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Objective We aimed to determine the safety and efficacy of irreversible electroporation (IRE) combined with chemotherapy for unresectable pancreatic carcinoma (stage III/IV). Methods We prospectively enrolled 54 patients (30 men; median age 61.0 years; range 41-73 years) undergoing IRE with or without chemotherapy for pancreatic cancer between July 2015 and August 2016. Kaplan-Meier estimates were used to analyze progression-free survival (PFS) and overall survival (OS). Safety was assessed based on the occurrence of adverse events. Results All patients successfully underwent IRE. Major IRE-related complications were observed in four patients (7.4%). Gastrointestinal hemorrhage only developed in cases undergoing IRE via the open method, and was successfully managed with interventional embolization and/or vascular ligation. Any minor complications in the cases were alleviated within 14 days after symptomatic treatment. Overall, the performance status score decreased from 1.06 to 0.89 at 3 months after IRE (P

Background: Surgery may trigger the release of inflammatory factors, including cytokines, growth factors and angiogenic factors, which may stimulate tumor growth and progression. The present study was undertaken to evaluate the impact of surgical exploration on survival of patients with potentially resectable pancreatic cancer, who intraoperatively were found to have unresectable disease. Methods: Patients with pancreatic adenocarcinoma undergoing surgical exploration, without tumor resection, at our institution between 2009 and 2014, were selected and case-matched to patients who underwent primary palliative treatment. Results: A total of 116 patients were included. The surgical exploration group (n = 29) had significantly lower CRP levels at the time of diagnosis compared to the palliative controls (n = 87), 4 mg/L vs 12 mg/L; p = 0.004. The percentage of patients who received palliative chemotherapy was comparable between groups, but the time until start of chemotherapy was significantly longer in the surgical exploration group, 2 months vs 1 months; p < 0.001. Median survival was 7.3 months (95% confidence interval (CI): 4.6 - 11.3 months) in the surgical exploration group and 6.8 months (95% CI: 4.7 - 8.6 months) in the palliative group, p = 0.898. In a multivariable Cox regression model, surgical exploration was not significantly associated with increased mortality risk (hazard ratio 1.06; 95% CI: 0.69 - 1.64, p = 0.782). Conclusion: In this case-control study, we could not detect any survival disadvantage due to surgical exploration in the setting of unresectable pancreatic cancer. Surgical exploration was associated with delayed start of palliative chemotherapy, but the percentage of patients who ultimately received chemotherapy was comparable to patients undergoing primary palliative treatment.

Pancreatic carcinoma (PC) is a highly malignant cancer featured by very poor prognosis. Radical surgical resection is the most curative way at present. However, owing to lack of symptoms at early stage and rapid progression, 80% of patients are considered not amenable to surgical resection because of locally advanced or metastatic condition when diagnosed. Up to a third of the remaining 20% of patients eligible for surgical exploration before operation are found to be unresectable during operation [1]. Unfortunately, most of patients are not amenable to toxic and side effects of radiotherapy or chemotherapy drug either. In addition, the sensitivity of pancreatic cancer cells to chemotherapy drug is very poor. So generally, therapeutic outcome of pancreatic cancer is dismal. What is worse, patients with PC often present with malignant obstructive jaundice and duodenal obstruction, the rate of incidence of which is 75% and 20%, respectively [1]. Jaundice would cause pruritus, nausea, coagulopathy, and, most severely, hepatorenal dysfunction and endotoxemia, which may directly lead to the death of patients. Duodenal obstruction leads to malnourishment and intractable vomiting [2]. Both obstructions negatively affect quality of life and prognosis. Therefore, aside from improving effectiveness of curative treatment to prolong survival, palliative treatment to relieve pain and improve quality of life is another significant aspect of treatment for patients with unresectable pancreatic carcinoma.

Objectives Percutaneous stenting is a palliative method to relieve obstructive jaundice caused by unresectable pancreatic carcinoma. In this study, we aimed to compare the safety and efficacy of irradiation stents and conventional metal stents. Methods A total of 32 patients who received irradiation stents or conventional metal stents to treat obstructive jaundice caused by locally advanced pancreatic cancer were included in this retrospective study. Chemotherapy using gemcitabine was performed after jaundice subsided. Stent patency, technical success, survival, and complications were compared between groups. Results Seventeen patients were enrolled in the irradiation stent group (ISG), and 15 patients were enrolled in the uncovered stent group (USG). Median and mean stent patency time were 9.8 months (95% CI, 7.682–11.981) and 9.506 months (95% CI, 8.0–11.012) in the ISG, respectively, vs 8.8 months (95% CI, 6.528–11.072) and 7.62 months (95% CI, 5.917–9.323) in the USG, respectively (P = 0.019). Median and mean overall survival were 10.4 months (95% CI, 8.383–12.417) and 9.953 months (95% CI, 8.408–11.498), respectively, in the ISG vs 9.7 months (95% CI, 7.901–11.499) and 8.14 months (95% CI, 6.44–9.84), respectively, in the USG (P = 0.027). Conclusions Irradiation stents extend stent patency and overall survival compared with conventional biliary stents for the treatment of pancreatic carcinoma complicated by obstructive jaundice. Irradiation stents combined with chemotherapy may be a better choice for the treatment of obstructive jaundice caused by unresectable pancreatic carcinoma.

Although different treatment methods have been introduced to treat advanced pancreatic carcinoma, the median overall survival rate remains unsatisfactory. Theoretically, combining different treatment methods should work in synergy to enhance locoregional disease control and improve survival. Therefore, the aim of the present retrospective study was to analyze the effectiveness of combined interventional therapy compared with trans-arterial chemoembolization (TACE) or chemotherapy alone for the treatment of unresectable pancreatic carcinoma. A total of 266 patients who were undergoing treatment for unresectable pancreatic carcinoma between July 2012 and November 2015 were included in the current study. The tumor responses and 3-year overall survival rates of patients treated with combined interventional therapy (TACE combined with iodine-125 seed implantation and/or radiofrequency ablation; CIT group; n=84) were compared with those of patients treated with TACE alone (TACE group; n=59), as well as patients treated with systemic chemotherapy alone (control group; n=123). Patients in the CIT group exhibited significantly improved tumor responses compared with patients in the TACE group (51.89 vs. 30.61%; P=0.028) or control group (51.89 vs. 17.20%; P

The purpose of the study was to investigate the role of iodine-125 seed implantation, guided by endoscopic ultrasound (EUS) and/or percutanous ultrasound, in patients with unresectable pancreatic carcinoma after relief of obstructive jaundice using endoscopic retrograde cholangiopancreatography (ERCP).A total of 101 patients with obstructive jaundice due to unresectable pancreatic carcinoma were enrolled between January 2010 and December 2017 in this retrospective study. Of these patients, 50 underwent implantation of iodine-125 seeds under EUS and/or percutaneous ultrasound guidance after receiving a stent via ERCP (treatment group), and 51 received a stent via ERCP without undergoing seed implantation (control group). The clinical data and therapeutic outcomes of these patients were analyzed.Compared with the control group, the treatment group obtained significant relief of abdominal pain at the 1-week, 1-month, and 3-month followup (p0.05), with a significantly lower visual analog scale pain score (p0.05). The treatment group obtained a longer median survival (8.8 vs. 6.5 months, p = 0.02), longer median duration of stent patency (10.8 ± 1.4 vs. 6.9 ± 0.8 months, p = 0.02), and prolonged average time to gastric outlet obstruction (6.8 ± 1.6 vs. 5.3 ± 1.3 months, p = 0.02). Differences between liver function and appetite for the two groups were not significant (p0.05 and p = 0.59, respectively).Iodine-125 seed implantation after relief of obstructive jaundice via ERCP prolongs survival, biliary stent patency, and time to gastric outlet obstruction and improves patient quality of life by relieving pancreatic pain in patients with unresectable pancreatic carcinoma.

