It warrants further investigation in the context of combination trials.
UI - 11807364
AU - Murakami H; Suzuki H; Nakamura T
TI - Pancreatic fibrosis correlates with delayed gastric emptying after pylorus-preserving pancreaticoduodenectomy with pancreaticogastrostomy.
SO - Ann Surg 2002 Feb;235(2):240-5
AD - Department of Surgery, Kainan Hospital, Aichi, Japan.
OBJECTIVE: To show that residual pancreatitis delays gastric emptying, the authors used surgical specimens and studied gastric stasis after pylorus-preserving pancreaticoduodenectomy (PPPD). SUMMARY BACKGROUND DATA: Delayed gastric emptying is a leading cause of complications after PPPD, occurring in 30% of patients. The pathogenesis of delayed gastric emptying remains unclear. METHODS: Surgical specimens of the pancreas from 25 patients undergoing PPPD and pancreaticogastrostomy were collected and examined by microscopy according to progressive pancreatic fibrosis and divided into three groups: no fibrosis, periductal fibrosis, and intralobular fibrosis. The authors then measured gastric output from the nasogastric tube, pancreatic output from the pancreatic tube, and the time until patients tolerated a solid diet. RESULTS: Pancreatic juice output was significantly related to the degree of pathologic findings, and gastric output was inversely related to them. A significant prolongation of postoperative solid diet tolerance correlated with increased pancreatic fibrosis and gastric fluid production. CONCLUSIONS: Pancreatic fibrosis and increased gastric fluid production correlate with delayed gastric emptying after PPPD with pancreaticogastrostomy.
UI - 11920457
AU - Colucci G; Giuliani F; Gebbia V; Biglietto M; Rabitti P; Uomo G;
TI - Cigolari S; Testa A; Maiello E; Lopez M Gemcitabine alone or with cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a prospective, randomized phase III study of the Gruppo Oncologia dell'Italia Meridionale.
SO - Cancer 2002 Feb 15;94(4):902-10
AD - Medical and Experimental Oncology Unit, Oncology Institute, Bari, Italy. email@example.com
BACKGROUND: A prospective, randomized Phase III trial was performed to determine whether, compared with gemcitabine (GEM) alone, the addition of cisplatin (CDDP) to GEM was able to improve the time to disease progression and the clinical benefit rate in patients with advanced pancreatic adenocarcinoma. The objective response rate, overall survival rate, and toxicity patterns of patients in the two treatment arms were evaluated as secondary end points. METHODS: Patients with measurable, locally advanced and/or metastatic pancreatic adenocarcinoma were randomized to receive GEM (Arm A) or a combination of GEM and CDDP (Arm B). In Arm A, a dose of 1000 mg/m(2) GEM per week was administered for 7 consecutive weeks, and, after a 2-week rest, treatment was resumed on Days 1, 8, and 15 of a 28-day cycle for 2 cycles. In Arm B, CDDP was given at a dose of 25 mg/m(2) per week 1 hour before GEM at the same dose that was used in Arm A. On Day 22, only GEM was administered. Patients were restaged after the first 7 weeks of therapy and then again after the other 2 cycles. RESULTS: A total of 107 patients entered the trial: Fifty-four patients were randomized to Arm A, and 53 patients were randomized to Arm B. The median time to disease progression was 8 weeks in Arm A and 20 weeks in Arm B; this difference was statistically significant (P = 0.048). In Arm A, one complete response and four partial responses were recorded on the basis of an intent-to-treat analysis, with an overall response rate of 9.2% (95% confidence interval [95%CI], 3-20%). In Arm B, there were no complete responses, whereas 14 partial responses were achieved, with an overall response rate of 26.4% (95%CI, 15-40%). This difference in the overall response rates was statistically significant (P = 0.02). The tumor growth control rate (i.e., total number of patients who achieved complete responses, partial responses, and stable disease) was 42.6% (95%CI, 29-57%) in Arm A and 56.6% (95%CI, 42-70%) in Arm B. A clinical benefit was observed in 21 of 43 patients (49%) in Arm A and in 20 of 38 patients (52.6%) in Arm B without any significant difference. The median overall survival was 20 weeks for patients in Arm A and 30 weeks for patients in Arm B (P = 0.43). Toxicity was mild in both treatment arms, with no significant differences between the two groups except for the statistically higher incidence of Grade 1-2 asthenia in Arm B (P = 0.046). CONCLUSIONS: The addition of CDDP to GEM significantly improved the median time to disease progression and the overall response rate compared with GEM alone. The clinical benefit rate was similar in both arms, whereas the median overall survival rate was more favorable for Arm B, although the difference did not attain statistical significance. The authors conclude that the combination of CDDP and GEM currently may be considered as an optimal treatment for patients with locally advanced and/or metastatic adenocarcinoma of the pancreas. Copyright 2002 American Cancer Society. DOI 10.1002/cncr.10323
UI - 11875595
AU - Wiersema MJ
TI - Identifying contraindications to resection in patients with pancreatic carcinoma: the role of endoscopic ultrasound.
