Influence of Resection Margins on Survival for Patients With Pancreatic Cancer Treated by Adjuvant Chemoradiation and/or Chemotherapy in the ESPAC-1 Randomized Controlled Trial

OBJECTIVE: To assess the influence of resection margins on survival for patients with resected pancreatic cancer treated within the context of the adjuvant European Study Group for Pancreatic Cancer-1 (ESPAC-1) study. SUMMARY BACKGROUND DATA: Pancreatic cancer is associated with a poor long-term survival rate of only 10% to 15% after resection. Patients with positive microscopic resection margins (R1) have a worse survival, but it is not known how they fare in adjuvant studies. METHODS: ESPAC-1, the largest randomized adjuvant study of resectable pancreatic cancer ever performed, set out to look at the roles of chemoradiation and chemotherapy. Randomization was stratified prospectively by resection margin status. RESULTS: Of 541 patients with a median follow-up of 10 months, 101 (19%) had R1 resections. Resection margin status was confirmed as an influential prognostic factor, with a median survival of 10.9 months for R1 versus 16.9 months months for patients with R0 margins. Resection margin status remained an independent factor in a Cox proportional hazards model only in the absence of tumor grade and nodal status. There was a survival benefit for chemotherapy but not chemoradiation, irrespective of R0/R1 status. The median survival was 19.7 months with chemotherapy versus 14.0 months without. For patients with R0 margins, chemotherapy produced longer survival compared with to no chemotherapy. This difference was less apparent for the smaller subgroup of R1 patients, but there was no significant heterogeneity between the R0 and R1 groups. CONCLUSIONS: Resection margin-positive pancreatic tumors represent a biologically more aggressive cancer; these patients benefit from resection and adjuvant chemotherapy but not chemoradiation. The magnitude of benefit for chemotherapy treatment is reduced for patients with R1 margins versus those with R0 margins. Patients with R1 tumors should be included in future trials of adjuvant treatments and randomization and analysis should be stratified by this significant prognostic factor.     

Molecular alterations associated with improved survival in pancreatic cancer patients treated with radiation or chemotherapy

Multiple genetic alterations, several of which may be important prognostic markers, characterize the development of cancer in pancreas. We review our findings from previously published studies with regard to molecular alterations associated with survival differences in patients treated with conventional radiation and chemotherapies used as adjuvant or palliative therapy. K-ras-negative patients with pancreas cancer show improved survival with radiation therapy compared to K-ras-positive patients with pancreas cancer. p53 expression is associated with shorter survival when compared to no p53 expression in pancreas cancer patients treated with radiation therapy or chemotherapy. Pancreas cancer patients whose tumors express p21 show significant survival advantages when treated with chemotherapy or radiation therapy. An inverse relationship is observed with respect to p21 and p53 expression and clinical stage. Although stage and surgical resectability remain the most important variables with respect to pancreas cancer survival, these findings suggest promising opportunities for gene therapies designed to enhance p21 expression or restore wild-type K-ras or p53 function in pancreatic tumors. Received for publication on June 17, 1998; accepted on July 27, 1998     

Is Adjuvant Chemotherapy Really Needed After Curative Surgery for Rectal Cancer Patients Who are Node-Negative After Neoadjuvant Chemoradiotherapy?

Purpose  

Adjuvant chemotherapy is currently offered, as standard, after curative resection for patients with rectal cancer who receive neoadjuvant chemoradiation (NCRT). We postulate that adjuvant chemotherapy adds minimal oncologic benefit for patients who undergo total mesorectal excision who are node-negative after neoadjuvant chemoradiation.     

Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience.