Recently, several reports demonstrated the efficacy of neoadjuvant chemotherapy (NAC) or chemoradiotherapy (NACRT) for patients with borderline resectable (BRPC) and locally advanced unresectable pancreatic carcinoma (LAPC). The aim of this study was to evaluate the treatment response after NACRT, especially for nerve plexuses, and the optimal resection area for superior mesenteric artery nerve plexuses in BRPC and LAPC patients after NACRT. A total of 17 patients with BRPC and LAPC received preoperative gemcitabine-based NACRT. The numbers of BRPC and LAPC patients were 13 and 4, respectively. We evaluated nerve plexus invasion by CT before and after NACRT, decided on the resection area of plexus invasion in SMA before NACRT, and compared the preoperative evaluation and clinicopathological findings. In the plexus of the supra-mesenteric artery (pl-SMA), arterial nerve plexus invasion, in cases

Background: The prognosis for unresectable locally advanced pancreatic adenocarcinoma (LAPC) remains poor. There is increasing interest in modern ablative techniques to improve outcomes. We report on the potential value of integrating percutaneous irreversible electroporation (IRE) in patients undergoing systemic chemotherapy. Methods: Seventy-five patients with unresectable pancreatic carcinoma underwent percutaneous IRE after chemotherapy using computerised tomography guidance under general anaesthesia. Postoperative immediate and 30-day morbidity and mortality, progression-free (PFS) and overall survival (OS) were evaluated. Results: Post-procedural immediate and 30-day mortality rates were both zero. All-grade adverse events were 25%. Median in-patient stay was 1 day (range 1–5 days). Median OS and PFS post-IRE for LAPC were 27 and 15 months respectively. Four patients with LAPC down-staged post-IRE ablation to be surgically resectable, with R0 resections in 3 cases. Conclusions: These results suggest that percutaneous IRE ablation of unresectable LAPC is safe to integrate with standard-of-care chemotherapy and may improve survival, which provides a template for further evaluation in prospective randomized clinical trials.

Pancreatic carcinoma is often inoperable, carries a poor prognosis, and is commonly complicated by malignant biliary obstruction. Phase I/II studies have demonstrated good safety and early stent patency using endoscopic biliary radiofrequency ablation (RFA) as an adjunct to self-expanding metal stent (SEMS) insertion for biliary decompression. To analyze the clinical efficacy of endobiliary RFA. Retrospective case–control analysis was carried out for 23 patients with surgically unresectable pancreatic carcinoma and malignant biliary obstruction undergoing endoscopic RFA and SEMS insertion and 46 controls (SEMS insertion alone) in a single tertiary care center. Controls were stringently matched for age, sex, metastases, ASA/comorbidities. Survival, morbidity, and stent patency rates were assessed. RFA and control groups were closely matched—ASA 2.35 ± 0.65 versus 2.54 ± 0.50, p = 0.086; metastases 9/23 (39.1 %) versus 18/46 (39.1 %), p = 0.800; chemotherapy 16/23 (69.6 %) versus 24/46 (52.2 %), p = 0.203. Median survival in RFA group was 226 days (IQR 140–526 days) versus 123.5 days (IQR 44–328 days) in controls (p = 0.010). RFA was independently predictive of survival at 90 days (OR 21.07, 95 % CI 1.45–306.64, p = 0.026) and 180 days (OR 4.48, 95 % CI 1.04–19.30, p = 0.044) in multivariate analysis. SEMS patency rates were equivalent in both groups. RFA was well tolerated with minimal side effects. Endoscopic RFA is a safe and efficacious adjunctive treatment in patients with advanced pancreatic malignancy and biliary obstruction and may confer early survival benefit. Randomized prospective clinical trials of this new modality are mandated.

For patients with unresectable pancreatic cancer, current chemotherapies have negligible survival benefits. Thus, developing effective minimally invasive therapies is currently underway. This study was conducted to evaluate the efficacy of transarterial chemoembolization plus radiofrequency ablation and/or 125I radioactive seed implantation on unresectable pancreatic cancer. We analyzed the outcome of 71 patients with unresectable pancreatic carcinoma who underwent chemoembolization plus radiofrequency ablation and/or radioactive seed implantation. Of the 71 patients, the median survival was 11 months, and the 1-, 2-, and 3-year overall survival rates were 32.4%, 9.9%, and 6.6% respectively. Patients who had no metastasis, who had oligonodular liver metastases (≤3 lesions), and who had multinodular liver metastases (>3 lesions) had median survival of 12, 18, and 8 months, respectively, and 1-year overall survival rates of 50.0%, 68.8%, and 5.7%, respectively. Although the survival of patients without liver metastases was worse than that of patients with oligonodular liver metastasis, the result was not significant (P = 0.239). In contrast, the metastasis-negative patients had significantly better survival than did patients with multinodular liver metastases (P < 0.001). Patients with oligonodular liver lesions had a significanthg longer median survival than did patients with multinodular lesions (P < 0.001). In conclusion, combined minimally invasive therapies had good efficacy on unresectable pancreatic cancer and resulted in a good control of liver metastases. In addition, the number of liver metastases was a significant factor in predicting prognosis and response to treatment.

Background: At the time of diagnosis most of pancreatic cancer is in the advanced stage and curative resection becomes impossible. These inoperable diseases are labeled as “uresectable carcinonma pancreas.” Accurate and early assessment is essential for such patients to gain a better outcome. Objective: This study was carried out to evaluate clinical presentations, laboratory investigations, histopa­thology and imaging modalities used to diagnose and label pancreatic carcinoma as unresectable. Methods: This retrospective study was carried out from July 2004 to June 2006 in BIRDEM Hospital, Dhaka. After careful scrutiny of clinical pres­entation, laboratory imaging studies, tissue diagnosis, tumor markers and operative findings it was seen that 50 patients (sample size n = 50) were labeled as unresectable carcinoma pancreas. Male patients were 28 ( n 1 = 28) and female patients were 22 ( n 2 = 22). Chi-square (χ 2 ) test was applied and P value

Wei Lv, Tao Yan, Guojin Wang, Wei Zhao, Tao Zhang, Dinghua Zhou Hepatobiliary Surgery Department, Second Artillery General Hospital, Xicheng District, Beijing, People’s Republic of China Objective: To investigate the therapeutic effect and safety of high-intensity focused ultrasound (HIFU) therapy combined with gemcitabine in treating unresectable pancreatic carcinoma. Methods: The 45 patients suffering from pancreatic carcinoma were randomized into two groups. The patients in the experimental group (n=23) received HIFU in combination with gemcitabine and those in the control group (n=22) received gemcitabine alone. The effect and clinical benefit rates in the two groups were compared. The median survival time and 6-month and 12-month survival rates were calculated by Kaplan–Meier method and log-rank test. Results: The median survival time and 6-month survival rate were significantly higher in the experimental group than in the control group (8.91months vs 5.53months, 73.9% vs 40.9%, respectively P0.05). The clinical benefit rates in the experimental group and the control group were 69.6% and 36.3%, respectively (P

Background Celiac plexus neurolysis for the palliative reduction of pain in unresectable pancreatic carcinoma (PC) is safe but provides limited relief. In a previous study, we found that EUS-guided implantation of iodine-125 ( 125 I) around the celiac ganglia is a safe procedure and can induce apoptosis of local neurons in a porcine model. Objective To evaluate the safety and efficacy of direct celiac ganglion irradiation with 125 I seeds for the relief of moderate to severe pain secondary to unresectable PC. Design Prospective study. Setting Single, tertiary care referral center. Patients This study enrolled consecutive patients who had moderate to severe pain resulting from biopsy-proven unresectable PC. Intervention All patients underwent EUS-guided direct celiac ganglion irradiation with 125 I seeds. Follow-up was conducted at least once weekly until death. Main Outcome Measurements Blood parameters, Visual Analog Scale (VAS) score, mean analgesic (MS Contin [morphine sulfate]) consumption, and complications were evaluated during follow-up. Results Twenty-three patients with unresectable PC underwent the procedure. The mean number of seeds implanted in the celiac ganglion per patient was 4 (range 2-6). Immediately after the procedure, pain relief and analgesic consumption showed no significant changes compared with preoperative values. Six patients (26%) reported pain exacerbation. Two weeks later, the VAS score and mean analgesic consumption were significantly less than preoperative values. No procedure-related deaths or major complications occurred. Limitations Uncontrolled study. Conclusions EUS-guided direct celiac ganglion irradiation with 125 I seeds can reduce the VAS score and analgesic drug consumption in patients with unresectable PC.