SO - Can J Gastroenterol 2002 Feb;16(2):109-14
AD - Eisenberg 8A, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. firstname.lastname@example.org
OBJECTIVE: To present recently published material comparing the performance of endosonography relative to other imaging modalities when evaluating the patient with a suspected or known pancreas carcinoma. METHODS: Medline was searched using the terms "endosonography" and "pancreas neoplasms". References from retrieved papers were reviewed to identify other reports. Emphasis was placed on peer-reviewed material published within the past three years that included comparison with other imaging modalities. RESULTS: Despite advances in cross-sectional imaging modalities, endosonography remains the most sensitive and specific method for identifying pancreatic mass lesions. The resectability of pancreatic carcinoma is best determined with dual-phase helical computed tomography, although endosonography may be slightly more accurate for lymph node assessment. Endoscopic ultrasound-guided fine needle aspiration biopsy has a high sensitivity (93%) and specificity (100%) when used in patients with masses in whom pancreatic cancer is suspected but prior biopsies have been negative. CONCLUSIONS: Endosonography helps in the diagnosis of pancreatic neoplasms through definitive inclusion or exclusion of a mass lesion as well as biopsy confirmation of malignancy. The role of endosonography in the determination of resectability has been eclipsed by dual-phase helical computed tomography. However, endoscopic ultrasound with fine needle aspiration of nonperitumoral lymph nodes may identify advanced disease with sufficient frequency to justify its routine use in patients with lesions that are thought to be resectable based on helical computed tomography.
UI - 11875596
AU - Beger HG; Gansauge F; Leder G
TI - Pancreatic cancer: who benefits from curative resection?
SO - Can J Gastroenterol 2002 Feb;16(2):117-20
AD - Department of General Surgery, University Hospital, University of Ulm, Steinhovelstrasse 9, D-89075 Ulm Donau, Germany. email@example.com
Surgical resection is the only chance for cure of pancreatic cancer. Unfortunately, the majority of patients have grossly unresectable disease. Patients with stage I or II disease according to the criteria of the International Union Against Cancer (UICC) should be considered for potentially curative surgery. The goal of surgery is to remove the entire tumour with no residual disease (oncological R0 resection), which requires extensive resection of the surrounding tissues. Even if lymph nodes are histologically free of disease, molecular biological techniques reveal infiltration with cancer cells in 50% of cases. Therefore, extensive local resection combined with radical resection of lymphatic tissue, including lymph nodes around the head of the pancreas, retroperitoneal tissue and neural plexus around the great vessels, affords a longer median survival time than standard resection alone. Even patients with UICC stage III disease can undergo aggressive surgical treatment, but their chances for long term survival are low. Some patients develop severe diarrhea after circumferential removal of nerve tissue around the superior mesenteric artery. Adjuvant radiochemotherapy also provides a modest prolongation of survival. Despite these advances, the prognosis for pancreatic cancer is still poor, and spread of tumour within the peritoneum and to the liver is common postoperatively.
UI - 11875597
AU - Moore MJ
TI - Pancreatic cancer: what the oncologist can offer for palliation.
SO - Can J Gastroenterol 2002 Feb;16(2):121-4
AD - Department of Medicine, Princess Margaret Hospital, University of Toronto, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada. firstname.lastname@example.org
Because pancreatic cancer has a poor survival rate and only 20% of patients present with potentially resectable disease, a key goal of therapy is to provide palliation. The poor medical condition of many patients interferes with their ability to tolerate traditional chemotherapy. Recently, however, a nucleoside analogue, gemcitabine, has been developed. This drug is more effective than 5-fluorouracil (5-FU), can be used in patients who fail to respond to 5-FU and has only modest toxicity. Combination therapies including gemcitabine and other agents are being tested. Local radiotherapy seems to provide pain relief, but gastrointestinal toxicity is significant. The effect of combined modality therapy (5-FU with radiotherapy) on survival is unclear, and it does not prevent local disease progression. Some novel biological agents, including angiogenesis inhibitors, matrix metalloproteinase inhibitors, antisense compounds, inhibitors of cell signalling such as epidermal growth factor and vascular endothelial growth factor, and inhibitors of oncogene activation, are undergoing phase II and III trials in patients with pancreatic cancer. Among the most promising are farnesyl protein transferase inhibitors, which modulate K-ras function. Such an approach is promising for the treatment of pancreatic cancer because this tumour frequently exhibits mutation of the ras gene.