OBJECTIVE: This study was designed to evaluate prospectively survival after pancreaticoduodenectomy for pancreatic adenocarcinoma, comparing two different postoperative adjuvant chemoradiation protocol to those of no adjuvant therapy. SUMMARY BACKGROUND DATA: Based on limited data from the Gastrointestinal Tumor Study Group, adjuvant chemoradiation therapy has been recommended after pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancrease. However, many patients continue to receive no such therapy. METHODS: From October 1991 through September 1995, all patients with resected, pathologically confirmed adenocarcinoma of the head, neck, or uncinate process of the pancreas were reviewed by a multidisciplinary group (surgery, radiation oncology, medical oncology, and pathology) and were offered three options for postoperative treatment after pancreaticoduodenectomy: 1) standard therapy: external beam radiation therapy to the pancreatic bed (4000-4500 cGy) given with two 3-day fluorouracil (5-FU) courses and followed by weekly bolus 5-FU (500 mg/m2 per day) for 4 months; 2) intensive therapy: external beam radiation therapy to the pancreatic bed (5040-5760 cGy) with prophylactic hepatic irradiation (2340-2700 cGy) given with and followed by infusional 5-FU (200 mg/m2 per day) plus leucovorin (5 mg/m2 per day) for 5 of 7 days for 4 months; or 3) no therapy: no postoperative radiation therapy or chemotherapy. RESULTS: Pancreaticoduodenectomy was performed in 174 patients, with 1 in-hospital death (0.6%). Ninety-nine patients elected standard therapy, 21 elected intensive therapy, and 53 patients declined therapy. The three groups were comparable with respect to race, gender, intraoperative blood loss, tumor differentiation, lymph node status, tumor diameter, and resection margin status. Univariate analyses indicated that tumor diameter < 3 cm, intraoperative blood loss < 700 mL, absence of intraoperative blood transfusions, and use of adjuvant chemoradiation therapy were associated with significantly longer survival (p < 0.05). By Cox proportional hazards survival analysis, the most powerful predictors of outcome were tumor diameter, intraoperative blood loss, status of resection margins, and use of postoperative adjuvant therapy. The use of postoperative adjuvant chemoradiation therapy was a predictor of improved survival (median survival, 19.5 months compared to 13.5 months without therapy; p = 0.003). The intensive therapy group had no survival advantage when compared to that of the standard therapy group (median survival, 17.5 months vs. 21 months, p = not significant). CONCLUSIONS: Adjuvant chemoradiation therapy significantly improves survival after pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas. Based on these survival data, standard adjuvant chemoradiation therapy appears to be indicated for patients treated by pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas. Intensive therapy conferred no survival advantage over standard therapy in this analysis.     

Chemoradiation followed by chemotherapy before resection for borderline pancreatic adenocarcinoma

BACKGROUND: For patients with borderline resectable pancreatic cancer, preoperative chemoradiation and standalone chemotherapy may allow for R0 resection and improved survival. METHODS: A retrospective review of patients with borderline resectable pancreatic cancer treated with preoperative chemoradiation and standalone chemotherapy was undertaken. Clinical variables, including disease-free and overall survival, were collected. Univariate analysis was used to identify factors impacting survival. RESULTS: Thirteen patients with borderline resectable pancreatic cancer were treated with preoperative chemoradiation and chemotherapy. Morbidity and mortality were 38% and 0. There were 2 R1 and 11 R0 resections. Nine patients are alive with a median follow-up of 20 months. Five patients recurred at a median of 4 months. Tumor fibrosis < or = 60% was associated with recurrence and poor survival. CONCLUSIONS: Preoperative chemoradiation and chemotherapy allow a select group of patients with borderline resectable pancreatic cancer to undergo an R0 or R1 resection with acceptable morbidity and mortality. Tumor response may be associated with survival.     

P21WA F_1/CIP_1和P53基因表达与膀胱癌生物学行为的关系

目的 :探讨膀胱癌 P2 1WAF1 / CIP1 、P5 3基因的表达、相互间的调控及其与生物学行为的关系。方法 :采用免疫组织化学 ABC方法检测 12 2例有随访结果的膀胱癌患者的 P2 1WAF1 / CIP1 、P5 3基因表达 ,并采用双变量相关分析、L ogistic回归分析和 Kaplan- Meier法分析。结果 :P5 3野生型肿瘤中 P2 1WA F1 / CIP1 阳性表达率明显高于 P5 3突变型肿瘤 ;P5 3突变型肿瘤中保持 P2 1WAF1 / CIP1 阳性表达者具有与 P5 3野生型肿瘤同样低的复发率和较长的生存期。结论 :维持 P2 1WAF1 / CIP1 的表达可清除 P5 3突变蛋白的有害作用 ;根据 P2 1WAF1 /CIP1 表达状况 ,结合临床分期可对膀胱癌的恶性程度及预后作出更准确的评估 ,对拟定治疗方案有重要的指导意义     