Locally advanced unresectable pancreatic adenocarcinoma is characterized by poor survival despite chemotherapy and conventional radiation therapy (RT). Recent advances in real-time image-guided stereotactic radiosurgery (SRS) have made it possible to treat these cancers in two to four fractions followed by systemic chemotherapy.The aims of this study includes the following: (1) obtain local control of the disease; (2) improve the survival of these unresectable patients; (3) evaluate the toxicity of SRS; and (4) report results of the largest series from a single center.Pancreatic SRS involves delivery of high doses of accurately targeted radiation given non-invasively in two to four fractions. We treated 85 consecutive patients with locally advanced and recurrent pancreatic adenocarcinoma from February 2004 to November 2009. Age range: 36-88 years, median 66 years; sex: 50 males, 35 females; race: 79 Caucasian, five African American, one Asian; histology: 80 adenocarcinoma, three islet cell, two other. Pre-SRS staging: T(3-4) 85; N(+) 16, N(x) 57, N(0) 12; M(0) 64, M(1) 21. All patients were unresectable at the time of SRS. Seventy-one had no prior surgical resection, and 14 had local recurrence after prior surgical resection. Twenty-nine patients had progression of disease after prior conventional RT. Location of the tumor: head, 57; body and tail, 28. Pre-SRS chemotherapy was given in 48 patients. All patients received gemcitabine-based chemotherapy regimen after SRS. Median tumor volume was 60 cm(3). PET/CT scans done in 55 patients were positive in 52 and negative in three patients. Average maximum standard uptake value was 6.9. Pain score on a scale of 1-10 was: 0-3 in 54, 4-7 in 18, and 8-10 in 13 patients. SRS doses ranged from 15 to 30 Gy with a mean dose of 25.5 Gy delivered in 3 days divided in equal fractions. Mean conformality index was 1.6, and mean isodose line was 80%.Tumor control: complete, partial, and stable disease were observed in 78 patients for the duration of 3-36 months with median of 8 months. Pain relief was noted in majority of patients lasting for 18-24 weeks. Most of the patients died of distant disease progression while their primary tumor was controlled. Overall median survival from diagnosis was 18.6 months and from SRS it was 8.65 months. For the group of 35 patients with adenocarcinoma without prior surgical resection or RT and no distant metastases, the average and 1-year survival from diagnosis was 15 months and 50%, respectively, and from SRS it was 11.15 months and 30.5%, respectively.A total of 19 (22.37%) patients developed grades III/IV GI toxicity including duodenitis, 12 (14.1%); gastritis, 11 (12.9%); diarrhea, three (3.5%); and renal failure was noted in one (1.2%). Three patient had both gastritis and duodenitis. Toxicity was significantly more prevalent in the first 40 patients compared with the last 45 patients (32.5 vs 13.9%).SRS for unresectable pancreatic carcinoma can be delivered in three fractions with minimal morbidity and a local tumor control rate of 91.7%. The survival is comparable or better than the reported results for advanced pancreatic cancer, specifically for the group of previously untreated patients with unresectable tumors. Development of distant metastases remains a significant factor.

Survival in patients with unresectable pancreatic carcinoma is poor. Studies by Mayo Clinic and the Gastrointestinal Tumor Study Group (GITSG) have established combined modality treatment with chemotherapy and radiation as the standard of care. Use of gemcitabine-based chemotherapy alone has also been shown to provide a benefit, but 5‑year overall survival still remains less than 5%. Conventional radiotherapy is traditionally delivered over a six week period and high toxicity is seen with the concomitant use of chemotherapy. In contrast, SBRT can be delivered in 3–5 days and, when used as a component of combined modality therapy with gemcitabine, disruption to the timely delivery of chemotherapy is minimal. Early single-institution reports of SBRT for unresectable pancreatic carcinoma demonstrate excellent local control with acceptable toxicity. Use of SBRT in unresectable pancreatic carcinoma warrants further investigation in order to improve the survival of patients with historically poor outcomes.

Purpose To accurately determine the maximal tolerated dose, feasibility, and antitumor activity of concurrent chemoradiotherapy including twice-weekly gemcitabine in patients with unresectable pancreatic adenocarcinoma. Methods and Materials Eligible patients with histologically proven adenocarcinoma of the pancreas were included in this Phase I trial. Radiotherapy was delivered to a total dose of 50 Gy. Concurrent chemotherapy with twice-weekly gemcitabine was administered during the 5 weeks of radiotherapy, from an initial dose of 30 mg/m 2 . The gemcitabine doses were escalated in 10-mg/m 2 increments in a three-plus-three design, until dose-limiting toxicities were observed. Results A total of 35 patients were included in the trial. The feasibility of chemoradiotherapy was high, because all the patients received the planned total radiation dose, and 26 patients (74%) received ≥70% of the planned chemotherapy dose. The mean total delivered dose of gemcitabine was 417 mg/m 2 ( i.e., 77% of the prescribed dose). The maximal tolerated dose of twice-weekly gemcitabine was 70 mg/m 2 . Of the 35 patients, 13 had a partial response (37%) and 21 had stable disease (60%). Overall, the median survival and the 6-, 12-, and 18-month survival rates were 10.6 months and 82%, 31%, and 11%, respectively. Survival was significantly longer in patients with an initial performance status of 0 or 1 ( p = .004). Conclusion Our mature data have indicated that gemcitabine doses can be increased ≤70 mg/m 2 , when delivered twice-weekly with concurrent radiotherapy. This combination shows promises to achieve better recurrence-free and overall survival. These results will serve as a basis for further implementation of the multimodal treatment of locally advanced pancreatic carcinoma.

Gemcitabine (GEM) is the key drug for the chemotherapy of unresectable pancreatic cancer. However, the efficacy and safety of GEM has not been established in elderly patients. We retrospectively examined the prognosis of elderly pancreatic cancer patients treated with GEM.Sixty-six patients with unresectable pancreatic cancer (pathologically identified) and no prior chemotherapy were divided into three groups. Group A: patients aged 70 years or more who received standard GEM (1000 mg/m(2)) on days 1, 8, and 15 and rest on day 21; Group B: patients less than 70 years old who received standard GEM therapy; and Group C: patients under best supportive care.Median survival times (MSTs) (days) were 311 in group A (p 0.05 vs. group C), 292 in group B (p 0.05 vs. group C), and 127 in group C. Among the patients who received GEM, 23% patients in group A and 16% patients in group B obtained partial responses. The response rates and MSTs were similar in groups A and B, as well as in more aged (≥75 years) patients. Bone marrow suppression was more frequently seen in elderly patients. Cox's hazard model in patients aged 70 years or more revealed that GEM therapy reduced the hazard ratio for death (hazard ratio: 0.683, p = 0.041).Chemotherapy with GEM appears to be effective and safe in elderly patients as well as in younger patients. Patients with unresectable pancreatic carcinoma should receive GEM therapy even if they are aged 70 or more, even if they are aged 75 or more.