UI - 11894005
AU - Heinemann V
TI - Gemcitabine-based combination treatment of pancreatic cancer.
SO - Semin Oncol 2002 Feb;29(1 Suppl 3):25-35
AD - Klinikum Grosshadern, III Medical Clinic, Munich, Germany.
Since the introduction of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN), pancreatic cancer may no longer be regarded as a completely chemotherapy-resistant tumor. Good treatment tolerability and a low incidence of side effects are clear advantages of single-agent gemcitabine and enable its integration into combination regimens. Currently, the most widely used regimens involve combination partners such as 5-fluorouracil (5-FU), cisplatin, and docetaxel. Combinations of gemcitabine with cisplatin or 5-FU appear comparably active and tolerable. Comparative analysis of multiple phase II studies performed with gemcitabine/cisplatin showed response rates in the range of 11.4% to 58% and median survival times of 7.4 to 10 months, whereas various gemcitabine/5-FU-based regimens achieved response rates of 3.7% to 25% and median survival times of 4.4 to 10.3 months. In view of the great variety of schedules and inconclusive treatment results, an optimal regimen for the combination of 5-FU and gemcitabine still needs to be defined. Although the combination of gemcitabine with docetaxel has demonstrated activity, data showing a clear survival benefit are not yet available. It is also premature to evaluate the activity of combinations with irinotecan or oxaliplatin. Four-drug regimens indicate a possible improvement in treatment outcome. However, their application may be limited to selected patients with good performance status. Copyright 2002, Elsevier Science (USA). All rights reserved.
UI - 11896099
AU - Louvet C; Andre T; Lledo G; Hammel P; Bleiberg H; Bouleuc C; Gamelin E;
TI - Flesch M; Cvitkovic E; de Gramont A Gemcitabine combined with oxaliplatin in advanced pancreatic adenocarcinoma: final results of a GERCOR multicenter phase II study.
SO - J Clin Oncol 2002 Mar 15;20(6):1512-8
AD - Service d'Oncologie-Medecine Interne, Hopital Saint-Antoine, Service d'Oncologie, Hopital Tenon, and GERCOR, Paris, France. email@example.com
PURPOSE: Based on preclinical in vitro synergy data, this study evaluated the activity and toxicity of a gemcitabine/oxaliplatin combination in patients with metastatic and locally advanced pancreatic adenocarcinoma. PATIENTS AND METHODS: Previously untreated metastatic and locally advanced unresectable pancreatic adenocarcinoma patients were enrolled onto this multicenter phase II study. Patients received gemcitabine 1,000 mg/m(2) as a 10-mg/m(2)/min infusion on day 1 and oxaliplatin 100 mg/m(2) as a 2-hour infusion on day 2 every 2 weeks. Patients with metastatic disease were treated until evidence of progressive disease, whereas patients with locally advanced disease received six cycles in the absence of progression, followed when appropriate by concomitant radiochemotherapy. RESULTS: Among 64 eligible patients included in eight centers, 30 had locally advanced and 34 had metastatic disease. Response rate for the 62 patients with measurable disease was 30.6% (95% confidence interval, 19.7% to 42.3%), 31.0% for locally advanced and 30.3% for metastatic patients. Among 58 assessable patients, 40% had clinical benefit. Median progression-free survival and median overall survival (OS) were 5.3 and 9.2 months, respectively, with 36% of patients alive at 1 year. Median OS for patients with metastatic disease and locally advanced disease were 8.7 and 11.5 months, respectively. With 574 treatment cycles (median per patient, nine; range, zero to 27), grade 3/4 toxicity per patient was 11% for neutropenia and thrombocytopenia, 14% for nausea or vomiting, 6.2% for diarrhea, and 11% for peripheral neuropathy, with no toxic deaths. CONCLUSION: Palliative effects, response rate, and survival observed with this well-tolerated gemcitabine/oxaliplatin combination deserve additional evaluation. A comparative study of combination therapy versus gemcitabine alone is ongoing.