Pancreatic intraepithelial neoplasia in association with intraductal papillary mucinous neoplasms of the pancreas: implications for disease progression and recurrence

The development of pancreatic cancer (PC) several years after curative resection for noninvasive intraductal papillary mucinous neoplasm (IPMN) and the presence of PC distant from IPMN suggest that PC may develop independently of the IPMN. Here, we identified pancreatic intraepithelial neoplasia (PanIN) lesions, the putative precursors of PC, in the ducts of pancreata resected for IPMN and assessed the frequency of molecular aberrations common to PanIN and PC, within these lesions. The protein expression of p53, p21(WAF1/CIP1), cyclin D1, p16(INK4A) and DPC4/Smad4 were examined by immunohistochemistry in 267 PanIN lesions from a cohort of 23 patients with IPMN. Overexpression of p21(WAF1/CIP1) was present in PanIN-1A and -1B lesions and increased in frequency in PanIN-2 and PanIN-3. Overexpression of p53 and cyclin D1, and loss of p16(INK4A) expression were detected in PanIN-2 and PanIN-3 lesions. Loss of DPC4/Smad4 expression occurred only in the PanIN-3 lesions. PanIN lesions that were more dysplastic than the coincident IPMN were identified in 5 of 12 patients, and 2 of these contained a greater number of aberrations in protein expression than the IPMN. PanIN lesions seen in association with IPMN demonstrate molecular and histologic changes identical to PanIN lesions found in association with PC and, in some cases, are more advanced than the associated IPMN. These data suggest that PanIN lesions found in the ducts of a pancreas with IPMN may be relevant to the development of PC either coincident with IPMN or in the remnant pancreas after curative resection of IPMN.     

Impact of medical and surgical intervention on survival in patients with cholangiocarcinoma

AIM:To examine surgical and medical outcomes for patients with cholangiocarcinoma using a populationbased cancer registry.METHODS:Using the California Cancer Registry’s Cancer Surveillance Program,patients with intrahepatic cholangiocarcinoma treated in Los Angeles County from 1988 to 2006 were identified and evaluated for clinical and pathologic factors and therapies received(surgery,radiation,and chemotherapy).The surgical cohort was further categorized into three treatment groups:patients who received adjuvant chemotherapy,adjuvant chemoradiation,or underwent surgery alone(no chemotherapy or radiation administered).Survival was assessed by Kaplan-Meier method;and Cox proportional hazard modeling was used in multivariate analysis.RESULTS:Of 825 patients,60.2% received no treatment.Of the remaining 328 patients,18.5% chemotherapy only,7.4% chemoradiation,and 13.8% underwent surgery.More male patients underwent surgical resection(P = 0.004).Surgical patients were younger than the patients receiving chemotherapy or chemoradiation(P < 0.001).Of the surgical cohort(n = 114),60.5% underwent surgery alone while 39.5% underwent surgery plus adjuvant therapy(chemotherapy n = 20;chemoradiation,n = 21)(P < 0.001).Median survival for all patients in the study was 6.6 mo.Median survival was highest for patients who underwent surgery(23 mo),whereas both chemotherapy(9 mo) and chemoradiation(8 mo) alone were each less effective(P < 0.001).By multivariate analysis,extent of disease,receipt of surgery,and administration of chemotherapy(with/without surgery) were independent predictors of overall survival.CONCLUSION:This study demonstrates that surgery is a critical treatment modality.Multimodality treatment has yet to be standardized,but play a role in optimal therapy for cholangiocarcinoma.     

Neo-adjuvant Chemoradiation Therapy Using S-1 Followed by Surgical Resection in Patients with Pancreatic Cancer

Objective

The aim of this study was to compare short-term surgical results in pancreatic cancer patients who underwent surgical resection after neo-adjuvant chemoradiation therapy (NACRT) using S-1.