Pancreatic cancer patients present late in their course and surgical resection as a modality of treatment is of limited value. Majority develop loco-regional failure and distant metastasis, therefore, adjuvant therapy comprising of radiotherapy and chemotherapy are useful treatment options to achieve higher loco-regional control. Specialized irradiation techniques like intra-operative radiotherapy that help to increase the total tumor dose have been used, however, controvertible survival benefit was observed. Various studies have shown improved median and overall survival with chemoradiotherapy for advanced unresectable pancreatic carcinoma. The role of new agents such as topoisomerase I inhibitors also needs further clinical investigations.

BACKGROUND AND STUDY AIMS: Intraoperative and transdermal ultrasonography-mediated brachytherapies have been proved to be effective in postponing the development of abdominal carcinomas. The main purpose of this study was to evaluate the clinical efficacy and safety of endoscopic ultrasonography (EUS)-guided interstitial implantation of radioactive iodine 125 seeds in advanced pancreatic cancer. PATIENTS AND METHODS: In total, 22 patients with advanced pancreatic cancer and positive fine-needle aspiration results underwent EUS-guided interstitial implantation of iodine seeds. All enrolled patients received routine gemcitabine-based 5-fluorouracil chemotherapy 1 week after brachytherapy. RESULTS: All 22 patients were successfully implanted with 125 I seeds via EUS, with a median of 10 seeds and a maximum of 30 seeds per procedure. The median follow-up time of patients was 9.3 months, and the estimated median survival time was 9.0 months (95 % confidence interval 6.7 - 11.3 months). Partial remission was achieved in three cases (13.6 %) during the 4-week period, and disease in 10 patients (45.5 %) remained stable. Cancer finally progressed in 20 patients, all of whom died during 2 years of follow-up. Visual analog scale pain score dropped from 5.07 ± 2.63 to 1.73 ± 1.91 ( P> 0.01) 1 week after brachytherapy but increased again to 3.53 ± 1.51 1 month later ( P> 0.05 vs. baseline). There were no obvious complications following therapy. CONCLUSIONS: EUS-guided interstitial implantation of 125 I seeds may represent a safe alternative treatment option for locally advanced pancreatic cancer. Our preliminary data suggest improvement in pain, but no long-term survival benefit.

Aims: Adenocarcinoma of the pancreas is a cancer with extremely poor prognosis and limited therapeutic options. Retinoids are derivatives of vitamin A involved in the control of many biological functions, including cell growth and differentiation and the induction of apoptosis. On the basis of pre-clinical evidence and some clinical data, we conducted a phase II study of 13-cis-retinoic acid (13-cis-RA) in combination with gemcitabine in patients with unresectable pancreatic carcinoma. Materials and methods: Patients with histologically confirmed unresectable pancreatic carcinoma were treated with gemcitabine 1000 mg/m2 on days 8, 15, 22 plus 13-cis-RA 1 mg/kg on days 1e14 for six cycles. The end points included the objective response rate and median survival. Results: Thirty patients were recruited, 15 men and 15 women; 20 patients were evaluable. The median age was 65 years (range 44e79 years) and the median Karnofsky performance status was 80% (range 60e100%). The median followup was 21 months. One patient achieved a partial remission, seven patients had stable disease and 12 patients developed progressive disease. Toxicity was mainly haematological, with eight cases of grade 3 and four cases of grade 4 neutropenia, thrombocytopenia and anaemia. The median survival was 7.8 months (range 2.6e21.6 months). Conclusions: The combination of gemcitabine and 13-cis-RA was well tolerated, but we did not see improvement in the response rate. Further studies with other retinoids may be beneficial to patients with unresectable pancreatic cancer.

Objectives To evaluate whether a short radiation treatment (30 Gy, 3.0 Gy/fraction) had analgesic efficacy in patients with unresectable pancreatic carcinoma. Methods Twelve patients were included in this analysis. Before starting and at four weeks after radiation therapy, pain intensity was evaluated and analgesic drug therapy was adjusted until a 0–3 pain score was reached (WHO). Results No radiotherapy interruptions, no hospitalisation due to toxic reactions, and no severe toxicity were observed. Six patients (50%) had pain control without pharmacological therapy, three patients (25%) reduced their use (35%–72%) of analgesics, while in the remaining three patients (25%) there was no change in analgesic use. Overall, mean reduction in the use of analgesics was 63.1% ± 43.8%. During follow-up (44 months), two patients (16.7%) showed a worsening of pain that required increased analgesia; in one patient, percutaneous splanchnicectomy was necessary. Conclusion In patients excluded from standard concomitant chemoradiation, hypofractionated-accelerated radiotherapy is feasible and results in pain relief in most patients, documented as a reduced need for analgesics.

To evaluate, in patients with locally advanced pancreatic carcinoma undergoing concomitant chemoradiation, the impact of pretreatment hemoglobin (Hb) concentration on the outcome in terms of clinical response, local control, metastasis-free survival, disease-free survival, and overall survival.30 patients undergoing concomitant chemoradiation (5-fluorouracil [5-FU], 1,000 mg/m(2)/day, continuous i.v. infusion days 1-4 of radiotherapy) and external beam radiotherapy (50.4-59.4 Gy) were divided into two groups based on pretreatment median Hb value (11.5 g/dl). The potential prognostic factors examined besides Hb concentration were: tumor site (head vs body-tail), sex (female vs male), cN (cN0 vs nC1), dose of external beam radiotherapy (50.4 Gy vs 59.4 Gy), presence of jaundice at diagnosis (yes vs no), weight loss at diagnosis (or = 5 kg vs5 kg), epigastric-lumbar pain at diagnosis (yes vs no), maximum tumor diameter (40 mm vsor = 40 mm).Pretreatment Hb ranged between 9.6 and 15.0 g/dl. No statistically significant differences were observed as for clinical response and local control between patients with an Hbor = 11.5 g/dl and those with an Hb11.5 g/dl. Metastasis-free survival was 5.1 months in patients with an Hbor = 11.5 g/dl and 10.7 months in patients with an Hb11.5 g/dl (p = 0,010). Median actuarial disease-free survival was 5.1 and 10.2 months in patients with an Hbor = 11.5 and11.5 g/dl, respectively (p = 0.026). Median actuarial overall survival was 7.5 and 10.3 months in patients with an Hbor = 11.5 and11.5 g/dl; respectively (p = 0.039). On multivariate analysis, Hb concentration at diagnosis was the only factor prognostically correlated with metastasis-free survival (p = 0.026), disease-free survival (p = 0.032), and overall survival (p = 0.048).In a group of patients with locally advanced pancreatic carcinoma treated with chemoradiation, a significant correlation was observed between pretreatment Hb levels and metastasis-free survival, disease-free survival, and overall survival.

BACKGROUND The analgetic treatment of inoperable pancreatic cancer patients is of paramount importance. The relative ineffectiveness of pharmacological agents has led many investigators to recommend chemical neurolysis of the celiac ganglions for pain control. However, the assessment of the results and the effectiveness of the block carried out during laparotomy have been unclear. PATIENTS AND METHODS After 41 intraoperative celiac neurolytic blocks pain intensity was retrospectively analysed in 38 patients suffering from unresectable pancreatic carcinoma. The mean age of the patients was 59 years, the observation period after neurolysis ranged to 6 months. All patients underwent definitive neurolysis using 50 % ethanol in 0.5 % prilocaine. Immediate and long-term efficacy, analgetic consumption and mortality were evaluated at follow-up. The calculated parenteral equivalent morphine dosage (mg per day) was evaluated before as well as at different time points after treatment as an objective parameter to describe pain intensity. RESULTS 7 to 34 days (at discharge from the hospital) after block pain intensity was statistically highly significant reduced (p=0.016). Long-term results were obtained from 17 (10 to 12 weeks after intervention) and 9 (up to 20 weeks after intervention) patients respectively, demonstrating a long-lasting effect of the neurolysis. A statistical analysis was not possible because of the small patient 's number. CONCLUSIONS Intraoperative celiac neurolytic block is a safe and effective method of pain treatment in patients with unresectable pancreatic carcinoma. However, it alone provides complete pain relief until death only in a few cases. Therefore, it should be considered as an adjuvant treatment in the analgesic strategy. Combined palliative therapy is necessary in most of the cases.