UI - 11819168
AU - Gebhardt C
TI - [Pancreaticojejunal anastomosis. Indication, technique and results]
SO - Zentralbl Chir 2001;126 Suppl 1():29-31
AD - Klinik fur Abdominal, Thorax und Endokrine Chirurgie, Klinikum Nurnberg Nord.
Pancreaticojejunal anastomosis. Indication, technique and results.Pancreaticojejunal anastomoses are performed for the treatment of chronic pancreatitis and after resection of pancreatic carcinomas. In chronic pancreatitis by drainage procedures (Partington-Rochelle and Puestow-Gillesby) one can expect good long term results, if the diameter of the pancreatic duct is at least 1 cm and the length of the anastomosis 6 cm. The duodenumpreserving head resection (Beger or Frey) is a combination of resection and drainage and is significant in the therapy of inflammatory head processes. In the surgical treatment of pancreatic carcinomas pancreaticojejunostomies are applied after head resection (Whipple-, pyloruspreserving modification). The end-to-side mucosa-mucosa anastomosis offers the best results concerning postoperativ complications and mortality rates.
UI - 11925720
AU - Ducreux M; Baudin E; Schlumberger M
TI - [Treatment strategy of neuroendocrine tumors]
SO - Rev Prat 2002 Feb 1;52(3):290-6
AD - Unite de gastroenterologie Institut Gustave Roussy 94805 Villejuif. firstname.lastname@example.org
Therapeutic strategy of neuroendocrine tumours is complex, due to their heterogeneity and to the fact that although generally slow growing, a significant proportion demonstrates aggressive tumour growth. Symptomatic carcinoid syndrome and various pancreatic endocrine tumours with symptomatic syndromes are well controlled with somatostatin analogues. Surgery remains the mainstay of treatment if the tumour can be resected. Metastatic pancreatic neuroendocrine tumour are treated when resection is not feasible with combination chemotherapy using adriamycin and streptozotocin, which remains a standard of care. In well differentiated tumour of the gut or the lung there is no clear standard of chemotherapy and treatment vary according to the tumour course. In indolent cases, somatostatin analogues are the best treatment, in case of aggressive tumours chemoembolisation should be preferred when the disease is located or predominant in the liver. Poorly differentiated tumours are treated by combination chemotherapy with etoposide and cisplatin, and surgery has no indication. Gastrinoma and other pancreatic tumours arising in the context of multiple endocrine neoplasia type I disease need a specific therapeutic strategy.
UI - 9717985
AU - Von Hoff DD; Goodwin AL; Garcia L
TI - Advances in the treatment of patients with pancreatic cancer: improvement in symptoms and survival time. The San Antonio Drug Development Team.
SO - Br J Cancer 1998;78 Suppl 3():9-13
AD - Institute for Drug Development, Cancer Therapy & Research Center, San Antonio, Texas 78245, USA.
Pancreatic cancer is a major cause of death from cancer in both men and women in the USA and Europe. The disease causes pain and has a significant impact on the performance status of the patient. In a randomized trial vs 5-fluorouracil, the novel nucleoside analogue gemcitabine (GEMZAR) has been shown to provide clinical benefit for patients (decreased pain and improved performance status) as well as to improve the time to tumour progression and survival for patients with the disease. There are also other new agents that are presented in this discussion, such as the multi-targeted antifolate MTA, capecitabine and the ONYX-015 adenovirus, which replicates in, and kills, only p53-abnormal cells, which have the potential to have an impact on this terrible disease.
UI - 10226533
AU - Kornmann M; Kleeff J; Debinski W; Korc M
TI - Pancreatic cancer cells express interleukin-13 and -4 receptors, and their growth is inhibited by Pseudomonas exotoxin coupled to interleukin-13 and -4.
SO - Anticancer Res 1999 Jan-Feb;19(1A):125-31
AD - Department of Medicine, University of California, Irvine 92697, USA. email@example.com
BACKGROUND: Interleukin (IL)-13 and -4 are multifunctional cytokines that bind to specific cell-surface receptors. The aim of this study was to determine whether pancreatic cancer cells express either receptor, and to assess the growth suppressive effects of chimeric proteins composed of a Pseudomonas exotoxin (PE) A mutant (PE38QQR) fused to IL-13 (IL-13-PE38QQR) or IL-4 (IL-4-PE38QQR) in these cells. MATERIALS AND METHODS: Northern and Western blot analysis were used to analyze the expression of IL-4/-13 receptors and the common gamma chain (gamma c) in pancreatic cancer cell lines. MTT growth assays were carried out to assess the effect