Methods

The study population comprised 77 patients with pancreatic cancer between 2006 and 2010. Out of 34 patients who underwent staging laparoscopy between 2008 and 2010, 31 patients without occult distant organ metastasis underwent chemoradiation and of whom 30 underwent pancreatectomy (NACRT group). Of the other 43 patients, 36 underwent surgical resection in 2006?C2008, followed by adjuvant therapy (adjuvant group). The primary endpoint was frequency of pathological curative resection (R0).

Results

The new regimen of NACRT was feasible and safe. Twenty-eight of 30 (93%) patients in the NACRT group had R0 resection, which was significantly higher than in the adjuvant group (21 of 36 patients, 58%, p?=?0.005). The number and extent of metastatic lymph nodes in the NACRT group (1 (0?C25), N0/1; 18 of 38) was significantly lower than in the adjuvant group (2 (0?C19), N0/1; 23 of 30), p?=?0.0363). The frequency of intractable ascites in the NACRT group (eight of 30) was significantly higher than in the adjuvant group (two of 36, p?=?0.035).

Conclusion

Neo-adjuvant chemoradiation therapy using S-1 followed by pancreatectomy can improve the rate of pathologically curative resection and reduces the number and extent of lymph node metastasis.     

Sensitivity to chemoradiation predicts development of metastasis in muscle-invasive bladder cancer patients

ObjectivesIn bladder-sparing approaches for muscle-invasive bladder cancer (MIBC) involving transurethral resection of the bladder tumor (TURBT) and chemoradiation, survival outcomes are excellent for patients who achieve tumor-free state after TURBT and chemoradiation but poor for those with persistent disease. Since metastatic disease accounts for most bladder cancer deaths, we hypothesized that tumor sensitivity to chemoradiation may reflect metastatic potential in MIBC.Materials and methodsFrom 1997 to 2010, 179 cT2-4aN0M0 bladder cancer patients underwent TURBT and induction chemoradiation (40 Gy with cisplatin 20 mg/d for 5 days × 2). Study subjects were 73 patients who had had macroscopic disease after TURBT and were evaluated for tumor sensitivity to the induction chemoradiation; of the 73 patients, chemoradiation response was evaluated pathologically in partial and radical cystectomy specimens for 8 and 44 patients, respectively, and clinically for the remaining 21 who did not undergo cystectomy. Tumors were defined as chemoradiation-sensitive when they regressed to T0 pathologically for the 52 patients undergoing cystectomy or clinically for the 21 undergoing no cystectomy; otherwise, they were defined as chemoradiation-resistant. Primary and secondary endpoints were metastasis-free and cancer-specific survival, respectively. The association between chemoradiation sensitivity and development of metastasis was investigated in MIBC patients.ResultsOf the 73 patients, 21 (29%: 13 pathologic and 8 clinical T0) had chemoradiation-sensitive tumors while 52 (71%) had chemoradiation-resistant tumors. Median follow-up was 53 months. Multivariate analysis identified chemoradiation resistance as the strongest independent predictor for the development of metastasis (hazard ratio (HR) 18.9, P < 0.0001). When stratified by chemoradiation sensitivity, 5-year metastasis-free and cancer-specific survival rates were 94.7% and 100%, respectively, for patients with chemoradiation-sensitive tumors, and 45.7% (P = 0.0005) and 41.0% (P < 0.0001), respectively, for patients with chemoradiation-resistant tumors.ConclusionsChemoradiation sensitivity predicts the development of metastasis in bladder cancer. Clinical and translational research results indicate that chemoradiation sensitivity is likely to reflect metastatic potential.     