BACKGROUND AND STUDY AIMS Our aim was to evaluate the feasibility and clinical outcome of intraluminal brachytherapy (ILBT) in the duct of Wirsung in patients with unresectable pancreatic adenocarcinoma. PATIENTS AND METHODS Nine patients (eight men, one woman; mean age 72.4 +/- 9.1, range 52 - 80) with unresectable pancreatic adenocarcinoma of the head or body underwent ERCP for biliary and/or pancreatic stent placement and placement of a nasopancreatic drain with/without nasobiliary drain. The ILBT dose administered was 30 - 50 Gy calculated at 1 cm from the iridium-192 wire axis. Seven patients received ILBT from the duct of Wirsung whereas two patients received dual-duct ILBT (duct of Wirsung and the common bile duct). Three patients received combined-modality treatment (ILBT with external beam radiotherapy and 5-fluorouracil). The patients were prospectively followed up. RESULTS No endoscopy-related complications occurred. No radiation-related toxicity occurred in patients treated with ILBT alone. One patient undergoing combined-modality treatment developed gastric bleeding. Intraluminal source dislodgement occurred in three patients. Obvious tumor mass reduction of greater than 50 % was seen in three patients at 8 weeks after brachytherapy. Median survival was 11 months (range 6 - 37 months) and the 1-year and 3-year actuarial survival rates were 44 % and 15 %, respectively. CONCLUSION Intraluminal brachytherapy in the duct of Wirsung in patients with unresectable pancreatic carcinoma is safe and feasible. Further clinical trials are warranted.

In patients with unresectable peripancreatic carcinoma, pain is generally treated with pain medication or with a celiac plexus blockade. Radiotherapy has also been reported to reduce pain. The efficacy of these treatment modalities is still under discussion. The aim of this study was to analyze the effects of the various types of pain management on patients who underwent palliative bypass surgery for unresectable peripancreatic carcinoma. During the period January 1995 to December 1998 a series of 98 patients underwent palliative bypass surgery, mostly for unresectable disease found during exploration. Patients were divided into three groups: palliative bypass surgery (BP), palliative bypass surgery with an intraoperative celiac plexus blockade (CPB), and palliative bypass surgery with or without celiac plexus blockade followed by high-dose conformal radiotherapy (RT). Radiotherapy was performed only in selected patients with locally advanced disease and without metastases, implying a better prognosis of the last group. The pain medication consumption, pain medication-free survival, hospital-free survival, and overall survival were analyzed. The preoperative consumption of pain medication was significantly higher in the CPB group than in the BP or RT group. The postoperative consumption of pain medication in the CPB, BP, and RT groups increased during follow-up from 15%, 17%, and 13% before surgery to 52%, 57%, and 46%, respectively, at three-fourths of the survival time (NS). This increase in consumption of pain medication was not different in the three groups. In the RT group the median pain medication-free survival was significantly longer than in the BP or CPB group (9.3 vs. 3.1 and 3.3 months; p = 0.02). The median hospital-free survival and median overall survival were significantly longer in the RT group than in the CPB group (10.3 vs. 6.8 months, p = 0.01; and 7.1 vs. 10.8 months, p = 0.01). Celiac plexus blockade as pain management did not result in an increase of the pain medication-free survival or overall survival. Therefore a positive effect of a celiac plexus blockade on pain could not be confirmed in the present study. Radiotherapy resulted in increased pain-medication survival, hospital-free survival, and overall survival compared to celiac plexus blockade. These effects are probably partly related to patient selection.

4120 Background: Predictive biomarkers of Overall Survival (OS) and Progression Free Survival (PFS) in locally advanced pancreatic cancer (LAPC) pts are mandatory. Baseline leukocyte, neutrophil and monocyte counts in addition to lymphocyte ratio (NLR) may predict OS in LAPC pts. Efficacy of chemoradiation (CRT) depending on neutrophil count was retrospectively analyzed in the largest Phase III cohort of LAPC. Methods: The international multicenter randomized LAP07 phase III trial (NCT00634725) has recruited 442 LAPC pts. We have studied the predictive and prognostic value of systemic inflammation, as defined: (i) baseline neutrophilia (neutrophil count > 7 G/L at first randomization) or (ii)increased absolute neutrophil count (IANC) after induction chemotherapy vs baseline. Univariate and multivariate Cox analysis evaluated the benefit of CRT for OS, PFS and Local Control (LC) in pts without systemic inflammation. Results: Patients with baseline neutrophilia (11%) had a worse OS (median 8.9 vs 13.3 months, p = 0.01). At 2nd randomization, 9% and 29% pts had baseline neutrophilia or IANC, respectively. Both neutrophilia (median OS 10.6 vs 16.1 months, p = 0.03) and IANC (median OS 14.6 vs 17.4 months, p = 0.02) predicted poor OS. Systemic inflammation predicted local resistance to CRT (p = 0.02, interaction = 0.015). After excluding pts with systemic inflammation, 1-year local control was 80% in CRT vs 54% in chemotherapy arms (p < 0.001). Pts without systemic inflammation in CRT arm had improved PFS vs chemotherapy arm (median 10.3 vs 8.3 months, p = 0.04). In multivariate analysis in this population, CRT increased PFS (HR = 0.66, 95%CI: 0.45 - 0.97, p = 0.03), after adjusting on age, tumor size, pain at enrollment, albumin, and CA 19.9 according to PROLAP nomogram parameters. Conclusions: In LAPC pts with tumor controlled after induction chemotherapy, systemic inflammation may help to better predict those who will benefit from CRT. This result may impact clinical management and the design of future clinical trials for LAPC. An external validation with a cohort from the ARCAD pancreas meta-analysis is under consideration. Clinical trial information: NCT00634725.

An Eastern Cooperative Oncology Group Study. J Clin Oncol 3:373-378, 1985 4. Moertel CG, Frytak S, Hahn RG, et al: Therapy of locally unresectable pancreatic carcinoma: A randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads 5-fluorouracil), and high dose radiation 5-flurouracil—The Gastrointestinal Tumor Study Group. Cancer 48:1705-1710, 1981 5. Gastrointestinal Tumor Study Group: Treatment of locally unresectable carcinoma of the pancreas: Comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy. J Natl Cancer Inst 80:751-755, 1988 6. Conroy T, Desseigne F, Ychou M, et al: FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364:1817-1825, 2011 7. Huguet F, Andre T, Hammel P, et al: Impact of chemoradiotherapy after disease control with chemotherapy in locally advanced pancreatic adenocarcinoma in GERCOR phase II and III studies. J Clin Oncol 25:326-331, 2007 8. Huguet F, Girard N, Guerche CS, et al: Chemoradiotherapy in the management of locally advanced pancreatic carcinoma: A qualitative systematic review. J Clin Oncol 27:2269-2277, 2009 9. Crane CH, Varadhachary GR, Yordy JS, et al: Phase II trial of cetuximab, gemcitabine, and oxaliplatin followed by chemoradiation with cetuximab for locally advanced (T4) pancreatic adenocarcinoma: correlation of Smad4 (Dpc4) immunostaining with pattern of disease progression. J Clin Oncol 29:3037-3043, 2011 10. Jones S, Zhang X, Parsons DW, et al: Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321:18011806, 2008 11. Philip PA, Mooney M, Jaffe D, et al: Consensus report of the National Cancer Institute Clinical Trials Planning Meeting on pancreas cancer treatment. J Clin Oncol 27:5660-5669, 2009

Summary Background Preclinical studies of liposomal doxorubicin (CAELYXTM) have demonstrated significant inhibition of growth of human pancreatic cancer explains in nude mice. This study evaluated the efficacy of CAELYXTM 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. CAELYXTM 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 CAELYXTM in this study. CAELYXTM 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.

This report describes the results of a phase II trial to evaluate the safety, feasibility and response of patients with irresectable, histologically proven, stage II-IV adenocarcinoma of the pancreas receiving high-dose octreotide treatment. Octreotide was self-administered subcutaneously (3 x 2000 micrograms per day) by 49 patients. Therapy was discontinued after progression of the disease. Due to the subseqment diagnosis of bile duct carcinoma and stage I disease, 2 patients were excluded, leaving 47 evaluable patients with measurable disease. The median Karnofsky score was 80%. 3 patients had stage II (6%), 19 stage III (40%), and 25 (53%) stage IV disease. Octreotide treatment resulted in stable disease in 9 patients (19%) for more than 12 weeks. No complete or partial response was observed. The median overall survival was 21.4 weeks and the median progression-free survival 9.0 weeks. Therapy with high-dose octreotide is feasible, well tolerated and might prolong survival. In a placebo-controlled phase III study the effects of octreotide in patients with pancreatic cancer will be confirmed.

Purpose: The combination of radiotherapy and fluorouracil (5-FU) in patients with locally unresectable pancreatic carcinoma has led to a significant increase in survival in comparison with radiotherapy alone. Doxifluridine (5-DFUR) is an orally active fluoropyrimidine, and its cytotoxic metabolite (5-FU) may concentrate in areas of high tumor vascularization. This trial was carried out with the aims of improving locoregional control and making lesions resectable in patients with unresectable pancreatic cancer. Methods: 5-DFUR was given at a dose of 500 mg/m 2 b.i.d. by way of mouth for 4 days every other week for a total of four courses, with leucovorin 25 mg b.i.d. orally being given 2 hours before each 5-DFUR administration. External beam RT was administered at a dose of 1000 cGy per week for 3 weeks, followed by a 2-week break and then by 1000 cGy per week for a further 2 weeks (a total dose of 5000 cGy). The patients were restaged 4 weeks after the end of treatment and explored for resection in cases of partial response (PR). Results: A total of 32 patients were treated between 1992 and 1997. Ab initio unresectability was shown by laparotomy (16 cases) or computed tomography (16 cases), and was due to vascular invasion in 27 patients, massive regional nodal metastases in nine, and both in four. The median age was 63 years (range 36–71); performance status (PS) (ECOG): 0–1 = 28 and PS 2 = 4. All the patients had measurable disease and were evaluable for response. There were seven PR (22%), 10 SD (31%), and 15 PD (47%). All of the responders underwent surgical exploration, and radical resection was possible in 5. Three of these patients are still disease-free with a follow-up of 18, 27, and 65 months; the other two cases relapsed 11 and 14 months after surgery. The median survival time was 9 months for the entire group, and 1-year survival rate was 31%. The treatment was never stopped because of toxicity. There were no CTC-NCI grade 3 or 4 toxic events; grade 1–2 diarrhea was observed in 10 cases. Conclusions: This preoperative regimen was feasible and led to a successful surgical resection in 16% of otherwise inoperable cases. The median survival was comparable with the results obtained after 5-FU infusion plus radiotherapy. The resectability rate, and the benefit in terms of survival in the resected patients, make these results worthy of confirmation by larger studies.

Exocrine pancreatic cancer is significantly more common in younger men than in younger women. The male-to-female sex ratio is, in most countries, between 1.25 and 1.75 to 1, but decreases with increasing age. Moreover, prior oophorectomy appeared in one study to be significantly more common in women with pancreatic cancer than in controls. This has raised interest in sex hormones in the development in pancreatic cancer. It has been questioned if there are estrogen receptors in ductal pancreatic cancer, but there are no doubt estrogen receptors and estrogen-binding protein in human healthy pancreas. It is also well proven that it is possible to influence experimental pancreatic cancer with estrogens. However, in clinical studies tamoxifen has repeatedly been shown to be without significant effects. On the other hand, there are also androgen receptors in pancreatic cancer and testosterone has been shown to strongly promote growth in experimental pancreatic cancers. It is therefore of considerable interest that an antiandrogen recently was shown to significantly prolong life in patients with unresectable pancreatic carcinoma. However, in patients with advanced pancreatic carcinoma the S-testosterone is low, far lower than what could be expected due to weight-loss and malnourishment alone. Pancreatic cancer has etiologically been connected to diet, for example the intake of fat. Cholecystokinin receptors have been found on human pancreatic cancer, possible to stimulate in vitro by cholecystokinin (CCK). Studies with CCK-receptor binding, hybridization with radiolabeled complementary DNA (cDNA) probes, or reverse-transcription polymerase chain reaction have shown that CCK-A receptors also are present in rat pancreatic putative preneoplastic lesions and cancer tissue, rat pancreatic-cancer cell lines, pancreatic carcinomas in transgenic mice, hamster pancreatic cancer, and human pancreatic cancer cell lines and tumors. Also, CCK-B receptors have been found in some human pancreatic cancers. There are a vast number of experiments done on CCK-stimulation of pancreatic cancer. They indicate that CCK may have a promotional effect on exocrine pancreatic cancer, but it is not probable that hyperstimulation with CCK alone induce pancreatic cancer. At present, however, despite a lot of evidence for a hormone-dependence of pancreatic cancer there are no data confirming a role for estrogens, androgens, CCK or their antagonists in clinical treatment of exocrine pancreatic cancer.

Most pancreatic carcinomas are unresectable at the time of diagnosis; therefore, palliative treatment is very often the main concern of clinicians in this setting. The main symptoms resulting in the need for palliation in pancreatic cancer are obstructive jaundice, duodenal obstruction and pain. Therapeutic endoscopy plays a major role in the palliation of obstructive jaundice by stent placement into the biliary ducts. Initial experience has also been gained recently with endoscopic placement of expandable metallic stents to treat gastric outlet obstruction. Much less is known about the possible role of endoscopic pancreatic stenting in patients with unresectable pancreatic carcinoma. The main indication for pancreatic ductal stenting is ‘obstructive’ pain related to meals in patients with dilated main pancreatic duct beyond the stricture and intraluminal brachyradiotherapy. The technique of endoscopic pancreatic stenting does not substantially differ from that applied on the biliary tree. When technically possible, placement of 10 French plastic stents is preferred. According to the authors’ indications, only about 15% of patients with advanced pancreatic cancer (55 of 355 in the present study) may potentially benefit from this technique. Pancreatic stenting may be obtained in more than 80% of these selected patients, with low morbidity (less than 10%) and no procedure-related mortality. According to the authors of the present and other studies reported in the literature, about 60% of patients treated because of ‘obstructive’ pain become symptom-free, and another 20% to 25% significantly reduce the amount of analgesic drugs required. Intraluminal brachyradiotherapy with 192iridium in the main pancreatic duct is a feasible and safe method to deliver high radiation doses to the tumour while sparing adjacent organs. Brachyradiotherapy may be performed alone or in conjunction with external beam radiotherapy. Because of the small number of patients suitable for this treatment, only a multicentre study will be able to detect whether intraluminal brachyradiotherapy in pancreatic cancer may have any positive impact on survival.