Location, not staging, of cholangiocarcinoma determines the role for adjuvant chemoradiation therapy

The role of adjuvant chemoradiation therapy (CT/XRT) in the treatment of cholangiocarcinoma is controversial. We undertook this study to determine whether CT/XRT is appropriate after resection of cholangiocarcinomas. One hundred ninety-two patients with cholangiocarcinomas were treated from 1988 to 1999. After resection, patients were assigned a stage (TNM) and were stratified by location of the tumor as intrahepatic, perihilar, and distal tumors. Data are presented as mean +/- standard deviation. Of 192 patients 92 (48%) underwent resections of cholangiocarcinomas. Thirty-four patients had liver resections, 25 had bile duct resections, and 33 underwent pancreaticoduodenectomies. Thirty-four patients had adjuvant CT/XRT, three had adjuvant chemotherapy, four had neoadjuvant CT/XRT, and 50 had no radiation or chemotherapy. Mean survival of resected patients with adjuvant CT/XRT was 42 +/- 37.0 months and without CT/XRT it was 29 24.5 months (P = 0.07). Mean survival of patients with distal tumors receiving or not receiving CT/XRT was 41 +/- 21.8 versus 25 +/- 20.1 months, respectively, (P = 0.04). Adjuvant chemoradiation improves survival after resection for cholangiocarcinoma (P = 0.07) particularly in patients undergoing resection for distal tumors (P = 0.04). Benefits of adjuvant CT/XRT are apparent when stratified by location of cholangiocarcinomas rather than staging.     

Radical transurethral resection in the management of muscle-invasive bladder cancer

The morbidity of radical cystectomy and early reports of good results have stimulated interest in radical transurethral resection of bladder tumors (TURBT) for muscle-invasive transitional-cell carcinoma of the bladder. Various investigators have used surgery alone or with adjuvant or neoadjuvant chemotherapy or radiation. Further research is necessary to define the indications, but at present, radical TURBT for muscle-invasive cancer appears to be appropriate for patients too ill to undergo radical cystectomy, those who decline the open operation, and those enrolled in clinical trials of this approach to bladder cancer.     

Effect of neoadjuvant therapy on local recurrence after resection of pancreatic adenocarcinoma

BACKGROUND: It is unknown whether neoadjuvant chemoradiotherapy, compared with adjuvant chemoradiotherapy, decreases the rate of local recurrence after resection of pancreatic adenocarcinoma. STUDY DESIGN: This is a retrospective case review of 102 patients with pancreatic adenocarcinoma who underwent pancreatic resection between 1993 and 2005. RESULTS: Of 102 patients with pancreatic adenocarcinoma who underwent surgical resection, 19 (19%) had no additional treatment, 41 (40%) underwent adjuvant chemoradiotherapy, and 42 (41%) were treated preoperatively with neoadjuvant chemoradiotherapy. Patients selected to receive neoadjuvant therapy were more likely to have locally advanced tumors. Based on initial CT scan, the percentage of patients with unresectable or borderline resectable tumors in the neoadjuvant group was 67%, compared with 22% in the adjuvant group. Nevertheless, patients receiving neoadjuvant chemoradiotherapy were less likely to have a local recurrence develop than patients receiving adjuvant chemoradiotherapy (5% versus 34%, p = 0.02). For those patients with tumors determined to be resectable on initial CT scan, local recurrences were observed in 31% (10 of 32) of patients in the adjuvant therapy group, compared with only 7% (1 of 14) of the neoadjuvant group. Intraoperative radiation therapy, administered to 51% of patients, was not associated with a lower rate of local recurrence. CONCLUSIONS: Neoadjuvant chemoradiotherapy is associated with improved local tumor control in patients undergoing resection for pancreatic carcinoma.     

Clinicopathologic Features and Treatment Trends of Pancreatic Neuroendocrine Tumors: Analysis of 9,821 Patients

The natural history of pancreatic neuroendocrine tumors (PNET) remains poorly defined. Our objectives were to examine the clinicopathologic features of PNETs, to assess treatment trends over time, and to identify factors associated with undergoing resection. From the National Cancer Data Base (1985–2004), 9,821 patients were identified with PNETs. Clinicopathologic features and treatment trends were examined. Multivariable logistic regression was used to assess factors associated with undergoing resection. Of 9,821 patients with PNETs, 85% were nonfunctional, 7.1% were functional, and 7.9% were carcinoid tumors. Of the 3,851 (39.0%) patients who underwent pancreatectomy, 449 (11.7%) received adjuvant chemotherapy, and 254 (6.6%) received adjuvant radiation. From 1985 to 2004, utilization of pancreatectomy increased from 39.4 to 44.3% (P < 0.0001). Patients were less likely to undergo resection if they were >55 years old, had tumors in the head of the pancreas, tumors ≥4 cm, or had distant metastases (P < 0.0001). Patients treated at NCCN/NCI, academic, or high-volume hospitals were more likely to undergo resection. There are disparities in the utilization of pancreatectomy for PNETs. As PNETs have a better prognosis than adenocarcinoma, concerns regarding the morbidity and mortality of pancreatic surgery and neoplasms should not preclude resection.     