BACKGROUND Advanced unresectable pancreatic adenocarcinoma has a dismal prognosis. The authors previously have shown that retinoic acid (RA) and interferon-α (IFN-α) inhibit growth and induce differentiation in human pancreatic carcinoma cells in vitro and in vivo. The purpose of this trial was to examine the feasibility and tolerability of a combination therapy of 13-cis RA and IFN-α in patients with advanced unresectable pancreatic carcinoma. METHODS Twenty-two patients (median age, 62 years) with histologically confirmed, unresectable pancreatic adenocarcinoma classified as International Union Against Cancer Stage III (5 patients) or IV (17 patients) were included. Patients received 1 mg/kg body weight 13-cis RA orally and 6 million IU IFN-α subcutaneously daily. Restaging by ultrasound, computed tomography scan, and chest X-ray was performed every 2 months. RESULTS No complete remission and 1 partial remission (PR) (4.5%) were observed. Fourteen patients (63.6%) demonstrated stable disease with a median duration of 5.0 months (range, 2.3-17.7+ months). Toxicity mainly was related to IFN-α and predominantly was hematologic (no toxicity was World Health Organization [WHO] Grade 4 and 13.6% were WHO Grade 3). Nonhematologic toxicities did not exceed Grade 2 (skin and oral mucosa) and mainly were related to 13-cis RA. The median survival of the patients with Stage III disease was 8.7 months (range, 6.8-23.9+ months) and was 7.4 months for patients with Stage IV disease (range, 0.9-19.2+ months), resulting in a median overall survival of 7.7 months (range, 0.9-23.9+ months). CONCLUSIONS Combination therapy with 13-cis RA and IFN-α is feasible and well tolerated in patients with advanced pancreatic carcinoma. Based on the median survival rates observed in this study this combination should be investigated further in Phase III trials. Cancer 1998;83:2317-2323. © 1998 American Cancer Society.

Background To assess the efficacy of intraoperative ultrasound-guided implantation of 125I seeds for the treatment of unresectable pancreatic carcinoma, and analyze the associated prognostic factors. Methods Twenty-eight patients with pancreatic carcinoma who underwent laparotomy and were considered to have unresectable tumors were included in this study. Nine patients were pathologically diagnosed with Stage II disease, and nineteen patients with Stage III disease. Twenty-eight patients received intraoperative ultrasound-guided 125I seed implantation and received a D90 (at least 90% of the tumor volume received the reference dose) ranging from 60 to 163 Gy, with a median of 120 Gy. Seven patients received an additional 35–50 Gy external beam radiotherapy after seed implantation, and ten patients received two to ten cycles of chemotherapy. Overall survival of the patients was calculated and prognostic factors were evaluated. Results Of the patients, 94.1% (16/17) achieved good to medium pain relief. The tumor response rate was 78.6% (22/28), and local control was achieved in 85.7% (24/28) of patients. The 1-, 2- and 3-year survival rates were 30%, 11% and 4%, and the median survival was 10.1 months (95% CI: 9.0-10.9). Analysis using the Cox proportional hazards model suggested that patients younger than 60 years and patients who received a D90 higher than 110 Gy may survive for a longer period. Conclusions I seed implantation provides a safe and effective method to relieve pain, control local tumor growth and, to some extent, prolong the survival of patients with stage II and III pancreatic disease, without additional complications. Age and accumulated dose may be factors predictive of a favorable outcome for patients with unresectable pancreatic carcinoma treated with 125I seeds. These findings need to be validated by conducting further studies with larger cohorts.

The indications and outcomes of aggressive reoperation in patients referred to the National Cancer Institute (NCI) for protocol therapy of locally advanced pancreatic carcinoma were investigated. Twenty-nine patients referred to the NCI after exploration and determination of unresectability elsewhere were considered to have localized disease after a metastatic work-up. These patients were then entered onto NCI adjuvant therapy protocols and taken to exploratory laparotomy. Intraoperatively, patients underwent complete resection if possible ; otherwise varying palliative surgical procedures were performed. Of the 29 patients, 16 underwent complete resection of their disease, and 13 were unresectable. Two patients suffered postoperative mortality. Disease-specific survival of the resected patients was significantly better than that of the unresectable patients (P 109 months) underwent definitive surgery after a palliative procedure elsewhere. Complete resection of pancreatic carcinoma contributes to increased survival. The intraoperative definition of unresectability in pancreatic cancer varies with the degree of pancreatitis present, the surgical expertise of the surgeon, and the available ancillary services. Given the extremely grave prognosis of patients with unresectable pancreatic carcinoma, locally unresectable patients without peritoneal seeding or distant metastases at exploration should be considered for referral for protocol therapy to centers where expertise in radical surgery for pancreatic cancer exists.

Pancreatic cancer is the fifth leading cause of death from malignant disease in the Western world. The majority of patients with carcinoma of the exocrine pancreas haveunresectable, incurable disease at the time of diagnosis. At present, no medical treatment can be considered as standard therapy in advanced or locally unresectable pancreatic carcinoma. Since no chemotherapeutic regimen has been demonstrated to offer a clear survival benefit for these patients, future clinical trials should be designed to evaluate quality of life and palliation of symptoms, such as recent observations with gemcitabine, a novel nucleoside analogue. In this review, recent developments in our understanding of the biology and pathogenesis of pancreatic carcinoma are described. Future progress in the cellular and molecular aspects of this disease may lead to potential new remedies.

The decision to perform surgical versus nonoperative palliation for unresectable pancreatic cancer is influenced by a number of factors. In most cases, patient symptoms clearly dictate the management. In patients with symptoms of duodenal obstruction at the time of presentation, surgery is the only option. In patients with obstructive jaundice alone, the options for management must be weighed against factors such as overall health status, projected survival, and procedure-related morbidity and mortality. A prospective multicenter trial recently analyzed factors influencing perioperative morbidity and mortality following both curative and palliative surgery for pancreatic cancer. This analysis demonstrated that preoperative diabetes, low Kanofsky's index, and liver metastases are significant risk factors in predicting perioperative morbidity and mortality in patients undergoing palliative procedures for pancreatic cancer. Another analysis focusing on tumor characteristics suggested that for patients with Stage I and Stage II disease (i.e., with no evidence of systemic metastases), survival and the potential for late duodenal obstruction favor surgical management. In summary, although patient management must be individualized, most patients with pancreatic cancer in good medical health and with no evidence of systemic disease are most appropriately managed with surgical palliation. This option affords patients the best chance of avoiding the late complications of recurrent jaundice, duodenal obstruction, and disabling pain. Surgical palliation can generally be completed with an acceptable perioperative morbidity and mortality and a hospital stay of approximately 2 weeks. Finally, only surgical exploration can offer full opportunity for resection for cure.

PURPOSE: To compare findings with computed tomography (CT) and magnetic resonance (MR) imaging in pancreatic adenocarcinoma and to determine optimal pulse sequences for MR imaging. MATERIALS AND METHODS: CT scans and MR images were compared of 189 adult patients with known or suspected adenocarcinoma of the pancreas. Levels of confidence were correlated with surgical and pathologic results. RESULTS: The accuracy of CT was 0.73 and of MR imaging was 0.70. The negative predictive value of CT was 0.28 and of MR imaging was 0.23. The positive predictive value of CT was 0.89 and of MR imaging was 0.88. Gradient-echo and T1-weighted spin-echo sequences ranked equally in evaluation of vascular invasion, T1-weighted spin-echo sequences were preferred for assessing lymphadenopathy, and T2-weighted spin-echo sequences were preferred for detecting hepatic metastases. CONCLUSIONS: Cross-sectional imaging modalities are useful in the identification of unresectable pancreatic carcinoma. CT is recommended for initial im...