The predictive value of p53 and p33ING1b in patients with Dukes'C colorectal cancer

Objective Identification of biological markers that may predict response to chemotherapy would allow the individualization of treatment by enabling selection of patients most likely to benefit from chemotherapy. The aims of this study were to determine whether p53 mutation status and p53 and p33^ING1b protein expression can predict which patients with Dukes’ C colorectal cancer following curative surgical resection respond to adjuvant chemotherapy with 5‐fluorouracil (5‐FU). Method Patients with Dukes'C colorectal cancer (n = 41) were studied. DNA was extracted and analysed for p53 mutation using PCR‐based direct DNA sequencing. Tumours were analysed for p53 protein expression by immunohistochemistry using DO‐7 monoclonal antibody and for p33^ING1b protein expression using GN1 monoclonal antibody. Results There was a significant association between p53 mutation status analysed by gene sequencing and overall and metastasis‐free survival (P = 0.03 and 0.004, respectively, log‐rank test). By contrast, no significant correlation was found between p53 and p33^ING1b protein expression and overall or metastasis‐free survival. Conclusion In patients with Dukes'C colorectal cancer who underwent curative surgical resection of the primary tumour, followed by 5‐FU‐based adjuvant chemotherapy, p53 mutation status as assessed by gene sequencing is a significant predictor of overall and metastasis‐free survival.     

A prospective study of adjuvant surgical resection after chemotherapy for limited small cell lung cancer. A University of Toronto Lung Oncology Group study

Seventy-two patients with limited small cell lung cancer were identified as candidates for adjuvant operation after chemotherapy. All patients received preoperative chemotherapy with cyclophosphamide, doxorubicin HCl (Adriamycin), and vincristine, or the epipodophyllotoxin derivative VP-16 and cisplatin. The rate of response to chemotherapy was 80% (complete response 38% and partial response 42%). After chemotherapy, 57 patients (79.1%) were candidates for adjuvant surgical resection, but only 38 underwent thoracotomy. Eight required a pneumonectomy, 25 a lobectomy, and five patients had no resection. Postoperative pathologic study revealed only small cell lung cancer for 29 patients, mixed and non-small cell lung cancer for two, non-small cell lung cancer for four, and no residual tumor in three patients. Pathologic staging revealed seven patients in stage I (N0), nine in stage II (N1), and 22 in stage III. The median survival time for the 38 surgical patients was 91 weeks and projected 5-year survival rate 36%. Patients with pathologic stage I disease had significantly longer survival times (median not reached) than did patients in stage II or stage III (median survival 69 and 52 weeks, respectively). Within the group not undergoing operation, 19 patients responded to therapy and were eligible for adjuvant surgical resection, but did not undergo thoracotomy (10 patients were randomized to radiation only, and nine patients refused operation). Their median survival of 51 weeks was inferior to that of the 38 surgical patients (p = 0.049). Adjuvant surgical resection after chemotherapy resulted in long-term survival and cure for a significant proportion of patients with pathologic stage I disease. A significant improvement in survival could not be documented for patients in stages II and III. Intensive pretreatment investigation including mediastinoscopy is essential to exclude patients who will not benefit from adjuvant surgical resection.     