A 79-year-old man was referred to our hospital with severe nemia. Laboratory data showed a hemoglobin level of 6.9 mg/dL. pper GI endoscopy showed hemorrhage from the papilla of Vater Fig. 1A). Computed tomography (CT) revealed a solid tumor in the ancreatic head, dilatation of the main pancreatic duct, liver metasasis and ascites (Fig. 1B). The celiac trunk, superior mesenteric rtery, and common hepatic artery were constricted by tumor invaion. Neither a pseudoaneurysm nor pseudocyst was apparent, and hus we diagnosed hemosuccus pancreaticus due to tumor hemrrhage. On endoscopic retrograde cholangiopancreatography, the ancreatic duct of the head was constricted. A plastic stent was laced to press upon the tumor to stop the hemorrhage, but this ailed.

BACKGROUND Preclinical and clinical data suggest that N-phosphonacetyl-L-aspartic acid (PALA) can augment the cytotoxic effects of 5-fluorouracil (5-FU). In addition, the combination of 5-FU and radiation therapy has been used with success in prolonging survival and providing palliation of symptoms in patients with advanced unresectable pancreatic carcinoma. This Phase I study was undertaken to determine the feasibility and evaluate the qualitative and quantitative toxicities of PALA and escalating doses of 5-FU administered concomitantly with radiation therapy in patients with locally advanced nonmetastatic pancreatic adenocarcinoma. METHODS Ten previously untreated patients with advanced nonmetastatic adenocarcinoma of the pancreas were treated with 250 mg/m2 of PALA given as an intravenous bolus followed 24 hours later by 5-FU, which was given by continuous 24-hour infusion every week. The 5-FU doses were assigned according to a Phase I drug escalation (1000 mg/m2, 1300 mg/m2, and 1700 mg/m2). Radiation therapy was delivered concurrently with chemotherapy at a dose of 180 cGy per fraction (900 cGy per week) over 6 1/2 weeks. PALA and 5-FU were continued weekly after the end of radiation therapy, with disease assessments made every 8 weeks. Chemotherapy was continued until the disease progressed. RESULTS All 10 patients were evaluable. The maximum tolerated dose (MTD) of 5-FU was 1300 mg/m2. Two of the four patients treated at the 1700 mg/m2 dose level experienced dose-limiting toxicities, nausea/vomiting and mucositis, respectively. Toxicities were mild to moderate at the 1000 mg/m2 and 1300 mg/m2 dose levels. Two patients treated with 5-FU at the 1300 mg/m2 dose level had complete responses, and one patient treated at the 1700 mg/m2 dose level had a partial response. The median survival was 12.5 months, and four patients survived more than 1 year. CONCLUSIONS PALA and 5-FU administered concomitantly with radiation therapy is an active regimen in locally advanced, unresectable pancreatic cancer. Dose-limiting toxicities are nausea/vomiting and mucositis. The MTD of 5-FU is 1300 mg/m2. The regimen is well tolerated and administered in an outpatient setting.

Eighty patients with pancreatic carcinoma were treated by intraoperative radiotherapy (IORT) with or without surgical resection of the tumor, and the results were compared with those of 111 patients treated by surgery alone. For resectable patients, the radiation dose was 30 Gy and the average field sizes were 8 or 10 cm; for unresectable patients, these values were 20–30 Gy and 6 or 8 cm, respectively. No side effects of IORT were observed. In 49 resectable stage III patients, the IORT group (n=16) had a higher survival rate than the non-IORT group (n=33); i.e., 1-year survival rates of 44.6% vs 23% and 2-year survival rates of 37.2% vs 7.7% after surgery (P

To assess the safety and efficacy of the combination of recombinant adenovirus-p53 (rAd-p53) with radiochemotherapy for treating unresectable pancreatic carcinoma.The eligible patients received concurrent rAd-p53 intratumoral injection and radiochemotherapy. Intratumoral injection of rAd-p53 was guided by B ultrasound. Radiochemotherapy consisted of intensity-modulated radiotherapy (IMRT) at two dose levels and intravenous gemcitabine (Gem). For radiotherapy, gross target volume (GTV) and clinical target volume (CTV) were 55-60 Gy and 45-55 Gy in 25-30 fractions, respectively. Concurrent intravenous gemcitabine was administered at 350 mg/m(2), weekly, for 6 weeks. The primary end points included toxicity, clinical benefit response (CBR) and disease control rate (DCR). The secondary end points included progression-free survival (PFS) and overall survival (OS).Fifteen eligible patients were enrolled. Eight patients (53.3%) were evaluated as CBR and 12 (80%) achieved DCR. The median PFS and OS were 6.7 and 13.8 months, respectively. One-year PFS and OS were 40.0% and 51.1%, respectively. There were 8 (53.3%) patients reported grade 3 toxicities including neutropenia (6 patients, 40%), fever (1 patient, 6.7%) and fatigue (1 patient, 6.7%). There was no grade 4 toxicity reported.Combination of rAd-p53 in unresectable pancreatic carcinoma showed encouraging efficacious benefit and was well tolerated. Long-term follow-up is needed to confirm the improvement of PFS and OS.

Ultrasound remains the most readily available and least expensive of the imaging techniques used in assessment of the upper abdomen. Ultrasound is very useful in the detection of pancreatic tumors as well as in the evaluation of the extent of the disease. If ultrasound fails technically or is inconclusive, CT is recommended. Determination of CA 19-9 may help to decide whether ultrasound should be followed by CT or other examinations (51). Patients with any equivocal or inconclusive abnormality on ultrasound or CT should undergo ERCP. Even when ultrasound and CT of the pancreas appear normal there may be an indication for performing ERCP if the clinical suspicion of pancreatic cancer is still strong (52). Angiography is a reliable method of assessing major vascular tumor involvement, which to most surgeons would be a sign of unresectability. Although for some investigators CT is superior to angiography in assessing vascular involvement, angiography is performed preoperatively in many cases because it delineates the vascular anatomy, which can be abnormal in up to one third of patients. Percutaneous biopsy is an important technique for confirming the radiologic diagnosis of unresectable pancreatic carcinoma, particularly for differentiating pancreas carcinoma from other focal pancreatic lesions such as islet cell tumor, lymphoma, and chronic pancreatitis.

Purpose: To evaluate the efficacy of gemcitabine-based chemoradiation (CT-RT) in treating patients (pts) affected by locally advanced pancreatic cancers (LAPC). Methods and Materials: Weekly gemcitabine (100 mg/m2) was given as a 24-hour infusion during the course of three-dimensional radiotherapy (50.4 Gy to the tumor, 39.6 Gy to the nodes). After CT-RT, pts received five cycles of sequential chemotherapy with gemcitabine (1000 mg/m2; 1, 8, q21). Response rate was assessed according to World Health Organization criteria 6 weeks after the end of CT-RT. Local control (LC), time to progression (TTP), metastases-free survival (MFS), and overall survival (OS) were analyzed by the Kaplan Meier method. Results: Forty pts (male/female 22/18; median age 62 years, range, 36-76) were treated from 2000 to 2005. The majority had T4 tumour (n = 34, 85%), six pts (15%) had T3 tumour. Sixteen pts (40%) were node positive at diagnosis. Grade 3-4 acute toxicity was observed in 21 pts (52.5%). Thirty pts (75%) completed the treatment schedule. A clinical response was achieved in 12 pts (30%). With a median follow-up of 76 months (range, 32-98), 2-year LC was 39.6% (median, 12 months), 2-year TTP was 18.4% (median, 10 months), and 2-year MFS was 29.7% (median, 10 months). Two-year OS (25%; median, 15.5 months) compared with our previous study on 5-fluorouracil-based CT-RT (2.8%) was significantly improved (p