Differences in gene expression in muscle-invasive bladder cancer: a comparison of Italian and American patients

OBJECTIVE: To seek differences in gene expression in the primary muscle-invasive bladder cancers of two cohorts of patients having different survival rates. An Italian group treated by transurethral resection of the bladder tumor (TURBT) and neo-adjuvant chemotherapy using methotrexate, vinblastine, adriamycin and cisplatin (M-VAC) followed by TURBT, partial cystectomy or radical cystectomy (75% 3-year survival) was compared to an American cohort treated by radical cystectomy (51% 3-year survival). METHODS: Immunohistochemistry was used to examine the protein expression levels of three genes that act at the G1/S cell cycle checkpoint, p53, p21/waf-1/cip1 (a downstream effector gene in the p53 pathway) and Rb, plus a major inhibitor of apoptosis, Bcl-2. RESULTS: For the bladder cancers of the Italian patient cohort, there was a significantly higher rate of p53 immunopositivity (93 vs. 63%, p = 0.002) and a significantly lower rate of Rb loss (25 vs. 54%, p = 0.009). In bivariate analysis, 72% of Italian tumors were immunopositive for both p53 and p21 (p53+/p21+) vs. 49% for the American tumors. The subset of Italian patients with p53+/p21+ tumors were more frequently disease-free (stage pT0) following chemotherapy and were less likely to fail therapy than those with p53+/p21- tumors (p = 0.0357). Loss of Rb staining was associated with a decreased 5-year survival in the Italian, but not in the American patients. CONCLUSIONS: (1) Significant differences in the expression of the p53, p21 and Rb genes were found between the 2 groups of patients. (2) Italian patients with p53+/p21+ tumors had significantly lower recurrence rates after TURBT and chemotherapy than those having p53+/p21- tumors. (3) Absence of p21 immunopositivity in the Italian tumors may identify alterations in the p53 pathway that predict poor outcome.     

Local therapy for rectal cancer

Local procedures for carefully selected distal rectal cancer offer significant advantages such as sphincter preservation and avoidance of radical surgery. However, since preoperative selection criteria including current imaging modalities are unable to definitively stage regional lymph node status, local therapies for rectal cancer have the inherent potential disadvantage of undertreating a fraction of patients due to unresected mesorectal/regional lymph node disease. Current available data suggests that the local approach may be appropriate only for carefully selected T1 tumors with favorable pathologic features. Inferior local control and survival reported for T2 tumors and T1 tumors with unfavorable features, despite the addition of chemoradiation, outweigh the advantages of the local approach. Patients with unfavorable tumors who are unable to tolerate radical resection or who refuse surgery may be treated with local excision with or without adjuvant chemoradiation. Other modalities, such as electrocoagulation and endocavitary radiation, may also be valuable in this setting, as well as preoperative chemoradiation followed by local excision. Regardless of the approach used, all patients undergoing local therapy of a rectal cancer require careful long-term follow-up, because these patients remain at significant risk for local recurrence and distant failure.     

Intraarterial Adjuvant Chemotherapy after Pancreaticoduodenectomy for Pancreatic Cancer: Significant Reduction in Occurrence of Liver Metastasis

The clinical benefit of adjuvant chemotherapy in pancreatic cancer patients is still questionable. Phase II studies using radiochemotherapy based on 5-fluorouracil (5-FU) provided evidence of an increase in median survival times. Because palliative chemotherapy by celiac artery infusion (CAI) led to an increase in survival in pancreatic cancer, we treated 24 patients with adjuvant CAI following resection of the head of the pancreas for pancreatic cancer (21 patients with Union Internationale contre le Cancer (UICC) stage III, 2 with UICC stage II, 1 with UICC stage I). Catheters were placed angiographically into the celiac artery and remained there for 5 consecutive days. One cycle of chemotherapy consisted of mitoxantrone, 5-FU, folinic acid, and cisplatinum. This treatment was repeated five times at monthly intervals. CAI was well tolerated, and World Health Organization (WHO) grade III toxicities were observed in 8%; WHO grade IV was seen in none of the treatment cycles. Furthermore, we observed pain reduction in nearly all patients under CAI. Median survival times in patients who received CAI were 23 months for all patients, whereas in patients who did not receive adjuvant treatment the median survival was 10.5 months. With Kaplan-Meier regression analysis of the patients who were curatively resected (R0 resection) and received CAI, the overall 4-year survival was 54%, whereas in patients without CAI the 4-year survival was 9.5%. The occurrence of liver metastases in the CAI group went down to 17%. These results demonstrate that CAI is well tolerated, reduces the risk of liver metastasis, and increases the survival time of pancreatic cancer patients.